Lyme disease vaccines comprising an adjuvant and borrelia outer surface protein a and c antigens

Abstract

The present disclosure relates to immunogenic compositions comprising a. Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and an adjuvant or adjuvants. In some aspects, the immunogenic composition further comprises a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen. In some aspects, the immunogenic compositions are suitable for stimulating an immune response against Borrelia in a subject. The present disclosure also relates to kits of, uses of, and methods of using the immunogenic compositions.

Description

LYME DISEASE VACCINES COMPRISING AN ADJUVANT AND BORRELIAOUTER SURFACE PROTEIN A AND C ANTIGENSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority from U.S. provisional application No. 63 / 512,871 filed July 10, 2023, U.S. provisional application No. 63 / 512,874 filed July 10, 2023, and U.S. provisional application No. 63 / 581,228 filed September 7, 2023, the contents of which are incorporated by reference in their entireties.SUBMISSION OF SEQUENCE LISTING AS XML FILE

[0002] The present application is being filed along with a Sequence Listing in electronic format. The contents of the electronic Sequence Listing (377882008740SEQLIST.xml; Size: 531,413 bytes; and Date of Creation: July 9, 2024) is herein incorporated by reference in its entirety.FIELD

[0003] The present disclosure relates to immunogenic compositions comprising Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen and an adjuvant or adjuvants. The present disclosure also relates to immunogenic compositions comprising a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen, a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and an adjuvant or adjuvants. In some aspects, the immunogenic compositions are suitable for stimulating an immune response against Borrelia in a subject. The present disclosure also relates to articles of manufacturing comprising, uses of, and methods of using the immunogenic compositions.BACKGROUND

[0004] Lyme borreliosis, or Lyme disease, is the most commonly reported tick-borne disease in Europe and North America. The disease is caused by infection with spirochetal bacteria from the genus Borrelia. A monovalent serotype 1-OspA-based vaccine (LYMErix™) was approved and marketed in the USA for the prevention of Lyme disease caused by B. burgdorferi sensu stricto (s.s. but the vaccine is no longer available. Currently, there is no commercially available preventative medicament for Lyme disease. Thus, there is an unmet need for a safe and effective Lyme disease vaccine.SUMMARY

[0005] Provided herein in some embodiments is an immunogenic composition, comprising (i) a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen, (ii) a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and (iii) an adjuvant selected from the group consisting of a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0006] Also provided herein in some embodiments is an immunogenic composition, comprising (i) a Borrelia outer surface protein A (OspA) antigen, (ii) a Borrelia outer surface protein C (OspC) antigen, and (iii) an adjuvant selected from the group consisting of a tolllike receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0007] Also provided herein in some embodiments is an immunogenic composition, comprising (i) a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen and (ii) an adjuvant selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0008] Also provided herein in some embodiments is an immunogenic composition, comprising (i) a Borrelia outer surface protein C (OspC) antigen and (ii) an adjuvant selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in- water emulsion comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0009] In some of any embodiments, the immunogenic composition does not comprise an RNA polynucleotide encoding a non-OspC Borrelia outer surface protein antigen. In some of any embodiments, the immunogenic composition does not comprise a non-OspC Borrelia outer surface protein antigen.

[0010] In some of any embodiments, the immunogenic composition comprises a Borrelia outer surface protein A (OspA) antigen.

[0011] In some of any embodiments, the adjuvant is a TLR9 agonist. In some of any embodiments, the immunogenic composition further comprises a second adjuvant. In some of any embodiments, the second adjuvant is selected from an aluminum salt adjuvant; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0012] In some of any embodiments, the adjuvant is a liposome-based adjuvant comprising a lipopolysaccharide and a saponin. In some of any embodiments, the immunogenic composition further comprises a second adjuvant. In some of any embodiments, the second adjuvant is selected from an aluminum salt adjuvant; a TLR9 agonist; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0013] In some of any embodiments, the adjuvant is an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester. In some of any embodiments, the immunogenic composition further comprises a second adjuvant. In some of any embodiments, the second adjuvant is selected from an aluminum salt adjuvant; a TLR9 agonist; and a liposome-based adjuvant comprising a lipopolysaccharide and a saponin.

[0014] In some of any embodiments, the TLR9 agonist is an oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. In some of any embodiments, the oligonucleotide is from 10 to 35 nucleotides in length.

[0015] In some of any embodiments, the oligonucleotide comprises the sequence 5’- AACGTTCGAG-3’ (SEQ ID NO:2). In some of any embodiments, the oligonucleotide comprises the sequence of 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO:1).

[0016] Also provided herein in some embodiments is an immunogenic composition, comprising a Borrelia outer surface protein A (OspA) antigen, a Bowe Ha outer surface protein C (OspC) antigen, and a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2) and an unmethylated cytidine-phospho-guanosine (CpG) motif.

[0017] Also provided herein in some embodiments is an immunogenic composition, comprising a Borrelia outer surface protein C (OspC) antigen, and a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising thesequence 5’-AACGTTCGAG-3’ (SEQ ID N0:2) and an unmethylated cytidine-phospho- guanosine (CpG) motif.

[0018] In some of any embodiments, the oligonucleotide comprises the sequence of 5’- TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO:1).

[0019] Also provided herein in some embodiments is an immunogenic composition, comprising a Borrelia outer surface protein A (OspA) antigen, a Borrelia outer surface protein C (OspC) antigen, and the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’- TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif.

[0020] Also provided herein in some embodiments is an immunogenic composition, comprising a Borrelia outer surface protein C (OspC) antigen, and the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO:1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif. In some of any embodiments, the immunogenic composition does not comprise a non-OspC Borrelia outer surface protein antigen.

[0021] In some of any embodiments, the immunogenic composition further comprises a second adjuvant. In some of any embodiments, the second adjuvant is selected from an aluminum salt adjuvant; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0022] In some of any embodiments, the second adjuvant is an aluminum salt adjuvant.

[0023] Also provided herein in some embodiments is an immunogenic composition, comprising: (i) a Borrelia outer surface protein A (OspA) antigen, (ii) a Borrelia outer surface protein C (OspC) antigen, (iii) the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif, and (iv) an aluminum salt adjuvant.

[0024] Also provided herein in some embodiments is an immunogenic composition, comprising: (i) a Borrelia outer surface protein C (OspC) antigen, (ii) a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2) and an unmethylated cytidine-phospho- guanosine (CpG) motif, and (iii) an aluminum salt adjuvant.

[0025] In some of any embodiments, the aluminum salt adjuvant comprises one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate. In some of any embodiments, the aluminum salt adjuvant comprises aluminum hydroxide.

[0026] In some of any embodiments, the immunogenic composition comprises from about 0.25 to about 1.25 mg Al3+, from about 0.25 mg to about 0.50 mg Al3+, or from about 0.30 mg to about 0.40 mg Al3+.

[0027] In some of any embodiments, the oligonucleotide is a single-stranded oligodeoxynucleotide. In some of any embodiments, the oligonucleotide is fully RNA. In some of any embodiments, the oligonucleotide is an RNA / DNA chimera.

[0028] In some of any embodiments, the oligonucleotide comprises at least one phosphorothioate linkage. In some of any embodiments, the oligonucleotide comprises only phosphorothioate linkages. In some of any embodiments, the oligonucleotide comprises a combination of one or more phosphodiester linkages and one or more phosphorothioate linkages.

[0029] In some of any embodiments, the immunogenic composition comprises from about 375 pg to about 6000 pg of the TLR9 agonist or from about 750 pg to about 3000 pg of the TLR9 agonist. In some of any embodiments, the immunogenic composition comprises about 375 pg, about 750 pg, about 1000 pg, about 1500 pg, about 3000 pg, or about 6000 pg of the TLR9 agonist.

[0030] In some of any embodiments, the lipopolysaccharide is a lipid A or a derivative thereof. In some of any embodiments, the lipopolysaccharide is a monophosphoryl lipid A or a derivative thereof. In some of any embodiments, the lipopolysaccharide is 3-O-desacyl-4'- monophosphoryl lipid A. In some of any embodiments, the lipopolysaccharide is 3-deacyl- phosphorylated hexa-acyl disaccharide.

[0031] In some of any embodiments, the immunogenic composition comprises from about 1 pg to about 100 pg, from about 10 pg to about 50 pg, from about 20 pg to about 30 pg, from about 21 pg to about 29 pg, from about 22 pg to about 28 pg, from about 23 pg to about 27 pg, or from about 24 pg to about 26 pg of the lipopolysaccharide. In some of any embodiments, the immunogenic composition comprises from about 1 pg to about 30 pg, from about 5 pg to about 15 pg, from about 6 pg to about 14 pg, from about 7 pg to about 13 pg, from about 8 pg to about 12 pg, or from about 9 pg to about 11 pg of the lipopolysaccharide.In some of any embodiments, the immunogenic composition comprises from about 1 pg to about 9 pg, from about 2 pg to about 8 pg, from about 3 pg to about 7 pg, or from about 4 pg to about 6 pg of the lipopolysaccharide.

[0032] In some of any embodiments, the saponin is derived from the bark of Quillaja saponaria Molina. In some of any embodiments, the saponin is Quil A or a derivative thereof. In some of any embodiments, the saponin is QS-17. In some of any embodiments, the saponin is QS-21.

[0033] In some of any embodiments, the immunogenic composition comprises from about 1 pg to about 100 pg, from about 10 pg to about 50 pg, from about 20 pg to about 30 pg, from about 21 pg to about 29 pg, from about 22 pg to about 28 pg, from about 23 pg to about 27 pg, or from about 24 pg to about 26 pg of the saponin. In some of any embodiments, the immunogenic composition comprises from about 1 pg to about 30 pg, from about 5 pg to about 15 pg, from about 6 pg to about 14 pg, from about 7 pg to about 13 pg, from about 8 pg to about 12 pg, or from about 9 pg to about 11 pg of the saponin. In some of any embodiments, the immunogenic composition comprises from about 1 pg to about 9 pg, from about 2 pg to about 8 pg, from about 3 pg to about 7 pg, or from about 4 pg to about 6 pg of the saponin.

[0034] In some of any embodiments, the liposome-based adjuvant further comprises a sterol. In some of any embodiments, the sterol is P-sitosterol, stigmasterol, ergosterol, ergocalciferol, or cholesterol. In some of any embodiments, the sterol is cholesterol.

[0035] In some of any embodiments, the ratio of saponin to sterol is from 1 : 1 to 1 : 100 w / w or from 1 : 1 to 1 :5 w / w. In some of any embodiments, the ratio of saponin to sterol is about 1 : 1 w / w.

[0036] In some of any embodiments, the liposome-based adjuvant further comprises a neutral lipid. In some of any embodiments, the neutral lipid is a phosphatidylcholine. In some of any embodiments, the phosphatidylcholine is eggyolk phosphatidylcholine, dioleoyl phosphatidylcholine (DOPC), or dilauryl phosphatidylcholine. In some of any embodiments, the phosphatidylcholine is DOPC.

[0037] In some of any embodiments, the sorbitan ester is sorbitan ester 20. In some of any embodiments, the sorbitan ester is sorbitan ester 85.

[0038] In some of any embodiments, the polyoxyethylene sorbitan ester is polyoxyethylene sorbitan ester 20. In some of any embodiments, the polyoxyethylene sorbitan ester is polyoxyethylene sorbitan ester 80.

[0039] In some of any embodiments, the immunogenic composition comprises from about 2% w / v to about 7% w / v, from about 3% w / v to about 6% w / v, or from about 4% w / v to about 5% w / v of the squalene.

[0040] In some of any embodiments, the immunogenic composition comprises from about 0.2% w / v to about 0.8% w / v, from about 0.3% w / v to about 0.7% w / v, or from about 0.4% w / v to about 0.6% w / v of the sorbitan ester.

[0041] In some of any embodiments, the immunogenic composition comprises from about 0.2% w / v to about 0.8% w / v, from about 0.3% w / v to about 0.7% w / v, or from about 0.4% w / v to about 0.6% w / v of the polyoxyethylene sorbitan ester.

[0042] In some of any embodiments, the OspA antigen is two or more OspA antigens. In some of any embodiments, the two or more OspA antigens are a first OspA antigen and a second OspA antigen. In some of any embodiments, the two or more OspA antigens are a first OspA antigen, a second OspA antigen, and a third OspA antigen. In some of any embodiments, each of the two or more OspA antigens have non-identical amino acid sequences.

[0043] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently is a B. burgdorferi, B. afzelii, B. bavariensis, B. garinii, B. mayonii, B. lusitaniae, B. bissettii, B. valasiana, or B. spielmanii OspA antigen. In some of any embodiments, the OspA antigen is a B. burgdorferi OspA antigen.

[0044] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises one or more epitopes from an OspA protein. In some of any embodiments, the one or more epitopes comprise at least 2, 3, 4, 5, or 6 epitopes from across one or more OspA proteins. In some of any embodiments, the one or more epitopes comprise at least 2, 3, 4, 5, or 6 epitopes from across at least 2, 3, 4, 5, or 6 OspA serotypes.

[0045] In some of any embodiments, the one or more epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO:4-49. In some of any embodiments, the one or more epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO:4-49.

[0046] In some of any embodiments, the one of more epitopes comprise an epitope selected from the sequences of amino acids set forth in any of SEQ ID NO:9, 10, 33, 34, 36, 47, and 49.

[0047] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any one of SEQ ID NO:50-62.

[0048] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any one of SEQ ID NO:50-62.

[0049] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises the sequence of amino acids set forth in any one of SEQ ID NO:50-62.

[0050] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently is an OspA chimeric antigen comprising a plurality of epitopes from one or more OspA proteins. In some of any embodiments, the plurality of epitopes comprise at least 2, 3, 4, 5, or 6 epitopes from across at least 2, 3, 4, 5, or 6 OspA serotypes.

[0051] In some of any embodiments, the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in any of SEQ ID NO:4-49. In some of any embodiments, the plurality of epitopes are independently selected from the sequences of amino acids set forth in any of SEQ ID NO: 4-49.

[0052] In some of any embodiments, the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in any of SEQ ID NO:9, 10, 33, 34, 36, 47, and 49. In some of any embodiments, the plurality of epitopes comprise are independently selected from the sequences of amino acids set forth in any of SEQ ID NO:9, 10, 33, 34, 36, 47, and 49.

[0053] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any one of SEQ ID NO:63-82.

[0054] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any one of SEQ ID NO:63-82.

[0055] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises the sequence of amino acids set forth in any one of SEQ ID NO:63-82.

[0056] In some of any embodiments, the OspA antigen (e.g., a first, second, and / or third OspA antigen) independently comprises a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any one of SEQ ID NO: 79-81.

[0057] In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:80. In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:80.

[0058] In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:81.

[0059] In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 80 and a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO: 80 and a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:81.

[0060] In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79, a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 80, and a third OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some of any embodiments, the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:79, a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:80, and a third OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:81.

[0061] In some of any embodiments, the OspA antigen independently is non-lipidated. In some of any embodiments, the OspA antigen independently is lipidated.

[0062] In some of any embodiments, the OspC antigen is a B. burgdorferi, B. afzelii, B. bavariensis, B. garinii, B. mayonii, B. lusitaniae, B. bissettii, B. valasiana, or B. spielmanii OspC antigen. In some of any embodiments, the OspC antigen is a B. burgdorferi OspC antigen.

[0063] In some of any embodiments, the OspC antigen comprises one or more epitopes from an OspC protein. In some of any embodiments, the one or more epitopes comprise atleast 2, 3, 4, or 5 epitopes from one or more OspC proteins. In some of any embodiments, the one or more epitopes comprise at least 2, 3, 4, or 5 epitopes from across at least 2, 3, 4, or 5 OspC serotypes.

[0064] In some of any embodiments, the one or more epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO:83-223 and 449-521. In some of any embodiments, the one or more epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 83-223 and 449-521.

[0065] In some of any embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:224- 307.

[0066] In some of any embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:224-307.

[0067] In some of any embodiments, the OspC antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:224-307.

[0068] In some of any embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 303.

[0069] In some of any embodiments, the OspC antigen is an OspC chimeric antigen comprising a plurality of epitopes from one or more OspC proteins. In some of any embodiments, the plurality of epitopes comprise at least 2, 3, 4, or 5 epitopes from across at least 2, 3, 4, or 5 OspC serotypes.

[0070] In some of any embodiments, the plurality of epitopes comprise linear epitopes from the loop 5 (L5) and alpha helix 5 (H5) regions of an OspC serotype. In some of any embodiments, the OspC serotype is selected from a group consisting of OspC serotypes A, B, C, D, E, F, G, H, I, K, M, N, and U.

[0071] In some of any embodiments, the OspC serotype comprises five OspC serotypes. In some of any embodiments, the five OspC serotypes are OspC serotypes C, F, H, M, and N.

[0072] In some of any embodiments, the OspC serotype comprises six OspC serotypes. In some of any embodiments, the six OspC serotypes are OspC serotypes C, F, H, I, M, and N.

[0073] In some of any embodiments, the OspC serotype comprises seven OspC serotypes.In some of any embodiments, the seven OspC serotypes are OspC serotypes C, D, F, H, I, M, and N.

[0074] In some of any embodiments, the OspC serotypes comprises ten OspC serotypes. In some of any embodiments, the ten OspC serotypes are OspC serotypes A, B, C, F, H, I, K, M, N, and U.

[0075] In some of any embodiments, the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO:83-223 and 449-521. In some of any embodiments, the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 83-223 and 449-521.

[0076] In some of any embodiments, the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO: 84-93. In some of any embodiments, the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 84-93. In some of any embodiments, the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93. In some of any embodiments, the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93.

[0077] In some of any embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:379- 448, 520, and 521.

[0078] In some of any embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

[0079] In some of any embodiments, the OspC antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

[0080] In some of any embodiments, the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 379, 520, and 521.

[0081] In some of any embodiments, the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 379.

[0082] In some of any embodiments, the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 520.

[0083] In some of any embodiments, the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 521.

[0084] In some of any embodiments, the OspC antigen is a first OspC antigen, and the immunogenic composition further comprises a second OspC antigen. In some of any embodiments, the first OspC antigen is an OspC chimeric antigen comprising a plurality of linear epitopes from one or more OspC proteins, and the second OspC antigen is an OspC protein comprising one or more conformational epitopes.

[0085] In some of any embodiments, the immunogenic composition is a 0.3 mL to 1.5 mL dose.

[0086] In some of any embodiments, the immunogenic composition is for stimulating an immune response against Borrelia in a subject by administering to the subject an effective amount of the immunogenic composition. In some of any embodiments, the immunogenic composition is for protecting a subject from infection by Borrelia by administering to the subject an effective amount of the immunogenic composition. In some of any embodiments, the immunogenic composition is for preventing a subject from contracting Lyme disease by administering to the subject an effective amount of the immunogenic composition. In some of any embodiments, the immunogenic composition is for preventing the onset of Lyme disease in a subject by administering to the subject an effective amount of the immunogenic composition. In some of any embodiments, the subject has previously been infected by Borrelia.

[0087] In some of any embodiments, the subject a human subject.

[0088] In some of any embodiments, the human subject is at least 18 years of age. In some of any embodiments, the human subject is from 18 years to 70 years of age.

[0089] In some of any embodiments, the human subject is under 18 years of age. In some of any embodiments, the human subject is from 2 years to 5 years of age. In some of any embodiments, the human subject is from 5 years to 18 years of age.

[0090] Also provided herein in some embodiments is a method for stimulating an immune response against Borrelia in a subject, comprising administering to a subject an effective amount of any of the provided immunogenic compositions.

[0091] Also provided herein in some embodiments is a method for protecting a subject from infection by Borrelia, comprising administering to a subject an effective amount of any of the provided immunogenic compositions.

[0092] Also provided herein in some embodiments is a method for preventing a subject from contracting Lyme disease, comprising administering to a subject an effective amount of any of the provided immunogenic compositions.

[0093] Also provided herein in some embodiments is a method for preventing the onset of Lyme disease in a subject, comprising administering to a subject an effective amount of any of the provided immunogenic compositions. In some of any embodiments, the subject has previously been infected by Borrelia.

[0094] In some of any embodiments, the immunogenic composition is administered by intramuscular injection.

[0095] In some of any embodiments, a first dose and a second dose of the immunogenic composition is administered to the subject. In some of any embodiments, the second dose of the immunogenic composition is administered from about 2 weeks to about 10 weeks after the administration of the first dose of the immunogenic composition. In some of any embodiments, the second dose of the immunogenic composition is administered about 1 month or about 2 months after the administration of the first dose of the immunogenic composition.

[0096] In some of any embodiments, a third dose of the immunogenic composition is administered to the subject. In some of any embodiments, the third dose of the immunogenic composition is administered from about 4 months to about 8 months after the administration of the first dose of the immunogenic composition. In some of any embodiments, the third dose of the immunogenic composition is administered about 6 months after the administration of the first dose of the immunogenic composition.

[0097] In some of any embodiments, a booster dose of the immunogenic composition is administered to the subject. In some of any embodiments, the booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose.

[0098] In some of any embodiments, a plurality of booster doses is administered to the subject. In some of any embodiments, the first booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose. In some of any embodiments, a booster dose is administered yearly.

[0099] In some of any embodiments, the subject a human subject.

[0100] In some of any embodiments, the human subject is at least 18 years of age. In some of any embodiments, the human subject is from 18 years to 70 years of age.

[0101] In some of any embodiments, the human subject is under 18 years of age. In some of any embodiments, the human subject is from 2 years to 5 years of age. In some of any embodiments, the human subject is from 5 years to 18 years of age.

[0102] Also provided herein in some embodiments is use of any of the provided immunogenic compositions for stimulating an immune response against Borrelia in a subject by administering to the subject an effective amount of the immunogenic composition.

[0103] Also provided herein in some embodiments is use of any of the provided immunogenic compositions for protecting a subject from infection by Borrelia by administering to the subject an effective amount of the immunogenic composition.

