Compositions and methods for generating immunity to bacterial infection

Abstract

The present disclosure relates, in part, to a polypeptide of formula (I), or a salt or solvate thereof, and a vaccine composition thereof further comprising at least one pharmaceutically acceptable excipient. The present disclosure further relates to isolated mRNA and / or isolated polynucleotides encoding the polypeptide of formula (I), vectors and / or LNPs comprising the same, and pharmaceutical compositions thereof. The present disclosure further relates to methods of treating, preventing, and / or ameliorating a bacterial infection, and / or generating immunity to infection by one or more pathogenic bacteria, in a subject in need thereof, the method comprising administering to the subject at least one composition of the present disclosure. In certain embodiments, the bacterial infection is a urinary tract infection, sepsis (e.g, neonatal sepsis), or pneumonia.

Description

[0001]Attorney Docket No. 375836-7000WO1(00007)TITLE OF THE INVENTIONCompositions and Methods for Generating Immunity to Bacterial InfectionCROSS-REFERENCE TO RELATED APPLICATIONSThis application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional PatentApplication No. 63 / 471,365, filed June 6, 2023, and U.S. Provisional Patent Application No.63 / 535,969, filed August 31, 2023, all of which applications are incorporated herein by referencein their entireties.REFERENCE TO AN ELECTRONIC SEQUENCE LISTINGThe XML filed named “375836_7000WO1_SequenceListing.xml” created on June 5,2024, comprising 245 KB, is hereby incorporated herein by reference in its entirety.BACKGROUNDBacterial infections (e.g., urinary tract infection (UTI), sepsis, and pneumonia, inter alia)pose a significant threat to human health, leading to substantial morbidity and mortalityworldwide, including infant mortality (e.g., neonatal sepsis).While infections such as UTIs, sepsis (e.g., neonatal sepsis), and pneumonia may becaused by any of a number of bacteria, viruses, and / or fungi, these infections most commonlyhave a bacterial origin (e.g., Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis aregenerally considered the most common cause of UTI). Accordingly, antibiotics are generallyprescribed as a first line treatment (e.g., ciprofloxacin). However, in addition to the risksassociated with overdependence on antibiotics (e.g., development of antibiotic resistance), suchantibiotics may cause side effects including, but not limited to, nausea, vomiting, stomach pain,heartburn, diarrhea, and fatigue.Thus, there is a need in the art for compositions and / or methods for preventing a bacterialinfection (e.g., UTI, sepsis, and / or pneumonia), and / or generating immunity to infection by oneor more bacterial pathogens, non-limiting examples including E. coli. The present disclosureaddresses this need.BRIEF SUMMARY52406514.1 - 1 -Attorney Docket No. 375836-7000WO1(00007)In one aspect, the disclosure provides a polypeptide comprising formula (I), or a salt orsolvate thereof, wherein n and each occurrence of B1, B2, B3, L1, L2, L3, L4, L5, L6, T1, T2, and T3are defined elsewhere herein:B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6n (I).In another aspect, 1 1 1 2 2 3 B -L -T -L -B -L -T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12, wherein B1, B2, B3, B4, B5, B6, B7, B8, B9,B10, B11, B12, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20,L21, L22, L23, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, and T12 are defined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12, wherein L1, L2, L3, L4, L5, L6, L7, L8,L9, L10, L11, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, and T12 are defined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9, wherein B1, B2, B3, B4, B5, B6, B7, B8, B9, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13,L14, L15, L16, L17, T1, T2, T3, T4, T5, T6, T7, T8, and T9 are defined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9, wherein L1, L2, L3, L4, L5, L6, L7, L8, T1, T2, T3, T4, T5, T6,T7, T8, and T9 are defined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T1-L10-B6-L11-T2-L12-B7-L13-T3-L14-B8-L15-T4-L16-B9-L17-T1-L18-B10-L19-T2-L20-B11-L21-T3-L22-B4-L23-T4, wherein B1, B2, B3, B4, B5, B6, B7, B8, B9, B10,B11, B12, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21,L22, L23, T1, T2, T3, and T4 are defined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13-L25-T13, wherein B1, B2, B3, B4, B5,B6, B7, B8, B9, B10, B11, B12, B13, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16,L17, L18, L19, L20, L21, L22, L23, L24, L25, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, and T13 aredefined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising T1-L1-T2-L2-T3-L3-52406514.1 - 2 -Attorney Docket No. 375836-7000WO1(00007)T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12-L12-T13, wherein L1, L2, L3, L4, L5, L6,L7, L8, L9, L10, L11, L12, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, and T13 are definedelsewhere herein.In another aspect, the disclosure provides a polypeptide comprising B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13, wherein B1, B2, B3, B4, B5, B6, B7,B8, B9, B10, B11, B12, B13, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17,L18, L19, L20, L21, L22, L23, L24, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, and T12 are definedelsewhere herein.In another aspect, the disclosure provides a polypeptide comprising B1-L1-B2-L2-B3-L3-B4-L4-T1-L5-T2-L6-T3-L7-T4-L8-B5-L9-B6-L10-B7-L11-B8-L12-T5-L13-T6-L14-T7-L15-T8-L16-B9-L17-B10-L18-B11-L19-B12-L20-T9-L21-T10-L22-T11-L23-T12, wherein B1, B2, B3, B4, B5, B6, B7, B8, B9,B10, B11, B12, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20,L21, L22, L23, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, and T12 are defined elsewhere herein.In another aspect, the disclosure provides a polypeptide comprising T1-L1-T2-L2-T3-L3-T4-L4-B1-L5-B2-L6-B3-L7-B4-L8-T5-L9-T6-L10-T7-L11-T8-L12-B5-L13-B6-L14-B7-L15-B8-L16-T9-L17-T10-L18-T11-L19-T12-L20-B9-L21-B10-L22-B11-L23-B12, wherein B1, B2, B3, B4, B5, B6, B7, B8, B9,B10, B11, B12, L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20,L21, L22, L23, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, and T12 are defined elsewhere herein.In another aspect, the disclosure provides an isolated messenger ribonucleic acid(mRNA) encoding a polypeptide of the disclosure.In another aspect, the disclosure provides an isolated deoxyribonucleic acid (DNA)encoding a polypeptide of the disclosure.In another aspect, the disclosure provides an isolated polynucleotide encoding an mRNAof the disclosure, wherein the polynucleotide comprises one or more promoters and / or apolyadenylation signal operably linked to a sequence encoding the mRNA.In another aspect, the disclosure provides a vector comprising an isolated mRNA of thedisclosure, an isolated DNA of the disclosure, and / or an isolated polynucleotide of thedisclosure.In another aspect, the disclosure provides a lipid nanoparticle (LNP) compositioncomprising an isolated mRNA of the disclosure, an isolated DNA of the disclosure, and / or an52406514.1 - 3 -Attorney Docket No. 375836-7000WO1(00007)isolated polynucleotide of the disclosure.In another aspect, the disclosure provides a pharmaceutical composition comprising anLNP of the disclosure and a pharmaceutically acceptable carrier.In another aspect, the disclosure provides a vaccine composition comprising an LNP ofthe disclosure and / or a pharmaceutical composition of the disclosure.In another aspect, the disclosure provides a vaccine composition comprising apolypeptide of the disclosure and at least one pharmaceutically acceptable excipient.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject a polypeptide of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject an isolated mRNA of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject an isolated DNA of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject an isolated polynucleotide of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject a vector of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject a LNP of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject a pharmaceutical composition of the disclosure.In another aspect, the disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof, the method comprisingadministering to the subject a vaccine composition of the disclosure.52406514.1 - 4 -Attorney Docket No. 375836-7000WO1(00007)In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject a polypeptide of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject an isolated mRNA of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject an isolated DNA of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject an isolated polynucleotide of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject a vector of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject a LNP of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject a pharmaceutical composition of the disclosure.In another aspect, the disclosure provides a method of generating immunity to infectionby one or more pathogenic bacteria in a subject, the method comprising administering to thesubject a vaccine composition of the disclosure.BRIEF DESCRIPTION OF THE FIGURESThe drawings illustrate generally, by way of example, but not by way of limitation,various embodiments of the present application.FIG. 1 provides a graph showing serum IL-6 concentration in HLA-DR4 mice 24 h aftersecond vaccination, wherein mice were vaccinated as follows: no vaccination (i.e., naïve; Group1); SEQ ID NO:127 (AlOH + dmLT adjuvant; Group 2); SEQ ID NO:128 (AlOH + dmLT52406514.1 - 5 -Attorney Docket No. 375836-7000WO1(00007)adjuvant; Group 3); SEQ ID NO:127 (AlOH + CpG adjuvant; Group 4); and SEQ ID NO:128(AlOH + CpG adjuvant; Group 5); following the vaccination protocol described elsewhere herein(Exp. No. 1).FIGs. 2A-2D provide graphs showing serum titers of IgG1 (FIG. 2A), IgG2b (FIG. 2B),and levels for serum IgA (FIG. 2C) and urine IgG(H) (FIG. 2D) in HLA-DR4 miceapproximately 14 days after second vaccination (i.e., day 35) with: no vaccination (i.e., naïve;Group 1); SEQ ID NO:127 (AlOH + dmLT adjuvant; Group 2); and SEQ ID NO:127 (AlOH +CpG adjuvant; Group 4); as determined by standard ELISA, following the vaccination protocoldescribed elsewhere herein (Exp. No. 1).FIGs. 3A-3B provide graphs showing serum titers of IgG1 (FIG. 3A) and IgG2b (FIG.3B) in HLA-DR4 mice approximately 14 days after second vaccination (i.e., day 35) with: novaccination (i.e., naïve; Group 1); SEQ ID NO:128 (AlOH + dmLT adjuvant; Group 3); andSEQ ID NO:128 (AlOH + CpG adjuvant; Group 5); as determined by standard ELISA, followingthe vaccination protocol described elsewhere herein (Exp. No. 1).FIGs. 4A-4C provide graphs showing serum (FIG. 4A) and urine (FIGs. 4B-4C) levels ofIgA (FIGs. 4A-4B) and IgG(H) (FIG. 4C) in HLA-DR4 mice approximately 14 days after secondvaccination (i.e., day 35) with: no vaccination (i.e., naïve; Group 1); SEQ ID NO:128 (AlOH +dmLT adjuvant; Group 3); and SEQ ID NO:128 (AlOH + CpG adjuvant; Group 5); asdetermined by standard ELISA, following the vaccination protocol described elsewhere herein(Exp. No. 1).FIG. 5 provides a bar graph showing the results of a peptide ELISA, wherein wells werecoated with certain polypeptides (i.e., SEQ ID NOs:17, 20, 24, 40, 197-199, 163-168, 176-182,188-192, 200-202, 206-207, 213-215, 218-219, and 127-128) and controls (i.e., tetanus toxin(TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 14 days after second vaccination with: no vaccination (Group 1); SEQ ID NO:127(AlOH + dmLT adjuvant; Group 2); and SEQ ID NO:128 (AlOH + CpG adjuvant; Group 4);following the vaccination protocol described elsewhere herein (Exp. No. 1). Three bars aredepicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein the left,center, and right bars represent data corresponding to Groups 1, 2, and 4 of Exp. No. 1,respectively.FIGs. 6A-6C provides bar graphs showing production of Th1 / Th17 / pro-inflammatory52406514.1 - 6 -Attorney Docket No. 375836-7000WO1(00007)cytokines IL-17A (FIG. 6A), IL-2 (FIG. 6B), and IL-6 (FIG. 6C) by splenocytes from HLA-DR4mice, approximately 22 days after the second vaccination (i.e., day 43), immunized with: novaccination (i.e., naïve; Group 1); SEQ ID NO:127 (AlOH + dmLT adjuvant; Group 2); SEQ IDNO:128 (AlOH + dmLT adjuvant; Group 3); SEQ ID NO:127 (AlOH + CpG adjuvant; Group 4);and SEQ ID NO:128 (AlOH + CpG adjuvant; Group 5); upon restimulation with SEQ IDNO:127 and SEQ ID NO:128, as determined by Cytometric Bead Array (CBA) (BDBiosciences).FIGs. 7A-7B provide bar graphs showing production of Th1 / pro-inflammatory cytokinesTNF-α (FIG. 7A) and IFN-γ (FIG. 7B) by splenocytes from HLA-DR4 mice, approximately 22days after the second vaccination (i.e., day 43), immunized with: no vaccination (i.e., naïve;Group 1); SEQ ID NO:127 (AlOH + dmLT adjuvant; Group 2); SEQ ID NO:128 (AlOH +dmLT adjuvant; Group 3); SEQ ID NO:127 (AlOH + CpG adjuvant; Group 4); and SEQ IDNO:128 (AlOH + CpG adjuvant; Group 5); upon restimulation with SEQ ID NO:127 and SEQID NO:128, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 8A-8B provide bar graphs showing production of Th2 / anti-inflammatory cytokinesIL-4 (FIG. 8A) and IL-10 (FIG. 8B) by splenocytes from HLA-DR4 mice, approximately 22days after the second vaccination (i.e., day 43), immunized with: no vaccination (i.e., naïve;Group 1); SEQ ID NO:127 (AlOH + dmLT adjuvant; Group 2); SEQ ID NO:128 (AlOH +dmLT adjuvant; Group 3); SEQ ID NO:127 (AlOH + CpG adjuvant; Group 4); and SEQ IDNO:128 (AlOH + CpG adjuvant; Group 5); upon restimulation with SEQ ID NO:127 and SEQID NO:128, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 9A-9B provide graphs showing serum titers of IgG1 (FIG. 9A) and IgG2b (FIG.9B) in HLA-DR4 mice approximately 14 days after second vaccination (i.e., day 28) with:placebo (i.e., AlOH + CpG adjuvant; Group A); or SEQ ID NO:132 (AlOH + CpG adjuvant;Group D); as determined by standard ELISA, following the vaccination protocol describedelsewhere herein (Exp. No. 2).FIGs. 10A-10B provide graphs showing serum titers of IgG1 (FIG. 10A) and IgG2b(FIG. 10B) in HLA-DR4 mice approximately 14 days after second vaccination (i.e., day 28)with: placebo (i.e., AlOH + CpG adjuvant; Group A); or SEQ ID NO:133 (AlOH + CpGadjuvant; Group E); as determined by standard ELISA, following the vaccination protocoldescribed elsewhere herein (Exp. No. 2).52406514.1 - 7 -Attorney Docket No. 375836-7000WO1(00007)FIGs. 11A-11B provide graphs showing serum titers of IgG1 (FIG. 11A) and IgG2b(FIG. 11B) in HLA-DR4 mice approximately 14 days after second vaccination (i.e., day 28)with: placebo (i.e., AlOH + CpG adjuvant; Group A); or SEQ ID NO:135 (AlOH + CpGadjuvant; Group F); as determined by standard ELISA, following the vaccination protocoldescribed elsewhere herein (Exp. No. 2).FIG. 12 provides a bar graph showing the results of a peptide ELISA, wherein wells werecoated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182,188-192, 200-202, 206-207, 213-215, 218-219, 132-133, and 135) and controls (i.e., tetanustoxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 28 days after initial vaccination with: placebo (i.e., AlOH + CpG adjuvant; GroupA); or SEQ ID NO:132 (AlOH + CpG adjuvant; Group D); following the vaccination protocoldescribed elsewhere herein (Exp. No. 2). Two bars are depicted for each coating indicated alongthe x-axis (e.g., SEQ ID NO:17), wherein the left and right bars represent data corresponding toGroups A and D of Exp. No. 2, respectively.FIGs. 13A-13C provide bar graphs showing production of Th1 / Th17 / pro-inflammatorycytokines IL-17A (FIG. 13A), IL-2 (FIG. 13B), and IL-6 (FIG. 13C) by splenocytes from HLA-DR4 mice immunized with: placebo (i.e., AlOH + CpG adjuvant; Group A); SEQ ID NO:127(AlOH + CpG adjuvant; Group B); SEQ ID NO:128 (AlOH + CpG adjuvant; Group C); SEQ IDNO:132 (AlOH + CpG adjuvant; Group D); SEQ ID NO:133 (AlOH + CpG adjuvant; Group E);or SEQ ID NO:135 (AlOH + CpG adjuvant; Group F); upon restimulation with SEQ ID NO:132,SEQ ID NO:133, or SEQ ID NO:135, as determined by Cytometric Bead