[0104] Also provided herein in some embodiments is use of any of the provided immunogenic compositions for preventing a subject from contracting Lyme disease by administering to the subject an effective amount of the immunogenic composition.

[0105] Also provided herein in some embodiments is use of any of the provided immunogenic compositions for preventing the onset of Lyme disease in a subject by administering to the subject an effective amount of the immunogenic composition. In some of any embodiments, the subject has previously been infected by Borrelia.

[0106] Also provided herein in some embodiments is use of any of the provided immunogenic compositions in the manufacture of a medicament for stimulating an immune response against Borrelia in a subject.

[0107] Also provided herein in some embodiments is use of any of the provided immunogenic compositions in the manufacture of a medicament for protecting a subject from infection by Borrelia.

[0108] Also provided herein in some embodiments is use of any of the provided immunogenic compositions in the manufacture of a medicament for preventing a subject from contracting Lyme disease.

[0109] Also provided herein in some embodiments is use of any of the provided immunogenic compositions in the manufacture of a medicament for preventing the onset ofLyme disease in a subject. In some of any embodiments, the subject has previously been infected by Borrelia.

[0110] In some of any embodiments, the immunogenic composition is administered by intramuscular injection.

[0111] In some of any embodiments, a first dose and a second dose of the immunogenic composition is administered to the subject. In some of any embodiments, the second dose of the immunogenic composition is administered from about 2 weeks to about 10 weeks after the administration of the first dose of the immunogenic composition. In some of any embodiments, the second dose of the immunogenic composition is administered about 1 month or about 2 months after the administration of the first dose of the immunogenic composition.

[0112] In some of any embodiments, a third dose of the immunogenic composition is administered to the subject. In some of any embodiments, the third dose of the immunogenic composition is administered from about 4 months to about 8 months after the administration of the first dose of the immunogenic composition. In some of any embodiments, the third dose of the immunogenic composition is administered about 6 months after the administration of the first dose of the immunogenic composition.

[0113] In some of any embodiments, a booster dose of the immunogenic composition is administered to the subject. In some of any embodiments, the booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose.

[0114] In some of any embodiments, a plurality of booster doses is administered to the subject. In some of any embodiments, the first booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose. In some of any embodiments, a booster dose is administered yearly.

[0115] In some of any embodiments, the subject a human subject.

[0116] In some of any embodiments, the human subject is at least 18 years of age. In some of any embodiments, the human subject is from 18 years to 70 years of age.

[0117] In some of any embodiments, the human subject is under 18 years of age. In some of any embodiments, the human subject is from 2 years to 5 years of age. In some of any embodiments, the human subject is from 5 years to 18 years of age.

[0118] Also provided herein in some embodiments is a vial comprising any of the provided immunogenic compositions.

[0119] In some of any embodiments, the immunogenic composition is in liquid form. In some of any embodiments, the immunogenic composition is in lyophilized form.

[0120] In some of any embodiments, the vial comprises a single dose of the immunogenic composition, the single dose is a 0.3 mL to 1.5 mL dose.

[0121] Also provided herein in some embodiments is a pre-filled syringe comprising any of the provided immunogenic compositions.

[0122] In some of any embodiments, the syringe comprises a single dose of the immunogenic composition. In some of any embodiments, the single dose is a 0.3 mL to 1.5 mL dose.

[0123] Also provided herein in some embodiments is a kit comprising: a) a first composition comprising an adjuvant selected from a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester; b) a second composition comprising a Borrelia outer surface protein A (OspA) antigen and a Borrelia outer surface protein C (OspC) antigen; and c) instructions for combining the first composition and the second composition to prepare any of the provided immunogenic compositions.

[0124] Also provided herein in some embodiments is a kit comprising: a) a first composition comprising an adjuvant selected from a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester; b) a second composition comprising a Borrelia outer surface protein C (OspC) antigen; and c) instructions for combining the first composition and the second composition to prepare the immunogenic composition to prepare any of the provided immunogenic compositions.

[0125] In some of any embodiments, the second composition is in liquid form. In some of any embodiments, the second composition is in lyophilized form.

[0126] In some of any embodiments, the instructions are for preparing a single dose of the immunogenic composition. In some of any embodiments, the kit is for a single dose of theimmunogenic composition. In some of any embodiments, the single dose is a 0.3 mL to 1.5 mL dose.

[0127] In some of any embodiments, the first and / or second composition comprises a second adjuvant.

[0128] In some of any embodiments, the OspC antigen is a first OspC antigen comprising a plurality of linear epitopes from one or more OspC proteins, the kit further comprises a third composition comprising a second Borrelia OspC antigen that is an OspC protein comprising one or more conformational epitopes, and the instructions are for combining the first, second, and third compositions to prepare the immunogenic composition.

[0129] In some of any embodiments, the third composition is in liquid form.

[0130] In some of any embodiments, the third composition is in lyophilized form.

[0131] In some of any embodiments, the third composition comprises a second adjuvant.

[0132] In some of any embodiments, the first composition comprises a second adjuvant. In some of any embodiments, the second composition comprises a second adjuvant. In some of any embodiments, the first and second compositions each comprise a second adjuvant.

[0133] In some of any embodiments, the second adjuvant is an aluminum salt adjuvant. In some of any embodiments, the aluminum salt adjuvant comprises one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate. In some of any embodiments, the aluminum salt adjuvant comprises aluminum hydroxide.

[0134] In some of any embodiments, the kit further comprises: d) a further set of instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

[0135] Also provided herein in some embodiments is a kit comprising: a) any of the provided immunogenic compositions; and b) instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

[0136] In some of any embodiments, the kit further comprises a syringe for intramuscular injection of the immunogenic composition. In some of any embodiments, the syringe is prefilled with the immunogenic composition.

[0137] Also provided herein in some embodiments is a kit comprising: a) any of the provided vials; and b) instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

[0138] In some of any embodiments, the kit further comprises a syringe for intramuscular injection of the immunogenic composition.

[0139] Also provided herein in some embodiments is a kit comprising: any of the provided pre-filled syringes; and b) instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

[0140] In some of any embodiments, the syringe is for intramuscular injection of the immunogenic composition.

[0141] In some of any embodiments, the administration is according to any of the provided methods.

[0142] In some of any embodiments, the subject a human subject.

[0143] In some of any embodiments, the human subject is at least 18 years of age. In some of any embodiments, the human subject is from 18 years to 70 years of age.

[0144] In some of any embodiments, the human subject is under 18 years of age. In some of any embodiments, the human subject is from 2 years to 5 years of age. In some of any embodiments, the human subject is from 5 years to 18 years of age.BRIEF DESCRIPTION OF DRAWINGS

[0145] FIG. 1A and FIG. IB show murine antibody response using ELISA to Borrelia burgdorferi outer surface protein antigens following administration of CpG 1018® adjuvant (Dynavax Technologies Corporation, Emeryville, CA; CpG) with a veterinary Lyme disease immunogenic composition (VANGUARD® crLyme) containing a Borrelia burgdorferi outer surface protein A (OspA) antigen, a Borrelia burgdorferi outer surface protein C (OspC) antigen, and an aluminum salt adjuvant. FIG. 1A shows murine antibody response to Borrelia outer surface protein A (OspA) antigen following administration of the Lyme disease immunogenic composition at different dilutions of the canine immunogenic composition dose with or without a fixed amount of the CpG 1018® adjuvant. FIG. IB shows murine antibody response to Borrelia outer surface protein C (OspC) antigen following administration of the Lyme disease immunogenic composition with or without the CpG 1018® adjuvant.

[0146] FIG. 2 shows murine antibody response using ELISA to OspC chimeritope following administration of either OspC chimeritope (OspC Chim; left) or a combination of OspC analog and OspC chimeritope (OspC Analog+Chim; right) without adjuvant or with one of the following adjuvant formulations: aluminum hydroxide (alum), CpG 1018® adjuvant (Dynavax Technologies Corporation, Emeryville, CA; CpG), or a combination of CpG and alum. Fold-change increases (FI) in antibody levels between the indicated conditions, as measured by comparing the median antibody levels from an indicated condition or conditions versus the other indicated condition or conditions, are also shown.

[0147] FIG. 3 shows murine antibody response using ELISA to OspC analog following administration of either OspC analog (OspC Analog; left) or a combination of OspC analog and OspC chimeritope (OspC Analog+Chim; right) without adjuvant or with one of the following adjuvant formulations: aluminum hydroxide (alum), CpG 1018® adjuvant (Dynavax Technologies Corporation, Emeryville, CA; CpG), or a combination of CpG and alum. Fold-change increases (FI) in antibody levels between the indicated conditions, as measured by comparing the median antibody levels from an indicated condition or conditions versus the other indicated condition or conditions, are also shown.

[0148] FIG. 4 shows a schematic of the three chimeric OspA antigens, each of which combines two different serotypes from OspA. On top is a schematic of the OspA protein, which is divided into the C-term portion (top; solid color) and N-term portion (bottom; hatched pattern). On the bottom are the three chimeric OspA antigens: S 1 / 2 (left), S6 / 4 (middle), and S5 / 3 (right), which contain different N-term and C-term portions from the indicated serotypes.

[0149] FIGS. 5A-5K show murine antibody response using ELISA to different indicated OspA or OspC antigens following administration of the indicated antigen or mixture of antigens without adjuvant or with one of the following adjuvant formulations: aluminum hydroxide (alum), CpG 1018® adjuvant (Dynavax Technologies Corporation, Emeryville, CA; CpG), or a combination of CpG and alum. Fold-change increases (FI) in antibody levels between the indicated conditions, as measured by comparing the median antibody levels from an indicated condition versus the other indicated condition, are also shown. Median antibody titer levels are also indicated directly above each condition. Following administration of lipidated OspA chimeric antigens (Lip OspA) or combination of lipidated OspA chimeric antigens and OspC chimeritope (Lip OspA + OspC Chim) with different adjuvant formulations, antibody response is shown against OspA Sl / 2 chimeric antigen (FIG. 5A),OspA S5 / 3 chimeric antigen (FIG. 5B), and OspA S6 / 4 chimeric antigen (FIG. 5C). Following administration of lipidated OspA chimeric antigens (Lip OspA) or combination of lipidated OspA chimeric antigens and OspC analog (Lip OspA + OspC Analog) with different adjuvant formulations, antibody response is shown against OspA S 1 / 2 chimeric antigen (FIG. 5D), OspA S5 / 3 chimeric antigen (FIG. 5E), and OspA S6 / 4 chimeric antigen (FIG. 5F). Following administration of a combination of lipidated OspA chimeric antigens and OspC chimeritope (Lip OspA + OspC Chim) or a combination of lipidated OspA antigens and OspC analog (Lip OspA + OspC Analog) with different adjuvant formulations, antibody response is shown against OspA S 1 / 2 chimeric antigen (FIG. 5G), OspA S5 / 3 chimeric antigen (FIG. 5H), and OspA S6 / 4 chimeric antigen (FIG. 51). Following administration of OspC chimeritope (OspC Chim) or a combination of lipidated OspA chimeric antigens and OspC chimeritope (Lip OspA + OspC Chim) with different adjuvant formulations, antibody response is shown against against OspC chimeritope (FIG. 5J).Following administration of OspC analog (OspC Analog) or a combination of lipidated OspA chimeric antigens and OspC analog (Lip OspA + OspC Analog) with different adjuvant formulations, antibody response is shown against OspC analog (FIG. 5K).

[0150] FIG. 6A-E shows antibody response using ELISA to the indicated antigen post-lstinjection (marked as “1”) or post-2ndinjection (marked as “2”) following administration of the indicated formulation of antigen and adjuvants. Numbers representing fold-change increases (FIs) in titer levels between the 1stand 2ndinjections are indicated at the top of each condition. Antibody response is measured against OspA S 1 / 2 chimeric antigen (FIG. 6A), OspA S5 / 3 chimeric antigen (FIG. 6B), OspA S6 / 4 chimeric antigen (FIG. 6C), OspC chimeritope (FIG. 6D), and OspC analog (FIG. 6E).DETAILED DESCRIPTION

[0151] The present disclosure relates to immunogenic compositions comprising Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and an adjuvant. In some aspects, the immunogenic compositions further comprise a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen. In some aspects, the immunogenic compositions comprise a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen, a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and an adjuvant. In some aspects, the immunogenic compositions are suitable for stimulating an immune response against Borrelia in a subject. The present disclosure alsorelates to articles of manufacture comprising, uses of, and methods of using the immunogenic compositions.

[0152] All publications, including patent documents, scientific articles and databases, referred to in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were individually incorporated by reference. If a definition set forth herein is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications and other publications that are herein incorporated by reference, the definition set forth herein prevails over the definition that is incorporated herein by reference.

[0153] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.General Techniques and Definitions

[0154] The practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry, and immunology, which are within the skill of the art.

[0155] As used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural references unless indicated otherwise. For example, “an” excipient includes one or more excipients.

[0156] The phrase “comprising” as used herein is open-ended, indicating that such embodiments may include additional elements. In contrast, the phrase “consisting of’ is closed, indicating that such embodiments do not include additional elements (except for trace impurities). The phrase “consisting essentially of’ is partially closed, indicating that such embodiments may further comprise elements that do not materially change the basic characteristics of such embodiments.

[0157] The term “about” as used herein in reference to a value encompasses from 90% to 110% of that value (e.g., about 3000 pg of CpG adjuvant refers to 2700 pg to 3300 pg of CpG adjuvant).

[0158] As used interchangeably herein, the terms “polynucleotide” and “oligonucleotide” include single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), single-stranded RNA (ssRNA), and double-stranded RNA (dsRNA); modified oligonucleotides andoligonucleosides; or combinations thereof. The oligonucleotide can be linearly or circularly configured, or the oligonucleotide can include both linear and circular segments.Oligonucleotides are polymers of nucleosides joined, generally, through phosphodiester linkages, although alternate linkages, such as phosphorothioate esters, may also be used in oligonucleotides. A nucleoside consists of a purine (adenine (A) or guanine (G) or derivative thereof) or pyrimidine (thymine (T), cytosine (C), or uracil (U), or derivative thereof) base bonded to a sugar. The four nucleoside units (or bases) in DNA are called deoxyadenosine, deoxyguanosine, thymidine, and deoxycytidine. A nucleotide is a phosphate ester of a nucleoside.

[0159] The terms “CpG”, “CpG motif’, and “cytosine-phosphate-guanosine” as used herein refer to an unmethylated cytidine-phospho-guanosine dinucleotide, which when present in an oligonucleotide contributes to a measurable immune response in vitro, in vivo, and / or ex vivo. Examples of measurable immune responses include antigen-specific antibody production, secretion of cytokines, and activation or expansion of lymphocyte populations, such as NK cells, CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes. Preferably, the CpG- containing oligonucleotide preferentially activates a Th 1 -type response.

[0160] The term “antigen” refers to a substance that is recognized and bound specifically by an antibody or by a T cell antigen receptor. Antigens can include peptides, polypeptides, proteins, glycoproteins, polysaccharides, complex carbohydrates, sugars, gangliosides, lipids, and phospholipids; portions thereof; and combinations thereof. In the context of the present disclosure, the term “antigen” typically refers to a polypeptide or protein antigen at least eight amino acid residues in length, which may comprise one or more post-translational modifications.

[0161] The terms “polypeptide” and “protein” are used interchangeably herein to refer to a polymer of amino acid residues and are not limited to a certain length unless otherwise specified. Polypeptides may include natural amino acid residues or a combination of natural and non-natural amino acid residues. The terms also include post-expression modifications of the polypeptide, for example glycosylation, sialylation, acetylation, phosphorylation, and the like. In some aspects, the polypeptides may include modifications with respect to a native or natural sequence, as long as the protein maintains the desired activity (e.g., antigenicity).

[0162] The terms “isolated” and “purified” as used herein refers to a material that is removed from at least one component with which it is naturally associated (e.g., removedfrom its original environment). The term “isolated” when used in reference to a recombinant protein refers to a protein that has been removed from the culture medium of the host cell that produced the protein. In some embodiments, an isolated protein (e.g., Borrelia antigen) is at least 75%, 90%, 95%, 96%, 97%, 98%, or 99% pure as determined by high-performance liquid chromatography (HPLC).

[0163] An “effective amount” or a “sufficient amount” of a substance is an amount sufficient to effect beneficial or desired results, including clinical results, and as such, an “effective amount” depends upon the context in which it is being applied. In the context of administering an immunogenic composition, an effective amount includes sufficient antigen and adjuvant(s) to stimulate an immune response (preferably a seroprotective level of antibody to the antigen).

[0164] In the present disclosure, the terms “individual” and “subject” refer to a mammal. Mammals include humans, non-human primates (e.g., monkeys), farm animals, sport animals, rodents (e.g., mice and rats), and pets (e.g., dogs and cats).

[0165] The term “dose” as used herein in reference to an immunogenic composition refers to a measured portion of the immunogenic composition taken by (administered to or received by) a subject at any one time.

[0166] “ Stimulation” of a response or parameter includes eliciting and / or enhancing that response or parameter when compared to otherwise same conditions except for a parameter of interest, or alternatively, as compared to another condition. For example, “stimulation” of an immune response means an increase in the response. Depending upon the parameter measured, the increase may be from 2-fold to 200-fold or over, from 5-fold to 500-fold or over, from 10-fold to 1000-fold or over, or from 2, 5, 10, 50, or 100-fold to 200, 500, 1,000, 5,000, or 10,000-fold.

[0167] Conversely, “inhibition” of a response or parameter includes reducing and / or repressing that response or parameter when compared to otherwise same conditions except for a parameter of interest, or alternatively, as compared to another condition. For example, “inhibition” of an immune response means a decrease in the response. Depending upon the parameter measured, the decrease may be from 2-fold to 200-fold, from 5-fold to 500-fold or over, from 10-fold to 1000-fold or over, or from 2, 5, 10, 50, or 100-fold to 200, 500, 1,000, 2,000, 5,000, or 10,000-fold.

[0168] The relative terms “higher” and “lower” refer to a measurable increase or decrease, respectively, in a response or parameter when compared to otherwise same conditions except for a parameter of interest, or alternatively, as compared to another condition. For instance, a “higher antibody titer” refers to an antigen-reactive antibody titer as a consequence of administration of an immunogenic composition of the present disclosure that is at least 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold above an antigen-reactive antibody titer as a consequence of a control condition. Likewise, a “lower antibody titer” refers to an antigen-reactive antibody titer as a consequence of a control condition that is at least 2, 3, 4, 5, 6, 7, 8, 9, or 10-fold below an antigen-reactive antibody titer as a consequence of administration of an immunogenic composition of the present disclosure.

[0169] As used herein, the term “immunization” refers to a process that increases a subject’s reaction to antigen and therefore improves its ability to resist or overcome infection and / or resist disease.

[0170] The term “vaccination” as used herein refers to the introduction of a vaccine into a body of a subject.

[0171] “Adjuvant” refers to a substance which, when added to a composition comprising an antigen, enhances or potentiates an immune response to the antigen in a subject upon exposure.

[0172] As used herein, “percent (%) amino acid sequence identity”, “percent identity”, and “sequence identity” when used with respect to an amino acid sequence (reference polypeptide sequence) is defined as the percentage of amino acid residues in a candidate sequence (e.g., the subject antigen) that are identical with the amino acid residues in the reference polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared.

[0173] An amino acid substitution may include replacement of one amino acid in a polypeptide with another amino acid. Amino acid substitutions may be introduced into anantigen of interest and the products screened for a desired activity, e.g., increased stability and / or immunogenicity.

[0174] Amino acids generally can be grouped according to the following common sidechain properties:(1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, He;(2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin;(3) acidic: Asp, Glu;(4) basic: His, Lys, Arg;(5) residues that influence chain orientation: Gly, Pro; and(6) aromatic: Trp, Tyr, Phe.

[0175] Conservative amino acid substitutions will involve exchanging a member of one of these classes with another member of the same class. Non-conservative amino acid substitutions will involve exchanging a member of one of these classes with a member of another class.I. Immunogenic Compositions

[0176] The present disclosure relates to immunogenic compositions containing Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and an adjuvant. In some embodiments, the immunogenic compositions further comprise Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen. In some embodiments, the immunogenic composition comprises a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen, a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and an adjuvant. In some embodiments, the immunogenic composition contains a Borrelia OspA antigen, a Borrelia OspC antigen, and an adjuvant. In some embodiments, the adjuvant is any described herein, for instance any described in Section LA. In some embodiments, the OspA antigen is any described herein, for instance any described in Section LB-1. In some embodiments, the OspC antigen is any described herein, for instance any described in Section LB-2. In some embodiments, the immunogenic composition contains an additional component, for instance any described in Section I-C.

[0177] In some aspects, the immunogenic compositions are for stimulating an immune response against Borrelia in a subject. In some embodiments, the antigen or antigens and adjuvant are present in the immunogenic composition in amounts effective to stimulate animmune response against Borrelia in a subject. In some embodiments, the stimulating is by administering to the subject an effective amount of the immunogenic composition.

[0178] In some embodiments, the immunogenic composition is for protecting a subject from infection by Borrelia. In some embodiments, the antigen or antigens and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject. In some embodiments, the protecting is by administering to the subject an effective amount of the immunogenic composition.

[0179] In some embodiments, the immunogenic composition is for preventing a subject from contracting Lyme disease. In some embodiments, the antigen or antigens and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject. In some embodiments, the preventing is by administering to the subject an effective amount of the immunogenic composition.

[0180] In some embodiments, the immunogenic composition is for preventing the onset of Lyme disease in a subject. In some embodiments, the subject has previously been infected by Borrelia. In some embodiments, the antigen or antigen and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject. In some embodiments, the preventing is by administering to the subject an effective amount of the immunogenic composition.