Array (CBA) (BDBiosciences).FIGs. 14A-14B provide bar graphs showing production of Th1 / pro-inflammatorycytokines TNF-α (FIG. 14A) and IFN-γ (FIG. 14B) by splenocytes from HLA-DR4 miceimmunized with: placebo (i.e., AlOH + CpG adjuvant; Group A); SEQ ID NO:132 (AlOH +CpG adjuvant; Group D); SEQ ID NO:133 (AlOH + CpG adjuvant; Group E); or SEQ IDNO:135 (AlOH + CpG adjuvant; Group F); upon restimulation with SEQ ID NO:132, SEQ IDNO:133, or SEQ ID NO:135, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 15A-15B provide bar graphs showing production of Th2 / anti-inflammatorycytokines IL-4 (FIG. 15A) and IL-10 (FIG. 15B) by splenocytes from HLA-DR4 miceimmunized with: placebo (i.e., AlOH + CpG adjuvant; Group A); SEQ ID NO:132 (AlOH +52406514.1 - 8 -Attorney Docket No. 375836-7000WO1(00007)CpG adjuvant; Group D); SEQ ID NO:133 (AlOH + CpG adjuvant; Group E); or SEQ IDNO:135 (AlOH + CpG adjuvant; Group F); upon restimulation with SEQ ID NO:132, SEQ IDNO:133, or SEQ ID NO:135, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 16A-16B provide graphs showing serum titers of IgG1 (FIG. 16A) and IgG2b(FIG. 16B) in HLA-DR4 mice as a function of time (days) after vaccination with SEQ IDNO:132 (AddaS03™ + CpG adjuvant); as determined by standard ELISA, following thevaccination protocol described herein (Exp. No. 3).FIGs. 17A-17C provide graphs showing serum (FIG. 17A) and urine (FIGs. 17B-17C)levels of IgA (FIGs. 17A-17B) and IgG(H) (FIG. 17C) in HLA-DR4 mice as a function of time(days) after vaccination with SEQ ID NO:132 (AddaS03™ + CpG adjuvant); as determined bystandard ELISA, following the vaccination protocol described herein (Exp. No. 3).FIG. 18 provides a bar graph showing the results of a peptide ELISA, wherein wells werecoated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182,188-192, 200-202, 206-207, 213-215, 218-219, 132-133, and 135) and controls (i.e., tetanustoxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 21 and 41 days after vaccination with SEQ ID NO:132 + CpGadjuvant); following the vaccination protocol described elsewhere herein (Exp. No. 3). Two barsare depicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein the leftand right bars represent data corresponding to samples collected from mice 21 days aftervaccination and 41 days after vaccination, respectively.FIGs. 19A-19B provide graphs showing serum titers of IgG1 (FIG. 19A) and IgG2b(FIG. 19B) in HLA-DR4 mice approximately 14 days after second vaccination with: placebo(i.e., AlOH adjuvant; Group A); or SEQ ID NO:132 (AlOH adjuvant; Group B); as determinedby standard ELISA, following the vaccination protocol described herein (Exp. No. 8).FIGs. 20A-20C provide graphs showing serum (FIG. 20A) and urine (FIGs. 20B-20C)levels of IgA (FIGs. 20A-20B) and IgG(H) (FIG. 20C) in HLA-DR4 mice approximately 14days after second vaccination with: placebo (i.e., AlOH adjuvant; Group A); or SEQ ID NO:132(AlOH adjuvant; Group B); as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 8).FIGs. 21A-21B provide graphs showing serum titers of IgG1 (FIG. 21A) and IgG2b(FIG. 21B) in HLA-DR4 mice approximately 14 days after second vaccination with: placebo52406514.1 - 9 -Attorney Docket No. 375836-7000WO1(00007)(i.e., AlOH adjuvant; Group A); or SEQ ID NO:135 (AlOH adjuvant; Group C); as determinedby standard ELISA, following the vaccination protocol described herein (Exp. No. 8).FIGs. 22A-22C provide graphs showing serum (FIG. 22A) and urine (FIGs. 22B-22C)levels of IgA (FIGs. 22A-22B) and IgG(H) (FIG. 22C) in HLA-DR4 mice approximately 14days after second vaccination with: placebo (i.e., AlOH adjuvant; Group A); or SEQ ID NO:135(AlOH adjuvant; Group C); as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 8).FIG. 23 provides a bar graph showing the results of a peptide ELISA, wherein wells werecoated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182,188-192, 200-202, 206-207, 213-215, 218-219, 132-133, and 135) and controls (i.e., tetanustoxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 14 days after second vaccination with: placebo (i.e., AlOH adjuvant; Group A); orSEQ ID NO:132 (AlOH adjuvant; Group B); following the vaccination protocol describedelsewhere herein (Exp. No. 8). Two bars are depicted for each coating indicated along the x-axis(e.g., SEQ ID NO:17), wherein the left and right bars represent data corresponding to Groups Aand B of Exp. No. 8, respectively.FIG. 24 provides a bar graph showing the results of a peptide ELISA, wherein wells werecoated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182,188-192, 200-202, 206-207, 213-215, 218-219, 132-133, and 135) and controls (i.e., tetanustoxin (TTX), serum albumin (SA) and no coating) and utilized sera from CD1 miceapproximately 14 days after second vaccination with: placebo (i.e., AlOH adjuvant; Group A); orSEQ ID NO:135 (AlOH adjuvant; Group C); following the vaccination protocol describedelsewhere herein (Exp. No. 8). Two bars are depicted for each coating indicated along the x-axis(e.g., SEQ ID NO:17), wherein the left and right bars represent data corresponding to Groups Aand C of Exp. No. 8, respectively.FIGs. 25A-25C provides bar graphs showing production of Th1 / Th17 / pro-inflammatorycytokines IL-17A (FIG. 25A), IL-2 (FIG. 25B), and IL-6 (FIG. 25C) by CD1 splenocytesimmunized with: placebo (i.e., AlOH adjuvant; Group A); SEQ ID NO:132 (AlOH adjuvant;Group B); or SEQ ID NO:135 (AlOH adjuvant; Group C); upon restimulation with SEQ IDNO:132 or SEQ ID NO:135, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 26A-26B provide bar graphs showing production of Th1 / pro-inflammatory52406514.1 - 10 -Attorney Docket No. 375836-7000WO1(00007)cytokines TNF-α (FIG. 26A) and IFN-γ (FIG. 26B) by CD1 splenocytes immunized with:placebo (i.e., AlOH adjuvant; Group A); SEQ ID NO:132 (AlOH adjuvant; Group B); or SEQ IDNO:135 (AlOH adjuvant; Group C); upon restimulation with SEQ ID NO:132 or SEQ IDNO:135, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 27A-27B provide bar graphs showing production of Th2 / anti-inflammatorycytokines IL-4 (FIG. 27A) and IL-10 (FIG. 27B) by CD1 splenocytes immunized with: placebo(i.e., AlOH adjuvant; Group A); SEQ ID NO:132 (AlOH adjuvant; Group B); or SEQ IDNO:135 (AlOH adjuvant; Group C); upon restimulation with SEQ ID NO:132 or SEQ IDNO:135, as determined by Cytometric Bead Array (CBA) (BD Biosciences).FIGs. 28A-28E provide graphs showing serum titers or levels of IgG1 (FIG. 28A), IgG2b(FIG. 28B), and IgA (FIG. 28C), and urine levels of IgA (FIG. 28D and IgG(H) (FIG. 28E) inHLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:136 (AddaS03™+ CpG adjuvant) or a placebo; as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 4).FIGs. 29A-29E provide graphs showing serum titers or levels of IgG1 (FIG. 29A), IgG2b(FIG. 29B), and IgA (FIG. 29C), and urine levels of IgA (FIG. 29D and IgG(H) (FIG. 29E) inHLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:137 (AddaS03™+ CpG adjuvant) or a placebo; as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 4).FIGs. 30A-30E provide graphs showing serum titers or levels of IgG1 (FIG. 30A), IgG2b(FIG. 30B), and IgA (FIG. 30C), and urine levels of IgA (FIG. 30D and IgG(H) (FIG. 30E) inHLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:138 (AddaS03™+ CpG adjuvant) or a placebo; as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 4).FIGs. 31A-31E provide graphs showing serum titers or levels of IgG1 (FIG. 31A), IgG2b(FIG. 31B), and IgA (FIG. 31C), and urine levels of IgA (FIG. 31D and IgG(H) (FIG. 31E) inHLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:139 (AddaS03™+ CpG adjuvant) or a placebo; as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 4).FIGs. 32A-32E provide graphs showing serum titers or levels of IgG1 (FIG. 32A), IgG2b(FIG. 32B), and IgA (FIG. 32C), and urine levels of IgA (FIG. 32D and IgG(H) (FIG. 32E) in52406514.1 - 11 -Attorney Docket No. 375836-7000WO1(00007)HLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:140 (AddaS03™+ CpG adjuvant) or a placebo; as determined by standard ELISA, following the vaccinationprotocol described herein (Exp. No. 4).FIGs. 33A-33C provides a bar graph showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 25, 27, 195, 197-199,163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203, and 136-140) and controls (i.e.,tetanus toxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 14 days after second vaccination with: placebo (Group A); SEQ ID NO:136(Group B) (FIG. 33A); SEQ ID NO:138 (Group D) (FIG. 33B); or SEQ ID NO:140 (Group F)(FIG. 33C); following the vaccination protocol described elsewhere herein (Exp. No. 4). Twobars are depicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein theleft and right bars represent data corresponding to Groups A and B (FIG. 33A), respectively;Groups A and D (FIG. 33B), respectively; and Groups A and F (FIG. 33C), respectively; of Exp.No. 4.FIGs. 34A-34F provide bar graphs showing production of Th1 / Th17 / pro-inflammatorycytokines or Th2 / anti-inflammatory cytokines: IFN-γ (FIG. 34A), IL-4 (FIG. 34B), IL-6 (FIG.34C), IL-22 (FIG. 34D), IL-10 (FIG. 34E), and IL-17A (FIG. 34F) by splenocytes from HLA-DR4 mice immunized with placebo (AddaS03™ + CpG; Group A); SEQ ID NO:136(AddaS03™ + CpG; Group B); SEQ ID NO:137 (AddaS03™ + CpG; Group C); SEQ IDNO:138 (AddaS03™ + CpG; Group D); SEQ ID NO:139 (AddaS03™ + CpG; Group E); andSEQ ID NO:140 (AddaS03™ + CpG; Group F) (Exp. No. 4), upon restimulation with SEQ IDNO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, or nostimulation, approximately 49 days post first vaccination and approximately 3 days afterUPEC25 challenge, as determined by Cytometric Bead Array (CBA) (MAGPIX® system).FIGs. 35A-35C provides bar graphs depicting the percentage of activation inducedmarkers (AIMs) OX40 and PD-L1 (FIG. 35A), CD69 and PD-L1 (FIG. 35B), and CD25 and PD-L1 (FIG. 35C) in splenocytes approximately 3 days post challenge with UPEC25, andapproximately 49 days after first vaccination with placebo (Group A); SEQ ID NO:136 (GroupB); SEQ ID NO:137 (Group C); SEQ ID NO:138 (Group D); SEQ ID NO:139 (Group E); andSEQ ID NO:140 (Group F); after restimulation with SEQ ID NO:136; SEQ ID NO:137; SEQ IDNO:138; SEQ ID NO:139; and SEQ ID NO:140; or no stimulation; following the vaccination52406514.1 - 12 -Attorney Docket No. 375836-7000WO1(00007)protocol described elsewhere herein (Exp. No. 4).FIGs. 36A-36E provide graphs showing serum titers or levels of IgG1 (FIG. 36A), IgG2b(FIG. 36B), and IgA (FIG. 36C), and urine levels of IgA (FIG. 36D and IgG(H) (FIG. 36E) inHLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:136 (Group B);SEQ ID NO:136 (Group E); or a placebo (Group A); as determined by standard ELISA,following the vaccination protocol described herein (Exp. No. 5).FIGs. 37A-37E provide graphs showing serum titers or levels of IgG1 (FIG. 37A), IgG2b(FIG. 37B), and IgA (FIG. 37C), and urine levels of IgA (FIG. 37D and IgG(H) (FIG. 37E) inHLA-DR4 mice as a function of time (days) after vaccination with SEQ ID NO:138 (Group C);SEQ ID NO:138 (Group F); or a placebo (Group D); as determined by standard ELISA,following the vaccination protocol described herein (Exp. No. 5).FIGs. 38A-38B provides a bar graph showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 16-17, 20, 25, 27, 195, 197-199,163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203and 136-140) and controls (i.e.,tetanus toxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 14 days after second vaccination with: SEQ ID NO:136 (Group B) or SEQ IDNO:138 (Group C) (FIG. 38A); and SEQ ID NO:136 (Group E) or SEQ ID NO:138 (Group F)(FIG. 38B); following the vaccination protocol described elsewhere herein (Exp. No. 5). Twobars are depicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein theleft and right bars represent data corresponding to Groups B and C (FIG. 38A), respectively; andGroups E and F (FIG. 38B), respectively; of Exp. No. 5.FIGs. 39A-39F provide bar graphs showing production Th1 / Th17 / pro-inflammatorycytokines or Th2 / anti-inflammatory cytokines: IFN-γ (FIG. 39A), IL-4 (FIG. 39B), IL-6 (FIG.39C), IL-22 (FIG. 39D), IL-10 (FIG. 39E), and IL-17A (FIG. 39F) by splenocytes from HLA-DR4 mice immunized with each of: placebo (Group A); SEQ ID NO:136 (Group B); SEQ IDNO:138 (Group C); placebo (Group D); SEQ ID NO:136 (Group E); and SEQ ID NO:138(Group F); (Exp. No. 5), upon restimulation with SEQ ID NO:136, SEQ ID NO:137, SEQ IDNO:138, SEQ ID NO:139, SEQ ID NO:140, or no stimulation, approximately 33 days post firstvaccination, as determined by Cytometric Bead Array (CBA).FIGs. 40A-40C provides bar graphs depicting the percentage of activation inducedmarkers (AIMs) OX40 and PD-L1 (FIG. 40A), CD69 and PD-L1 (FIG. 40B), and CD69 and52406514.1 - 13 -Attorney Docket No. 375836-7000WO1(00007)CD86 (FIG. 40C) in splenocytes approximately 7 days post challenge with UPEC25, andapproximately 53 days after first vaccination with placebo (Group A); SEQ ID NO:136 (GroupB); SEQ ID NO:138 (Group C); placebo (Group D); SEQ ID NO:136 (Group E); and SEQ IDNO:138 (Group F); after restimulation with SEQ ID NO:136; SEQ ID NO:137; SEQ ID NO:138;and SEQ ID NO:139; or no stimulation; following the vaccination protocol described elsewhereherein (Exp. No. 5).FIGs. 41A-41E provide graphs showing serum titers or levels of IgG1 (FIG. 41A), IgG2b(FIG. 41B), and IgA (FIG. 41C), and urine levels of IgA (FIG. 41D and IgG(H) (FIG. 41E) inHLA-DR4 mice approximately 34 days after vaccination with SEQ ID NO:141 (Group B); SEQID NO:142 (Group C); SEQ ID NO:143 (Group D); SEQ ID NO:144 (Group E); and SEQ IDNO:145 (Group F); as compared to placebo (Group A); as determined by standard ELISA,following the vaccination protocol described herein (Exp. No. 6).FIGs. 42A-42D provides a bar graph showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 16-17, 20, 25, 27, 195, 197-199,163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203, and 141-145) and controls (i.e.,tetanus toxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 34 days after first vaccination with: placebo (Group A) and SEQ ID NO:141(Group B) (FIG. 42A); SEQ ID NO:142 (Group C) (FIG. 42B); SEQ ID NO:143 (Group D)(FIG. 42C); or SEQ ID NO:144 (Group E) (FIG. 42D); following the vaccination protocoldescribed elsewhere herein (Exp. No. 6). Two bars are depicted for each coating indicated alongthe x-axis (e.g., SEQ ID NO:17), wherein the left and right bars represent data corresponding toGroups A and B (FIG. 42A), respectively; Groups A and C (FIG. 42B), respectively; Groups Aand D (FIG. 42C), respectively; and Groups A and E (FIG. 42D), respectively; of Exp. No. 6.FIG. 43A-43F provide bar graphs showing production Th1 / Th17 / pro-inflammatorycytokines or Th2 / anti-inflammatory cytokines: IFN-γ (FIG. 43A), IL-4 (FIG. 43B), IL-6 (FIG.43C), IL-22 (FIG. 43D), IL-10 (FIG. 43E), and IL-17A (FIG. 43F) by splenocytes from HLA-DR4 mice immunized with each of: placebo (Group A); SEQ ID NO:141 (Group B); SEQ IDNO:142 (Group C); SEQ ID NO:143 (Group D); SEQ ID NO:144 (Group E); and SEQ IDNO:145 (Group F) as described elsewhere herein (Exp. No. 6), upon restimulation with SEQ IDNO:141; SEQ ID NO:142; SEQ ID NO:143; SEQ ID NO:144; SEQ ID NO:145; and SEQ IDNO:137, approximately 47 days post first vaccination, and approximately 7 days after UPEC2552406514.1 - 14 -Attorney Docket No. 375836-7000WO1(00007)challenge as determined by Cytometric Bead Array (CBA) Magpix®.FIGs. 44A-44C provides bar graphs depicting the percentage of activation inducedmarkers (AIMs) OX40 and PD-L1 (FIG. 44A), CD69 and PD-L1 (FIG. 44B), and CD69 andCD86 (FIG. 44C) in splenocytes approximately 7 days post challenge with UPEC25, andapproximately 47 days after first vaccination with placebo (Group A); SEQ ID NO:141 (GroupB); SEQ ID NO:142 (Group C); SEQ ID NO:143 (Group D); SEQ ID NO:144 (Group E); andSEQ ID NO:145 (Group F); after restimulation with SEQ ID NO:141; SEQ ID NO:142; SEQ IDNO:143; SEQ ID NO:144; SEQ ID NO:145; or no stimulation; following the vaccinationprotocol described elsewhere herein (Exp. No. 6).FIGs. 45A-45E provide graphs showing serum titers or levels of IgG1 (FIG. 45A), IgG2b(FIG. 45B), and IgA (FIG. 45C), and urine levels of IgA (FIG. 45D and IgG(H) (FIG. 45E) inHLA-DR4 mice approximately 35 days after vaccination with placebo (Group A); SEQ IDNO:138(1) (Group B); SEQ ID NO:138(2) (Group C); placebo (Group D); SEQ ID NO:138(2)(Group E); placebo (Group F); or SEQ ID NO:138(2) (Group G); as determined by standardELISA, following the vaccination protocol described herein (Exp. No. 7).FIG.46 provides a bar graph showing the results of a peptide ELISA, wherein wells werecoated with certain polypeptides (i.e., SEQ ID NOs: 16-17, 20, 25, 27, 195, 197-199, 163-168,176-182, 188-192, 207, 213-215, 218-219, 200-203, and 141-145) and controls (i.e., tetanustoxin (TTX), serum albumin (SA) and no coating) and utilized sera from HLA-DR4 miceapproximately 35 days after first vaccination with: placebo (Group A); SEQ ID NO:138 (GroupB); or SEQ ID NO:138 (Group C); following the vaccination protocol described elsewhereherein (Exp. No. 7). Three bars are depicted for each coating indicated along the x-axis (e.g.,SEQ ID NO:17), wherein the left, center, and right bars represent data corresponding to GroupsA, B, and C of Exp. No. 7, respectively.FIGs. 47A-47F provide bar graphs showing production Th1 / Th17 / pro-inflammatorycytokines or Th2 / anti-inflammatory cytokines: IFN-γ (FIG. 47A), IL-4 (FIG. 47B), IL-6 (FIG.47C), IL-22 (FIG. 47D), IL-10 (FIG. 47E), and IL-17A (FIG. 47F) by splenocytes of HLA-DR4mice immunized with each of: placebo (Group A); SEQ ID NO:138(1) (Group B); SEQ IDNO:138(2) (Group C); placebo (Group D); SEQ ID NO:138(2) Group E); placebo (Group F); orSEQ ID NO:138(2) (Group G); as described elsewhere herein (Exp. No. 7), upon restimulationwith SEQ ID NO:138(1); SEQ ID NO:138(2); or SEQ ID NO:139; approximately 55 days post52406514.1 - 15 -Attorney Docket No. 375836-7000WO1(00007)first vaccination and approximately 7 days after UPEC25 challenge as determined by CytometricBead Array (CBA) Magpix®.FIGs. 48A-48F provide bar graphs showing production Th1 / Th17 / pro-inflammatorycytokines or Th2 / anti-inflammatory cytokines: IFN-γ (FIG. 48A), IL-4 (FIG. 48B), IL-6 (FIG.48C), IL-22 (FIG. 48D), IL-10 (FIG. 48E), and IL-17A (FIG. 48F) by bladder cells of HLA-DR4mice immunized with each of: placebo (Group A); SEQ ID NO:138(1) (Group B); SEQ IDNO:138(2) (Group C); placebo (Group D); SEQ ID NO:138(2) (Group E); placebo (Group F); orSEQ ID NO:138(2) (Group G); as described elsewhere herein (Exp. No. 7), upon restimulationwith SEQ ID NO:138(1); or SEQ ID NO:138(2); approximately 55 days post first vaccinationand approximately 7 days after UPEC25 challenge as determined by Cytometric Bead Array(CBA) Magpix®.FIGs. 49A-49C provides bar graphs depicting the percentage of activation inducedmarkers (AIMs) OX40 and PD-L1 (FIG. 49A), CD69 and PD-L1 (FIG. 49B), and CD69 andCD86 (FIG. 49C) in splenocytes of HLA-DR4 mice approximately 7 days post challenge withUPEC25, and approximately 55 days after first vaccination with placebo (Group A); SEQ IDNO:138(1) (Group B); SEQ ID NO:138(2) (Group C); placebo (Group D); SEQ ID NO:138(2)(Group E); placebo (Group F); or SEQ ID NO:138(2) (Group G); after restimulation with SEQID NO:138(1); SEQ ID NO:138(2); SEQ ID NO:139; or no stimulation; following thevaccination protocol described elsewhere herein (Exp. No. 7).FIGs. 50A-50B provide bar graphs depicting the percentage of activation inducedmarkers (AIMs) OX40 and PD-L1 (FIG. 50A) and CD69 and PD-L1 (FIG. 50B) bladder cells ofHLA-DR4 mice approximately 7 days post challenge with UPEC25, and approximately 55 daysafter first vaccination with placebo (Group A); SEQ ID NO:138(1) (Group B); SEQ IDNO:138(2) (Group C); placebo (Group D); SEQ ID NO:138(2) (Group E); placebo (Group F); orSEQ ID NO:138(2) (Group G); after restimulation with SEQ ID NO:138(1); SEQ ID NO:138(2);or no stimulation; following the vaccination protocol described elsewhere herein (Exp. No. 7).FIGs. 51A-51E provide graphs showing serum titers or levels of IgG1 (FIG. 51A), IgG2b(FIG. 51B), and IgA (FIG. 51C), and urine levels of IgA (FIG. 51D and IgG(H) (FIG. 51E) inC57BL / 6 mice approximately 34 days after vaccination with placebo (Group A); SEQ IDNO:136 (Group B); SEQ ID NO:137 (Group C); SEQ ID NO:138 (Group D); and SEQ IDNO:139 (Group E); as determined by standard ELISA, following the vaccination protocol52406514.1 - 16 -Attorney Docket No. 375836-7000WO1(00007)described herein (Exp. No. 9).FIGs. 52A-52B provide a bar graph showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 25, 27, 195, 197-199,163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203, and 136-139) and controls (i.e.,tetanus toxin (TTX), serum albumin (SA) and no coating) and utilized sera from C57BL / 6 mice34 approximately days after first vaccination with: placebo (Group A); SEQ ID NO:136 (GroupB); or SEQ ID NO:138 (Group D) (FIG. 52A); and placebo (Group A); SEQ ID NO:137 (GroupC) (FIG. 52B); or SEQ ID NO:139 (Group E); following the vaccination protocol describedelsewhere herein (Exp. No. 9). Three bars are depicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein the left, center, and right bars represent data correspondingto Groups A, B, and D (FIG. 52A), respectively; and Groups A, C, and E (FIG. 52B),respectively; of Exp. No. 9.FIGs. 53A-53F provide bar graphs showing production Th1 / Th17 / pro-inflammatorycytokines or Th2 / anti-inflammatory cytokines: IL-17A (FIG. 53A), IL-6 (FIG. 53B), TNF-α(FIG. 53C), IFN-γ (FIG. 53D), IL-4 (FIG. 53E), and IL-10 (FIG. 53F) by splenocytes fromC57BL / 6 mice immunized with each of: placebo (Group A); SEQ ID NO:136 (Group B); orSEQ ID NO:138 (Group D) (FIG. 52A); and placebo (Group A); SEQ ID NO:137 (Group C)(FIG. 52B); or SEQ ID NO:139 (Group E); as described elsewhere herein (Exp. No. 9), uponrestimulation with SEQ ID NO:136; SEQ ID NO:137; SEQ ID NO:138; (FIG. 52B); or SEQ IDNO:139; or no stimulus; approximately 52 days post first vaccination, approximately 7 days afterUPEC25 challenge as determined by Cytometric Bead Array (CBA) Magpix®.FIGs. 54A-54B provide bar graphs depicting the percentage of activation inducedmarkers (AIMs) OX40 and PD-L1 (FIG. 54A) and CD86 and CD69 (FIG. 54B) in splenocytes ofC57BL / 6 mice approximately 7 days post challenge with UPEC25, and approximately 52 daysafter first vaccination with placebo (Group A); SEQ ID NO:136 (Group B); SEQ ID NO:137(Group C); SEQ ID NO:138 (Group D); and SEQ ID NO:139 (Group E); after restimulation withSEQ ID NO:136; SEQ ID NO:137; SEQ ID NO:138; SEQ ID NO:139; or no stimulation;following the vaccination protocol described elsewhere herein (Exp. No. 9).FIG. 55 provides a bar graph depicting the percentage of activation induced markers(AIMs) OX40 and PD-L1 in bladder cells of C57BL / 6 mice approximately 7 days post challengewith UPEC25, and approximately 52 days after first vaccination with placebo (Group A); SEQ52406514.1 - 17 -Attorney Docket No. 375836-7000WO1(00007)ID NO:136 (Group B); SEQ ID NO:137 (Group C); SEQ ID NO:138 (Group D); and SEQ IDNO:139 (Group E); after restimulation with SEQ ID NO:136; SEQ ID NO:138; or nostimulation; following the vaccination protocol described elsewhere herein (Exp. No. 9).FIGs. 56A-56E provide graphs showing serum titers or levels of IgG1 (FIG. 56A), IgG2a(FIG. 56B), and IgA (FIG. 56C), and urine levels of IgA (FIG. 56D and IgG(H) (FIG. 56E) inC3H / HeN mice approximately 33 days after first vaccination with placebo (Group A); SEQ IDNO:225 (Group B); placebo (Group C); and SEQ ID NO:225 (Group D); as determined bystandard ELISA, following the vaccination protocol described herein (Exp. No. 12).FIGs. 57A-57B provide bar graphs showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 25, 27, 40, 163-168, 176-182, 188-192, 195, 197-202, 207, 213-215, 218-219, and 225) and controls (i.e., tetanus toxin(TTX), serum albumin (SA) and no coating) and utilized sera from C3H / HeN miceapproximately 33 days after first vaccination with: placebo (Group A; FIG. 57A); SEQ IDNO:225 (Group B; FIG. 57A); placebo (Group C; FIG. 57B); and SEQ ID NO:225 (Group D;FIG. 57B); following the vaccination protocol described elsewhere herein (Exp. No. 12). Twobars are depicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein theleft and right bars represent data corresponding to Groups A and B (FIG. 57A), respectively; andGroups C and D (FIG. 57B), respectively; of Exp. No. 12.FIG. 58 provides a bar graph showing production of IFN-γ in the spleen, lymph node, andbladder of C3H / HeN mice immunized with each of placebo (Group A); SEQ ID NO:225 (GroupB); placebo (Group C); and SEQ ID NO:225 (Group D); as described elsewhere herein (Exp. No.12), upon restimulation with SEQ ID NO:225 or no stimulus (i.e., Unstim); approximately 33days post first vaccination, as determined by Cytometric Bead Array (CBA) Magpix®.FIGs. 59A-59E provide graphs showing serum titers or levels of IgG1 (FIG. 59A), IgG2b(FIG. 59B), and IgA (FIG. 59C), and urine levels of IgA (FIG. 59D and IgG(H) (FIG. 59E) inC57BL / 6 mice approximately 33 days after first vaccination with placebo (Group A); SEQ IDNO:225 (Group B); placebo (Group C); and SEQ ID NO:225 (Group D); as determined bystandard ELISA, following the vaccination protocol described herein (Exp. No. 10).FIGs. 60A-60B provide bar graphs showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 25, 27, 40, 163-168, 176-182, 188-192, 195, 197-202, 207, 213-215, 218-219, and 225) and controls (i.e., tetanus toxin52406514.1 - 18 -Attorney Docket No. 375836-7000WO1(00007)(TTX), serum albumin (SA) and no coating) and utilized sera from C57BL / 6 mice 33approximately days after first vaccination with: placebo (Group A; FIG. 60A); SEQ ID NO:225(Group B; FIG. 60A); placebo (Group C; FIG. 60B); and SEQ ID NO:225 (Group D; FIG. 60B);following the vaccination protocol described elsewhere herein (Exp. No. 10). Two bars aredepicted for each coating indicated along the x-axis (e.g., SEQ ID NO:17), wherein the left andright bars represent data corresponding to Groups A and B (FIG. 60A), respectively; and GroupsC and D (FIG. 60B), respectively; of Exp. No. 10.FIG. 61 provides a bar graph showing production of IFN-γ in the spleen, lymph node, andbladder of C57BL / 6 mice immunized with each of placebo (Group A); SEQ ID NO:225 (GroupB); placebo (Group C); and SEQ ID NO:225 (Group D); as described elsewhere herein (Exp. No.10), upon restimulation with SEQ ID NO:225 or no stimulus (i.e., Unstim); approximately 33days post first vaccination, as determined by Cytometric Bead Array (CBA) Magpix®.FIGs. 62A-62E provide graphs showing serum titers or levels of IgG1 (FIG. 62A), IgG2b(FIG. 62B), and IgA (FIG. 62C), urine levels of IgA (FIG. 62D) and IgG(H) (FIG. 62E) inC57BL / 6 mice approximately 33 days after first vaccination (approximately 12 days after secondvaccination) with SEQ ID NO:225 (Groups A, C, E, G, and I) or placebo (Groups B, D, F, andH); as determined by standard ELISA, following the vaccination protocol described herein (Exp.No. 11).FIGs. 63A-63E provide bar graphs showing the results of a peptide ELISA, whereinwells were coated with certain polypeptides (i.e., SEQ ID NOs: 17, 20, 25, 27, 40, 163-168, 176-182, 188-192, 195, 197-202, 207, 213-215, 218-219, and 225) and controls (i.e., tetanus toxin(TTX), serum albumin (SA) and no coating) and utilized sera from C57BL / 6 mice approximately33 days after first vaccination (approximately 12 days after second vaccination) with: SEQ IDNO:225 (Group A; FIG. 63A); placebo (Group B; FIG. 63B); SEQ ID NO:225 (Group C; FIG.63B); placebo (Group D; FIG. 63C); SEQ ID NO:225 (Group E; FIG. 63C); placebo (Group F;FIG. 63D); SEQ ID NO:225 (Group G; FIG. 63D); placebo (Group H; FIG. 63E); and SEQ IDNO:225 (Group I; Group 63E); following the vaccination protocol described herein (Exp. No.11). For FIGs. 63B-63E, two bars are depicted for each coating indicated along the x-axis (e.g.,SEQ ID NO:17), wherein the left and right bars represent data corresponding to Groups B and C(FIG. 63B), respectively; Groups D and E (FIG. 63C), respectively; Groups F and G (FIG. 63D),respectively; and Groups H and I (FIG. 63E), respectively; of Exp. No. 11.52406514.1 - 19 -Attorney Docket No. 375836-7000WO1(00007)FIG. 64 provides a bar graph depicting the percentage of activation induced markers(AIMs) OX40 and PDL1 in splenocytes obtained from C57BL / 6 mice approximately 45 daysafter first vaccination with: SEQ ID NO:225 (Group A); placebo (Group B); SEQ ID NO:225(Group C); placebo (Group D); SEQ ID NO:225 (Group E); placebo (Group F); SEQ ID NO:225(Group G); placebo (Group H); and SEQ ID NO:225 (Group I); following the vaccinationprotocol described herein (Exp. No. 11). Splenocytes derived from the designated treatment orplacebo groups (i.e., Groups A-I) were either restimulated (+) or not restimulated (-) with SEQID NO:225.FIG. 65 provides a bar graph showing production of IFN-γ in the spleen of C57BL / 6mice immunized with: SEQ ID NO:225 (Group A); placebo (Group B); SEQ ID NO:225 (GroupC); placebo (Group D); SEQ ID NO:225 (Group E); placebo (Group F); SEQ ID NO:225 (GroupG); placebo (Group H); and SEQ ID NO:225 (Group I); upon restimulation with SEQ IDNO:225 or no stimulus (i.e., Unstim); approximately 12 days post second vaccination, followingthe vaccination protocol described herein (Exp. No. 11), as determined by Cytometric BeadArray (CBA) Magpix®.DETAILED DESCRIPTION OF THE INVENTIONReference will now be made in detail to certain embodiments of the disclosed subjectmatter, examples of which are illustrated in part in the accompanying drawings. While thedisclosed subject matter will be described in conjunction with the enumerated claims, it will beunderstood that the exemplified subject matter is not intended to limit the claims to the disclosedsubject matter.Throughout this document, values expressed in a range format should be interpreted in aflexible manner to include not only the numerical values explicitly recited as the limits of therange, but also to include all the individual numerical values or sub-ranges encompassed withinthat range as if each numerical value and sub-range is explicitly recited. For example, a range of“about 0.1% to about 5%” or “about 0.1% to 5%” should be interpreted to include not just about0.1% to about 5%, but also the individual values (e.g., 1%, 2%, 3%, and 4%) and the sub-ranges(e.g., 0.1% to 0.5%, 1.1% to 2.2%, 3.3% to 4.4%) within the indicated range. The statement“about X to Y” has the same meaning as “about X to about Y,” unless indicated otherwise.Likewise, the statement “about X, Y, or about Z” has the same meaning as “about X, about Y, or52406514.1 - 20 -Attorney Docket No. 375836-7000WO1(00007)about Z,” unless indicated otherwise.In this document, the terms “a,” “an,” or “the” are used to include one or more than oneunless the context clearly dictates otherwise. The term “or” is used to refer to a nonexclusive“or” unless otherwise indicated. The statement “at least one of A and B” or “at least one of A orB” has the same meaning as “A, B, or A and B.” In addition, it is to be understood that thephraseology or terminology employed herein, and not otherwise defined, is for the purpose ofdescription only and not of limitation. Any use of section headings is intended to aid reading ofthe document and is not to be interpreted as limiting; information that is relevant to a sectionheading may occur within or outside of that particular section. All publications, patents, andpatent documents referred to in this document are incorporated by reference herein in theirentirety, as though individually incorporated by reference.In this document, the term “each” is used to refer to every one of two or more membersof a group, and is further used to refer to a single element where a group has only one member.For example, where Group 1 consists of A, B, and C, the term “each,” as applied to Group 1,refers to every one of A, B, and C. Further, where Group 2 consists of A, the term “each,” asapplied to Group 2, refers to A.In the methods described herein, the acts can be carried out in any order, except when atemporal or operational sequence is explicitly recited. Furthermore, specified acts can be carriedout concurrently unless explicit claim language recites that they be carried out separately. Forexample, a