[0181] In some embodiments, the subject is a human subject. In some embodiments, the human subject is at least 18 years of age. In some embodiments, the human subject is about 18 to about 70 years of age. In some embodiments, the human subject is about 18 to about 55 years of age.

[0182] In some embodiments, the human subject is under 18 years of age. In some embodiments, the human subject is about 2 to about 5 years of age. In some embodiments, the human subject is about 5 to about 18 years of age.

[0183] In some embodiments, the immunogenic composition is a 0.3 mL to 1.5 mL dose. In some embodiments, the immunogenic composition is about a 0.25 mL, 0.50 mL, 0.75 mL, or 1.0 mL dose. In some embodiments, the immunogenic composition is about a 0.50 mL dose. In some embodiments, the immunogenic composition is about a 0.75 mL dose. In some embodiments, the immunogenic composition is a unit dose.A. Adjuvants

[0184] Adjuvants that can be used in the present immunogenic compositions include mineral salts, such as aluminum salts, e.g., aluminum hydroxide, aluminum hydroxide gels (e.g., Rehydragel®), aluminum phosphate, and calcium phosphate; surface-active agents and microparticles, e.g., nonionic block polymer surfactants, cholesterol, virosomes, saponins (e.g., Quil A, QS-21, and GPI-0100, such as in Matrix-M™ (Lovgren et al., Biotechnol Appl Biochem, 10(2): 161-172, 1988)), proteosomes, immune stimulating complexes, cochleates, quarterinary amines (dimethyl diocatadecyl ammonium bromide (DDA)), pyridine, vitamin A, vitamin E, and poly(lactide-co-glycolide) microparticles (Shah et al., Methods Mol Biol, 1494: 1-14, 2017); bacterial products, such as the RIBI adjuvant system (Ribi Inc.), cell wall skeleton of Mycobacterum phlei (Detox®), muramyl dipeptides (MDP) and tripeptides (MTP), monophosphoryl lipid A, Bacillus Calmete-Guerin, heat labile E. coli enterotoxins, cholera toxin, trehalose dimycolate, and CpG oligodeoxnucleotides; cytokines and hormones, e.g., interleukins (IL-1, IL-2, IL-6, IL-12, IL-15, and IL-18), granulocyte-macrophage colony stimulating factor, dehydroepiandrosterone, and 1,25-dihydroxy vitamin D3; polyanions, e.g., dextran; polyacrylics (e.g., polymethylmethacrylate and Carbopol 934P); carriers, e.g., tetanus toxid, diptheria toxoid, cholera toxin B subnuit, mutant heat labile enterotoxin of enterotoxigenic E. coli (rmLT), and heat shock proteins; oil-in-water emulsions, e.g., AMPHIGEN® (Hydronics, USA); water-in-oil emulsions, e.g., Freund's complete and incomplete adjuvants; and liposome-based adjuvants. Further adjuvants that can be used in the present immunogenic compositions are described in Pulendran et al., Nat Rev Drug Discov 20:454-475, 2021; and Facciola et al., Vaccines (Basel) 10(5): 819, 2022.

[0185] In some embodiments, the adjuvant is selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant; and an oil-in-water emulsion-based adjuvant. In some embodiments, the adjuvant is selected from the group consisting of an aluminum salt adjuvant; a TLR9 agonist that is an oligonucleotide containing an unmethylated cytidine-phospho-guanosine (CpG) motif; a liposome-based adjuvant containing a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant containing squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0186] In some embodiments, the adjuvant is an aluminum salt adjuvant, such as any described herein, for instance in Section I-A-l. In some embodiments, the adjuvant is a TLR9 agonist, e.g., a TLR9 agonist that is an oligonucleotide containing an unmethylated CpGmotif, such as any described herein, for instance in Section I-A-2. In some embodiments, the adjuvant is a liposome-based adjuvant, e.g., a liposome-based adjuvant containing a lipopolysaccharide and a saponin, such as any described herein, for instance in Section I-A-3. In some embodiments, the adjuvant is an oil-in-water emulsion-based adjuvant, e.g., an oil- in-water emulsion-based adjuvant containing squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester, such as any described herein, for instance in Section I-A-4.

[0187] In some embodiments, the immunogenic composition contains a second adjuvant that is different from the first adjuvant. In some embodiments, the first and second adjuvants are individually any of the adjuvants described herein. In some embodiments, the first and second adjuvants are selected from the group consisting of an aluminum salt adjuvant; a TLR9 agonist; a liposome-based adjuvant; and an oil-in-water emulsion-based adjuvant. In some embodiments, the first and second adjuvants are selected from the group consisting of an aluminum salt adjuvant; a TLR9 agonist that is an oligonucleotide containing an unmethylated CpG motif; a liposome-based adjuvant containing a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant containing squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0188] In some embodiments, the second adjuvant is a polycationic carrier. In some embodiments, the first adjuvant is a TLR9 agonist, e.g., a TLR9 agonist that is an oligonucleotide containing an unmethylated CpG motif, and the second adjuvant is a polycationic carrier. In some embodiments, the first adjuvant, e.g., TLR9 agonist, forms cationic complexes with the polycationic carrier. In some embodiments, the development of the cationic complexes leads to a heightened immune response, relative to the immune response induced by the first adjuvant alone. In some embodiments, the polycationic carrier is any described in Dong et al. ACS Appl. Mater. Interfaces 14(5):6331-6342, 2022; and Fu et al., European Polymer Journal 113: 115-132, 2019. In some embodiments, the polycationic carrier is polycationic polyethylenimine (PEI). In some embodiments, the polycationic carrier is an aluminum salt adjuvant, such as any described herein, for instance in Section I-A-l.

[0189] In some embodiments, the second adjuvant is an aluminum salt adjuvant, which can be any described herein and in any of the amounts described herein. In some embodiments, the first adjuvant is a TLR9 agonist, e.g., a TLR9 agonist that is an oligonucleotide containing an unmethylated CpG motif, and the second adjuvant is an aluminum salt adjuvant. In some embodiments, the first adjuvant is a liposome-based adjuvant, e.g., a liposome-based adjuvant containing a lipopolysaccharide and a saponin, and the secondadjuvant is an aluminum salt adjuvant. In some embodiments, the first adjuvant is an oil-in- water emulsion-based adjuvant, e.g., an oil-in-water emulsion-based adjuvant containing squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester, and the second adjuvant is an aluminum salt adjuvant. In some embodiments, the aluminum salt adjuvant is one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate. In some embodiments, the aluminum salt adjuvant is one or both of aluminum hydroxide and aluminum phosphate. In some embodiments, the aluminum salt adjuvant is aluminum hydroxide. In some embodiments, the aluminum salt adjuvant is potassium aluminum sulfate.

[0190] In some embodiments, the first adjuvant is a TLR9 agonist, e.g., a TLR9 agonist that is an oligonucleotide containing an unmethylated CpG motif, and the second adjuvant is potassium aluminum sulfate. In some embodiments, the first adjuvant is a liposome-based adjuvant, e.g., a liposome-based adjuvant containing a lipopolysaccharide and a saponin, and the second adjuvant is potassium aluminum sulfate. In some embodiments, the first adjuvant is an oil-in-water emulsion-based adjuvant, e.g., an oil-in-water emulsion-based adjuvant containing squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester, and the second adjuvant is potassium aluminum sulfate.

[0191] In some embodiments, the first adjuvant is a lipopolysaccharide, and the second adjuvant is an aluminum salt adjuvant. In some embodiments, the lipopolysaccharide is adsorbed on the aluminum salt adjuvant. In some embodiments, the lipopolysaccharide is a lipid A or a derivative thereof. In some embodiments, the lipopolysaccharide is a monophosphoryl lipid A or a derivative thereof. In some embodiments, the lipopolysaccharide is 3-O-desacyl-4'-monophosphoryl lipid A. In some embodiments, the lipopolysaccharide is 3-deacyl-phosphorylated hexa-acyl disaccharide. In some embodiments, the aluminum salt adjuvant is one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate. In some embodiments, the aluminum salt adjuvant is one or both of aluminum hydroxide and aluminum phosphate. In some embodiments, the aluminum salt adjuvant is aluminum hydroxide. In some embodiments, the aluminum salt adjuvant is potassium aluminum sulfate. In some embodiments, the first adjuvant is 3-O-desacyl-4'- monophosphoryl lipid A, and the second adjuvant is aluminum hydroxide. In some embodiments, the first and second adjuvants together are the adjuvant AS04. In some embodiments, the adjuvant is AS04.

[0192] In some embodiments, the adjuvant is a synthetic TLR7 / 8 agonist. In some embodiments, the adjuvant is 3M-052 (Kasturi et al., Sci Immunol 5(48):eabbl025, 2020 Jun 19). In some embodiments, 3M-052 is formulated in poly(lactic-co-gly colic) or PLGA nanoparticles. In some embodiments, 3M-052 is formulated with an aluminum salt adjuvant. In some embodiments, 3M-052 is formulated with potassium aluminum sulfate. In some embodiments, the first adjuvant is 3M-052, and the second adjuvant is any described herein. In some embodiments, the first adjuvant is 3M-052, and the second adjuvant is a TLR4 agonist. In some embodiments, the TLR4 agonist is GLA.

[0193] In some embodiments, the adjuvant is a saponin-based adjuvant. In some embodiments, the adjuvant is composed of nanoparticles containing a saponin. In some embodiments, the saponin is extracted from Quillaja saponaria (soapbark) trees. In some embodiments, the nanoparticles contain a saponin, cholesterol, and a phospholipid. In some embodiments, the adjuvant is Matrix-M™.1. Aluminum Salt Adjuvants

[0194] In some embodiments, the adjuvant is an aluminum salt adjuvant. In some embodiments, one or both of the OspA and OspC antigens are adsorbed to the aluminum salt adjuvant. In some embodiments, the OspC antigen is adsorbed to the aluminum salt adjuvant. In some embodiments, the aluminum salt adjuvant is one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate. In some embodiments, the aluminum salt adjuvant is one or both of aluminum hydroxide and aluminum phosphate. In some embodiments, the aluminum salt adjuvant is aluminum hydroxide. In some embodiments, the aluminum salt adjuvant is potassium aluminum sulfate.

[0195] In some embodiments, the immunogenic composition contains from about 0.25 to about 1.25 mg Al3+. In some embodiments, the immunogenic composition contains from about 0.5 to about 1 mg Al3+. In some embodiments, the immunogenic composition contains from about 0.25 mg to about 0.50 mg Al3+. In some embodiments, the immunogenic composition contains from about 0.30 mg to about 0.40 mg Al3+. In some embodiments, the immunogenic composition contains about 0.25 mg, about 0.50 mg, about 0.75 mg, about 1.00 mg, or about 1.25 mg Al3+.2. Oligonucleotide Toll-Like Receptor 9 (TLR9) Agonists

[0196] Toll-like receptors (TLRs) are expressed in and on dendritic cells and other innate immune cells and are among the most important receptors for stimulating a response to the presence of invading pathogens. Humans have multiple types of TLRs that are similar in structure but recognize different parts of viruses or bacteria. By activating specific TLRs, it is possible to stimulate and control specific types of innate immune responses that can be harnessed to enhance adaptive responses.

[0197] In some embodiments, the adjuvant in the present immunogenic compositions is an oligonucleotide TLR9 agonist. In some embodiments, the oligonucleotide contains an unmethylated cytidine-phospho-guanosine (CpG) motif. TLR9 (CD289) recognizes unmethylated CpG motifs found in microbial DNA, which can be mimicked using synthetic CpG-containing oligodeoxynucleotides (CpG-ODNs). CpG-ODNs are known to enhance antibody production and to stimulate T helper 1 (Thl) cell responses (Coffman et al., Immunity, 33:492-503, 2010). Based on structure and biological function, CpG-ODNs have been divided into three general classes: CpG-A, CpG-B, and CpG-C (Campbell, Methods Mol Biol, 1494: 15-27, 2017). The degree of B cell activation varies between the classes, with CpG-A ODNs being weak, CpG-C ODNs being good, and CpG-B ODNs being strong B cell activators. Oligonucleotide TLR9 agonists in the present immunogenic compositions are preferably good B cell activators (CpG-C ODN) or more preferably strong (CpG-B ODN) B cell activators.

[0198] Oligonucleotide TLR9 agonists often contain a palindromic sequence following the general formula of 5’-purine-purine-CG-pyrimidine-pyrimidine-3’ or 5’-purine-purine-CG- pyrimidine-pyrimidine-CG-3’ (U.S. Patent No. 6,589,940). TLR9 agonism is also observed with certain non-palindromic CpG-enriched phosphorothioate oligonucleotides, but may be affected by changes in the nucleotide sequence. Additionally, TLR9 agonism can be abolished by methylation of the cytosine within the CpG dinucleotide. In some embodiments, the TLR9 agonist in the present immunogenic compositions is an oligonucleotide of from 8 to 35 nucleotides in length. In some embodiments, the TLR9 agonist in the present immunogenic compositions is an oligonucleotide of from 8 to 35 nucleotides in length comprising the sequence 5’-AACGTTCG-3’. In some embodiments, the oligonucleotide is greater than 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length, and the oligonucleotide is less than 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, or 24 nucleotides in length. In some embodiments, the TLR9 agonist is an oligonucleotide of from 10 to 35 nucleotides in length. In some embodiments, the TLR9 agonist is an oligonucleotide of from10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2). In some embodiments, the oligonucleotide is greater than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length, and the oligonucleotide is less than 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, or 24 nucleotides in length. In some embodiments, the oligonucleotide does not comprise the sequence 5’-TCGTCGTTTT GTCGTTTTGT CGTT-3’ (ODN 2006 or ODN 7909, set forth in SEQ ID NO:3).

[0199] Researchers at Dynavax Technologies Corporation (Emeryville, CA) have identified a 22-mer phosphorothioate linked oligodeoxynucleotide, CpG 1018® adjuvant, which contains specific sequences that can substantially enhance the immune response to coadministered antigens across species (Campbell, Methods Mol Biol, 1494: 15-27, 2017). CpG 1018® adjuvant(5’-TGACTGTGAA CGTTCGAGAT GA-3’, set forth in SEQ ID NO: 1) was chosen after screening a broad panel of oligonucleotides for immunostimulatory activity in vitro and in vivo. CpG 1018® adjuvant is a CpG-B ODN that is active in mice, rabbits, dogs, baboons, cynomolgus monkeys, and humans. In some embodiments, the oligonucleotide is from 22 to 35 nucleotides in length and comprises the sequence 5’-TGACTGTGAA CGTTCGAGAT GA-3’ (SEQ ID NO: 1). In some embodiments, the oligonucleotide is greater than 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, or 33 nucleotides in length, and the oligonucleotide is less than 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, or 24 nucleotides in length, provided the maximum is below the minimum length.

[0200] Although the exemplary oligonucleotide CpG 1018® adjuvant is a CpG-ODN, oligonucleotides that are not fully DNA molecules can also be used in the present immunogenic compositions. In some embodiments, the oligonucleotide is a DNA / RNA chimeric molecule in which the CpG(s) and the palindromic sequence are deoxyribonucleic acids, and one or more nucleic acids outside of these regions are ribonucleic acids. In some embodiments, the oligonucleotide is linear. In other embodiments, the oligonucleotide is circular or includes hairpin loop(s). In some embodiments, the oligonucleotide is single stranded. In some embodiments, the oligonucleotide is double stranded.

[0201] In some embodiments, the oligonucleotide may contain modifications. Modifications can be modifications of the 3 ’OH or 5 ’OH group, modifications of the nucleotide base, modifications of the sugar component, and modifications of the phosphate group. Modified bases may be included in the palindromic sequence of the oligonucleotide as long as the modified base(s) maintains the same specificity for its natural complementthrough Watson-Crick base pairing (e.g., the palindromic portion is still self-complementary). In some embodiments, the oligonucleotide comprises a non-canonical base. In some embodiments, the oligonucleotide comprises a modified nucleoside. In some embodiments, the modified nucleoside is selected from the group consisting of 2’-deoxy-7-deazaguanosine, 2’-deoxy-6-thioguanosine, arabinoguanosine, 2’-deoxy-2’substituted-arabinoguanosine, and 2’-O-substituted-arabinoguanosine.

[0202] The oligonucleotide may contain a modification of the phosphate group. For example, in addition to phosphodiester linkages, phosphate modifications include methyl phosphonate, phosphorothioate, phosphorami date (bridging or non-bridging), phosphotriester, and phosphorodithioate and may be used in any combination. Other nonphosphate linkages may also be used. In some embodiments, the oligonucleotide contains only phosphorothioate backbones. In some embodiments, the oligonucleotide contains only phosphodiester backbones. In some embodiments, the oligonucleotide contains a combination of phosphate linkages in the phosphate backbone, such as a combination of phosphodiester and phosphorothioate linkages. Oligonucleotides with phosphorothioate backbones can be more immunogenic than those with phosphodiester backbones and can be more resistant to degradation after injection into the host (Braun et al., J Immunol, 141 :2084-2089, 1988; and Latimer et al., Mol Immunol, 32: 1057-1064, 1995). In some embodiments, the oligonucleotide includes at least one, two, or three internucleotide phosphorothioate ester linkages. In some embodiments, when a plurality of oligonucleotide molecules are present in a pharmaceutical composition containing at least one excipient, both stereoisomers of the phosphorothioate ester linkage are present in the plurality of oligonucleotide molecules. In some embodiments, all of the internucleotide linkages of the oligonucleotide are phosphorothioate linkages, or said another way, the oligonucleotide has a phosphorothioate backbone.

[0203] In some embodiments, the immunogenic composition contains from about 375 pg to about 6000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains from about 750 pg to about 6000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains from about 750 pg to about 3000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains from about 750 pg to about 1500 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains from about 1500 pg to about 3000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains from about 3000 pg to about 6000 pgof the oligonucleotide. In some embodiments, the immunogenic composition contains greater than or equal to about 750, 1000, 1250, or 1500 pg of the oligonucleotide, and less than or equal to about 6000, 5000, 4000, or 3000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 375, 750, 1500, 3000, or 6000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 375 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 750 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 1000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 1500 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 3000 pg of the oligonucleotide. In some embodiments, the immunogenic composition contains about 6000 pg of the oligonucleotide.

[0204] In some embodiments, the oligonucleotide is in its pharmaceutically acceptable salt form. Exemplary basic salts include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, zinc salts, salts with organic bases (for example, organic amines) such as N-Me-D-glucamine, N-[l-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride, choline, tromethamine, dicyclohexylamines, and t-butyl amines, and salts with amino acids such as arginine, lysine, and the like. In some embodiment, the oligonucleotide is in the ammonium, sodium, lithium, or potassium salt form. In some embodiments, the oligonucleotide is in the sodium salt form.3. Liposome-Based Adjuvants

[0205] In some embodiments, the adjuvant in the present immunogenic compositions is a liposome-based adjuvant, such as any described in Tretiakova et al., Biochem (Mose) Suppl Ser A Membr Cell Biol, 16(1): 1-20, 2022; or Alving et al., Expert Rev Vaccines 19(3) :279- 292, 2020. In some embodiments, the liposome-based adjuvant includes a lipopolysaccharide. In some embodiments, the liposome-based adjuvant includes a saponin. In some embodiments, the liposome-based adjuvant includes a lipopolysaccharide and a saponin.

[0206] In some embodiments, the lipopolysaccharide is a lipid A or a derivative thereof. In some embodiments, the lipopolysaccharide is a monophosphoryl lipid A or a derivative thereof. In some embodiments, the lipopolysaccharide is naturally occurring. In some embodiments, the lipopolysaccharide is synthetic. In some embodiments, the lipopolysaccharide is 3-O-desacyl-4'-monophosphoryl lipid A. In some embodiments, the lipopolysaccharide is 3-deacyl-phosphorylated hexa-acyl disaccharide.

[0207] In some embodiments, the immunogenic composition contains from about 1 pg to about 100 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 10 pg to about 50 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 20 pg to about 30 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 21 pg to about 29 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 22 pg to about 28 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 23 pg to about 27 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 24 pg to about 26 pg of the lipopolysaccharide.

[0208] In some embodiments, the immunogenic composition contains from about 1 pg to about 30 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 5 pg to about 15 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 6 pg to about 14 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 7 pg to about 13 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 8 pg to about 12 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 9 pg to about 11 pg of the lipopolysaccharide.

[0209] In some embodiments, the immunogenic composition contains from about 1 pg to about 9 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 2 pg to about 8 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 3 pg to about 7 pg of the lipopolysaccharide. In some embodiments, the immunogenic composition contains from about 4 pg to about 6 pg of the lipopolysaccharide.

[0210] In some embodiments, the saponin is naturally occurring. In some embodiments, the saponin is synthetic. In some embodiments, the saponin is derived from the bark of Quillaja saponaria Molina. In some embodiments, the saponin is Quil A or a derivative thereof. In some embodiments, the saponin is QS-17. In some embodiments, the saponin is QS-21.

[0211] In some embodiments, the immunogenic composition contains from about 1 pg to about 100 pg of the saponin. In some embodiments, the immunogenic composition containsfrom about 10 pg to about 50 pg of the saponin. In some embodiments, the immunogenic composition contains from about 20 pg to about 30 pg of the saponin. In some embodiments, the immunogenic composition contains from about 21 pg to about 29 pg of the saponin. In some embodiments, the immunogenic composition contains from about 22 pg to about 28 pg of the saponin. In some embodiments, the immunogenic composition contains from about 23 pg to about 27 pg of the saponin. In some embodiments, the immunogenic composition contains from about 24 pg to about 26 pg of the saponin.

[0212] In some embodiments, the immunogenic composition contains from about 1 pg to about 30 pg of the saponin. In some embodiments, the immunogenic composition contains from about 5 pg to about 15 pg of the saponin. In some embodiments, the immunogenic composition contains from about 6 pg to about 14 pg of the saponin. In some embodiments, the immunogenic composition contains from about 7 pg to about 13 pg of the saponin. In some embodiments, the immunogenic composition contains from about 8 pg to about 12 pg of the saponin. In some embodiments, the immunogenic composition contains from about 9 pg to about 11 pg of the saponin.