claimed act of doing X and a claimed act of doing Y can be conductedsimultaneously within a single operation, and the resulting process will fall within the literalscope of the claimed process.DefinitionsThe term “about” as used herein can allow for a degree of variability in a value or range,for example, within 10%, within 5%, or within 1% of a stated value or of a stated limit of arange, and includes the exact stated value or range.The term “adjuvant” as used herein refers to a substance that increases and / or modulatesthe immune response to a vaccine. In certain embodiments, an adjuvant may act to accelerate,prolong, and / or enhance antigen-specific immune responses in a subject when administered incombination with one or more antigens.52406514.1 - 21 -Attorney Docket No. 375836-7000WO1(00007)An infection, disease, or disorder is “ameliorated” if the severity of a symptom of thedisease or disorder, the frequency with which such a symptom is experienced by a patient, orboth, is reduced.The term “anionic lipid” refers to any lipid that is negatively charged at physiological pH(e.g., pH of about 7.0). These lipids include phosphatidylglycerol, cardiolipin,diacylphosphatidylserine, diacylphosphatidic acid, N-dodecanoylphosphatidylethanolamines, N-succinylphosphatidylethanolamines, N-glutarylphosphatidylethanolamines,lysylphosphatidylglycerols, palmitoyloleyolphosphatidylglycerol (POPG), and other anionicmodifying groups joined to neutral lipids.The term “antigen” as used herein refers to a substance capable of eliciting an immuneresponse, for example, by a major histocompatibility complex (MHC) cell surface protein, orcapable of binding to an antigen binding region of an immunoglobulin molecule. A T cell-mediated immune response achieved by presenting the antigen. An “antigen” as used hereinincludes, but is not limited to, an antigenic determinant, a hapten, and an immunogen, which maybe a peptide, a small molecule, a carbohydrate, a lipid, a nucleic acid, or a combination thereof.A skilled immunologist should recognize that when discussing an antigen that is processed forpresentation to a T cell, the term “antigen” refers to a portion of an antigen that is a T cellepitope that is presented by MHC to a T cell receptor (e.g., a peptide fragment). When used inthe context of a B cell-mediated immune response in the form of an antibody specific for an“antigen”, the portion (i.e., binding portion) of the complementarity determining region of thevariable domain of the binding antibody (i.e., light and heavy chains) in the antigen may be alinear or three-dimensional epitope.The term “antigenic peptide” as used herein refers to a portion of a polypeptide antigenthat is specifically recognized by a B cell or a T cell. B cells respond to foreign antigenicdeterminants via antibodies, while T-lymphocytes mediate cellular immunity. Thus, an antigenicpeptide is a portion of an antigen that is recognized by an antibody or by a T cell receptor in thecase of MHC.The term “bacterial infection” as used herein refers to any infection(s) caused, directly orindirectly, by one or more species of gram-negative, gram-positive, or atypical bacteria. Theterm is not limited to infections which are caused exclusively by bacteria. Non-limiting examplesof bacterial infections contemplated within the scope of the present disclosure include urinary52406514.1 - 22 -Attorney Docket No. 375836-7000WO1(00007)tract infection (UTI), sepsis (e.g., neonatal sepsis), and pneumonia.The term “cationic lipid” refers to any of a number of lipid species that carry a netpositive charge at a selected pH, such as physiological pH (e.g., pH of about 7.0). It has beenfound that cationic lipids comprising alkyl chains with multiple sites of unsaturation, e.g., at leasttwo or three sites of unsaturation, are particularly useful for forming lipid particles withincreased membrane fluidity. Certain cationic lipids and related analogs, which are also useful inthe present disclosure, have been described in U.S. Patent Publication Nos. 20060083780 and20060240554; U.S. Patent Nos. 5,208,036; 5,264,618; 5,279,833; 5,283,185; 5,753,613; and5,785,992; and PCT Publication No. WO 96 / 10390, the disclosures of which are hereinincorporated by reference in their entirety for all purposes. Non-limiting examples of cationiclipids are described in detail herein. In some cases, the cat-ionic lipids comprise a protonatabletertiary amine (e.g., pH titratable) head group, C18 alkyl chains, ether linkages between the headgroup and alkyl chains, and 0 to 3 double bonds. Such lipids include, e.g., DSDMA, DLinDMA,DLenDMA, and DODMA.As used herein, the term “composition” or “pharmaceutical composition” refers to amixture of at least one polypeptide or compound useful within the invention with apharmaceutically acceptable carrier. The pharmaceutical composition facilitates administrationof the polypeptide or compound to a patient or subject. Multiple techniques of administering acompound exist in the art including, but not limited to, intravenous, subcutaneous, oral,aerosol, parenteral, ophthalmic, pulmonary and topical administration.The term “conjugated lipid” as used herein refers to a lipid which is conjugated to one ormore polymeric groups, which inhibits aggregation of lipid particles. Such lipid conjugatesinclude, but are not limited to, polyamide oligomers (e.g., ATTA-lipid conjugates), PEG-lipidconjugates, such as PEG coupled to dialkyloxypropyls, PEG coupled to diacylglycerols, PEGcoupled to cholesterol, PEG coupled to phosphatidylethanolamines, PEG conjugated toceramides (e.g., U.S. Patent No. 5,885,613, the disclosure of which is herein incorporated byreference in its entirety for all purposes), cationic PEG lipids, and mixtures thereof. PEG can beconjugated directly to the lipid or may be linked to the lipid via a linker moiety. Any linkermoiety suitable for coupling the PEG to a lipid can be used including, e.g., non-ester containinglinker moieties and ester-containing linker moieties. In preferred embodiments, non-estercontaining linker moieties are used.52406514.1 - 23 -Attorney Docket No. 375836-7000WO1(00007)An “effective amount” or “therapeutically effective amount” of a compound is thatamount of compound that is sufficient to provide a beneficial effect to the subject to which thepolypeptide or compound is administered. An “effective amount” of a delivery vehicle is thatamount sufficient to effectively bind or deliver a compound.In particular, in the case of a mRNA, and “effective amount” or “therapeuticallyeffective amount” of a therapeutic nucleic acid as relating to a mRNA is an amount sufficientto produce the desired effect, e.g., mRNA-directed expression of an amount of a polypeptideor protein that causes a desirable biological effect in the organism within which thepolypeptide or protein is expressed. Suitable assays for measuring the expression of an mRNAor protein include, but are not limited to dot blots, Northern blots, in situ hybridization,ELISA, immunoprecipitation, enzyme function, as well as phenotypic assays known to thoseof skill in the art.The term “encode” as used herein refers to the product specified (e.g., protein and RNA)by a given sequence of nucleotides in a nucleic acid (i.e., DNA and / or RNA), upon transcriptionor translation of the DNA or RNA, respectively. In certain embodiments, the term “encode”refers to the RNA sequence specified by transcription of a DNA sequence. In certainembodiments, the term “encode” refers to the amino acid sequence (e.g., polypeptide or protein)specified by translation of mRNA. In certain embodiments, the term “encode” refers to theamino acid sequence specified by transcription of DNA to mRNA and subsequent translation ofthe mRNA encoded by the DNA sequence. In certain embodiments, the encoded product maycomprise a direct transcription or translation product. In certain embodiments, the encodedproduct may comprise post-translational modifications understood or reasonably expected by oneskilled in the art.The term “fetus” as used herein refers to any prenatal organism between conception andbirth which is normally developed in utero (e.g., zygote and embryo). This definition alsoincludes a prenatal organism which is first conceived in vitro and later implanted in a uterus.Upon birth, and for a period of about 28 days thereafter, the fetus is referred to herein as a“neonate” (e.g., “neonate thereof”).The term “fully encapsulated” indicates that the active agent or therapeutic agent in thelipid particle is not significantly degraded after exposure to serum or a nuclease or protease assaythat would significantly degrade free DNA, RNA, or protein. In a fully encapsulated system,52406514.1 - 24 -Attorney Docket No. 375836-7000WO1(00007)preferably less than about 25% of the active agent or therapeutic agent in the particle is degradedin a treatment that would normally degrade 100% of free active agent or therapeutic agent, morepreferably less than about 10%, and most preferably less than about 5% of the active agent ortherapeutic agent in the particle is degraded. In the context of nucleic acid therapeutic agents, fullencapsulation may be determined by an OLIGREEN® assay. OLIGREEN® is an ultra-sensitivefluorescent nucleic acid stain for quantitating oligonucleotides and single-stranded DNA or RNAin solution (available from Invitrogen Corporation; Carlsbad, Calif.). “Fully encapsulated” alsoindicates that the lipid particles are serum stable, that is, that they do not rapidly decompose intotheir component parts upon in vivo administration.The term “helper lipid” as used herein refers to a lipid capable of increasing theeffectiveness of delivery of lipid-based particles such as cationic lipid-based particles to a target,preferably into a cell. The helper lipid can be neutral, positively charged, or negatively charged.In certain embodiments, the helper lipid is neutral or negatively charged. Non-limiting examplesof helper lipids include 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).The term “immune cell,” as used herein refers to any cell involved in the mounting of animmune response. Such cells include, but are not limited to, T cells, B cells, NK cells, antigen-presenting cells (e.g., dendritic cells and macrophages), monocytes, neutrophils, eosinophils,basophils, and the like.The term “immunogenic fragment” as used herein refers to a portion of a polypeptidesequence which specifically binds to, or is specifically bound by, an antibody produced in animmune response.The term “independently selected from” as used herein refers to referenced groups beingthe same, different, or a mixture thereof, unless the context clearly indicates otherwise. Thus,under this definition, the phrase “X1, X2, and X3 are independently selected from noble gases”would include the scenario where, for example, X1, X2, and X3 are all the same, where X1, X2,and X3 are all different, where X1 and X2 are the same but X3 is different, and other analogouspermutations.The term “ionizable lipid” as used herein refers to a lipid (e.g., a cationic lipid) having atleast one protonatable or deprotonatable group, such that the lipid is positively charged at a pH at52406514.1 - 25 -Attorney Docket No. 375836-7000WO1(00007)or below physiological pH (e.g., pH 7.4), and neutral at a second pH, preferably at or abovephysiological pH. It will be understood by one of ordinary skill in the art that the addition orremoval of protons as a function of pH is an equilibrium process, and that the reference to acharged or neutral lipid refers to the nature of the predominant species and does not require thatall of the lipid be present in the charged or neutral form. Generally, ionizable lipids have a pKa ofthe protonatable group in the range of about 4 to about 7.“Isolated” means altered or removed from the natural state. An isolated nucleic acid canexist in substantially purified form, or can exist in a non-native environment such as, forexample, a host cell. An “isolated” nucleic acid encompasses a nucleic acid segment or fragmentwhich has been separated from sequences which flank it in a naturally occurring state, e.g., aDNA fragment which has been removed from the sequences which are normally adjacent to thefragment in a genome in which it naturally occurs. The term also applies to nucleic acids whichhave been substantially purified from other components which naturally accompany the nucleicacid (e.g., RNA or DNA or proteins, which naturally accompany it in the cell). The termtherefore includes, for example, a mRNA, or recombinant DNA which is incorporated into avector, into an autonomously replicating plasmid or virus, or into the genomic DNA of aprokaryote or eukaryote, or which exists as a separate molecule (e.g., as a cDNA or a genomic orcDNA fragment produced by PCR or restriction enzyme digestion) independent of othersequences. Isolated does not require absolute purity, and can include protein, peptide, nucleicacid, or virus molecules that are at least 50% isolated, such as at least 75%, 80%, 90%, 95%,98%, 99%, or even 99.9% isolated.The term “lipid” refers to a group of organic compounds that include, but are not limitedto, esters of fatty acids and are characterized by being insoluble in water, but soluble in manyorganic solvents. They are usually divided into at least three classes: (1) “simple lipids,” whichinclude fats and oils as well as waxes; (2) “compound lipids,” which include phospholipids andglycolipids; and (3) “derived lipids” such as steroids.As used herein, “lipid encapsulated” can refer to a lipid particle that provides an activeagent or therapeutic agent, such as a nucleic acid (e.g., a mRNA cargo), with full encapsulationor partial encapsulation. In a preferred embodiment, the nucleic acid is fully encapsulated in thelipid particle.The term “lipid nanoparticle” refers to a particle having at least one dimension on the52406514.1 - 26 -Attorney Docket No. 375836-7000WO1(00007)order of nanometers (e.g., 1-1,000 nm) which includes one or more lipids and / or additionalagents.The term “lipid particle” is used herein to refer to a lipid formulation that can be used todeliver an active agent or therapeutic agent, such as a nucleic acid (e.g., mRNA), to a target siteof interest. In the lipid particle of the disclosure, which is typically formed from one or morecationic lipids or ionizable lipids, one or more non-cationic lipids (e.g., helper lipids and / orcholesterol), and one or more conjugated lipids that prevent aggregation of the particle, the activeagent or therapeutic agent may be encapsulated in the lipid, thereby protecting the agent fromenzymatic degradation.The term “mRNA” or “messenger RNA” as used herein refers to a ribonucleic acidsequences which encodes a peptide or protein. In certain embodiments, the mRNA may comprisea “transcript” that is produced by using a DNA template and encodes a peptide or protein.Typically, mRNA comprises 5’-UTR, protein coding region and 3’-UTR. mRNA can beproduced by in vitro transcription from a DNA template. Methods of in vitro transcription areknown to those of skill in the art. For example, various in vitro transfer kits are commerciallyavailable. According to the present invention, mRNA can be modified by further stabilizingmodifications and cap formation in addition to the modifications according to the invention.The term “neutral amino acid” refers to any of a number of amino acids having a sidechain which comprises a substituent that is uncharged at physiologically relevant pH (e.g., H,methyl, iso-propyl, iso-butyl, hydroxyl, and thiol, inter alia). Non-limiting examples of neutralamino acids and / or amino acids having a neutral side chain include glycine, alanine, valine,leucine, isoleucine, methionine, serine, threonine, cysteine, proline, glutamine, phenylalanine,tyrosine, tryptophane, asparagine, and glutamine.The term “neonate” as used herein refers to an infant (e.g., human infant) which has anage of 0 to about 28 days.The term “neutral lipid” refers to any of a number of lipid species that exist either in anuncharged or neutral zwitterionic form at a selected pH. At physiological pH, such lipids include,for example, diacylphosphatidylcholine, diacylphosphatidylethanolamine, ceramide,sphingomyelin, cephalin, cholesterol, cerebrosides, and diacylglycerols.The term “non-cationic lipid” refers to any amphipathic lipid as well as any other neutrallipid or anionic lipid.52406514.1 - 27 -Attorney Docket No. 375836-7000WO1(00007)The term “nucleic acid” as used herein refers to a polymer containing at least twodeoxyribonucleotides or ribonucleotides in either single- or double-stranded form and includesDNA and RNA. DNA may be in the form of, e.g., antisense molecules, plasmid DNA, pre-condensed DNA, a PCR product, vectors (Pl, PAC, BAC, YAC, artificial chromosomes),expression cassettes, chimeric sequences, chromosomal DNA, or derivatives and combinationsof these groups. RNA may be in the form of siRNA, asymmetrical interfering RNA (aiRNA),microRNA (miRNA), mRNA, tRNA, rRNA, tRNA, viral RNA (vRNA), and combinationsthereof. Nucleic acids include nucleic acids containing known nucleotide analogs or modifiedbackbone residues or linkages, which are synthetic, naturally occurring, and non-naturallyoccurring, and which have similar binding properties as the reference nucleic acid. Examples ofsuch analogs include, without limitation, phosphorothioates, phosphoramidates, methylphosphonates, chiral-methyl phosphonates, 2’-O-methyl ribonucleotides, and peptide-nucleicacids (PNAs). Unless specifically limited, the term encompasses nucleic acids containing knownanalogues of natural nucleotides that have similar binding properties as the reference nucleicacid. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompassesconservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs,SNPs, and complementary sequences as well as the sequence explicitly indicated. Specifically,degenerate codon substitutions may be achieved by generating sequences in which the thirdposition of one or more selected (or all) codons is substituted with mixed-base and / ordeoxyinosine residues (Batzer et al., Nucleic Acid Res., 19:5081 (1991); Ohtsuka et al., J. Biol.Chem., 260:2605-2608 (1985); Rossolini et al., Mal. Cell. Probes, 8:91-98 (1994)).As used herein, the term “nucleic acid” includes any oligonucleotide or polynucleotide,with fragments containing up to 60 nucleotides generally termed oligonucleotides, and longerfragments termed polynucleotides. In particular embodiments, oligonucleotides of the disclosureare from about 15 to about 60 nucleotides in length. Nucleic acid may be administered alone inthe lipid particles of the disclosure, or in combination (e.g., co-administered) with lipid particlesof the disclosure comprising peptides, polypeptides, or small molecules such as conventionaldrugs. In other embodiments, the nucleic acid may be administered in a viral vector.“Nucleotides” contain a sugar deoxyribose (DNA) or ribose (RNA), a base, and aphosphate group. Nucleotides are linked together through the phosphate groups. “Bases” includepurines and pyrimidines, which further include natural compounds adenine, thymine, guanine,52406514.1 - 28 -Attorney Docket No. 375836-7000WO1(00007)cytosine, uracil, inosine, and natural analogs, and synthetic derivatives of purines andpyrimidines, which include, but are not limited to, modifications which place new reactivegroups such as, but not limited to, amines, alcohols, thiols, carboxylates, and alkyl halides.Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompassesconservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs,SNPs, and complementary sequences as well as the sequence explicitly indicated. Specifically,degenerate codon substitutions may be achieved by generating sequences in which the thirdposition of one or more selected (or all) codons is substituted with mixed-base and / ordeoxyinosine residues (Batzer et al., Nucleic Acid Res., 19:5081 (1991); Ohtsuka et al., J. Biol.Chem., 260:2605-2608 (1985); Rossolini et al., Mol. Cell. Probes, 8:91-98 (1994)).The term “oil-in-water emulsion adjuvant” as used herein refers to a biocompatibleformulation comprising fine droplets (e.g., micro- and / or nanodroplets) of oil (e.g., squalene)dispersed within an aqueous phase, stabilized by surfactants or emulsifying agents (e.g.,polysorbate 80). In certain embodiments, the oil phase comprises metabolizable oils (e.g.,squalene and / or α-tocopherol). In certain embodiments, the aqueous phase comprises water orbuffered saline (e.g., phosphate buffered saline). In certain embodiments, the surfactantcomprises a nonionic, cationic, or anionic agent suitable to stabilize the emulsion and ensureuniform distribution of oil droplets. Non-limiting examples of oil-in-water emulsion adjuvantscontemplated for use in the present invention include AddaS03™ and AS03®. In certainembodiments, AddaS03™ and / or AS03® comprise a nano-emulsion of DL-α-tocopherol (5%v / v) (i.e., racemic α-tocopherol) in squalene oil (5% v / v) and Tween® 80 (1.8% v / v) inphosphate buffered saline (PBS) (pH 6.8). In certain embodiments, the nano-emulsion isproduced using a microfluidizer and filtered through a 0.22 µm filter to substantially reduce orremove large droplets from the final product, sterilize the final product, and / or substantiallyreduce or remove endotoxins from the final product.The term “operably linked” or “operationally linked” refers to functional linkage betweena regulatory sequence and a heterologous nucleic acid sequence permitting them to function intheir intended manner (e.g., resulting in expression of the latter). The term encompassespositioning of a regulatory region and a sequence to be transcribed in a nucleic acid so as toinfluence transcription or translation of such a sequence. For example, to bring a codingsequence under the control of a promoter, the translation initiation site of the translational52406514.1 - 29 -Attorney Docket No. 375836-7000WO1(00007)reading frame of the polypeptide is typically positioned between one and about fifty nucleotidesdownstream of the promoter. A promoter can, however, be positioned as much as about 5,000nucleotides upstream of the translation initiation site or about 2,000 nucleotides upstream of thetranscription start site.The terms “patient,” “subject,” “individual,” and the like are used interchangeablyherein, and refer to any animal, or cells thereof whether in vitro or in situ, amenable to themethods described herein. In certain non-limiting embodiments, the patient, subject orindividual is a human.The terms “peptide,” “polypeptide,” and “protein” are used interchangeably herein, andrefer to a compound comprised of amino acid residues covalently linked by peptide bonds. Aprotein or peptide must contain at least two amino acids, and no limitation is placed on themaximum number of amino acids that can comprise a protein’s or peptide’s sequence.Polypeptides include any peptide or protein comprising two or more amino acids joined to eachother by peptide bonds. As used herein, the term refers to both short chains, which alsocommonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and tolonger chains, which generally are referred to in the art as proteins, of which there are manytypes. “Polypeptides” include, for example, biologically active fragments, substantiallyhomologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides,modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptidesinclude natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.As used herein, the term “pharmaceutically acceptable” refers to a material, such as acarrier or diluent, which does not abrogate the biological activity or properties of thecompound, and is relatively non-toxic, i.e., the material may be administered to an individualwithout causing undesirable biological effects or interacting in a deleterious manner with anyof the components of the composition in which it is contained.As used herein, the term “pharmaceutically acceptable carrier” means apharmaceutically acceptable material, composition or carrier, such as a liquid or solid filler,stabilizer, dispersing agent, suspending agent, diluent, excipient, thickening agent, solvent orencapsulating material, involved in carrying or transporting a compound useful within theinvention within or to the patient such that it may perform its intended function. Typically,such constructs are carried or transported from one organ, or portion of the body, to another52406514.1 - 30 -Attorney Docket No. 375836-7000WO1(00007)organ, or portion of the body. Each carrier must be “acceptable” in the sense of beingcompatible with the other ingredients of the formulation, including the polypeptide orcompound useful within the invention, and not injurious to the patient. Some examples ofmaterials that may serve as pharmaceutically acceptable carriers include: sugars, such aslactose, glucose and sucrose; starches, such as corn starch and potato starch; cellulose, and itsderivatives, such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate;powdered tragacanth; malt; gelatin; talc; excipients, such as cocoa butter and suppositorywaxes; oils, such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil andsoybean oil; glycols, such as propylene glycol; polyols, such as glycerin, sorbitol, mannitoland polyethylene glycol; esters, such as ethyl oleate and ethyl laurate; agar; buffering agents,such as magnesium hydroxide and aluminum hydroxide; surface active agents; alginic acid;pyrogen-free water; isotonic saline; Ringer’s solution; ethyl alcohol; phosphate buffersolutions; and other non-toxic compatible substances employed in pharmaceuticalformulations. As used herein, “pharmaceutically acceptable carrier” also includes any and allcoatings, antibacterial and antifungal agents, and absorption delaying agents, and the like thatare compatible with the activity of the polypeptide or compound useful within the invention,and are physiologically acceptable to the patient. Supplementary active compounds may alsobe incorporated into the compositions. The “pharmaceutically acceptable carrier” may furtherinclude a pharmaceutically acceptable salt of the polypeptide or compound useful within theinvention. Other additional ingredients that may be included in the pharmaceuticalcompositions used in the practice of the invention are known in the art and described, forexample in Remington’s Pharmaceutical Sciences (Genaro, Ed., Mack Publishing Co., 1985,Easton, PA), which is incorporated herein by reference.The term “pneumonia” as used herein refers to an inflammatory condition of the lungprimarily affecting the small air sacs known as alveoli. Symptoms typically include somecombination of productive or dry cough, chest pain, fever, and difficulty breathing. Pneumonia isusually caused by a bacterial or viral infection. Non-limiting, exemplary bacteria which arecommonly isolated from subjects with pneumonia include Klebsiella pneumoniae, Streptococcuspneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae,Staphylococcus aureus, Moraxella catarrhalis, and Legionella pneumophila.The term “polymer conjugated lipid” refers to a molecule comprising both a lipid portion52406514.1 - 31 -Attorney Docket No. 375836-7000WO1(00007)and a polymer portion. An example of a polymer conjugated lipid is a pegylated lipid. The term“pegylated lipid” refers to a molecule comprising both a lipid portion and a polyethylene glycolportion. Pegylated lipids are known in the art and include1-(monomethoxy-polyethyleneglycol)-2,3-dimyristoylglycerol (PEG-s-DMG), DSPE-PEG-DBCO, DOPE-PEG-Azide, DSPE-PEG-Azide, DPPE-PEG-Azide, DSPE-PEG-Carboxy-NHS,DOPE-PEG-Carboxylic Acid, DSPE-PEG-Carboxylic acid and the like.The term “prevent,” “preventing,” or “prevention” as used herein means avoiding ordelaying the onset or recurrence of symptoms associated with an infection, disease, or conditionin a subject not presenting such symptoms at the time the administering of an agent or compoundcommences. Infection, disease, condition and / or disorder may be used interchangeably herein.The term “sepsis” as used herein refer to a life-threatening condition that arises when thebody’s response to infection causes injury to its own tissues and organs. Common symptomsinclude fever, increased heart rate, increasing breathing rate, confusion, cough, and painfulurination, inter alia. Infections leading to sepsis generally comprise bacterial infections, althoughfungal, parasitic, and / or viral infections may also lead to sepsis. In certain embodiments, thebacterial infection which causes and / or contributes to the onset of sepsis may comprise gram-positive or gram-negative bacteria. Non-limiting, exemplary bacteria which may cause and / orcontribute to the onset of sepsis include Staphylococci species, Klebsiella species, Streptococcuspyogenes, Escherichia coli, and Pseudomonas aeruginosa, inter alia. The term “neonatal sepsis”as used herein specifically refers to the occurrence of sepsis in a new born infant (i.e., neonate).The terms “sequence homology,” “percent identity (%),” “sequence identity,” “sequenceidentity percent,” or “percent identity” in the context of amino acid sequences refers to aquantitative measurement of the similarity between two amino acid sequences over an alignedregion of the two amino acid sequences.By the term “specifically bind” or “specifically binds” as used herein is meant that a firstmolecule (e.g., antibody) preferentially binds to a second molecule (e.g., antigen and / orimmunogenic fragment), but does not necessarily bind only to that second molecule.The term “substantially” as used herein refers to a majority of, or mostly, as in at leastabout 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.9%, 99.99%, or atleast about 99.999% or more, or 100%. The term “substantially free of” as used herein can meanhaving none or having a trivial amount of, such that the amount of material present does not52406514.1 - 32 -Attorney Docket No. 375836-7000WO1(00007)affect the material properties of the composition including the material, such that thecomposition is about 0 wt% to about 5 wt% of the material, or about 0 wt% to about 1 wt%, orabout 5 wt% or less, or less than, equal to, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1,0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1, 0.01, or about 0.001 wt% or less. The term “substantiallyfree of” can mean having a trivial amount of, such that a composition is about 0 wt% to about 5wt% of the material, or about 0 wt% to about 1 wt%, or about 5 wt% or less, or less than, equalto, or greater than about 4.5 wt%, 4, 3.5, 3, 2.5, 2, 1.5, 1, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1,0.01, or about 0.001 wt% or less, or about 0 wt%.The terms “treat,” “treating” and “treatment,” as used herein, means reducing thefrequency or severity with which symptoms of a disease or condition are experienced by asubject by virtue of administering an agent (e.g., polypeptide or compound) to the subject.The terms “UPEC” or “UPEC25” as used herein refers to “uropathogenic Escherichiacoli” having a diameter of about 25 µm to about 250 µm, which is a pathotype of E. coli towhich urinary tract infections (UTIs) are commonly attributed.As used herein, the term “urinary tract infection” or “UTI” refers to a bacterial infectionthat affects parts of the body that produce and / or carry urine (i.e., the urinary tract), including thekidney, ureter, bladder and / or urethra. When it affects the lower urinary tract it is also known asa bladder infection (cystitis), and when it infects the upper urinary tract it is also known askidney infection (pyelonephritis). Symptoms from a lower UTI can include pain with urination,frequent urination, and feeling the need to urinate despite having an empty bladder, whilesymptoms of kidney infection can include fever and flank pain usually in combination with thesymptoms of a lower UTI. UTI can also lead to life-threatening invasive E. coli disease (e.g.,bacteremia, sepsis, or urosepsis). The most common cause of UTI is E. coli. However, UTI canalso be caused by other gram-negative bacteria (e.g., Klebsiella pneumonia and Proteusmirabilis, inter alia). Risk factors include female anatomy, sexual intercourse, diabetes, obesityand family history. UTIs are more common in women than in men, and occur frequently betweenthe ages of 16 and 