[0213] In some embodiments, the immunogenic composition contains from about 1 pg to about 9 pg of the saponin. In some embodiments, the immunogenic composition contains from about 2 pg to about 8 pg of the saponin. In some embodiments, the immunogenic composition contains from about 3 pg to about 7 pg of the saponin. In some embodiments, the immunogenic composition contains from about 4 pg to about 6 pg of the saponin.

[0214] In some embodiments, the liposome-based adjuvant further contains a sterol. In some embodiments, the sterol is P-sitosterol, stigmasterol, ergosterol, ergocalciferol, or cholesterol. In some embodiments, the sterol is cholesterol.

[0215] In some embodiments, the ratio of saponin to sterol is from 1: 1 to 1 : 100 w / w. In some embodiments, the ratio of saponin to sterol is from 1 : 1 to 1 :5 w / w.

[0216] In some embodiments, the liposome-based adjuvant further contains a neutral lipid. In some embodiments, the neutral lipid is a phosphatidylcholine. In some embodiments, the phosphatidylcholine is eggyolk phosphatidylcholine, dioleoyl phosphatidylcholine (DOPC), or dilauryl phosphatidylcholine. In some embodiments, the phosphatidylcholine is DOPC.

[0217] In some embodiments, the liposome-based adjuvant contains 3-O-desacyl-4'- monophosphoryl lipid A and QS-21. In some embodiments, the liposome-based adjuvant contains 3-O-desacyl-4'-monophosphoryl lipid A, QS-21, and cholesterol. In someembodiments, the liposome-based adjuvant contains 3-O-desacyl-4'-monophosphoryl lipid A, QS-21, cholesterol, and DOPC. In some embodiments, the liposome-based adjuvant is AS01, AS01B, or AS01E, for instance as described in US 10,039,823. In some embodiments, the liposome-based adjuvant is AS01. In some embodiments, the liposome-based adjuvant is AS01B. In some embodiments, the liposome-based adjuvant is AS01E.

[0218] In some embodiments, the liposome-based adjuvant contains 3-deacyl- phosphorylated hexa-acyl disaccharide and QS-21. In some embodiments, the liposomebased adjuvant is ALFQ.4. Oil-in-Water Emulsion-Based Adjuvants

[0219] In some embodiments, the adjuvant in the present immunogenic compositions is an oil-in-water emulsion-based adjuvant, such as any described in Zhang et al., BMC Vet Res 14:415, 2018. In some embodiments, the oil-in-water emulsion-based adjuvant contains squalene. In some embodiments, the oil-in-water emulsion-based adjuvant contains a sorbitan ester (also known as a Span). In some embodiments, the oil-in-water emulsion-based adjuvant contains a polyoxyethylene sorbitan ester (also known as a Tween). In some embodiments, the oil-in-water emulsion-based adjuvant contains squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

[0220] In some embodiments, the sorbitan ester is sorbitan ester 20. In some embodiments, the sorbitan ester is sorbitan ester 85.

[0221] In some embodiments, the polyoxyethylene sorbitan ester is polyoxyethylene sorbitan ester 20. In some embodiments, the polyoxyethylene sorbitan ester is polyoxyethylene sorbitan ester 80.

[0222] In some embodiments, the immunogenic composition contains from about 2% w / v to about 7% w / v of the squalene. In some embodiments, the immunogenic composition contains from about 3% w / v to about 6% w / v of the squalene. In some embodiments, the immunogenic composition contains from about 4% w / v to about 5% w / v of the squalene.

[0223] In some embodiments, the immunogenic composition contains from about 0.2% w / v to about 0.8% w / v of the sorbitan ester. In some embodiments, the immunogenic composition contains from about 0.3% w / v to about 0.7% w / v of the sorbitan ester. In some embodiments, the immunogenic composition contains from about 0.4% w / v to about 0.6% w / v of the sorbitan ester.

[0224] In some embodiments, the immunogenic composition contains from about 0.2% w / v to about 0.8% w / v of the polyoxyethylene sorbitan ester. In some embodiments, the immunogenic composition contains from about 0.3% w / v to about 0.7% w / v of the polyoxyethylene sorbitan ester. In some embodiments, the immunogenic composition contains from about 0.4% w / v to about 0.6% w / v of the polyoxyethylene sorbitan ester.

[0225] In some embodiments, the oil-in-water emulsion-based adjuvant contains squalene, sorbitan ester 85, and polyoxyethylene sorbitan ester 80. In some embodiments, the immunogenic composition contains from about 2% w / v to about 7% w / v of the squalene; from about 0.2% w / v to about 0.8% w / v of the sorbitan ester 85; and from about 0.2% w / v to about 0.8% w / v of the polyoxyethylene sorbitan ester 80. In some embodiments, the oil-in- water emulsion-based adjuvant is MF59. In some embodiments, oil-in-water emulsion-based adjuvant is AddaVax™.

[0226] In some embodiments, the oil-in-water emulsion-based adjuvant contains an additional immune-enhancing component. In some embodiments, the oil-in-water emulsionbased adjuvant contains a vitamin. In some embodiments, the oil-in-water emulsion-based adjuvant contains vitamin E.

[0227] In some embodiments, the oil-in-water emulsion-based adjuvant contains squalene, vitamin E, and polyoxyethylene sorbitan ester 80. In some embodiments, the oil-in-water emulsion-based adjuvant is AS03. In some embodiments, the immunogenic composition contains about 11 mg squalene, about 12 mg vitamin E, and about 5 mg polyoxyethylene sorbitan ester 80.B. Borrelia Outer Surface Protein Antigens and RNA Polynucleotides

[0228] In some embodiments, the immunogenic composition contains a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen. In some embodiments, the immunogenic composition contains a OspC antigen.

[0229] In some embodiments, the immunogenic composition does not contain a non-OspC antigen or an RNA polynucleotide encoding the non-OspC Borrelia outer surface protein antigen. In some embodiments, the immunogenic composition does not contain a non-OspC Borrelia outer surface protein antigen.

[0230] In some embodiments, the immunogenic composition further contains a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen. In some embodiments, the immunogenic composition contains a Borrelia outersurface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen and a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen. In some embodiments, the immunogenic composition contains a Borrelia OspA antigen and a Borrelia OspC antigen.

[0231] In some embodiments, the OspA antigen is any described herein, for instance in Section I-B-l. In some embodiments, the OspC antigen is any described herein, for instance in Section I-B-2.

[0232] In some embodiments, the immunogenic composition contains an RNA polynucleotide encoding the OspC antigen. In some embodiments, the immunogenic composition does not contain an RNA polynucleotide encoding a non-OspC Borrelia outer surface protein antigen. In some embodiments, the RNA polynucleotide further includes a 5' untranslated region (UTR) and a 3' UTR. In some embodiments, the RNA polynucleotide further includes a poly(A) tail. In some embodiments, the RNA polynucleotide further includes a 5' cap analog. In some embodiments, the RNA polynucleotide is a modified polynucleotide, such as described in US 10,898,574, US 10,703,789, and US 10,577,403.

[0233] In some embodiments, the OspA and OspC antigens are from the same Borrelia species. In some embodiments, the OspA and OspC antigens are from different Borrelia species. In some embodiments, the OspA and OspC antigens are independently selected from B. burgdorferi, B. afzelii, B. bavariensis, B. garinii, B. mayonii, B. lusitaniae, B. bissettii, B. valasiana, and B. spielmanii antigens. In some embodiments, the OspA and OspC antigens are both B. burgdorferi antigens.

[0234] In some embodiments, the immunogenic composition contains an RNA polynucleotide encoding the OspA antigen and an RNA polynucleotide encoding the OspC antigen. In some embodiments, the RNA polynucleotides further include a 5' untranslated region (UTR) and a 3' UTR. In some embodiments, the RNA polynucleotides further include a poly(A) tail. In some embodiments, the RNA polynucleotides further include a 5' cap analog. In some embodiments, the RNA polynucleotides are modified polynucleotides, such as described in US 10,898,574, US 10,703,789, and US 10,577,403.

[0235] The RNA polynucleotide or polynucleotides can be formulated using one or more excipients to: (1) increase stability; (2) increase cell transfection; (3) permit sustained or delayed release; (4) alter the biodistribution to specific tissues or cell types; (5) increase the translation of encoded protein in vivo; and / or (6) alter the release profile of encoded proteinin vivo. Excipients can include solvents, dispersion media, diluents, other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, lipidoids, liposomes, lipid nanoparticles, polymers, lipoplexes, core-shell nanoparticles, peptides, proteins, hyaluronidase, nanoparticle mimics, and combinations thereof. Exemplary formulations for the RNA polynucleotides are described in US 10,898,574, US 10,703,789, and US 10,577,403.

[0236] In some embodiments, the RNA polynucleotide or polynucleotides are formulated in lipid nanoparticles. Examples of lipid nanoparticle compositions and methods of making same are described, for example, in Semple et al. (2010) Nat. Biotechnol. 28:172-176; Jayarama et al. (2012), Angew. Chem. Int. Ed., 51: 8529-8533; and Maier et al. (2013) Molecular Therapy 21, 1570-1578. In some embodiments, the lipid nanoparticles contain a cationic lipid. In some embodiments, the lipid nanoparticles contain a sterol. In some embodiments, the lipid nanoparticles contain a PEG-modified lipid. In some embodiments, the lipid nanoparticles contain a neutral lipid. In some embodiments, the lipid nanoparticles contain a cationic lipid, a sterol, and a PEG-modified lipid. In some embodiments, the lipid nanoparticles contain a cationic lipid, a neutral lipid, a sterol, and a PEG-modified lipid.

[0237] Exemplary lipids include DLin-DMA, DLin-K-DMA, 98N12-5, C12-200, DLin- MC3-DMA, DLin-KC2-DMA, DODMA, PLGA, PEG, PEG-DMG, PEGylated lipids and amino alcohol lipids. In another aspect, the lipid may be a cationic lipid such as DLin-DMA, DLin-D-DMA, DLin-MC3-DMA, DLin-KC2-DMA, DODMA and amino alcohol lipids. The amino alcohol cationic lipid may be the lipids described in and / or made by the methods described in U.S. Patent Publication No. US20130150625. For example, the cationic lipid may be 2-amino-3-[(9Z, 12Z)-octadeca-9,12-dien-l-yloxy]-2-{[(9Z,2Z)-octadeca-9,12-dien- l-yloxy]methyl}propan-l-ol (Compound 1 in US20130150625); 2-amino-3-[(9Z)-octadec-9- en-l-yloxy]-2-{[(9Z)-octadec-9-en-l-yloxy]methyl}propan-l-ol (Compound 2 in US20130150625); 2-amino-3 -[(9Z, 12Z)-octadeca-9, 12-dien- 1 -yloxy]-2- [(octyloxy)methyl]propan-l-ol (Compound s in US20130150625); and 2-(dimethylamino)-3- [(9Z, 12Z)-octadeca-9, 12-dien- 1 -yloxy]-2-{ [(9Z, 12Z)-octadeca-9, 12-dien- 1 - yloxy]methyl}propan-l-ol (Compound 4 in US20130150625); or any pharmaceutically acceptable salt or stereoisomer thereof.

[0238] In some embodiments, the lipid nanoparticles contain an ionizable cationic lipid, for example, 2,2-dilinoleyl-4-dimethylaminoethyl-[l,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3-DMA), or di((Z)-non-2-en-l-yl) 9-((4-(di methyl ami no)butanoyl)oxy)heptadecanedioate (L319), and further contain a neutral lipid, a sterol and a molecule capable of reducing particle aggregation, for example a PEG or PEG-modified lipid.

[0239] In some embodiments, the lipid nanoparticle formulation consists essentially of (i) at least one lipid selected from the group consisting of 2,2-dilinoleyl-4-dimethylaminoethyl- [l,3]-dioxolane (DLin-KC2-DMA), dilinoleyl-methyl-4-dimethylaminobutyrate (DLin-MC3- DMA), and di((Z)-non-2-en-l-yl) 9-((4-(dimethylamino)butanoyl)oxy)heptadecanedioate (L319); (ii) a neutral lipid selected from DSPC, DPPC, POPC, DOPE and SM; (iii) a sterol, e.g., cholesterol; and (iv) a PEG-lipid, e.g., PEG-DMG or PEG-cDMA, in a molar ratio of about 20-60% cationic lipid: 5-25% neutral lipid: 25-55% sterol; 0.5-15% PEG-lipid. In some embodiments, the lipid nanoparticles contain 50% ionizable cationic lipid, 10% neutral lipid, 38.5% sterol, and 1.5% PEG-modified lipid. In some embodiments, the neutral lipid is 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), the sterol is cholesterol, and the PEG- modified lipid is l,2-dimyristoyl-racalycero-3-methoxypolyethylene glycol-2000 (PEG- DMG) or PEG-cDMA.1. Borrelia Outer Surface Protein A (OspA) Antigens

[0240] Seven principal OspA serotypes have been recognized among European isolates (designated serotypes 1 to 7, see Wilske et al., J. Clin. Microbiol. 31:340-50, 1993). In some aspects, OspA serotypes tend to correlate with species, for instance with serotype 1 corresponding to B. burgdorferi s.s., serotype 2 corresponding to B. afzelii, and serotypes 3 to 7 corresponding to B. garinii. Serotype 4, in some aspects, is alternatively considered to correspond to B. bavariensis (Margos et al., Appl. Environ. Microbiol. 75: 5410-6, 2009).

[0241] In some embodiments, the OspA antigen is any of the OspA antigens described in WO2021207615, W02021205022, WO2010132758, US 9,975,927, US 10,766,931, US 11,572,392, US 9,023,367, US 8,623,375, US 8,623,376, US 9,303,073, US 9,334,311, US 9,895,434, US 11,305,000, US 9,562,079, US 9,534,021, US 10,266,571, US 8,821,893, US 7,887,815, US 7,582,304, US 7,605,248, and US20090324638.

[0242] In some embodiments, the OspA antigen includes one or more OspA antigens, such as 1, 2, 3, 4, 5 or 6 OspA antigens. It is understood that reference to the OspA antigen in the disclosure herein independently describes embodiments of any one of the OspA antigens of the one or more OspA antigens.

[0243] In some embodiments, the OspA antigen is a single OspA antigen. In some embodiments, the OspA antigen includes two or more OspA antigens. For example, each of the OspA antigens have non-identical amino acid sequences that can be overlapping or entirely non-overlapping sequences.

[0244] In some embodiments, the OspA antigen is aB. burgdorferi OspA antigen. In some embodiments, the OspA antigen is aB. afzelii OspA antigen. In some embodiments, the OspA antigen is aB. bavariensis OspA antigen. In some embodiments, the OspA antigen is a B. garinii OspA antigen. In some embodiments, the OspA antigen is a B. mayonii OspA antigen. In some embodiments, the OspA antigen is aB. lusitaniae OspA antigen. In some embodiments, the OspA antigen is aB. bissettii OspA antigen. In some embodiments, the OspA antigen is aB. spielmanii OspA antigen. In some embodiments, the OspA antigen is a B. valasiana OspA antigen.

[0245] In some embodiments, each of the different OspA antigens is an OspA antigen from a different Borrelia species. In some embodiments, the OspA antigen includes a first OspA antigen and a second OspA antigen. In some embodiments, the first OspA antigen and the second OspA antigen have non-identical amino acid sequences. In some embodiments, the two or more OspA antigens further includes a third OspA antigen. In some embodiments, the first OspA antigen, the second OspA antigen, and the third OspA antigen have non-identical amino acid sequences.

[0246] In some embodiments, the OspA antigen is a naturally occurring OspA protein or a fragment thereof. In some embodiments, the OspA antigen is a recombinant OspA protein.

[0247] In some embodiments, the OspA antigen contains one or more epitopes from an OspA protein. In some embodiments, the one or more epitopes include at least one linear epitope. In some embodiments, the one or more epitopes are linear epitopes. In some embodiments, the one or more epitopes include at least one conformational epitope. In some embodiments, the one or more epitopes are conformational epitopes.

[0248] In some embodiments, the one or more epitopes contain at least 2, 3, 4, 5, or 6 epitopes from one or more OspA proteins. In some embodiments, the one or more epitopes are from the same OspA protein. In some embodiments, the one or more epitopes are from the same OspA serotype. In some embodiments, the one or more epitopes are from multiple OspA proteins. In some embodiments, the one or more epitopes contain at least 2, 3, 4, 5, or 6 epitopes from at least 2, 3, 4, 5, or 6 OspA proteins. In some embodiments, the one or moreepitopes are from multiple OspA serotypes. In some embodiments, the one or more epitopes contain at least 2, 3, 4, 5, or 6 epitopes from at least 2, 3, 4, 5, or 6 OspA serotypes.

[0249] In some embodiments, the one or more epitopes include an OspA epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:50-82. In some embodiments, the one or more epitopes are independently selected from OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-82. In some embodiments, the one or more epitopes include any of the linear OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO: 50-82. In some embodiments, the one or more epitopes include any of the conformational OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:50-82. In some embodiments, the one or more epitopes include linear and conformational OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-82.

[0250] In some embodiments, the one or more epitopes include an OspA epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:50-62. In some embodiments, the one or more epitopes are independently selected from OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-62. In some embodiments, the one or more epitopes include any of the linear OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO: 50-62. In some embodiments, the one or more epitopes include any of the conformational OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:50-62. In some embodiments, the one or more epitopes include linear and conformational OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-62.

[0251] In some embodiments, the one or more epitopes include an OspA epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the one or more epitopes are independently selected from OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the one or more epitopes include any of the linear OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the one or more epitopes include any of the conformational OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the one or more epitopes include linear and conformational OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:63-82.

[0252] In some embodiments, the one or more epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO:4-49. In some embodiments, the one or more epitopes are independently selected from any of the linear epitopes whose sequences of amino acids are set forth in SEQ ID NO:4-49.

[0253] In some embodiments, the OspA antigen is an OspA protein containing one or more conformational epitopes. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that contains one or more conformational epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that contains one or more conformational epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that contains one or more conformational epitopes.

[0254] In some embodiments, the OspA antigen is an OspA protein containing one or more conformational epitopes. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO: 50-62 that contains one or more conformational epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-62 that contains one or more conformational epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-62 that contains one or more conformational epitopes.

[0255] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:50-62.

[0256] In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:50-62.

[0257] In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:50-62.

[0258] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:50. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:50. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:50.

[0259] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:51. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:51. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:51.

[0260] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:52. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:52. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:52.

[0261] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 53. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:53. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:53.

[0262] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 54. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:54. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:54.

[0263] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 55. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:55. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO: 55.

[0264] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:56. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:56. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:56.

[0265] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 57. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:57. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:57.

[0266] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 58. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:58. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO: 58.

[0267] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 59. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:59. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:59.

[0268] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:60. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:60. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:60.

[0269] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:61. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:61. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:61.

[0270] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:62. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:62. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:62.

[0271] In some embodiments, the OspA antigen is an OspA chimeric antigen. In some embodiments, the OspA chimeric antigen contains a plurality of epitopes from one or more OspA proteins. In some embodiments, the OspA antigen is an OspA chimeritope.

[0272] In some embodiments, the plurality of epitopes are from the same OspA protein. In some embodiments, the plurality of epitopes are from the same OspA serotype. In some embodiments, the plurality of epitopes are from multiple OspA proteins. In some embodiments, the plurality of epitopes contain at least 2, 3, 4, or 5 epitopes from at least 2, 3, 4, or 5 OspA proteins. In some embodiments, the plurality of epitopes are from multiple OspA serotypes. In some embodiments, the plurality of epitopes contain at least 2, 3, 4, 5, or 6 epitopes from at least 2, 3, 4, 5, or 6 OspA serotypes.

[0273] In some embodiments, the plurality of epitopes include an OspA epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:50-82. In some embodiments, the plurality of epitopes are independently selected from OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-82. In some embodiments, the plurality of epitopes include any of the linear OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO: 50-82. In some embodiments, the plurality of epitopes include any of the conformational OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:50-82. In some embodiments, the plurality of epitopes include linear and conformational OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-82.

[0274] In some embodiments, the plurality of epitopes include an OspA epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:50-62. In some embodiments, the plurality of epitopes are independently selected from OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-62. In some embodiments, the plurality of epitopes include any of the linear OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO: 50-62. In some embodiments, the plurality of epitopes include any of the conformational OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:50-62. In some embodiments, the plurality of epitopes include linear and conformational OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:50-62.

[0275] In some embodiments, the plurality of epitopes include an OspA epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the plurality of epitopes are independently selected from OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the plurality of epitopes include any of the linear OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the plurality of epitopesinclude any of the conformational OspA epitopes contained in the sequences of amino acids set forth in SEQ ID NO:63-82. In some embodiments, the plurality of epitopes include linear and conformational OspA epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:63-82.

[0276] In some embodiments, the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO:4-49. In some embodiments, the plurality of epitopes are independently selected from any of the linear epitopes whose sequences of amino acids are set forth in SEQ ID NO:4-49.

[0277] In some embodiments, the OspA antigen is an OspA protein containing one or more linear epitopes. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that contains one or more linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that contains one or more linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO: 50-82 that contains one or more linear epitopes.

[0278] In some embodiments, the OspA antigen is an OspA protein containing one or more linear epitopes. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO: 63 -82 that contains one or more linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO: 63 -82 that contains one or more linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO: 63 -82 that contains one or more linear epitopes.

[0279] In some embodiments, the OspA antigen is an OspA chimeric antigen containing a plurality of epitopes from one or more OspA proteins. In some embodiments, the plurality of epitopes are linear epitopes. In some embodiments, the OspA antigen is an OspA chimeritope. In some embodiments, the OspA antigen has any of the sequences of aminoacids set forth in SEQ ID NO:50-82 that is an OspA chimeric antigen containing a plurality of linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that is an OspA chimeric antigen containing a plurality of linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:50-82 that is an OspA chimeric antigen containing a plurality of linear epitopes.

[0280] In some embodiments, the OspA antigen is an OspA chimeric antigen containing a plurality of epitopes from one or more OspA proteins. In some embodiments, the plurality of epitopes are linear epitopes. In some embodiments, the OspA antigen is an OspA chimeritope. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:63-82 that is an OspA chimeric antigen containing a plurality of linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:63-82 that is an OspA chimeric antigen containing a plurality of linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspA antigen has any of the sequences of amino acids set forth in SEQ ID NO:63-82 that is an OspA chimeric antigen containing a plurality of linear epitopes.

[0281] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:63-82.

[0282] In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:63-82.

[0283] In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in any of SEQ ID NO: 63-82.

[0284] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO: 63. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:63. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO: 63.

[0285] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:64. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:64. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:64.

[0286] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 65. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:65. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:65.

[0287] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:66. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:66. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:66.

[0288] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:67. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:67. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:67.

[0289] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 68. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:68. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO: 68.

[0290] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:69. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:69. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:69.

[0291] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:70. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:70. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:70.

[0292] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:71. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:71. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:71.

[0293] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:72. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:72. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:72.

[0294] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:73. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:73. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO: 73.

[0295] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:74. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:74. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:74.

[0296] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 75. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:75. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO: 75.

[0297] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:76. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:76. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:76.

[0298] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:77. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:77. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:77.

[0299] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:78. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:78. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:78.

[0300] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:79.

[0301] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 80. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:80. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:80.

[0302] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:81.

[0303] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 82. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:82. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:82.

[0304] In some embodiments, the OspA antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:79-81. In some embodiments, the OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:79-81. In some embodiments, the OspA antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:79-81.

[0305] In some embodiments, the immunogenic composition comprises a first OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:80. In some embodiments, the first OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the first OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the second OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:80. In some embodiments, the second OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:80.

[0306] In some embodiments, the immunogenic composition comprises a first OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the first OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the first OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the second OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the second OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:81.

[0307] In some embodiments, the immunogenic composition comprises a first OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:80 and a second OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the first OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:80. In some embodiments, the first OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:80. In some embodiments, the second OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the second OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:81.

[0308] In some embodiments, the immunogenic composition comprises a first OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79, a second OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 80, and a third OspA antigen that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the first OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the first OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:79. In some embodiments, the second OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO: 80. In some embodiments, the second OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:80. In some embodiments, the third OspA antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:81. In some embodiments, the third OspA antigen comprises the sequence of amino acids set forth in SEQ ID NO:81.

[0309] In some embodiments, the OspA antigen is non-lipidated. In some embodiments, the first OspA antigen is non-lipidated. In some embodiments, the second OspA antigen is non-lipidated. In some embodiments, the third OspA antigen is non-lipidated.

[0310] In some embodiments, the OspA antigen is lipidated. In some embodiments, the first OspA antigen is lipidated. In some embodiments, the second OspA antigen is lipidated. In some embodiments, the third OspA antigen is lipidated. In some embodiments, the first OspA antigen and the second OspA antigen are lipidated. In some embodiments, the first OspA antigen and the third OspA antigen are lipidated. In some embodiments, the second OspA antigen and the third OspA antigen are lipidated. In some embodiments, the first OspA antigen, the second OspA antigen, and the third OspA antigen are lipidated.

[0311] Lipidation may confer adjuvant properties or stabilize the OspA antigen. Lipidation of a protein may occur using a number of different known methods (see, e.g., US 8,986,704, US 11,305,000, Bouchon et al., Anal Biochem, 1997, Hantke et al., Eur. J. Biochem, 1973, and Erdile et al., Infect Immun, 1993). In some embodiments, lipidation occurs through a chemical lipidation process. In some embodiments, lipidation occurs using an E. coli expression system. In some embodiments, lipidation is assisted through the presence of a lipidation signal peptide sequence, such as those present on an OspA antigen. In some embodiments, the E. coli expression system is BL21 DE3. In some embodiments, the E. coliexpression system uses any one or all of the enzymes diacylglyceryl transferase, signal peptidase II and transacylase. In some embodiments, the first step is the transfer of a diacylglyceride to the cysteine sulphydryl group of the unmodified prolipoprotein, followed by the cleavage of the signal peptide by signal peptidase II and, finally, the acylation of the a- amino group of the N-terminal cysteine of the apolipoprotein. The result is the placement of one lipid and a glycerol group substituted with two further lipids on the N-terminal cysteine residue of the polypeptide. The lipidation signal sequence, which is cleaved off during lipidation, is not present in the final polypeptide sequence.

[0312] In some embodiments, the lipidated OspA antigen is purified. In some embodiments, purification occurs using detergent extraction and / or ion-exchange chromatography. In some embodiments, purification occurs using ion-exchange chromatography and Triton XI 00 extraction. In some embodiments, the purification process decreases endotoxin levels. In some embodiments, the purification decreases the endotoxin level below 10 EU / mg.

[0313] In some embodiments, the OspA antigen is lipidated through the addition or presence of a lipid moiety to the OspA antigen. In some embodiments, lipid moieties, such as fatty acids, are added to the OspA antigen, such as at the C-terminus and / or N-terminus. In some embodiments, glycerol is added to the OspA antigen, such as at the C-terminus and / or N-terminus. In some embodiments, lipid moieties, such as fatty acids, are added to the OspA antigen at the N-terminus. In some embodiments, lipid molecules, such as fatty acids, and glycerol are added to the OspA antigen at the N-terminus. In some embodiments, the lipidated OspA antigen has a 3 fatty acid group and a glycerol added to the N-terminus of the lipidated OspA antigen.

[0314] In some embodiments, a lipid moiety comprises one to three lipids, such as C14-20 alkyl and / or C14-20 alkenyl. In some embodiments, a lipid moiety comprises saturated fatty acids (ranging from Ci4-Cis), unsaturated fatty acids (Cie / Cis), and / or palmitate (C16:0) as major components. In some embodiments, the lipid moiety is attached to a glycerol. In some embodiments, the lipid moiety is attached to an N-terminal cysteine of the polypeptide of the OspA antigen. In some embodiments, the N-terminal cysteine is present on a signal peptide sequence. In some embodiments, the lipid moiety is attached at the amino terminal cysteine residue of the signal peptide sequence. In some embodiments, the lipid moiety is attached at the sulfhydryl group of the cysteine residue of the signal peptide sequence. In some embodiments, the N-terminal cysteine can be lipidated on both the amino group (-HN2) andsulfhydryl group (-SH). In some embodiments, the N-terminal cysteine can be lipidated to form around 1-3 fatty acid modifications. In some embodiments, the lipid moiety attached to the N-terminal cysteine is S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-N-palmitoylcysteine.

[0315] In some embodiments, the OspA antigen may further comprise a lipidation signal peptide sequence. Lipidation signal peptide sequences are known in the art (see, e.g., US 8,986,704 and US 11,305,000). Exemplary lipidation signal peptide sequences include, but are not limited to, the lipidation signal peptide sequences set forth in SEQ ID NOs: 522-524. In some embodiments, the at least one OspA antigen further comprises a lipidation signal peptide sequence as set forth in SEQ ID NO: 522. In some embodiments, the OspA antigen further comprises a lipidation signal peptide sequence as set forth in SEQ ID NO: 523. In some embodiments, the OspA antigen further comprises a lipidation signal peptide sequence as set forth in SEQ ID NO: 524. In some embodiments, the OspA antigen comprises an OspB leader sequence. In some embodiments, the OspB leader sequence comprises the sequence set forth in SEQ ID NO: 522.

[0316] Lipidation signal peptide sequences are cleaved off during processing, thus the lipidated OspA antigens may not contain the lipidation signal peptide sequence in the mature lipidated protein.2. Borrelia Outer Surface Protein C (OspC) Antigens

[0317] In some aspects, OspC antigens can be grouped into one of 30 serotypes (see US 10,086,057). In some aspects, OspC serotypes T, U, B, E, K, H, N, C, M, Pwa, Pli, PBes, Pki, PFim, Smar, HT22, and A have been shown to be more commonly associated with human infection. Exemplary OspC serotypes and associated alleles and GenBank numbers are shown in Table 1, the corresponding sequences for which are incorporated by reference. In some aspects, Borrelia burgdorferi OspC serotype K comprises strains having the OspC alleles 272, 297, sh-2-82, CS9, OEAI 1 MUL, OC12, or OC13. In some aspects, OspC serotype B comprises strains having the OspC alleles CS7, 109a, PMi, 160b, LDP73, MI415, 61BV3, VS219, 51405UT, MR623, OC2, or OC3. In some aspects, OspC serotype J comprises strains having the OspC alleles MIL, 188a, MI403, or OCI 1. In some aspects, OspC serotype E comprises strains having the OspC alleles N40, 88a, 167BJM, SD91, NP 14,28691, 48102UT, or OC5. In some aspects, OspC serotype F comprises strains having the OspC alleles 27579, B 156, cawtb32, MI407, B. pacificus strain, or OC6.Table 1: OspC Serotypes, Alleles, and GenBank Numbers

[0318] In some embodiments, the OspC antigen is any of the OspC antigens described in WO2010132758, W02024076960, US 10,086,057, US 9,562,079, US 8,808,705, US 9,556,239, US 10,466,240, US 9,534,021, US 10,266,571, US 7,794,727, US 8,778,352, US 9,376,472, US 8,821,893, US 7,887,815, US 7,582,304, US 7,605,248, US20090324638, and Di et al., The ISME Journal 16:447-464, 2022.

[0319] In some embodiments, the OspC antigen is a B. burgdorferi OspC antigen. In some embodiments, the OspC antigen is a B. afzelii OspC antigen. In some embodiments, the OspC antigen is a B. bavariensis OspC antigen. In some embodiments, the OspC antigen is a B. garinii OspC antigen. In some embodiments, the OspC antigen is a B. mayonii OspC antigen. In some embodiments, the OspC antigen is a B. lusitaniae OspC antigen. In some embodiments, the OspC antigen is a B. bissettii OspC antigen. In some embodiments, the OspC antigen is a B. spielmanii OspC antigen. In some embodiments, the OspC antigen is a B. valasiana OspC antigen.

[0320] In some embodiments, the OspC antigen is a naturally occurring OspC protein or a fragment thereof. In some embodiments, the OspC antigen is a recombinant OspC protein.

[0321] In some embodiments, the OspC antigen contains one or more epitopes from an OspC protein. In some embodiments, the one or more epitopes include at least one linearepitope. In some embodiments, the one or more epitopes are linear epitopes. In some embodiments, the one or more epitopes include at least one conformational epitope. In some embodiments, the one or more epitopes are conformational epitopes.

[0322] In some embodiments, the one or more epitopes contain at least 2, 3, 4, or 5 epitopes from one or more OspC proteins. In some embodiments, the one or more epitopes are from the same OspC protein. In some embodiments, the one or more epitopes are from the same OspC serotype. In some embodiments, the one or more epitopes are from multiple OspC proteins. In some embodiments, the one or more epitopes contain at least 2, 3, 4, or 5 epitopes from at least 2, 3, 4, or 5 OspC proteins. In some embodiments, the one or more epitopes contain at least 5, 6, 7, 8, 9, or 10 epitopes from at least 5, 6, 7, 8, 9 or 10 OspC proteins. In some embodiments, the one or more epitopes are from multiple OspC serotypes. In some embodiments, the one or more epitopes contain at least 2, 3, 4, or 5 epitopes from at least 2, 3, 4, or 5 OspC serotypes. In some embodiments, the one or more epitopes contain at least 5, 6, 7, 8, 9, or 10 epitopes from at least 5, 6, 7, 8, 9, or 10 OspC serotypes.

[0323] In some embodiments, the one or more epitopes include linear epitopes from the loop 5 (L5) region of OspC. In some embodiments, the one or more epitopes include linear epitopes from the alpha helix 5 (H5) region of OspC. In some embodiments, the one or more epitopes include linear epitopes from the L5 and H5 regions of OspC. Exemplary L5 and H5 linear epitope sequences described herein, as well as other exemplary OspC antigen sequences described herein, are in some instances further distinguished by OspC serotype or strain (e.g., A, Smar, etc.).

[0324] In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of an OspC serotype. In some embodiments, the OspC serotype is one OspC serotype. In some embodiments, the OspC serotype is two OspC serotypes. In some embodiments, the OspC serotype is three OspC serotypes. In some embodiments, the OspC serotype is four OspC serotypes. In some embodiments, the OspC serotype is five OspC serotypes. In some embodiments, the OspC serotype is six OspC serotypes. In some embodiments, the OspC serotype is seven OspC serotypes. In some embodiments, the OspC serotype is eight OspC serotypes. In some embodiments, the OspC serotype is nine OspC serotypes. In some embodiments, the OspC serotype is ten OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of five OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of six OspC serotypes. In some embodiments, the one ormore epitopes comprise linear epitopes from the L5 and H5 regions of seven OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of eight OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of nine OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of ten OspC serotypes.

[0325] In some embodiments, the OspC serotype is selected from the OspC serotypes consisting of A, B, C, D, E, F, G, H, I, K, M, N, and U. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of five OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of five OspC serotypes, wherein the five OspC serotypes are C, F, H, M, and N. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of six OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of six OspC serotypes, wherein the six OspC serotypes are C, F, H, I, M, and N. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of seven OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of seven OspC serotypes, wherein the seven OspC serotypes are C, D, F, H, I, M, and N. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of eight OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of eight OspC serotypes, wherein six of the eight OspC serotypes are C, F, H, I, M, and N and two of the eight OspC serotypes are independently selected from the OspC serotypes consisting of A, B, D, E, G, K, and U. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of nine OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of nine OspC serotypes, wherein six of the eight OspC serotypes are C, F, H, I, M, and N and three of the nine OspC serotypes are independently selected from the OspC serotypes consisting of A, B, D, E, G, K, and U. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of ten OspC serotypes. In some embodiments, the one or more epitopes comprise linear epitopes from the L5 and H5 regions of ten OspC serotypes, wherein the ten OspC serotypes are A, B, C, F, H, I, K, M, N, and U.

[0326] In some embodiments, the one or more epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:83-519. In some embodiments, the one or more epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:83-519. In some embodiments, the one or more epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:83-519. In some embodiments, the one or more epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-378. In some embodiments, the one or more epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:83-519.

[0327] In some embodiments, the one or more epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO: 84-93. In some embodiments, the one or more epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO: 84-93. In some embodiments, the one or more epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO: 84-93.

[0328] In some embodiments, the one or more epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93. In some embodiments, the one or more epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93. In some embodiments, the one or more epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93.

[0329] In some embodiments, the one or more epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521. In some embodiments, the one or more epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521. In some embodiments, the one or more epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521. In some embodiments, the one or more epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-378. In some embodiments, the one or more epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521.

[0330] In some embodiments, the one or more epitopes include an OspC epitope from a naturally occurring OspC antigen. In some embodiments, the one or more epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:224- 273 and 308-378. In some embodiments, the one or more epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-273 and 308-378. In some embodiments, the one or more epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224- 273 and 308-378. In some embodiments, the one or more epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-273 and 308-378. In some embodiments, the one or more epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-273 and 308-378.

[0331] In some embodiments, the one or more epitopes include an OspC epitope from a recombinant OspC antigen. In some embodiments, the one or more epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521. In some embodiments, the one or more epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521. In some embodiments, the one or more epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521. In some embodiments, the one or more epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:274-307. In some embodiments, the one or more epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521.

[0332] In some embodiments, the OspC antigen contains one or more epitope-containing regions, such as at least one, two, three, or four epitope-containing regions. In some embodiments, the one or more epitope-containing regions are or include conformational epitope-containing regions. In some embodiments, at least one of the one or more epitopecontaining regions has the sequence of amino acids set forth in any of SEQ ID NO:308-378. In some embodiments, each of the one or more epitope-containing regions has the sequence of amino acids set forth in any of SEQ ID NO:308-378 or a sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the one or more epitope-containing regions are independently selected from the sequences of amino acids set forth in SEQ ID NO: 308-378.

[0333] In some embodiments, the one or more epitopes include one or more linear OspC epitopes. In some embodiments, at least one of the one or more linear OspC epitopes has the sequence of amino acids set forth in any of SEQ ID NO:83-223 and 449-521. In some embodiments, the one or more linear OspC epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 83 -223 and 449-521. In some embodiments, the one or more epitopes are linear epitopes independently selected from the sequences of amino acids set forth in SEQ ID NO:83-223 and 449-521.

[0334] In some embodiments, the OspC antigen is an OspC protein containing one or more conformational epitopes. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-378 that contains one or more conformational epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-378 that contains one or more conformational epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-378 that contains one or more conformational epitopes.

[0335] In some embodiments, the OspC antigen is an OspC protein containing one or more conformational epitopes. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO: 224-307 that contains one or more conformational epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-307 that contains one or more conformational epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-307 that contains one or more conformational epitopes.

[0336] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:224-307.

[0337] In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:224-307.

[0338] In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:224-307.

[0339] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:224. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:224. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:224.

[0340] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:225. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:225. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:225.

[0341] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:226. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:226. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:226.

[0342] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:227. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:227. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:227.

[0343] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:228. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:228. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:228.

[0344] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:229. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:229. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:229.

[0345] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 230. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:230. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:230.

[0346] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:231. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:231. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:231.

[0347] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:232. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:232. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:232.

[0348] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:233. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:233. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:233.

[0349] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:234. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:234. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:234.

[0350] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:235. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:235. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:235.

[0351] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:236. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:236. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:236.

[0352] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:237. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:237. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:237.

[0353] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:238. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:238. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:238.

[0354] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:239. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:239. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:239.

[0355] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:240. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:240. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:240.

[0356] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:241. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:241. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:241.

[0357] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 242. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:242. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:242.

[0358] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:243. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:243. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:243.

[0359] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:244. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:244. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:244.

[0360] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:245. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:245. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:245.

[0361] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:246. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:246. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:246.

[0362] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:247. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:247. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:247.

[0363] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:248. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:248. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:248.

[0364] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:249. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:249. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:249.

[0365] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:250. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:250. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:250.

[0366] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:251. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:251. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:251.

[0367] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:252. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:252. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:252.

[0368] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:253. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:253. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:253.

[0369] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:254. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:254. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:254.

[0370] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 255. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:255. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:255.

[0371] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:256. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:256. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:256.

[0372] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:257. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:257. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:257.

[0373] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:258. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:258. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:258.

[0374] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:259. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:259. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:259.

[0375] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:260. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:260. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:260.

[0376] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:261. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:261. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:261.

[0377] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:262. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:262. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:262.

[0378] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 263. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:263. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:263.

[0379] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:264. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:264. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:264.

[0380] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:265. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:265. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:265.

[0381] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:266. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:266. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:266.

[0382] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:267. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:267. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:267.

[0383] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:268. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:268. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:268.

[0384] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:269. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:269. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:269.

[0385] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:270. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:270. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:270.

[0386] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 271. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:271. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:271.

[0387] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:272. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino- n -acids set forth in SEQ ID NO:272. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:272.

[0388] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:273. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:273. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:273.

[0389] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:274. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:274. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:274.

[0390] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 275. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:275. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:275.

[0391] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:276. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:276. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:276.

[0392] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:277. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:277. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:277.

[0393] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:278. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:278. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:278.

[0394] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:279. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:279. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:279.

[0395] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:280. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:280. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:280.

[0396] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:281. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:281. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:281.

[0397] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:282. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:282. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:282.

[0398] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:283. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:283. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:283.

[0399] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:284. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:284. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:284.

[0400] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:285. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:285. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:285.

[0401] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:286. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:286. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:286.

[0402] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:287. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:287. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:287.

[0403] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:288. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:288. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:288.

[0404] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 289. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:289. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:289.

[0405] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:290. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:290. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:290.

[0406] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:291. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:291. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:291.

[0407] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:292. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:292. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:292.

[0408] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:293. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:293. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:293.

[0409] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:294. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:294. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:294.

[0410] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO: 295. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:295. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:295.

[0411] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:296. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:296. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:296.

[0412] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:297. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:297. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:297.

[0413] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:298. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:298. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:298.

[0414] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:299. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of aminoacids set forth in SEQ ID NO:299. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:299.

[0415] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:300. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:300. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:300.

[0416] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 301. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:301. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:301.

[0417] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:302. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:302. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:302.

[0418] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:303. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO: 303. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 303.

[0419] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%sequence identity to the sequence of amino acids set forth in SEQ ID NO:304. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:304. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:304.

[0420] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 305. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:305. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 305.

[0421] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:306. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:306. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:306.

[0422] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:307. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:307. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:307.

[0423] In some embodiments, the OspC antigen is an OspC chimeric antigen. In some embodiments, the OspC chimeric antigen contains a plurality of epitopes from one or more OspC proteins. In some embodiments, the OspC antigen is an OspC chimeritope.

[0424] In some embodiments, the plurality of epitopes are from the same OspC protein. In some embodiments, the plurality of epitopes are from the same OspC serotype. In some embodiments, the plurality of epitopes are from multiple OspC proteins. In someembodiments, the plurality of epitopes contain at least 2, 3, 4, or 5 epitopes from at least 2, 3, 4, or 5 OspC proteins. In some embodiments, the plurality of epitopes contain at least 5, 6, 7, 8, 9, or 10 epitopes from at least 5, 6, 7, 8, 9, or 10 OspC proteins. In some embodiments, the plurality of epitopes are from multiple OspC serotypes. In some embodiments, the plurality of epitopes contain at least 2, 3, 4, or 5 epitopes from at least 2, 3, 4, or 5 OspC serotypes. In some embodiments, the plurality of epitopes contain at least 5, 6, 7, 8, 9, or 10 epitopes from at least 5, 6, 7, 8, 9 or 10 OspC serotypes.