35 years. UTIs also occur frequently in elderly men and women.A “vector” is a composition of matter which comprises an isolated nucleic acid and / orpolypeptide and which can be used to deliver the isolated nucleic acid and / or polypeptide to theinterior of a cell. Examples of vectors include but are not limited to, linear polynucleotides,polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Thus,52406514.1 - 33 -Attorney Docket No. 375836-7000WO1(00007)the term “vector” includes an autonomously replicating plasmid or a virus. The term is alsoconstrued to include non-plasmid and non-viral compounds which facilitate transfer of nucleicacid into cells, such as, for example, polylysine compounds, liposomes, and the like. Examplesof viral vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors,retroviral vectors, and the like. “Expression vector” refers to a vector containing a polynucleotidehaving expression control sequences operatively linked to a nucleotide sequence to be expressed.An expression vector contains sufficient cis-acting elements for expression; other elements forexpression can be supplied by the host cell or in an in vitro expression system. Expressionvectors include all those known in the art, such as cosmids, plasmids (e.g., naked or contained inliposomes), phagemids, BACs, YACs, and viral vectors (e.g., vectors derived from lentiviruses,retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the recombinantpolynucleotide.DescriptionAs described elsewhere herein, bacterial infections, including urinary tract infections(UTIs), sepsis (e.g., neonatal sepsis), and pneumonia pose a substantial public health risk,infecting millions of individuals each year. Prophylactic agents against such infections, oftencaused by E. coli, K. pneumonia, and / or P. mirabilis, are lacking, thereby creating an unmet needfor compositions and / or methods of treating, preventing, and / or ameliorating a bacterial infection(e.g., urinary tract infection (UTI), sepsis and / or neonatal sepsis, and pneumonia), and / orgenerating immunity to infection by one or more pathogenic bacteria broadly.Thus, the present disclosure relates, in one aspect, to compositions and / or methods fortreating, preventing, and / or ameliorating a bacterial infection and / or generating immunity toinfection by one or more bacterial pathogens in a subject. In one aspect, the present disclosurerelates to vaccine compositions, and methods of use thereof, to address this unmet need.In certain embodiments, the compositions and / or methods described herein are suitablefor maternal immunization (i.e., use in a pregnant subject). In certain embodiments, thecompositions and / or methods described herein are useful for treating, preventing, and / orameliorating a bacterial infection and / or generating immunity to infection by one or morebacterial pathogens in a subject and / or fetus, or the corresponding neonate thereof. In one aspect,maternal immunization utilizing the compositions and / or methods described herein is useful for52406514.1 - 34 -Attorney Docket No. 375836-7000WO1(00007)decreasing infant morbidity and / or mortality associated with bacterial infections (e.g., neonatalsepsis).Vaccination has been widely used as a method for preventing viral infections (e.g.,SARS-CoV-2 virus and COVID-19 infection), but has been employed to only a modest extent inthe prevention of bacterial infection (e.g., Mycobacterium tuberculosis bacterium andtuberculosis infection). However, vaccinations operate in an analogous manner in both cases.Briefly, vaccination comprises exposure of a subject to one or more antigens typicallypresent on the surface of a foreign particle (e.g., bacterium), thereby stimulating an immuneresponse. The first exposure of a subject to one or more of such antigens results in a primaryimmune response, wherein B cells create antibodies specific to the antigen, ultimately leading todestruction of the foreign particle by the host immune system (e.g., T cells). Additionally, B cellscreate memory cells which facilitate a more rapid response upon iterative exposures to the one ormore antigens.The surface of E. coli comprises certain proteins which may be detected by a hostimmune system, including iron receptor proteins, flagellar proteins, and non-flagellar proteins(e.g., pili, curli, and / or fimbriae), inter alia, which may result in an immune response andelimination of the infectious bacteria. Non-limiting examples of proteins which may be detectedby a host immune system include AfaD, Afa / Dr, Ag43, BmaE, CfaE, CFA / I, ChuA, Cnf1, CsgA,dmLT, EatA, ECOK1_3385, EibD, EstA, F17G, FdeC, FimH, FliC, FmlH, FyuA, GspK, Hia,HlyA, HRA-1, IatA, IatB, IatC, IatD, Iha, intimin, IroN, IutA, MrpH, NaIP, OmpA, OmpT,OmpX, PapG, PapC, pertactin, PNAG, SfaS, SsIE, S pili, TolC, TosA, UpaB, UpaC, YadC, YadPili, YeeJ, YghA, YghJ, YgiL, Ygi pili, and YncE.Thus, in one aspect, the present disclosure relates to compositions comprising bacterialsurface proteins, and / or immunogenic fragments thereof, suitable to elicit an immune response ina subject, thereby generating immunity to infection by one or more pathogenic bacteria, and / ortreating, preventing, and / or ameliorating a bacterial infection (e.g., urinary tract infection, sepsis,or pneumonia, inter alia) in a subject. In certain embodiments, the present disclosure relates tomaternal immunization. In other embodiments, the present disclosure relates to compositionsencoding bacterial surface proteins, and / or immunogenic fragments thereof, which upon deliveryand translation, are suitable to elicit an immune response in a subject, thereby generatingimmunity to infection by one or more pathogenic bacteria, and / or to treat, prevent, and / or52406514.1 - 35 -Attorney Docket No. 375836-7000WO1(00007)ameliorate a bacterial infection (e.g., urinary tract infection) in a subject.LipidsIonizable and / or Cationic LipidsThe terms “cationic lipid” and “ionizable lipid” are used interchangeably herein. Non-limiting examples of ionizable and / or cationic lipids contemplated for use in the lipidnanoparticles of the present disclosure include 1,2-dilinoleyloxy-N,N-dimethylaminopropane(DLinDMA), 1,2-dilinolenyloxy-N,N-dimethylaminopropane (DLenDMA), 2,2-dilinoleyl-4-(2-dimethylaminoethyl)-[1,3]-dioxolane (DLin-K-C2-DMA; “XTC2”), 2,2-dilinoleyl-4-(3- 45dimethy laminopropyl )-[ 1,3 ]-dioxolane (D Lin-K-C3-D MA), 2,2-dilinoleyl-4-( 4-dimethylaminobutyl)-[1,3]-dioxolane (DLin-K-C4-DMA), 2,2-dilinoleyl-5-dimethylaminom-ethyl-[1,3]-dioxane (DLin-K6-DMA), 2,2-dilinoleyl-4-N-methylpepiazino-[1,3]-dioxolane(DLin-K-MPZ), 2,2-dili-noleyl-4-dimethylaminomethyl-[1,3]-dioxolane (DLin-KDMA), 1,2-dilinoleylcarbamoyloxy-3-dimethy laminopropane (D Lin-C-DAP), 1,2-dilinoleyoxy-3-(dimethylaminoacetoxypropane (DLin-DAC), 1-2dilinoleyoxy-3-morpholinopropane (DLin-MA), 1,2-dilinoleoyl-3-dimethylaminopropane (DLinDAP), 1,2-dilinoleylthio-3-dimethylaminopropane (DLin-2-DMAP), 1,2-dilinoleyloxy-3-trimethylaminopropane chloridesalt (DLin-TMA.Cl), 1,2-dilinoleoyl-3-trimethylaminopropane chloride salt (DLin-TAP.Cl), 1,2-dilinoleyloxy-3-(N-methy lpiperazino )propane (D Lin-MPZ), 3-(N,Ndilinoley lamino )-1,2-propanediol (D LinAP), 3-(N,Ndioley lamino )-1,2-propanedio (DOAP), 1,2-dilinoleyloxo-3-(2-N,N-dimethy lamino )ethoxypropane (D Lin-EG-DMA), N,N-dioleyl-N,N-dimethylanrmoniumchloride (DODAC), 1,2-dioleyloxy-N,N-dimethylaminopropane (DODMA), 1,2-disteary loxy-N,N-dimethy laminopropane (DSDMA), N-(1-(2,3-dioleyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTMA), N,N-distearyl-N,N-dimethylammonium bromide(DDAB), N-(1-(2,3-dioleoyloxy)propyl)-N,N, N-trimethylammonium chloride (DOTAP), 3-(N-(N',N'dimethylaminoethane)-carbamoyl)cholesterol (DC-Chol), N-(l,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl anrmonium bromide (DMRIE), 2,3-dioleyloxy-N-[2 ( spermine-carboxamidoethyl]-N,N-dimethy 1-1-propanaminiumtrifluoroacetate (DOSPA),dioctadecylamidoglycyl spermine (DOGS), 3-dimethylamino-2-( cholest-5-en-3-beta-oxybutan-4-oxy )-1-(cis,cis-9,12-octadecadienoxy )propane (CLinDMA), 2-[5'-(cholest-5-en-3-beta-oxy)-3'-oxapentoxy )-3-dimethyl-1-(cis,cis-9',1-2'-octadecadienoxy) propane (CpLinDMA), N,N-52406514.1 - 36 -Attorney Docket No. 375836-7000WO1(00007)dimethyl-3,4-dioleyloxybenzylamine (DMOBA), 1,2-N,N'dioleylcarbamyl-3-dimethylaminopropane (DOcarbDAP), 1,2-N,N'-dilinoleylcarbamyl-3-dimethylaminopropane(DLincarbDAP), or mixtures thereof. In certain embodiments, the cationic lipid is DLinDMA,DLin-K-C2-DMA (“XTC2”), or mixtures thereof.The synthesis of cationic lipids such as DLin-K-C2-DMA (“XTC2”), DLin-K-C3-DMA,DLin-K-C4-DMA, DLin-K6-DMA, and DLin-K-MPZ, as well as additional cationic lipids, isdescribed in U.S. Provisional Application No. 61 / 104, 212, filed Oct. 9, 2008, the disclosure ofwhich is herein incorporated by reference in its entirety for all purposes. The synthesis ofcationic lipids such as DLin-K-DMA, DLin-CDAP, DLin-DAC, DLin-MA, DLinDAP, DLin-S-DMA, DLin-2-DMAP, DLin-TMA.Cl, DLin-TAP.Cl, DLin-MPZ, DLinAP, DOAP, and DLin-EG-DMA, as well as additional cationic lipids, is described in PCT Application No. PCT / US08 / 88676, filed Dec 31, 2008, the disclosure of which is herein incorporated by reference inits entirety for all purposes. The synthesis of cationic lipids such as CLinDMA, as well asadditional cationic lipids, is described in U.S. Patent Publication No. 20060240554, thedisclosure of which is herein incorporated by reference in its entirety for all purposes.The scope of ionizable and / or cationic lipids contemplated for use in the lipidnanoparticles of the present disclosure is not limited to the species recited herein and mayinclude any ionizable and / or cationic lipid known to one skilled in the art.Non-cationic LipidIn the lipid nanoparticles of the present disclosure, the non-cationic lipid may comprise,e.g., one or more anionic lipids, helper lipids and / or neutral lipids. In some embodiments, thenon-cationic lipid comprises one of the following neutral lipid components: (1) cholesterol or aderivative thereof (2) a phospholipid; or (3) a mixture of a phospholipid and cholesterol or aderivative thereof.Examples of cholesterol derivatives include, but are not limited to, cholestanol,cholestanone, cholestenone, coprostanol, cholesteryl-2'-hydroxyethyl ether, cholesteryl-4'-hydroxybutyl ether, and mixtures thereof. The synthesis of cholesteryl-2'-hydroxyethyl ether isknown to one skilled in the art and described in U.S. Patent Nos. 8,058,069, 8,492,359,8,822,668, 9,364,435, 9,504,651, and 11,141,378, all of which are hereby incorporated herein intheir entireties for all purposes.52406514.1 - 37 -Attorney Docket No. 375836-7000WO1(00007)Non-limiting examples of non-cationic lipids or helper lipids include phospholipids suchas lecithin, phosphatidylethanolamine, lysolecithin, lysophosphatidylethanolamine,phosphatidylserine, phosphatidylinositol, sphingomyelin, egg sphingomyelin (ESM), cephalin,cardiolipin, phosphatidic acid, cerebrosides, dicetylphosphate, distearoylphosphatidylcholine(DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC),dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG),ioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC),palmitoyloleoylphosphatidylethanolamine (POPE), palmitoyloleyolphosphatidylglycerol(POPG), dioleoylphosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-l-carboxylateDOPE-mal), dipalmitoylphosphatidylethanolamine (DPPE),dimyristoylphosphatidylethanolamine (DMPE), distearoylphosphatidylethanolamine (DSPE),monomethylphosphatidylethanolamine, dimethylphosphatidylethanolamine,dielaidoylphosphatidylethanolamine (DEPE), stearoyloleoylphosphatidylethanolamine (SOPE),lysophosphatidylcholine, dilinoleoylphosphatidylcholine, and mixtures thereof.Other diacylphosphatidylcholine and diacylphosphatidylethanolamine phospholipids canalso be used. The acyl groups in these lipids can be, for example, acyl groups derived from fattyacids having C10-C24 carbon chains, e.g., lauroyl, myristoyl, palmitoyl, stearoyl, or oleoyl.Additional examples of non-cationic lipids include sterols such as cholesterol and derivativesthereof such as cholestanol, cholestanone, cholestenone, coprostanol, cholesteryl-2'-hydroxyethylether, cholesteryl-4'-hydroxybutyl ether, and mixtures thereof. In certain embodiments, thephospholipid is DPPC, DSPC, or mixtures thereof.Conjugated LipidIn the lipid nanoparticles of the present disclosure, the conjugated lipid that inhibitsaggregation of particles may comprise, e.g., one or more of the following: a polyethyleneglycol(PEG) lipid conjugate, a polyamide (ATTA)-lipid conjugate, a cationic-polymer-lipid conjugates(CPLs), or mixtures thereof. In some embodiments, the nucleic acid-lipid particles compriseeither a PEG-lipid conjugate or an ATTA-lipid conjugate.PEG is a linear, water-soluble polymer of ethylene PEG repeating units with two terminalhydroxyl groups. PEGs are classified by their molecular weights; for example, PEG 2000 has anaverage molecular weight of about 2,000 daltons, and PEG 5000 has an average molecular52406514.1 - 38 -Attorney Docket No. 375836-7000WO1(00007)weight of about 5,000 daltons. PEGs are commercially available from Sigma Chemical Co. andother companies and include, for example, the following: monomethoxypolyethylene glycol(MePEGOH), monomethoxypolyethylene glycolsuccinate (MePEGS),monomethoxypolyethylene glycolsuccinimidyl succinate (MePEG-S-NHS),monomethoxypolyethylene glycolamine (MePEG-NH2), monomethoxypolyethyleneglycoltresylate (MePEG-TRES), and monomethoxypolyethylene glycolimidazolylcarbonyl(MePEG-IM). Other PEGs such as those described in U.S. Patent Nos. 6,774,180 and 7,053,150(e.g., mPEG (20 KDa) amine) are also useful for preparing the PEG-lipid conjugates of thepresent disclosure. The disclosures of these patents are herein incorporated by reference in theirentirety for all purposes. In addition, monomethoxypolyethyleneglycolacetic acid (MePEG-CH2COOH) is particularly useful for preparing PEG-lipid conjugates including, e.g., PEG-DAAconjugates.In certain embodiments, the PEG-lipid conjugate or ATTA-lipid conjugate is usedtogether with a CPL. The conjugated lipid that inhibits aggregation of particles may comprise aPEG-lipid including, e.g., a PEG-diacylglycerol (DAG), a PEG dialkyloxypropyl (DAA), a PEG-phospholipid, a PEG-ceramide (Cer), or mixtures thereof. The PEGDAA conjugate may be PEG-dilauryloxypropyl (C12), a PEG-dimyristyloxypropyl (C14), a PEG-dipalmityloxypropyl (C16), aPEG-distearyloxypropyl (C18), or mixtures thereof.Additional PEG-lipid conjugates suitable the disclosure include, but are notlimited to, mPEG2000-l,2-diO-alkyl-sn3-carbomoylglyceride (PEG-C-DOMG). The synthesis ofPEG-C-DOMG is described in PCT Application No. PCT / US08 / 88676, filed December 31,2008, the disclosure of which is herein incorporated by reference in its entirety for all purposes.Yet additional PEG-lipid conjugates suitable for use in the disclosure include, without limitation,l-[8'-(l,2-dimyristoyl-3-propanoxy)-carboxamido-3',6'-dioxaoctanyl] carbamoyl-methyl-poly(ethylene glycol) (2 KPEG-DMG). The synthesis of 2 KPEG-DMG is described in U.S.Patent No. 7,404,969, the disclosure of which is herein incorporated by reference in its entiretyfor all purposes.The PEG moiety of the PEG-lipid conjugates described herein may comprise an averagemolecular weight ranging from about 550 daltons to about 10,000 daltons. In certain instances,the PEG moiety has an average molecular weight of from about 750 daltons to about 5,000daltons (e.g., from about 1,000 daltons to about 5,000 daltons, from about 1,500 daltons to about52406514.1 - 39 -Attorney Docket No. 375836-7000WO1(00007)3,000 daltons, from about 750 daltons to about 3,000 daltons, from about 750 daltons to about2,000 daltons, etc.). In some embodiments, the PEG moiety has an average molecular weight ofabout 2,000 daltons or about 750 daltons.In addition to the foregoing, it will be readily apparent to those of skill in the art thatother hydrophilic polymers can be used in place of PEG. Examples of suitable polymers that canbe used in place of PEG include, but are not limited to, polyvinylpyrrolidone,polymethyloxazoline, polyethyloxazoline, polyhydroxypropyl