[0425] In some embodiments, the plurality of epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:83-519. In some embodiments, the plurality of epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:83-519. In some embodiments, the plurality of epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:83-519. In some embodiments, the plurality of epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-378. In some embodiments, the plurality of epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:83-519.

[0426] In some embodiments, the plurality of epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521. In some embodiments, the plurality of epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521. In some embodiments, the plurality of epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521. In some embodiments, the plurality of epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-378. In some embodiments, the plurality of epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-448, 520, and 521.

[0427] In some embodiments, the plurality of epitopes include an OspC epitope from a naturally occurring OspC antigen. In some embodiments, the plurality of epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:224- 273 and 308-378. In some embodiments, the plurality of epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ IDNO:224-273 and 308-378. In some embodiments, the plurality of epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224- 273 and 308-378. In some embodiments, the plurality of epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:224-273 and 308-378. In some embodiments, the plurality of epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:224-273 and 308-378.

[0428] In some embodiments, the plurality of epitopes include an OspC epitope from a recombinant OspC antigen. In some embodiments, the plurality of epitopes include an OspC epitope contained in any of the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521. In some embodiments, the plurality of epitopes are independently selected from OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521. In some embodiments, the plurality of epitopes include any of the linear OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521. In some embodiments, the plurality of epitopes include any of the conformational OspC epitopes contained in the sequences of amino acids set forth in SEQ ID NO:274-307. In some embodiments, the plurality of epitopes include linear and conformational OspC epitopes contained in any of the sequences of amino acids set forth in SEQ ID NO:274-307 and 379-448, 520, and 521.

[0429] In some embodiments, the OspC antigen contains one or more epitope-containing regions, such as at least one, two, three, or four epitope-containing regions. In some embodiments, the one or more epitope-containing regions are or include conformational epitope-containing regions. In some embodiments, at least one of the one or more epitopecontaining regions has the sequence of amino acids set forth in any of SEQ ID NO:308-378. In some embodiments, each of the one or more epitope-containing regions has the sequence of amino acids set forth in any of SEQ ID NO:308-378 or a sequence that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the one or more epitopecontaining regions are independently selected from the sequences of amino acids set forth in SEQ ID NO: 308-378.

[0430] In some embodiments, the plurality of epitopes include one or more linear OspC epitopes. In some embodiments, at least one of the one or more linear OspC epitopes has the sequence of amino acids set forth in any of SEQ ID NO:83-223 and 449-521. In someembodiments, the one or more linear OspC epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO:83-223 and 449-521. In some embodiments, the plurality of epitopes are linear epitopes independently selected from the sequences of amino acids set forth in SEQ ID NO: 83 -223 and 449-521.

[0431] In some embodiments, the OspC antigen is an OspC protein containing one or more linear epitopes. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-307 and 379-448, 520, and 521 that contains one or more linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-307 and 379-448, 520, and 521 that contains one or more linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-307 and 379-448, 520, and 521 that contains one or more linear epitopes.

[0432] In some embodiments, the OspC antigen is an OspC protein containing one or more linear epitopes. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-273 that contains one or more linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-273 that contains one or more linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:224-273 that contains one or more linear epitopes.

[0433] In some embodiments, the OspC antigen is an OspC protein containing one or more linear epitopes. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:274-307 that contains one or more linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:274-307 that contains one or more linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In someembodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:274-307 that contains one or more linear epitopes.

[0434] In some embodiments, the OspC antigen is an OspC chimeric antigen containing a plurality of epitopes from one or more OspC proteins. In some embodiments, the plurality of epitopes are linear epitopes. In some embodiments, the OspC antigen is an OspC chimeritope. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:379-448, 520, and 521 that is an OspC chimeric antigen containing a plurality of linear epitopes or has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity thereto. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:379-448, 520, and 521 that is an OspC chimeric antigen containing a plurality of linear epitopes or has at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids thereof. In some embodiments, the OspC antigen has any of the sequences of amino acids set forth in SEQ ID NO:379-448, 520, and 521 that is an OspC chimeric antigen containing a plurality of linear epitopes.

[0435] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

[0436] In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

[0437] In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

[0438] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:379. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:379. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:379.

[0439] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:380. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:380. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:380.

[0440] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:381. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:381. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:381.

[0441] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:382. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:382. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:382.

[0442] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 383. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:383. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 383.

[0443] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:384. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:384. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:384.

[0444] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:385. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:385. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:385.

[0445] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:386. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:386. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:386.

[0446] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:387. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:387. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:387.

[0447] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:388. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:388. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:388.

[0448] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:389. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:389. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:389.

[0449] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:390. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:390. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:390.

[0450] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:391. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:391. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:391.

[0451] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:392. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:392. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:392.

[0452] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:393. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:393. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 393.

[0453] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:394. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:394. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:394.

[0454] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 395. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:395. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 395.

[0455] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:396. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:396. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:396.

[0456] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:397. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:397. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:397.

[0457] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 398. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:398. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:398.

[0458] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:399. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:399. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:399.

[0459] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:400. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:400. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:400.

[0460] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:401. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:401. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:401.

[0461] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:402. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:402. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:402.

[0462] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:403. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:403. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:403.

[0463] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:404. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:404. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:404.

[0464] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:405. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:405. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:405.

[0465] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:406. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:406. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:406.

[0466] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:407. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:407. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:407.

[0467] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:408. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:408. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:408.

[0468] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:409. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:409. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:409.

[0469] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:410. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:410. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:410.

[0470] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:411. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:411. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:411.

[0471] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:412. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:412. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:412.

[0472] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:413. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:413. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:413.

[0473] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:414. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:414. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:414.

[0474] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:415. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:415. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:415.

[0475] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:416. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:416. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:416.

[0476] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:417. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:417. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:417.

[0477] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:418. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:418. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:418.

[0478] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:419. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:419. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:419.

[0479] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:420. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:420. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:420.

[0480] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:421. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:421. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:421.

[0481] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:422. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:422. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:422.

[0482] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:423. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:423. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:423.

[0483] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:424. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:424. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:424.

[0484] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:425. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:425. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:425.

[0485] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:426. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:426. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:426.

[0486] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:427. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:427. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:427.

[0487] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:428. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:428. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:428.

[0488] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:429. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:429. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:429.

[0489] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:430. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:430. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:430.

[0490] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:431. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:431. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:431.

[0491] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:432. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:432. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:432.

[0492] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:433. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:433. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:433.

[0493] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:434. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:434. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:434.

[0494] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:435. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:435. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:435.

[0495] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:436. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:436. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:436.

[0496] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 437. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:437. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:437.

[0497] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:438. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:438. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:438.

[0498] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:439. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:439. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:439.

[0499] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:440. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:440. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:440.

[0500] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:441. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:441. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:441.

[0501] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:442. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:442. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:442.

[0502] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:443. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:443. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:443.

[0503] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:444. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:444. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:444.

[0504] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:445. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:445. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:445.

[0505] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:446. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:446. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:446.

[0506] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:447. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170,180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:447. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:447.

[0507] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:448. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:448. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:448.

[0508] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 520. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:520. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:520.

[0509] In some embodiments, the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO: 521. In some embodiments, the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in SEQ ID NO:521. In some embodiments, the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO: 521.

[0510] In some embodiments, the OspC antigen is non-lipidated.

[0511] In some embodiments, the OspC antigen is lipidated. Lipidation may confer adjuvant properties or stabilize the OspC antigen. Lipidation of a protein may occur using a number of different known methods (see, e.g., Bouchon et al., Anal Biochem. 1997, Hantke et al., Eur. J. Biochem, 1973, and Erdile et al., Infect Immun, 1993). In some embodiments, lipidation occurs through a chemical lipidation process. In some embodiments, lipidation occurs using ancoli expression system. In some embodiments, lipidation is assisted through the presence of a lipidation signal peptide sequence, such as those present on anOspC antigen. In some embodiments, the E. coli expression system is BL21 DE3. In some embodiments, the E. coli expression system uses any one or all of the enzymes diacylglyceryl transferase, signal peptidase II and transacylase. In some embodiments, the first step is the transfer of a diacylglyceride to the cysteine sulphydryl group of the unmodified prolipoprotein, followed by the cleavage of the signal peptide by signal peptidase II and, finally, the acylation of the a-amino group of the N-terminal cysteine of the apolipoprotein. The result is the placement of one lipid and a glycerol group substituted with two further lipids on the N-terminal cysteine residue of the polypeptide. The lipidation signal sequence, which is cleaved off during lipidation, is not present in the final polypeptide sequence.

[0512] In some embodiments, the lipidated OspC antigen is purified. In some embodiments, purification occurs using detergent extraction and / or ion-exchange chromatography. In some embodiments, purification occurs using ion-exchange chromatography and Triton XI 00 extraction. In some embodiments, the purification process decreases endotoxin levels. In some embodiments, the purification decreases the endotoxin level below 10 EU / mg.

[0513] In some embodiments, the OspC antigen is lipidated through the addition or presence of a lipid moiety to or on the OspC antigen. In some embodiments, lipid moieties, such as fatty acids, are added to the OspC antigen, such as at the C-terminus and / or N- terminus. In some embodiments, glycerol is added to the OspC antigen, such as at the C- terminus and / or N-terminus. In some embodiments, lipid moieties, such as fatty acids, are added to the OspC antigen at the N-terminus. In some embodiments, lipid molecules, such as fatty acids, and glycerol are added to the OspC antigen at the N-terminus. In some embodiments, the lipidated OspC antigen has a 3 fatty acid group and a glycerol added to the N-terminus of the lipidated OspC antigen.

[0514] In some embodiments, a lipid moiety comprises one to three lipids, such as C14-20 alkyl and / or C14-20 alkenyl. In some embodiments, a lipid moiety comprises saturated fatty acids (ranging from Ci4-Cis), unsaturated fatty acids (Cie / Cis), and / or palmitate (C16:0) as major components. In some embodiments, the lipid moiety is attached to a glycerol. In some embodiments, the lipid moiety is attached to an N-terminal cysteine of the polypeptide of the OspC antigen. In some embodiments, the N-terminal cysteine is present on a signal peptide sequence. In some embodiments, the lipid moiety is attached at the amino terminal cysteine residue of the signal peptide sequence. In some embodiments, the lipid moiety is attached at the sulfhydryl group of the cysteine residue of the signal peptide sequence. In someembodiments, the N-terminal cysteine can be lipidated on both the amino group (-HN2) and sulfhydryl group (-SH). In some embodiments, the N-terminal cysteine can be lipidated to form around 1-3 fatty acid modifications. In some embodiments, the lipid moiety attached to the N-terminal cysteine is S-[2,3-bis(palmitoyloxy)-(2R,S)-propyl]-N-palmitoylcysteine.

[0515] In some embodiments, the OspC antigen may further comprise a lipidation signal peptide sequence. Lipidation signal peptide sequences are known in the art (see, e.g., US 8,986,704 and US 11,305,000). Exemplary lipidation signal peptide sequences include, but are not limited to, the lipidation signal peptide sequences set forth in SEQ ID NOs: 522-524. In some embodiments, the at least one OspC antigen further comprises a lipidation signal peptide sequence as set forth in SEQ ID NO: 522. In some embodiments, the OspC antigen further comprises a lipidation signal peptide sequence as set forth in SEQ ID NO: 523. In some embodiments, the OspC antigen further comprises a lipidation signal peptide sequence as set forth in SEQ ID NO: 524. In some embodiments, the OspC antigen comprises an OspB leader sequence. In some embodiments, the OspB leader sequence comprises the sequence set forth in SEQ ID NO: 522.

[0516] Lipidation signal peptide sequences are cleaved off during processing, thus the lipidated OspC antigens may not contain the lipidation signal peptide sequence in the mature lipidated protein.C. Additional Components

[0517] The immunogenic compositions of the present disclosure may comprise one or more additional components, such as one or more excipients, one or more stabilizers, one or more preservatives, and / or additional antigens.

[0518] Pharmaceutically acceptable excipients for the present immunogenic compositions include solvents, bulking agents, buffering agents, tonicity adjusting agents, preservatives, surfactants, and emulsifying agents (Pramanick et al., Pharma Times, 45:65-77, 2013). In some embodiments, the immunogenic composition contains an excipient that functions as one or more of a solvent, a bulking agent, a buffering agent, and a tonicity adjusting agent (e.g., sodium chloride in saline may serve as both an aqueous vehicle and a tonicity adjusting agent). In some embodiments, the immunogenic composition contains an excipient that functions as one or both of a surfactant and an emulsifier (e.g., the nonionic surfactant polysorbate 80).

[0519] In some embodiments, the immunogenic compositions contains an aqueous vehicle as a solvent. Suitable vehicles include sterile water, saline solution, phosphate buffered saline, and Ringer’s solution. In some embodiments, the immunogenic composition is isotonic.

[0520] In some embodiments, the immunogenic composition contains a buffering agent. Buffering agents control pH to inhibit degradation of the active agent during processing, storage, and optionally reconstitution. Suitable buffers include salts comprising acetate, citrate, phosphate, sulfate, or Tris. In some embodiments, the buffer is not a phosphate- containing buffer. In certain other embodiments, the buffer is a Tris buffer. Other suitable buffers include amino acids such as arginine, glycine, histidine, and lysine. The buffering agent may further comprise hydrochloric acid or sodium hydroxide. In some embodiments, the buffering agent maintains the pH of the immunogenic composition within a range of 6 to 9. In some embodiments, the pH is greater than (lower limit) 6, 7, or 8. In some embodiments, the pH is less than (upper limit) 9, 8, or 7. That is, the pH is in the range of from about 6 to 9 in which the lower limit is less than the upper limit. In some embodiments, the pH is about 6.5, about 7.0, or about 7.5.

[0521] In some embodiments, the immunogenic composition contains a tonicity adjusting agent. Suitable tonicity adjusting agents include dextrose, glycerol, sodium chloride, glycerin, and mannitol.

[0522] In some embodiments, the immunogenic composition contains a bulking agent. Bulking agents are particularly useful when the immunogenic composition is to be lyophilized before administration. In some embodiments, the bulking agent is a protectant that aids in the stabilization and prevention of degradation of the active agents during freeze or spray drying and / or during storage. Suitable bulking agents include sugars (e.g., mono-, di- , and polysaccharides) such as sucrose, lactose, trehalose, mannitol, sorbital, glucose, and raffinose.

[0523] In some embodiments, the immunogenic composition contains a stabilizer. Suitable stabilizers include sugars such as sucrose and lactose, amino acids such as glycine or the monosodium salt of glutamic acid, and proteins such as human serum albumin or gelatin.

[0524] In some embodiments, the immunogenic composition contains a preservative. Suitable preservatives include antioxidants and antimicrobial agents. In some embodiments,the immunogenic composition is prepared under sterile conditions and is in a single use container, and thus does not necessitate inclusion of a preservative.II. Articles of Manufacture

[0525] The present disclosure also provides vials, syringes (e.g., pre-filled syringes), and kits containing any of the immunogenic compositions described herein, such as in Section I. In some embodiments, the immunogenic composition is in liquid form. In some embodiments, the immunogenic composition is in lyophilized form. In some embodiments, the provided vial, syringe, or kit contains a single dose of the immunogenic composition, such as a 0.3 mL to 1.5 mL dose.

[0526] The present disclosure also provides kits containing a first composition and a second composition. In some embodiments, the first composition contains an adjuvant, which can be any adjuvant described herein, such as in Section I-A. In some embodiments, the second composition contains a Borrelia outer surface protein C (OspC) antigen, which can be any described herein, such as in Section I-B-2. In some embodiments, the second composition contains a second OspC antigen, which can be any described herein, such as in Section I-B-2. In some embodiments, the kit contains a third composition containing a second OspC antigen, which can be any described herein, such as in Section I-B-2.

[0527] In some embodiments, the first OspC antigen is an OspC chimeric antigen containing a plurality of linear epitopes from one or more OspC proteins, and the second OspC antigen is an OspC antigen containing one or more conformational epitopes. In some embodiments, the first OspC antigen is any of the OspC chimeric antigens containing a plurality of linear epitopes from one or more OspC proteins described herein, such as in Section I-B-2. In some embodiments, the second OspC antigen is any of the OspC proteins containing one or more conformational epitopes described herein, such as in Section I-B-2.

[0528] In some embodiments, the second composition is in liquid form. In some embodiments, the second composition is in lyophilized form. In some embodiments, the third composition is in liquid form. In some embodiments, the third composition is in lyophilized form.

[0529] In some embodiments, the kit further contains instructions for combining the first composition and the second composition to prepare any of the immunogenic compositions described herein, such as in Section I. In some embodiments, the kit further contains instructions for combining the first, second, and third compositions to prepare any of theimmunogenic compositions described herein, such as in Section I. In some embodiments, the instructions are for preparing a single dose of the immunogenic composition. In some embodiments, the kit is for preparing a single dose of the immunogenic composition, such as a 0.3 mL to 1.5 mL dose.

[0530] In some embodiments, combining the first composition with the second composition and optionally the third composition involves mixing the first and the second compositions and optionally the third composition. In some embodiments, combining the first composition with the second composition and optionally the third composition involves mixing the first and the second compositions and optionally the third composition in a single vial. In some embodiments, combining the first composition with the second composition and optionally the third composition involves mixing the first and the second compositions and optionally the third composition in a single vial by gentle inversion. In some embodiments, the mixing is for a maximum of about one hour at room temperature.

[0531] In some embodiments, the first composition contains a second adjuvant, which can be any described herein, such as in Section I-A. In some embodiments, the second composition contains a second adjuvant, which can be any described herein, such as in Section I-A. In some embodiments, the third composition contains a second adjuvant, which can be any described herein, such as in Section I-A. In some embodiments, the third composition contains a third adjuvant, which can be any described herein, such as in Section I-A.

[0532] In some embodiments, the kit contains an immunogenic composition packaged appropriately. In some embodiments, the kit contains i) a first composition and ii) a second composition and optionally iii) a third composition that are packaged appropriately, such that the first composition and the second composition and optionally the third composition may be combined to form an immunogenic composition. For example, if the immunogenic composition is a freeze-dried power, a vial with a resilient stopper can be used so that the powder may be easily resuspended by injecting fluid (e.g., sterile water, saline, etc.) through the resilient stopper. In some embodiments, the kit contains a device for administration (e.g., syringe). In some embodiments, the syringe is pre-filled with the immunogenic composition. In some embodiments, the administration is by intramuscular injection. The instructions relating to the use of the immunogenic composition generally include information as to dosage, schedule, and route of administration for the intended methods of use.

[0533] The present disclosure also provides kits containing a first composition and a second composition. In some embodiments, the first composition contains an adjuvant, which can be any adjuvant described herein, such as in Section I-A. In some embodiments, the second composition contains a Borrelia outer surface protein A (OspA) antigen and a Borrelia outer surface protein C (OspC) antigen, which can be any described herein, such as in Sections I-B-l and I-B-2, respectively. In some embodiments, the second composition is in liquid form. In some embodiments, the second composition is in lyophilized form.

[0534] In some embodiments, the kit further contains instructions for combining the first composition and the second composition to prepare any of the immunogenic compositions described herein, such as in Section I. In some embodiments, the instructions are for preparing a single dose of the immunogenic composition. In some embodiments, the kit is for preparing a single dose of the immunogenic composition, such as a 0.3 mL to 1.5 mL dose.

[0535] In some embodiments, combining the first composition with the second composition involves mixing the first and the second compositions. In some embodiments, combining the first composition with the second composition involves mixing the first and the second compositions in a single vial. In some embodiments, combining the first composition with the second composition involves mixing the first and the second compositions in a single vial by gentle inversion. In some embodiments, the mixing is for a maximum of about one hour at room temperature.

[0536] In some embodiments, the first composition contains a second adjuvant, which can be any described herein, such as in Section I-A. In some embodiments, the second composition contains a second adjuvant, which can be any described herein, such as in Section I-A.

[0537] In some embodiments, the kit contains an immunogenic composition packaged appropriately. In some embodiments, the kit contains i) a first composition and ii) a second composition that are packaged appropriately, such that the first composition and the second composition may be combined to form an immunogenic composition. For example, if the immunogenic composition is a freeze-dried power, a vial with a resilient stopper can be used so that the powder may be easily resuspended by injecting fluid (e.g., sterile water, saline, etc.) through the resilient stopper. In some embodiments, the kit contains a device for administration (e.g., syringe). In some embodiments, the syringe is pre-filled with the immunogenic composition. In some embodiments, the administration is by intramuscular- I l l -injection. The instructions relating to the use of the immunogenic composition generally include information as to dosage, schedule, and route of administration for the intended methods of use.

[0538] In some embodiments, the kit further contains instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject. In some embodiments, the administration is according to any of the methods described herein, for instance any described in Section III. In some embodiments, the subject is a human subject. In some embodiments, the human subject is at least 18 years of age. In some embodiments, the human subject is about 18 to about 70 years of age. In some embodiments, the human subject is about 18 to about 55 years of age. In some embodiments, the human subject is under 18 years of age. In some embodiments, the human subject is about 2 to about 5 years of age. In some embodiments, the human subject is about 5 to about 18 years of age.III. Methods Of Use

[0539] The present disclosure also relates to methods for stimulating an immune response against Borrelia in a subject, involving administering to the subject an effective amount of any of the immunogenic compositions described herein, for instance in Section I. In some embodiments, the antigen or antigens and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject.

[0540] The present disclosure also relates to methods for protecting a subject from infection by Borrelia, involving administering to the subject an effective amount of any of the immunogenic compositions described herein, for instance in Section I. In some embodiments, the antigen or antigens and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject.

[0541] The present disclosure also relates to methods for preventing a subject from contracting Lyme disease, involving administering to the subject an effective amount of any of the immunogenic compositions described herein, for instance in Section I. In some embodiments, the antigen or antigens and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject.

[0542] The present disclosure also relates to methods for preventing the onset of Lyme disease in a subject, involving administering to the subject an effective amount of any of the immunogenic compositions described herein, for instance in Section I. In some embodiments, the subject has previously been infected by Borrelia. In some embodiments, the antigen and adjuvant are present in the immunogenic composition in amounts effective to stimulate an immune response against Borrelia in a subject.

[0543] In some embodiments, the subject is a human subject. In some embodiments, the human subject is at least 18 years of age. In some embodiments, the human subject is about 18 to about 70 years of age. In some embodiments, the human subject is about 18 to about 55 years of age. In some embodiments, the human subject is under 18 years of age. In some embodiments, the human subject is about 2 to about 5 years of age. In some embodiments, the human subject is about 5 to about 18 years of age.

[0544] In some embodiments, the methods of the present disclosure are suitable for increasing the immune response against Borrelia in the subject relative to a baseline immune response against Borrelia in the subject prior to administration of the immunogenic composition. Stimulating an immune response, which means increasing the immune response, can arise from eliciting a de novo immune response (e.g., as a consequence of an initial vaccination regimen) or enhancing an existing immune response (e.g., as a consequence of a booster vaccination regimen). In some embodiments, stimulating an immune response includes one or more of stimulating cytokine production; stimulating B lymphocyte proliferation; stimulating antibody production; stimulating interferon pathway- associated gene expression; stimulating chemoattractant-associated gene expression; and stimulating plasmacytoid dendritic cell maturation. In some embodiments, the immune response prevents the subject from infection with Borrelia. In some embodiments, the immune response prevents the subject from contracting Lyme disease. In some embodiments, the immune response prevents the onset of Lyme disease. In some embodiments, the immune response prevents the onset of Lyme disease in a subject previously infected by Borrelia.

[0545] In some embodiments, a first dose and a second dose of the immunogenic composition is administered to the subject. In some embodiments, the second dose of the immunogenic composition is administered from about 2 weeks to about 12 weeks after the administration of the first dose of the immunogenic composition. In some embodiments, the second dose of the immunogenic composition is administered from about 2 weeks to about 10 weeks after the administration of the first dose of the immunogenic composition. In someembodiments, the second dose is administered from about 2 weeks to about 2 months after the administration of the first dose. In some embodiments, the second dose is administered from about 2 weeks to about 6 weeks after the administration of the first dose. In some embodiments, the second dose is administered from about 2 weeks to about 4 weeks after the administration of the first dose. In some embodiments, the second dose is administered about 3 weeks after the first dose.

[0546] In some embodiments, the second dose is administered from about 2 weeks to about 6 weeks after the administration of the first dose. In some embodiments, the second dose is administered from about 3 weeks to about 5 weeks after the administration of the first dose. In some embodiments, the second dose is administered about 1 month after the first dose.

[0547] In some embodiments, the second dose is administered from about 6 weeks to about 10 weeks after the administration of the first dose. In some embodiments, the second dose is administered from about 7 weeks to about 9 weeks after the administration of the first dose. In some embodiments, the second dose is administered about 2 months after the first dose.

[0548] In some embodiments, a third dose of the immunogenic composition is administered to the subject. In some embodiments, the third dose is administered from about 4 months to about 8 months after the first dose. In some embodiments, the third dose is administered from about 5 months to about 7 months after the first dose. In some embodiments, the third dose is administered from about 22 weeks to about 26 weeks after the first dose. In some embodiments, the third dose is administered about 6 months after the first dose.

[0549] In some embodiments, a booster dose of the immunogenic composition is administered to the subject. In some embodiments, the booster dose is administered at least 1 year after the first dose. In some embodiments, the booster dose is administered at least 2 years after the first dose.

[0550] In some embodiments, the booster dose is administered from about 10 months to about 5 years after the first dose. In some embodiments, the booster dose is administered from about 1 year to about 5 years after the first dose. In some embodiments, the booster dose is administered from about 20 months to about 5 years after the first dose. In some embodiments, the booster dose is administered from about 2 years to about 5 years after the first dose. In some embodiments, the booster dose is administered from about 2 years to about 4 years after the first dose. In some embodiments, the booster dose is administered from about 2 years to about 3 years after the first dose.

[0551] In some embodiments, the booster dose is administered from about 10 months to about 14 months after the first dose. In some embodiments, the booster dose is administered about 1 year after the first dose.

[0552] In some embodiments, the booster dose is administered from about 20 months to about 28 months after the first dose. In some embodiments, the booster dose is administered about 2 years after the first dose.

[0553] In some embodiments, a plurality of booster doses is administered to the subject. In some embodiments, a plurality of yearly booster doses is administered to the subject. In some embodiments, the first booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose. In some of any embodiments, a booster dose is administered yearly.

[0554] In some embodiments, a first and second dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 1 month after the first dose.

[0555] In some embodiments, a first, second, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 1 month after the first dose, and the booster dose is administered at least 2 years after the first dose. In some embodiments, a first, second, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 1 month after the first dose, and the booster dose is administered about 2 years after the first dose.

[0556] In some embodiments, a first and second dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose.

[0557] In some embodiments, a first, second, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, and the booster dose is administered at least 1 year after the first dose. In some embodiments, a first, second, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, and the booster dose is administered about 1 year after the first dose.

[0558] In some embodiments, a first, second, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, and the booster dose is administered at least 2 years after the first dose. In some embodiments, a first, second, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, and the booster dose is administered about 2 years after the first dose.

[0559] In some embodiments, a first, second, and third dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, and the third dose is administered about 6 months after the first dose.

[0560] In some embodiments, a first, second, third, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, the third dose is administered about 6 months after the first dose, and the booster dose is administered at least 2 years after the first dose. In some embodiments, a first, second, third, and booster dose of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, the third dose is administered about 6 months after the first dose, and the booster dose is administered about 2 years after the first dose.

[0561] In some embodiments, a first, second, third, and plurality of booster doses of the immunogenic composition is administered to the subject, wherein the second dose is administered about 2 months after the first dose, the third dose is administered about 6 months after the first dose, the first booster dose is administered about 1 year after the first dose, and a booster dose is administered every year.

[0562] In some embodiments, the immunogenic composition is administered by intramuscular injection. In some embodiments, the injection site is in an arm of the subject. In some embodiments, the injection site is in a deltoid muscle of the subject.EXEMPLARY EMBODIMENTS

[0563] Among the provided embodiments are:1. An immunogenic composition, comprising (i) a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen, (ii) a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and(iii) an adjuvant selected from the group consisting of a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.2. An immunogenic composition, comprising (i) a. Borrelia outer surface protein A (OspA) antigen, (ii) Borrelia outer surface protein C (OspC) antigen, and (iii) an adjuvant selected from the group consisting of a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.3. An immunogenic composition, comprising (i) a. Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen and (ii) an adjuvant selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.4. An immunogenic composition, comprising (i) a. Borrelia outer surface protein C (OspC) antigen and (ii) an adjuvant selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.5. The immunogenic composition of embodiment 3 or embodiment 4, wherein the immunogenic composition does not comprise an RNA polynucleotide encoding a non- OspC Borrelia outer surface protein antigen.6. The immunogenic composition of any one of embodiments 3-5, wherein the immunogenic composition does not comprise a non-OspC Borrelia outer surface protein antigen.7. The immunogenic composition of embodiment 3 or embodiment 4, wherein the immunogenic composition comprises a Borrelia outer surface protein A (OspA) antigen.8. The immunogenic composition of any one of embodiments 1-7, wherein the adjuvant is a TLR9 agonist.9. The immunogenic composition of embodiment 8, further comprising a second adjuvant.10. The immunogenic composition of embodiment 9, wherein the second adjuvant is selected from an aluminum salt adjuvant; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.11. The immunogenic composition of any one of embodiments 1-7, wherein the adjuvant is a liposome-based adjuvant comprising a lipopolysaccharide and a saponin.12. The immunogenic composition of embodiment 11, further comprising a second adjuvant.13. The immunogenic composition of embodiment 12, wherein the second adjuvant is selected from an aluminum salt adjuvant; a TLR9 agonist; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.14. The immunogenic composition of any one of embodiments 1-7, wherein the adjuvant is an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.15. The immunogenic composition of embodiment 14, further comprising a second adjuvant.16. The immunogenic composition of embodiment 15, wherein the second adjuvant is selected from an aluminum salt adjuvant; a TLR9 agonist; and a liposome-based adjuvant comprising a lipopolysaccharide and a saponin.17. The immunogenic composition of any one of embodiments 1-10, 13, and 16, wherein the TLR9 agonist is an oligonucleotide comprising an unmethylated cytidinephospho-guanosine (CpG) motif.18. The immunogenic composition of embodiment 17, wherein the oligonucleotide is from 10 to 35 nucleotides in length.19. The immunogenic composition of embodiment 17 or embodiment 18, wherein the oligonucleotide comprises the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2).20. The immunogenic composition of any one of embodiments 17-19, wherein the oligonucleotide comprises the sequence of 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1).21. An immunogenic composition, comprising a Borrelia outer surface protein A (OspA) antigen, a Borrelia outer surface protein C (OspC) antigen, and a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising thesequence 5’-AACGTTCGAG-3’ (SEQ ID N0:2) and an unmethylated cytidine-phospho- guanosine (CpG) motif.22. An immunogenic composition, comprising a Borrelia outer surface protein C (OspC) antigen, and a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2) and an unmethylated cytidine-phospho-guanosine (CpG) motif.23. The immunogenic composition of embodiment 21 or embodiment 22, wherein the oligonucleotide comprises the sequence of 5’-TGACTGTGAA CGTTCGAGAT GA- 3’(SEQ ID NO:1).24. An immunogenic composition, comprising a Borrelia outer surface protein A (OspA) antigen, a Borrelia outer surface protein C (OspC) antigen, and the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif.25. An immunogenic composition, comprising a Borrelia outer surface protein C (OspC) antigen, and the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’- TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif.26. The immunogenic composition of embodiment 22 or embodiment 25, wherein the immunogenic composition does not comprise a non-OspC Borrelia outer surface protein antigen.27. The immunogenic composition of any one of embodiments 21-26, further comprising a second adjuvant.28. The immunogenic composition of embodiment 27, wherein the second adjuvant is selected from an aluminum salt adjuvant; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethy...

Claims

CLAIMS1. An immunogenic composition, comprising (i) a Borrelia outer surface protein A (OspA) antigen or an RNA polynucleotide encoding the OspA antigen, (ii) a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen, and (iii) an adjuvant selected from the group consisting of a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

2. An immunogenic composition, comprising (i) Borrelia outer surface protein A (OspA) antigen, (ii) a Borrelia outer surface protein C (OspC) antigen, and (iii) an adjuvant selected from the group consisting of a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

3. An immunogenic composition, comprising (i) a Borrelia outer surface protein C (OspC) antigen or an RNA polynucleotide encoding the OspC antigen and (ii) an adjuvant selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

4. An immunogenic composition, comprising (i) a Borrelia outer surface protein C (OspC) antigen and (ii) an adjuvant selected from the group consisting of an aluminum salt adjuvant; a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

5. The immunogenic composition of claim 3 or claim 4, wherein the immunogenic composition does not comprise an RNA polynucleotide encoding a non-OspC Borrelia outer surface protein antigen.

6. The immunogenic composition of any one of claims 3-5, wherein the immunogenic composition does not comprise a non-OspC Borrelia outer surface protein antigen.

7. The immunogenic composition of claim 3 or claim 4, wherein the immunogenic composition comprises Borrelia outer surface protein A (OspA) antigen.

8. The immunogenic composition of any one of claims 1-7, wherein the adjuvant is a TLR9 agonist.

9. The immunogenic composition of claim 8, further comprising a second adjuvant.

10. The immunogenic composition of claim 9, wherein the second adjuvant is selected from an aluminum salt adjuvant; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

11. The immunogenic composition of any one of claims 1-7, wherein the adjuvant is a liposome-based adjuvant comprising a lipopolysaccharide and a saponin.

12. The immunogenic composition of claim 11, further comprising a second adjuvant.

13. The immunogenic composition of claim 12, wherein the second adjuvant is selected from an aluminum salt adjuvant; a TLR9 agonist; and an oil-in-water emulsionbased adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

14. The immunogenic composition of any one of claims 1-7, wherein the adjuvant is an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

15. The immunogenic composition of claim 14, further comprising a second adjuvant.

16. The immunogenic composition of claim 15, wherein the second adjuvant is selected from an aluminum salt adjuvant; a TLR9 agonist; and a liposome-based adjuvant comprising a lipopolysaccharide and a saponin.

17. The immunogenic composition of any one of claims 1-10, 13, and 16, wherein the TLR9 agonist is an oligonucleotide comprising an unmethylated cytidine-phospho- guanosine (CpG) motif.

18. The immunogenic composition of claim 17, wherein the oligonucleotide is from 10 to 35 nucleotides in length.

19. The immunogenic composition of claim 17 or claim 18, wherein the oligonucleotide comprises the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2).

20. The immunogenic composition of any one of claims 17-19, wherein the oligonucleotide comprises the sequence of 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1).

21. An immunogenic composition, comprising a Borrelia outer surface protein A (OspA) antigen, a Borrelia outer surface protein C (OspC) antigen, and a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2) and an unmethylated cytidine-phospho- guanosine (CpG) motif.

22. An immunogenic composition, comprising a Borrelia outer surface protein C (OspC) antigen, and a toll-like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2) and an unmethylated cytidine-phospho-guanosine (CpG) motif.

23. The immunogenic composition of claim 21 or claim 22, wherein the oligonucleotide comprises the sequence of 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1).

24. An immunogenic composition, comprising a Borrelia outer surface protein A (OspA) antigen, a Borrelia outer surface protein C (OspC) antigen, and the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif.

25. An immunogenic composition, comprising a Borrelia outer surface protein C (OspC) antigen, and the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’- TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif.

26. The immunogenic composition of claim 22 or claim 25, wherein the immunogenic composition does not comprise a non-OspC Borrelia outer surface protein antigen.

27. The immunogenic composition of any one of claims 21-26, further comprising a second adjuvant.

28. The immunogenic composition of claim 27, wherein the second adjuvant is selected from an aluminum salt adjuvant; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester.

29. The immunogenic composition of any one of claims 9, 10, 12, 13, 15-20, 27, and 28, wherein the second adjuvant is an aluminum salt adjuvant.

30. An immunogenic composition, comprising: (i) a Borrelia outer surface protein A (OspA) antigen, (ii) a Borrelia outer surface protein C (OspC) antigen, (iii) the toll-like receptor 9 (TLR9) agonist oligonucleotide 5’-TGACTGTGAA CGTTCGAGAT GA-3’(SEQ ID NO: 1), the oligonucleotide comprising an unmethylated cytidine-phospho-guanosine (CpG) motif, and (iv) an aluminum salt adjuvant.

31. An immunogenic composition, comprising: (i) a Borrelia outer surface protein C (OspC) antigen, (ii) a toll -like receptor 9 (TLR9) agonist oligonucleotide of from 10 to 35 nucleotides in length comprising the sequence 5’-AACGTTCGAG-3’ (SEQ ID NO:2) and an unmethylated cytidine-phospho-guanosine (CpG) motif, and (iii) an aluminum salt adjuvant.

32. The immunogenic composition of any one of claims 9, 12, 16-20, and 28-31, wherein the aluminum salt adjuvant comprises one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate.

33. The immunogenic composition of any one of claims 9, 12, 16-20, and 28-32, wherein the aluminum salt adjuvant comprises aluminum hydroxide.

34. The immunogenic composition of any one of claims 1-33, wherein the immunogenic composition comprises from about 0.25 to about 1.25 mg Al3+, from about 0.25 mg to about 0.50 mg Al3+, or from about 0.30 mg to about 0.40 mg Al3+.

35. The immunogenic composition of any one of claims 17-34, wherein the oligonucleotide is a single-stranded oligodeoxynucleotide.

36. The immunogenic composition of any one of claims 17-34, wherein the oligonucleotide is fully RNA.

37. The immunogenic composition of any one of claims 17-34, wherein the oligonucleotide is an RNA / DNA chimera.

38. The immunogenic composition of any one of claims 17-37, wherein the oligonucleotide comprises at least one phosphorothioate linkage.

39. The immunogenic composition of any one of claims 17-38, wherein the oligonucleotide comprises only phosphorothioate linkages.

40. The immunogenic composition of any one of claims 17-38, wherein the oligonucleotide comprises a combination of one or more phosphodiester linkages and one or more phosphorothioate linkages.

41. The immunogenic composition of any one of claims 1-10, 13, and 16-40, wherein the immunogenic composition comprises from about 375 pg to about 6000 pg of the TLR9 agonist or from about 750 pg to about 3000 pg of the TLR9 agonist.

42. The immunogenic composition of any one of claims 1-10, 13, and 16-41, wherein the immunogenic composition comprises about 375 pg, about 750 pg, about 1000 pg, about 1500 pg, about 3000 pg, or about 6000 pg of the TLR9 agonist.

43. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-42, wherein the lipopolysaccharide is a lipid A or a derivative thereof.

44. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-43, wherein the lipopolysaccharide is a monophosphoryl lipid A or a derivative thereof.

45. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-44, wherein the lipopolysaccharide is 3-O-desacyl-4'-monophosphoryl lipid A.

46. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-44, wherein the lipopolysaccharide is 3-deacyl-phosphorylated hexa-acyl di saccharide.

47. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-46, wherein the immunogenic composition comprises from about 1 pg to about 100 pg, from about 10 pg to about 50 pg, from about 20 pg to about 30 pg, from about 21 pg to about 29 pg, from about 22 pg to about 28 pg, from about 23 pg to about 27 pg, or from about 24 pg to about 26 pg of the lipopolysaccharide.

48. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-46, wherein the immunogenic composition comprises from about 1 pg to about 30 pg, from about 5 pg to about 15 pg, from about 6 pg to about 14 pg, from about 7 pg to about 13 pg, from about 8 pg to about 12 pg, or from about 9 pg to about 11 pg of the lipopolysaccharide.

49. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-46, wherein the immunogenic composition comprises from about 1 pg to about 9 pg, from about 2 pg to about 8 pg, from about 3 pg to about 7 pg, or from about 4 pg to about 6 pg of the lipopolysaccharide.

50. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-49, wherein the saponin is derived from the bark of Quillaja saponaria Molina.

51. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-50, wherein the saponin is Quil A or a derivative thereof.

52. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-51, wherein the saponin is QS-17.

53. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-51, wherein the saponin is QS-21.

54. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-53, wherein the immunogenic composition comprises from about 1 pg to about 100 pg, from about 10 pg to about 50 pg, from about 20 pg to about 30 pg, from about 21 pg toabout 29 pg, from about 22 pg to about 28 pg, from about 23 pg to about 27 pg, or from about 24 pg to about 26 pg of the saponin.

55. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-53, wherein the immunogenic composition comprises from about 1 pg to about 30 pg, from about 5 pg to about 15 pg, from about 6 pg to about 14 pg, from about 7 pg to about 13 pg, from about 8 pg to about 12 pg, or from about 9 pg to about 11 pg of the saponin.

56. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-53, wherein the immunogenic composition comprises from about 1 pg to about 9 pg, from about 2 pg to about 8 pg, from about 3 pg to about 7 pg, or from about 4 pg to about 6 pg of the saponin.

57. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-56, wherein the liposome-based adjuvant further comprises a sterol.

58. The immunogenic composition of claim 57, wherein the sterol is P-sitosterol, stigmasterol, ergosterol, ergocalciferol, or cholesterol.

59. The immunogenic composition of claim 57 or claim 58, wherein the sterol is cholesterol.

60. The immunogenic composition of any one of claims 57-59, wherein the ratio of saponin to sterol is from 1 : 1 to 1 : 100 w / w or from 1 :1 to 1 :5 w / w.

61. The immunogenic composition of any one of claims 57-60, wherein the ratio of saponin to sterol is about 1 : 1 w / w.

62. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-61, wherein the liposome-based adjuvant further comprises a neutral lipid.

63. The immunogenic composition of claim 62, wherein the neutral lipid is a phosphatidylcholine.

64. The immunogenic composition of claim 63, wherein the phosphatidylcholine is eggyolk phosphatidylcholine, dioleoyl phosphatidylcholine (DOPC), or dilauryl phosphatidylcholine.

65. The immunogenic composition of claim 63 or claim 64, wherein the phosphatidylcholine is DOPC.

66. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-65, wherein the sorbitan ester is sorbitan ester 20.

67. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-65, wherein the sorbitan ester is sorbitan ester 85.

68. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-67, wherein the polyoxyethylene sorbitan ester is polyoxyethylene sorbitan ester 20.

69. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-68, wherein the polyoxyethylene sorbitan ester is polyoxyethylene sorbitan ester 80.

70. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-69, wherein the immunogenic composition comprises from about 2% w / v to about 7% w / v, from about 3% w / v to about 6% w / v, or from about 4% w / v to about 5% w / v of the squalene.

71. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-70, wherein the immunogenic composition comprises from about 0.2% w / v to about 0.8% w / v, from about 0.3% w / v to about 0.7% w / v, or from about 0.4% w / v to about 0.6% w / v of the sorbitan ester.

72. The immunogenic composition of any one of claims 1-7, 10-13, 16-20, 28, 29, and 32-71, wherein the immunogenic composition comprises from about 0.2% w / v to about 0.8% w / v, from about 0.3% w / v to about 0.7% w / v, or from about 0.4% w / v to about 0.6% w / v of the polyoxyethylene sorbitan ester.

73. The immunogenic composition of any one of claims 1, 2, 7-21, 23, 24, 27-30, and 32-72, wherein the OspA antigen is two or more OspA antigens.

74. The immunogenic composition of claim 73, wherein the two or more OspA antigens are a first OspA antigen and a second OspA antigen.