methacrylamide,polymethacrylamide and polydimethylacrylamide, polylactic acid, polyglycolic acid, andderivatized celluloses such as hydroxymethylcellulose or hydroxyethylcellulose.In addition to the foregoing components, the particles (e.g., LNP) of the presentdisclosure can further comprise cationic poly(ethylene glycol) (PEG) lipids or CPLs (e.g., Chenet al., Bioconj. Chem., 11:433-437 (2000)). Suitable SPLPs and SPLP-CPLs for use in thepresent disclosure, and methods of making and using SPLPs and SPLP-CPLs, are disclosed, e.g.,in U.S. Patent No. 6,852,334 and PCT Publication No. WO 00 / 62813, the disclosures of whichare herein incorporated by reference in their entirety for all purposes.In certain instances, the conjugated lipid that inhibits aggregation of particles (e.g., PEG-lipid conjugate) may comprise from about 0.1 mol% to about 2 mol%, from about 0.5 mol% toabout 2 mol%, from about 1 mol% to about 2 mol%, from about 0.6 mol% to about 1.9 mol%,from about 0.7 mol% to about 1.8 mol%, from about 0.8 mol% to about 1.7 mol%, from about 1mol% to about 1.8 mol%, from about 1.2 mol% to about 1.8 mol%, from about 1.2 mol% toabout 1.7 mol%, from about 1.3 mol% to about 1.6 mol%, from about 1.4 mol% to about 1.5mol%, or about 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2 mol% (or any fraction thereof orrange therein) of the total lipid present in the particle.In the lipid nanoparticles of the present disclosure, the active agent or therapeutic agentmay be fully encapsulated within the lipid portion of the particle, thereby protecting the activeagent or therapeutic agent from enzymatic degradation. In some embodiments, a nucleic acid-lipid particle comprising a nucleic acid such as a messenger RNA (i.e., mRNA) is fullyencapsulated within the lipid portion of the particle, thereby protecting the nucleic acid fromnuclease degradation. In certain instances, the nucleic acid in the nucleic acid-lipid particle is notsubstantially degraded after exposure of the particle to a nuclease at 37° C. for at least about 20,30, 45, or 60 minutes. In certain other instances, the nucleic acid in the nucleic acid-lipid particle52406514.1 - 40 -Attorney Docket No. 375836-7000WO1(00007)is not substantially degraded after incubation of the particle in serum at 37° C. for at least about30, 45, or 60 minutes or at least about 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28,30, 32, 34, or 36 hours. In other embodiments, the active agent or therapeutic agent (e.g., nucleicacid such as siRNA) is complexed with the lipid portion of the particle. One of the benefits of theformulations of the present disclosure is that the lipid particle compositions are substantiallynon-toxic to mammals such as humans.Lipid Nanoparticles (LNPs)In another aspect, the present disclosure provides a lipid nanoparticle (LNP) compositioncomprising an isolated nucleic acid of the present disclosure. In certain embodiments, theisolated nucleic acid of the present disclosure is an isolated mRNA. In certain embodiments, theisolated nucleic acid of the present disclosure is an isolated DNA. In certain embodiments, theLNP has a ratio of lipid to isolated mRNA ranging from about 5:1 to about 25:1. In certainembodiments, the isolated mRNA is at least partially encapsulated in the LNP. In certainembodiments, the LNP has a ratio of lipid to isolated DNA ranging from about 5:1 to about 25:1.In certain embodiments, the isolated DNA is at least partially encapsulated in the LNP.In certain embodiments, the isolated polynucleotide is at least partially encapsulated inthe LNP. In certain embodiments, the isolated polynucleotide is fully encapsulated in the LNP.In another aspect, the present disclosure provides a lipid nanoparticle (LNP) compositioncomprising the isolated polynucleotide of the present disclosure. In certain embodiments, theLNP has a ratio of lipid to isolated polynucleotide ranging from about 5:1 to about 25:1. Incertain embodiments, the isolated mRNA is fully encapsulated in the LNP. In certainembodiments, the isolated DNA is fully encapsulated in the LNP.In certain embodiments, the LNP comprises:(a) at least one ionizable lipid;(b) at least one helper lipid;(c) cholesterol, or a modified derivative thereof, and any combinations thereof; and(d) at least one conjugated lipid.In certain embodiments, the ionizable lipid is at least one selected from the groupconsisting of DLinDMA, DLenDMA, DLin-K-C2-DMA, D Lin-K-C3-D MA, DLin-K-C4-DMA, DLin-K6-DMA, DLin-K-MPZ, DLin-KDMA, D Lin-C-DAP, DLin-DAC, DLin-MA,52406514.1 - 41 -Attorney Docket No. 375836-7000WO1(00007)DLinDAP, DLin-2-DMAP, DLin-TMA.Cl, DLin-TAP.Cl, D Lin-MPZ, D LinAP, DOAP, D Lin-EG-D MA, DODAC, DODMA, DSD MA, DOTMA, DDAB, DOTAP, DC-Chol, DMRIE,DOSPA, DOGS, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, and DLincarbDAP.In certain embodiments, the at least one ionizable lipid comprises about 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59,60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85,86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or about 99 mol% of the LNP.In certain embodiments, the at least one ionizable lipid comprises less than about 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57,58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or about 99 mol% of the LNP.In certain embodiments, the at least one ionizable lipid comprises more than about 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57,58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83,84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or about 99 mol% of the LNP.In certain embodiments, the helper lipid is at least one selected from the group consistingof 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), and1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).In certain embodiments, the at least one helper lipid comprises about 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or about 25 mol% of the LNP.In certain embodiments, the at least one helper lipid comprises less than about 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or about 25 mol% of theLNP.In certain embodiments, the at least one helper lipid comprises more than about 1, 2, 3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or about 25 mol% of theLNP.In certain embodiments, cholesterol comprises about 20, 21, 22, 23, 24, 25, 26, 27, 28,52406514.1 - 42 -Attorney Docket No. 375836-7000WO1(00007)29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54,55, 56, 57, 58, 59, or about 60 mol% of the LNP.In certain embodiments, cholesterol comprises less than about 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, or about 60 mol% of the LNP.In certain embodiments, cholesterol comprises more than about 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52,53, 54, 55, 56, 57, 58, 59, or about 60 mol% of the LNP.In certain embodiments, the conjugated lipid is at least one selected from the groupconsisting of 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG-DMG), 1,2-Distearoyl-sn-glycerol, methoxypolyethylene glycol (PEG-DSG), 1,2-Dipalmitoyl-sn-glycerol,methoxypolyethylene glycol (PEG-DPG), mPEG-OH, mPEG-AA (mPEG-CM), mPEG-CH2CH2CH2-NH2, mPEG-DMG, mPEG-N,N-Ditetradecylacetamide (ALC-0159), mPEG-DSPE, and mPEG-DPPE.In certain embodiments, the at least one conjugated lipid comprises about 0.1, 0.2, 0.3,0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5,2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7,4.8, 4.9, or about 5.0 mol% of the LNP.In certain embodiments, the at least one conjugated lipid comprises less than about 0.1,0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3,2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5,4.6, 4.7, 4.8, 4.9, or about 5.0 mol% of the LNP.In certain embodiments, the at least one conjugated lipid comprises more than about 0.1,0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3,2.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2, 4.3, 4.4, 4.5,4.6, 4.7, 4.8, 4.9, or about 5.0 mol% of the LNP.Nucleic acidsMessenger RNA (mRNA)In one aspect, the present disclosure provides an isolated messenger ribonucleic acid(mRNA) encoding the polypeptide of the present disclosure. In certain embodiments, the mRNA52406514.1 - 43 -Attorney Docket No. 375836-7000WO1(00007)is codon optimized for expression in a mammal. In certain embodiments, the mammal is ahuman. In certain embodiments, the mRNA is codon optimized for expression in a prokaryote. Incertain embodiments, the prokaryote is E. coli.In another aspect, the present disclosure provides an isolated polynucleotide encoding themRNA of the present disclosure, wherein the polynucleotide comprises one or more promotersand / or a polyadenylation signal operably linked to a sequence encoding the mRNA.In certain embodiments, the disclosed nucleic acids are, or include, ribonucleic acids. Anon-limiting ribonucleic acid is messenger RNA (mRNA). The term messenger RNA (mRNA)can refer to any ribonucleic acid which directly encodes a polypeptide of interest. Thus, thedisclosed mRNAs are capable of being translated to produce one or more encoded polypeptidesof interest. In certain non-limiting embodiments, the mRNAs are produced by in vitrotranscription.The mRNAs can be of any suitable length. For example, the length can vary dependingupon the size of the encoded polypeptide. mRNA molecules are typically between 200 and10,000 nucleotides in length. In certain non-limiting embodiments, a mRNA includes about 35,40, 45, 50, 55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600,700, 800, 900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500,and 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 20,000, 30,000, 40,000, 50,000,60,000, 70,000, 80,000, 90,000 or 100,000 nucleotides, with or without the poly(A) tail, 5’ UTR,and / or 3’ UTR.The mRNAs can be codon optimized. For example, the mRNAs can be codon optimizedfor expression in a eukaryotic cell or prokaryotic cell (e.g., E. coli). The eukaryotic cell can bethose of or derived from a particular organism, such as a plant or a mammal, including but notlimited to human, or non-human eukaryote or animal or mammal, e.g., mouse, rat, rabbit, dog,livestock, or non-human mammal or primate. Codon-optimization describes gene engineeringapproaches that use changes of rare codons to synonymous codons that are more frequently usedin the cell type of interest with the aim of increasing protein production. In general, codonoptimization involves modifying a nucleic acid sequence for enhanced expression in the hostcells of interest by replacing at least one codon (e.g., about or more than about 1, 2, 3, 4, 5, 10,15, 20, 25, 50, or more codons) of the native sequence with codons that are more frequently ormost frequently used in the genes of that host cell while maintaining the native amino acid52406514.1 - 44 -Attorney Docket No. 375836-7000WO1(00007)sequence. Various species exhibit particular bias for certain codons of a particular amino acid.Codon bias (differences in codon usage between organisms) often correlates with the efficiencyof translation of messenger RNA, which is in turn believed to be dependent on, among otherthings, the properties of the codons being translated and the availability of particular transferRNA (tRNA) molecules. The predominance of selected tRNAs in a cell is generally a reflectionof the codons used most frequently in peptide synthesis. Accordingly, genes can be tailored foroptimal gene expression in a given organism based on codon optimization. Codon usage tablesare readily available, for example, at the “Codon Usage Database” available atwww.kazusa.orjp / codon / and these tables can be adapted in a number of ways. See for example,Nakamura, Y., et al., Nucl. Acids Res., 28:292 (2000). Computer algorithms for codonoptimizing a particular sequence for expression in a particular host cell are also available, such asGene Forge (Aptagen; Jacobus, PA). In certain non-limiting embodiments, one or more codons(e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 50, or more, or all codons) in a mRNA corresponds to the mostfrequently used codon for a particular amino acid.Typically, the disclosed isolated messenger ribonucleic acids (mRNAs) contain a 5′untranslated region (UTR), a 3′ UTR, and an open reading frame (also referred to as codingregion). In certain non-limiting embodiments, the mRNAs further include a 5’ cap or an analogthereof, a poly(A) tail, one or more modified nucleotides, or a combination thereof. In certainembodiments, the mRNAs include at least a 5′ cap or analog thereof, a 5′ UTR, a 3′ UTR, one ormore open reading frames, and a poly(A) tail. In certain embodiments, the mRNAs include atleast a 5′ cap or analog thereof, a 5′ UTR, a 3′ UTR, one or more open reading frames, a poly(A)tail, and one or more modified nucleotides.The mRNA can include different caps or cap analogs (e.g., ARCA). The body of themRNA can use modified nucleosides. The one or more coding sequences or open reading framescan include various elements such as signal peptides, localization signals (e.g., NLSs), inteins,etc. The structures of the mRNA can be engineered to optimize GC motifs, folding,circularization signals, and / or structured UTR elements.5’ capTypically, the 5′ cap of an mRNA is involved in nuclear export, increasing mRNAstability and binding the mRNA Cap Binding Protein (CBP), which is responsible for mRNA52406514.1 - 45 -Attorney Docket No. 375836-7000WO1(00007)stability in the cell and translation competency through the association of CBP with poly(A)binding protein to form the mature cyclic mRNA species. Endogenous mRNA molecules may be5′-end capped generating a 5′-ppp-5′-triphosphate linkage between a terminal guanosine capresidue and the 5′-terminal transcribed sense nucleotide of the mRNA molecule. This 5′-guanylate cap may then be methylated to generate an N7-methyl-guanylate residue. In certainnon-limiting embodiments, the mRNA contains a non-hydrolyzable cap, which can prevent orhinder decapping and thus increase the mRNA half-life. Because cap structure hydrolysisrequires cleavage of 5′-ppp-5′ phosphodiester linkages, the 5’ cap can include modifiednucleotides to prevent such hydrolysis.The 5’ cap may be a single nucleotide or a series of nucleotides. For example, the capmay include from 1 to 10, e.g., 2-9, 3-8, 4-7, 1-5, 5-10, or at least 1 or 2, or 10 or fewernucleotides in length. In certain non-limiting embodiments, the cap is absent.Cap analogs differ from natural (e.g., endogenous, wild-type or physiological) 5′-caps intheir chemical structure, while retaining cap function. Cap analogs may be chemically (e.g., non-enzymatically) or enzymatically synthesized and / or linked to a nucleic acid molecule. Forexample, the Anti-Reverse Cap Analog (ARCA) cap contains two guanines linked by a 5′-5′-triphosphate group, wherein one guanine contains an N7 methyl group as well as a 3′-O-methylgroup (i.e., N7,3′-O-dimethyl-guanosine-5′-triphosphate-5′-guanosine (m7G-3′mppp-G; whichmay equivalently be designated 3′ O-Me-m7G(5′)ppp(5′)G). The 3′-O atom of the other,unmodified, guanine becomes linked to the 5′-terminal nucleotide of the capped nucleic acidmolecule (e.g., mRNA). The N7- and 3′-O-methlyated guanine provides the terminal moiety ofthe capped nucleic acid molecule. Another exemplary cap is mCAP, which is similar to ARCAbut has a 2′-O-methyl group on guanosine (i.e., N7,2′-O-dimethyl-guanosine-5′-triphosphate-5′-guanosine, m7Gm-ppp-G).In certain non-limiting embodiments, a 5′ cap may include endogenous caps or capanalogs. For example, a 5′ cap may include a guanine analog. Useful guanine analogs include,but are not limited to, inosine, N1-methyl-guanosine, 2′-fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, and 2-azido-guanosine.Suitable 5’ caps or analogs that can be included in the mRNAs are known in the art andinclude, without limitation, 7mG(5′)ppp(5′)N,pN2p (cap 0), 7mG(5′)ppp(5′)NlmpNp (cap 1),7mG(5′)-ppp(5′)NlmpN2mp (cap 2), ARCA, beta-S-ARCA, m7G, mCAP, inosine, N1-methyl-52406514.1 - 46 -Attorney Docket No. 375836-7000WO1(00007)guanosine, 2′-fluoro-guanosine, 7-deaza-guanosine, 8-oxo-guanosine, 2-amino-guanosine, LNA-guanosine, tri-methylgranosine (TMG), nicotinamide adenine dinucleotide (NAD), cap AG, capAU, cap GG, and 2-azido-guanosine.Deoxyribonucleic acid (DNA)In one aspect, the present disclosure provides an isolated deoxyribonucleic acid (DNA)encoding the polypeptide of the present disclosure. In certain embodiments, the DNA is codonoptimized for expression in a mammal. In certain embodiments, the mammal is a human.The DNAs can be of any suitable length. For example, the length can vary dependingupon the size of the encoded polypeptide. DNA molecules are typically between 200 and 10,000nucleotides in length. In certain non-limiting embodiments, a DNA includes about 35, 40, 45, 50,55, 60, 70, 80, 90, 100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800,900, 1,000, 1,100, 1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, and3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000,70,000, 80,000, 90,000 or 100,000 nucleotides, with or without the poly(A) tail, 5’ UTR, and / or3’ UTR.The DNAs can be codon optimized. For example, the DNAs can be codon optimized forexpression in a prokaryotic cell. In certain embodiments, the prokaryotic cell is E. coli. In otherembodiments, the DNAs can be codon optimized for expression in a eukaryotic cell. Theeukaryotic cell can be those of or derived from a particular organism, such as a plant or amammal, including but not limited to human, or non-human eukaryote or animal or mammal,e.g., mouse, rat, rabbit, dog, livestock, or non-human mammal or primate.In certain embodiments, the DNA (e.g., DNA which is codon optimized for mammalianexpression) can be administered to a mammal in a vector, wherein expression may occur in themammal (e.g., human) to impart therapeutic effects. In other embodiments, the DNA (e.g., DNAwhich is codon optimized for prokaryotic expression) can be administered and / or delivered to aprokaryotic cell (e.g., E. coli) for manufacture and isolation of the protein product thereof.Untranslated RegionsUntranslated regions (UTRs) are regions of a gene that are transcribed, but not translated.Generally, the 5′UTR starts at the transcription start site and continues to the start codon but does52406514.1 - 47 -Attorney Docket No. 375836-7000WO1(00007)not include the start codon; whereas the 3′UTR starts immediately following the stop codon andcontinues until the transcriptional termination signal. 