75. The immunogenic composition of claim 73 or claim 74, wherein the two or more OspA antigens are a first OspA antigen, a second OspA antigen, and a third OspA antigen.

76. The immunogenic composition of any one of claims 73-75, wherein each of the two or more OspA antigens have non-identical amino acid sequences.

77. The immunogenic composition of any one of claims 1, 2, 7-21, 23, 24, 27-30, and 32-76, wherein the OspA antigen independently is a . burgdorferi, B. cfzelii, B. bavariensis, B. garinii, B. mctyonii, B. lusilaniae, B. bisseUii, B. valasiana, or B. spielmanii OspA antigen.

78. The immunogenic composition of any one of claims 1, 2, 7-21, 23, 24, 27-30, and 32-77, wherein the OspA antigen is independently aB. burgdorferi OspA antigen.

79. The immunogenic composition of any one of claims 1, 2, 7-21, 23, 24, 27-30, and 32-78, wherein the OspA antigen independently comprises one or more epitopes from an OspA protein.

80. The immunogenic composition of claim 79, wherein the one or more epitopes comprise at least 2, 3, 4, 5, or 6 epitopes from across one or more OspA proteins.

81. The immunogenic composition of claim 79 or claim 80, wherein the one or more epitopes comprise at least 2, 3, 4, 5, or 6 epitopes from across at least 2, 3, 4, 5, or 6 OspA serotypes.

82. The immunogenic composition of any one of claims 79-81, wherein the one or more epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO:4-49.

83. The immunogenic composition of any one of claims 79-82, wherein the one of more epitopes comprise an epitope selected from the sequences of amino acids set forth in any of SEQ ID NO:9, 10, 33, 34, 36, 47, and 49.

84. The immunogenic composition of any one of claims 79-82, wherein the one or more epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO:4-49.

85. The immunogenic composition of any one of claims 1-82 and 84, wherein the OspA antigen independently has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any one of SEQ ID NO:50-62.

86. The immunogenic composition of any one of claims 1-82, 84, and 85, wherein the OspA antigen independently comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any one of SEQ ID NO:50-62.

87. The immunogenic composition of any one of claims 1-82 and 84-86, wherein the OspA antigen independently comprises the sequence of amino acids set forth in any one of SEQ ID NO:50-62.

88. The immunogenic composition of any one of claims 1-82 and 84, wherein the OspA antigen independently is an OspA chimeric antigen comprising a plurality of epitopes from one or more OspA proteins.

89. The immunogenic composition of claim 88, wherein the plurality of epitopes comprise at least 2, 3, 4, 5, or 6 epitopes from across at least 2, 3, 4, 5, or 6 OspA serotypes.

90. The immunogenic composition of claim 88 or claim 89, wherein the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO:4-49.

91. The immunogenic composition of any one of claims 88-90, wherein the plurality of epitopes are independently selected from the sequences of amino acids set forth in any of SEQ ID NO: 4-49.

92. The immunogenic composition of any one of claims 88-90, wherein the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in any of SEQ ID NO:9, 10, 33, 34, 36, 47, and 49.

93. The immunogenic composition of any one of claims 88-92, wherein the plurality of epitopes comprise are independently selected from the sequences of amino acids set forth in any of SEQ ID NO:9, 10, 33, 34, 36, 47, and 49.

94. The immunogenic composition of any one of claims 1-84 and 88-93, wherein the OspA antigen independently comprises a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any one of SEQ ID NO:63-82.

95. The immunogenic composition of any one of claims 1-84 and 88-93, wherein the OspA antigen independently comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any one of SEQ ID NO:63-82.

96. The immunogenic composition of any one of claims 1-84 and 88-95, wherein the OspA antigen independently comprises the sequence of amino acids set forth in any one of SEQ ID NO:63-82.

97. The immunogenic composition of any one of claims 1-84 and 88-94, wherein the OspA antigen independently comprises a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any one of SEQ ID NO: 79-81.

98. The immunogenic composition of any one of claims 1-84, 88-94, and 97, wherein the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:80.

99. The immunogenic composition of any one of claims 1-84, 88-94, 97, and 98, wherein the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:80.

100. The immunogenic composition of any one of claims 1-84, 88-94, and 97, wherein the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81.

101. The immunogenic composition of any one of claims 1-84, 88-94, 97, and 100, wherein the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:79 and a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:81.

102. The immunogenic composition of any one of claims 1-84, 88-94, and 97, wherein the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:80 and a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81.

103. The immunogenic composition of any one of claims 1-84, 88-94, 97, and 102, wherein the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:80 and a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:81.

104. The immunogenic composition of any one of claims 1-84, 88-94, 97, and 98, wherein the immunogenic composition comprises a first OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:79, a second OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to thesequence of amino acids set forth in SEQ ID NO:80, and a third OspA antigen comprising a sequence of amino acids that has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in SEQ ID NO:81.

105. The immunogenic composition of any one of claims 1-84, 88-94, 97-99, and 104, wherein the immunogenic composition comprises a first OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:79, a second OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO: 80, and a third OspA antigen comprising the sequence of amino acids set forth in SEQ ID NO:81.

106. The immunogenic composition of any one of claims 1-105, wherein the OspA antigen independently is non-lipidated.

107. The immunogenic composition of any one of claims 1-105, wherein the OspA antigen independently is lipidated.

108. The immunogenic composition of any one of claims 1-107, wherein the OspC antigen is a B. burgdorferi, B. cfzelii, B. bavariensis, B. garinii, B. mctyonii, B. lusilaniae, B. bissettii, B. valasiana, or B. spielmanii OspC antigen.

109. The immunogenic composition of any one of claims 1-108, wherein the OspC antigen is a B. burgdorferi OspC antigen.

110. The immunogenic composition of any one of claims 1-109, wherein the OspC antigen comprises one or more epitopes from an OspC protein.

111. The immunogenic composition of claim 110, wherein the one or more epitopes comprise at least 2, 3, 4, or 5 epitopes from one or more OspC proteins.

112. The immunogenic composition of claim 110 or claim 111, wherein the one or more epitopes comprise at least 2, 3, 4, or 5 epitopes from across at least 2, 3, 4, or 5 OspC serotypes.

113. The immunogenic composition of any one of claims 110-112, wherein the one or more epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO: 83 -223 and 449-521.

114. The immunogenic composition of any one of claims 110-113, wherein the one or more epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 83-223 and 449-521.

115. The immunogenic composition of any one of claims 1-114, wherein the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:224-307.

116. The immunogenic composition of any one of claims 1-115, wherein the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:224-307.

117. The immunogenic composition of any one of claims 1-116, wherein the OspC antigen comprises the sequence of amino acids set forth in any of SEQ ID NO:224-307.

118. The immunogenic composition of any one of claims 1-117, wherein the OspC antigen comprises the sequence of amino acids set forth in SEQ ID NO:303.

119. The immunogenic composition of any one of claims 1-114, wherein the OspC antigen is an OspC chimeric antigen comprising a plurality of epitopes from one or more OspC proteins.

120. The immunogenic composition of claim 119, wherein the plurality of epitopes comprise at least 2, 3, 4, or 5 epitopes from across at least 2, 3, 4, or 5 OspC serotypes.

121. The immunogenic composition of any one of claims 1-120, wherein the plurality of epitopes comprise linear epitopes from the loop 5 (L5) and alpha helix 5 (H5) regions of an OspC serotype.

122. The immunogenic composition of claim 121, wherein the OspC serotype is selected from a group consisting of OspC serotypes A, B, C, D, E, F, G, H, I, K, M, N, and U.

123. The immunogenic composition of claim 121 or claim 122, wherein the OspC serotype comprises five OspC serotypes.

124. The immunogenic composition of claim 123, wherein the five OspC serotypes are OspC serotypes C, F, H, M, and N.

125. The immunogenic composition of any one of claims 121-124, wherein the OspC serotype comprises six OspC serotypes.

126. The immunogenic composition of claim 125, wherein the six OspC serotypes are OspC serotypes C, F, H, I, M, and N.

127. The immunogenic composition of any one of claims 121-126, wherein the OspC serotype comprises seven OspC serotypes.

128. The immunogenic composition of claim 127, wherein the seven OspC serotypes are OspC serotypes C, D, F, H, I, M, and N.

129. The immunogenic composition of any one of claims 121-128, wherein the OspC serotypes comprises ten OspC serotypes.

130. The immunogenic composition of claim 129, wherein the ten OspC serotypes are OspC serotypes A, B, C, F, H, I, K, M, N, and U.

131. The immunogenic composition of any one of claims 119-130, wherein the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO: 83 -223 and 449-521.

132. The immunogenic composition of any one of claims 119-131, wherein the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 83-223 and 449-521.

133. The immunogenic composition of any one of claims 119-131, wherein the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO: 84-93.

134. The immunogenic composition of any one of claims 119-133, wherein the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 84-93.

135. The immunogenic composition of any one of claims 119-131 and 133, wherein the plurality of epitopes comprise an epitope selected from the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93.

136. The immunogenic composition of any one of claims 119-135, wherein the plurality of epitopes are independently selected from the sequences of amino acids set forth in SEQ ID NO: 84 and 86-93.

137. The immunogenic composition of any one of claims 1-114 and 119-130, wherein the OspC antigen has at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

138. The immunogenic composition of any one of claims 1-114, 119-130, and 137, wherein the OspC antigen comprises at least 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, or 250 contiguous amino acids of the sequence of amino acids set forth in any of SEQ ID NO:379-448, 520, and 521.

139. The immunogenic composition of any one of claims 1-114, 119-130, 137, and138, wherein the OspC antigen comprises the sequence of amino acids set forth in any of SEQ ID NO: 379-448, 520, and 521.

140. The immunogenic composition of any one of claims 1-114, 119-130, and 137-139, wherein the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 379, 520, and 521.

141. The immunogenic composition of any one of claims 1-114, 119-130, and 137- 139, wherein the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 379.

142. The immunogenic composition of any one of claims 1-114, 119-130, and 137- 139, wherein the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 520.

143. The immunogenic composition of any one of claims 1-114, 119-130, and 137- 139, wherein the OspC antigen comprises the sequence set forth in any of SEQ ID NO: 521.

144. The immunogenic composition of any one of claims 1-143, wherein the OspC antigen is a first OspC antigen, and the immunogenic composition further comprises a second OspC antigen.

145. The immunogenic composition of claim 144, wherein the first OspC antigen is an OspC chimeric antigen comprising a plurality of linear epitopes from one or more OspC proteins, and the second OspC antigen is an OspC protein comprising one or more conformational epitopes.

146. The immunogenic composition of any one of claims 1-145, wherein the immunogenic composition is a 0.3 mL to 1.5 mL dose.

147. The immunogenic composition of any one of claims 1-146, wherein the immunogenic composition is for stimulating an immune response against Borrelia in a subject by administering to the subject an effective amount of the immunogenic composition.

148. The immunogenic composition of any one of claims 1-147, wherein the immunogenic composition is for protecting a subject from infection by Borrelia by administering to the subject an effective amount of the immunogenic composition.

149. The immunogenic composition of any one of claims 1-147, wherein the immunogenic composition is for preventing a subject from contracting Lyme disease by administering to the subject an effective amount of the immunogenic composition.

150. The immunogenic composition of any one of claims 1-147, wherein the immunogenic composition is for preventing the onset of Lyme disease in a subject by administering to the subject an effective amount of the immunogenic composition.

151. The immunogenic composition of claim 150, wherein the subject has previously been infected by Borrelia.

152. The immunogenic composition of any one of claims 147-151, wherein the subject a human subject.

153. The immunogenic composition of claim 152, wherein the human subject is at least 18 years of age.

154. The immunogenic composition of claim 152 or claim 153, wherein the human subject is from 18 years to 70 years of age.

155. The immunogenic composition of claim 152, wherein the human subject is under 18 years of age.

156. The immunogenic composition of claim 152 or claim 155, wherein the human subject is from 2 years to 5 years of age.

157. The immunogenic composition of claim 152 or claim 155, wherein the human subject is from 5 years to 18 years of age.

158. A method for stimulating an immune response against Borrelia in a subject, comprising administering to a subject an effective amount of the immunogenic composition of any one of claims 1-157.

159. A method for protecting a subject from infection by Borrelia, comprising administering to a subject an effective amount of the immunogenic composition of any one of claims 1-157.

160. A method for preventing a subject from contracting Lyme disease, comprising administering to a subject an effective amount of the immunogenic composition of any one of claims 1-157.

161. A method for preventing the onset of Lyme disease in a subject, comprising administering to a subject an effective amount of the immunogenic composition of any one of claims 1-157.

162. The method of claim 161, wherein the subject has previously been infected by Borrelia.

163. The method of any one of claims 158-162, wherein the immunogenic composition is administered by intramuscular injection.

164. The method of any one of claims 158-163, wherein a first dose and a second dose of the immunogenic composition is administered to the subject.

165. The method of claim 164, wherein the second dose of the immunogenic composition is administered from about 2 weeks to about 10 weeks after the administration of the first dose of the immunogenic composition.

166. The method of claim 164 or claim 165, wherein the second dose of the immunogenic composition is administered about 1 month or about 2 months after the administration of the first dose of the immunogenic composition.

167. The method of any one of claims 164-166, wherein a third dose of the immunogenic composition is administered to the subject.

168. The method of claim 167, wherein the third dose of the immunogenic composition is administered from about 4 months to about 8 months after the administration of the first dose of the immunogenic composition.

169. The method of claim 167 or claim 168, wherein the third dose of the immunogenic composition is administered about 6 months after the administration of the first dose of the immunogenic composition.

170. The method of any one of claims 158-169, wherein a booster dose of the immunogenic composition is administered to the subject.

171. The method of claim 170, wherein the booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose.

172. The method of any one of claims 158-171, wherein a plurality of booster doses is administered to the subject.

173. The method of claim 172, wherein the first booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose.

174. The method of claim 172 or claim 173, wherein a booster dose is administered yearly.

175. The method of any one of claims 158-174, wherein the subject is a human subject.

176. The method of claim 175, wherein the human subject is at least 18 years of age.

177. The method of claim 175 or claim 176, wherein the human subject is from 18 years to 70 years of age.

178. The method of claim 175, wherein the human subject is under 18 years of age.

179. The method of claim 175 or claim 178, wherein the human subject is from 2 years to 5 years of age.

180. The method of claim 175 or claim 178, wherein the human subject is from 5 years to 18 years of age.

181. Use of the immunogenic composition of any one of claims 1-157 for stimulating an immune response against Borrelia in a subject by administering to the subject an effective amount of the immunogenic composition.

182. Use of the immunogenic composition of any one of claims 1-157 for protecting a subject from infection by Borrelia by administering to the subject an effective amount of the immunogenic composition.

183. Use of the immunogenic composition of any one of claims 1-157 for preventing a subject from contracting Lyme disease by administering to the subject an effective amount of the immunogenic composition.

184. Use of the immunogenic composition of any one of claims 1-157 for preventing the onset of Lyme disease in a subject by administering to the subject an effective amount of the immunogenic composition.

185. The use of claim 184, wherein the subject has previously been infected by Borrelia.

186. Use of the immunogenic composition of any one of claims 1-157 in the manufacture of a medicament for stimulating an immune response against Borrelia in a subject.

187. Use of the immunogenic composition of any one of claims 1-157 in the manufacture of a medicament for protecting a subject from infection by Borrelia.

188. Use of the immunogenic composition of any one of claims 1-157 in the manufacture of a medicament for preventing a subject from contracting Lyme disease.

189. Use of the immunogenic composition of any one of claims 1-157 in the manufacture of a medicament for preventing the onset of Lyme disease in a subject.

190. The use of claim 189, wherein the subject has previously been infected by Borrelia.

191. The use of any one of claims 181-190, wherein the immunogenic composition is administered by intramuscular injection.

192. The use of any one of claims 181-191, wherein a first dose and a second dose of the immunogenic composition is administered to the subject.

193. The use of claim 192, wherein the second dose of the immunogenic composition is administered from about 2 weeks to about 10 weeks after the administration of the first dose of the immunogenic composition.

194. The use of claim 192 or claim 193, wherein the second dose of the immunogenic composition is administered about 1 month or about 2 months after the administration of the first dose of the immunogenic composition.

195. The use of any one of claims 192-194, wherein a third dose of the immunogenic composition is administered to the subject.

196. The use of claim 195, wherein the third dose of the immunogenic composition is administered from about 4 months to about 8 months after the administration of the first dose of the immunogenic composition.

197. The use of claim 195 or claim 196, wherein the third dose of the immunogenic composition is administered about 6 months after the administration of the first dose of the immunogenic composition.

198. The use of any one of claims 181-197, wherein a booster dose of the immunogenic composition is administered to the subject.

199. The use of claim 198, wherein the booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose.

200. The use of any one of claims 181-199, wherein a plurality of booster doses is administered to the subject.

201. The use of claim 200, wherein the first booster dose is administered at least about 1 year or at least about 2 years after the administration of the first dose.

202. The use of claim 200 or claim 201, wherein a booster dose is administered yearly.

203. The use of any one of claims 181-202, wherein the subject is a human subject.

204. The use of claim 203, wherein the human subject is at least 18 years of age.

205. The use of claim 203 or claim 204, wherein the human subject is from 18 years to 70 years of age.

206. The use of claim 203, wherein the human subject is under 18 years of age.

207. The use of claim 203 or claim 206, wherein the human subject is from 2 years to 5 years of age.

208. The use of claim 203 or claim 206, wherein the human subject is from 5 years to 18 years of age.

209. A vial comprising the immunogenic composition of any one of claims 1-157.

210. The vial of claim 209, wherein the immunogenic composition is in liquid form.

211. The vial of claim 209, wherein the immunogenic composition is in lyophilized form.

212. The vial of any one of claims 209-211, wherein the vial comprises a single dose of the immunogenic composition.

213. The vial of claim 212, wherein the single dose is a 0.3 mL to 1.5 mL dose.

214. A pre-filled syringe comprising the immunogenic composition of any one of claims 1-157.

215. The pre-filled syringe of claim 214, wherein the syringe comprises a single dose of the immunogenic composition.

216. The pre-filled syringe of claim 215, wherein the single dose is a 0.3 mL to 1.5 mL dose.

217. A kit compri sing : a) a first composition comprising an adjuvant selected from a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester; b) a second composition comprising a Borrelia outer surface protein A (OspA) antigen and a Borrelia outer surface protein C (OspC) antigen; and c) instructions for combining the first composition and the second composition to prepare the immunogenic composition of any one of claims 1-108.

218. A kit compri sing : a) a first composition comprising an adjuvant selected from a toll-like receptor 9 (TLR9) agonist; a liposome-based adjuvant comprising a lipopolysaccharide and a saponin; and an oil-in-water emulsion-based adjuvant comprising squalene, a sorbitan ester, and a polyoxyethylene sorbitan ester; b) a second composition comprising a Borrelia outer surface protein C (OspC) antigen; and c) instructions for combining the first composition and the second composition to prepare the immunogenic composition of any one of claims 1-157.

219. The kit of claim 217 or claim 218, wherein the second composition is in liquid form.

220. The kit of claim 217 or claim 218, wherein the second composition is in lyophilized form.

221. The kit of any one of claims 217-220, wherein the instructions are for preparing a single dose of the immunogenic composition.

222. The kit of any one of claims 217-221, wherein the kit is for a single dose of the immunogenic composition.

223. The kit of claim 221 or claim 222, wherein the single dose is a 0.3 mL to 1.5 mL dose.

224. The kit of any one of claims 217-223, wherein the first and / or second composition comprises a second adjuvant.

225. The kit of claim 217 or claim 218, wherein the OspC antigen is a first OspC antigen comprising a plurality of linear epitopes from one or more OspC proteins, the kit further comprises a third composition comprising a second Borrelia OspC antigen that is an OspC protein comprising one or more conformational epitopes, and the instructions are for combining the first, second, and third compositions to prepare the immunogenic composition.

226. The kit of claim 225, wherein the third composition is in liquid form.

227. The kit of claim 225, wherein the third composition is in lyophilized form.

228. The kit of any one of claims 225-227, wherein the third composition comprises a second adjuvant.

229. The kit of claim 224, wherein the second adjuvant is an aluminum salt adjuvant.

230. The kit of claim 224 or claim 229, wherein the aluminum salt adjuvant comprises one or more of amorphous aluminum hydroxyphosphate sulfate, aluminum hydroxide, aluminum phosphate, and potassium aluminum sulfate.

231. The kit of any one of claims 224-230, wherein the aluminum salt adjuvant comprises aluminum hydroxide.

232. The kit of any one of claims 217-231, further comprising: d) a further set of instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

233. A kit comprising: a) the immunogenic composition of any one of claims 1-157; and b) instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

234. The kit of claim 232 or claim 233, further comprising a syringe for intramuscular injection of the immunogenic composition.

235. The kit of claim 234, wherein the syringe is pre-filled with the immunogenic composition.

236. A kit compri sing : a) the vial of any one of claims 209-213; and b) instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

237. The kit of claim 236, further comprising a syringe for intramuscular injection of the immunogenic composition.

238. A kit compri sing : a) the pre-filled syringe of any one of claims 214-216; and b) instructions for administration of the immunogenic composition to a subject to stimulate an immune response against Borrelia in the subject.

239. The kit of claim 238, wherein the syringe is for intramuscular injection of the immunogenic composition.

240. The kit of any one of claims 232-239, wherein the administration is according to the method of any one of claims 158-180.

241. The kit of any one of claims 232-240, wherein the subject is a human subject.

242. The kit of claim 241, wherein the human subject is at least 18 years of age.

243. The kit of claim 241 or claim 242, wherein the human subject is from 18 years to 70 years of age.

244. The kit of claim 241, wherein the human subject is under 18 years of age.

245. The kit of claim 241 or claim 244, wherein the human subject is from 2 years to 5 years of age.

246. The kit of claim 241 or claim 244, wherein the human subject is from 5 years to 18 years of age.

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