5’ UTRs can harbor specific regions, likeKozak sequences which are be involved in the initiation of translation by the ribosome. 5′ UTRsalso have been known to form secondary structures which are involved in elongation factorbinding. The UTRs can have important regulatory effects on an associated mRNA, for exampleimpacting stability and / or translation of the mRNA. Generally, translational efficiency (includingactivation or inhibition of translation) of mRNAs can be controlled by the UTRs. In certain non-limiting embodiments, the regulatory features of a UTR can be incorporated into the disclosedmRNAs, to enhance the stability of the molecule. In certain non-limiting embodiments, themRNAs are engineered to contain the UTRs found in abundantly expressed genes to enhance theenhance the stability and protein production from the mRNA. For example, introduction of 5′UTR of liver-expressed mRNA, such as albumin, serum amyloid A, Apolipoprotein A / B / E,transferrin, alpha fetoprotein, erythropoietin, or Factor VIII, could be used to enhance expressionof an mRNA. Likewise, use of 5′ UTR from other tissue-specific mRNA to improve expressionin that tissue is possible for muscle (MyoD, Myosin, Myoglobin, Myogenin, Herculin), forendothelial cells (Tie-1, CD36), for myeloid cells (C / EBP, AML1, G-CSF, GM-CSF, CD11b,MSR, Fr-1, i-NOS), for leukocytes (CD45, CD18), for adipose tissue (CD36, GLUT4, ACRP30,adiponectin) and for lung epithelial cells (SP-A / B / C / D).Poly A TailsDuring RNA processing, a long chain of adenine nucleotides, referred to as the poly(A)tail, may be added to a polynucleotide such as an mRNA in order to increase stability.Immediately after transcription, the 3′ end of the transcript may be cleaved to free a 3′ hydroxyl.Then, poly-A polymerase adds a chain of adenine nucleotides to the RNA. The process, calledpolyadenylation, adds a poly(A) tail that can be between, for example, approximately 100 and250 residues long.In certain non-limiting embodiments, the poly(A) tail includes about 10-100, about 100-300, about 100-250, or about 100-200 adenines. In certain non-limiting embodiments, thepoly(A) tail contains about 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95,100, 120, 140, 160, 180, 200, 250, 300, 350, 400, 450, 500, 600, 700, 800, 900, 1,000, 1,100,1,200, 1,300, 1,400, 1,500, 1,600, 1,700, 1,800, 1,900, 2,000, 2,500, or 3,000 nucleotides.52406514.1 - 48 -Attorney Docket No. 375836-7000WO1(00007)Open Reading Frame (ORF) Encoded PolypeptidesThe mRNAs contain sequences that encode polypeptides of interest. For example, anmRNA can contain one or more open reading frames, each of which encodes one or morepolypeptides. Typically, the open reading frame encodes an antigen (e.g., protein or peptide)from a pathogenic microorganism, such as bacteria, fungi, protozoa, or virus. In certain non-limiting embodiments, the open reading frame encodes one or more proteins from a virus, or animmune-response inducing fragment or variant thereof.Suitable variants can include at least one point mutation or substitution (e.g., 1, 2, 3, 4, 5or more mutations) at any amino acid residue relative to a reference. Amino acid substitutions incertain non-limiting embodiments include conservative amino acid substitutions, although non-conservative substitutions can also be used. Examples of conservative amino acid substitutionsinclude those in which the substitution is within one of the five following groups: 1) smallaliphatic, nonpolar or slightly polar residues (Ala, Ser, Thr, Pro, Gly); 2) polar, negativelycharged residues and their amides (Asp, Asn, Glu, Gln); polar, positively charged residues (His,Arg, Lys); large aliphatic, nonpolar residues (Met, Leu, Ile, Val, Cys); and large aromatic resides(Phe, Tyr, Trp). Examples of non-conservative amino acid substitutions are those where 1) ahydrophilic residue, e.g., seryl or threonyl, is substituted for (or by) a hydrophobic residue, e.g.,leucyl, isoleucyl, phenylalanyl, valyl, or alanyl; 2) a cysteine or proline is substituted for (or by)any other residue; 3) a residue having an electropositive side chain, e.g., lysyl, arginyl, orhistidyl, is substituted for (or by) an electronegative residue, e.g., glutamyl or aspartyl; or 4) aresidue having a bulky side chain, e.g., phenylalanine, is substituted for (or by) a residue thatdoes not have a side chain, e.g., glycine.Other PolynucleotidesThe polynucleotides of the present disclosure may further comprise functionalpolynucleotide regions (e.g., non-coding polynucleotides). The polynucleotide can include one ormore promoters and / or a polyadenylation signal operably linked to a sequence encoding themRNA. In certain non-limiting embodiments, the polynucleotide is, or is contained within, aplasmid. In certain non-limiting embodiments, the polynucleotide is, or is contained within, avector, such as an expression vector.52406514.1 - 49 -Attorney Docket No. 375836-7000WO1(00007)Expression vectors include all those known in the art, such as cosmids, plasmids (e.g.,naked or contained in liposomes), phagemids, artificial chromosomes (e.g., BACs, YACs), andviral vectors (e.g., vectors derived from lentiviruses, retroviruses, adenoviruses, and adeno-associated viruses) that incorporate the polynucleotide.In certain non-limiting embodiments, a polynucleotide (e.g., the portion thereof encodinga mRNA) is operably linked to a control element, e.g., a transcriptional control element, such asa promoter. The transcriptional control element may be functional in either a eukaryotic cell,e.g., a mammalian cell, or a prokaryotic cell (e.g., bacterial or archaeal cell). In certain non-limiting embodiments, a polynucleotide (e.g., the portion thereof encoding a mRNA thereof) isoperably linked to multiple control elements that allow expression of the polynucleotidesequence encoding a mRNA in either prokaryotic or eukaryotic cells. Depending on thehost / vector system utilized, any of certain suitable transcription and translation control elements,including constitutive and inducible promoters, transcription enhancer elements, transcriptionterminators, etc. may be used in the expression vector (e.g., U6 promoter, HI promoter, CMVpromoter, T7 promoter, SV40 promoter, bGH poly(A) signal, SV40 poly(A) signal, etc.).Numerous vectors and expression systems are commercially available from commercialvendors including Addgene, Novagen (Madison, WI), Clontech (Palo Alto, CA), Stratagene (LaJolla, CA), and Invitrogen / Life Technologies (Carlsbad, CA). Suitable expression vectorsinclude, but are not limited to, viral vectors such as viral vectors based on vaccinia virus,poliovirus, adenovirus, adeno-associated virus, SV40, herpes simplex virus, humanimmunodeficiency virus, retroviral vectors (e.g., Murine Leukemia Virus, spleen necrosis virus,and vectors derived from retroviruses such as Rous Sarcoma Virus, Harvey Sarcoma Virus,avian leukosis virus, lentivirus, human immunodeficiency virus, myeloproliferative sarcomavirus, and mammary tumor virus), and the like. The viral vector can be derived from a DNAvirus (e.g., dsDNA or ssDNA virus) or an RNA virus (e.g., a ssRNA virus).Numerous suitable expression vectors are known to those of skill in the art, and many arecommercially available, including, pET29 (Novagen), pXTl, pSG5 (Stratagene), pSVK3, pBPV,pMSG, pCDNA 3.1, and pSVLSV40 (Pharmacia). However, any other vector may be used solong as it is compatible with the host cell.Any cell may be used in accordance with the foregoing. In certain non-limitingembodiments, the cell is a prokaryotic cell (e.g., an archaeal or bacterial cell). In certain non-52406514.1 - 50 -Attorney Docket No. 375836-7000WO1(00007)limiting embodiments, the cell is E. coli. In other forms, the cell is a eukaryotic cell. Forexample, the cell can be a cell of a single-cell eukaryotic organism, a plant cell, an algal cell, afungal cell (e.g., a yeast cell). The cell can be a mammalian cell. The mammalian cell can behuman or non-human mammal, e.g., primate, bovine, ovine, porcine, canine, rodent, monkey, rat,or mouse cell.Generation of the polynucleotides can be accomplished using any suitable geneticengineering techniques well known in the art, including, without limitation, the standardtechniques of restriction endonuclease digestion, ligation, transformation, plasmid purification,and DNA sequencing, for example as described in Sambrook et al. (Molecular Cloning: ALaboratory Manual. Cold Spring Harbor Laboratory Press, N.Y. (1989)).VectorsIn another aspect, the present disclosure provides a vector comprising the isolated nucleicacid of the present disclosure. In certain embodiments, the isolated nucleic acid comprises RNA.In certain embodiments, the nucleic acid comprises DNA. In certain embodiments, the vector is aviral vector. In certain embodiments, the viral vector is a Adeno-Associated Virus (AAV). Incertain embodiments, the AAV is AAV9.In another aspect, the present disclosure provides a vector comprising the isolatedpolynucleotide of the present disclosure. In certain embodiments, the vector is a viral vector. Incertain embodiments, the viral vector is a Adeno-Associated Virus (AAV). In certainembodiments, the AAV is AAV9.In certain non-limiting embodiments, the vector encoding a vaccine antigen (e.g., mRNAand / or polypeptide) is a viral vector. In certain non-limiting embodiments, the viral vector is anadeno-associated virus (AAV) vector. In certain embodiments, an AAV2-derived ITR sequence,or a deleted form thereof (ΔITR), is used for convenience and for accelerated regulatoryapproval. However, ITRs from other AAV sources may be selected. If the source of the ITR isfrom AAV2 and the AAV capsid is from another source of AAV, the resulting vector can bereferred to as a pseudoform.AAV is a non-pathogenic, single-stranded DNA virus that has been actively employedover the years for delivering therapeutic genes in both in vitro and in vivo systems (Choi, et al.,Curr. Gene Ther., 5:299-310, (2005)). AAV belongs to the parvovirus family and is dependent52406514.1 - 51 -Attorney Docket No. 375836-7000WO1(00007)on co-infection with other viruses, mainly adenoviruses, in order to replicate. Each end of thesingle-stranded DNA genome contains an inverted terminal repeat (ITR), which is the only cis-acting element required for genome replication and packaging. The single-stranded AAVgenome contains three genes, Rep (Replication), Cap (Capsid), and aap (Assembly). These threegenes give rise to at least nine gene products through the use of three promoters, alternativetranslation start sites, and differential splicing. These coding sequences are flanked by the ITRs.The Rep gene encodes four proteins (Rep78, Rep68, Rep52, and Rep40), while Cap expressiongives rise to the viral capsid proteins (VP; VP1 / VP2 / VP3), which form the outer capsid shell thatprotects the viral genome, as well as being actively involved in cell binding and internalization.It is estimated that the viral coat is comprised of 60 proteins arranged into an icosahedralstructure with the capsid proteins in a molar ratio of 1:1:10 (VP1:VP2:VP3).Recombinant AAV vectors having no Rep and / or Cap genes can be non-integrating. Inthe absence of Rep proteins, ITR-flanked transgenes encoded within rAAV can form circularconcatemers that persist as episomes in the nucleus of transduced cells. Because recombinantepisomal DNA does not integrate into host genomes, it will eventually be diluted over time asthe cell undergoes repeated rounds of replication. This will eventually result in the loss of thetransgene and transgene expression.The sequences placed between the ITRs will typically include a promoter, gene of interest(e.g., encoding a disclosed mRNA), and a terminator. The promoter can be naturally-occurring ornon-naturally occurring. In many cases, strong, constitutively active promoters are desired forhigh-level expression of the gene of interest. Examples of promoters, include, but are not limitedto, viral promoters, plant promoters and mammalian promoters. Commonly used promotersinclude the CMV (cytomegalovirus) promoter / enhancer, EF1a (elongation factor 1a), SV40(simian virus 40), chicken β-actin and CAG (CMV, chicken β-actin, rabbit β-globin) and variantsthereof. All of these promoters provide constitutively active, high-level gene expression in mostcell types. Some of these promoters are subject to silencing in certain cell types, therefore thisconsideration can be evaluated for each application.Examples of terminators include, but are not limited to, polyadenylation signal sequences.Examples of polyadenylation signal sequences include, but are not limited to, Bovine growthhormone (BGH) poly(A), SV40 late poly(A), rabbit beta-globin (RBG) poly(A), thymidinekinase (TK) poly(A) sequences, and any variants thereof.52406514.1 - 52 -Attorney Docket No. 375836-7000WO1(00007)The viral vectors (e.g., AAV vector) can also have one or more restriction site(s) locatednear the promoter sequence to provide for the insertion of nucleic acid sequences encoding amRNA / protein of interest.The AAV vector used in the disclosed compositions and methods can be a naturallyoccurring serotype of AAV including, but not limited to, AAV1, AAV2, AAV3, AAV4, AAV5,AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, artificial variants such as AAV.rhlO,AAV.rh32 / 33, AAV.rh43, AAV.rh64Rl, rAAV2-retro, AAV-DJ, AAV-PHP.B, AAV-PHP.S,AAV-PHP.eB, or other engineered versions of AAV. In a particular form, the AAV vector isAAV9. These serotypes differ in their tropism, or the types of cells they infect, making AAV avery useful system for in certain embodiments transducing specific cell types. Typically, AAVvectors have a packaging limit of ~4.7kb. The AAV itself may be immunogenic, which in somesettings, can be used for its adjuvant effects.Expression cassettes for AAV vectors typically include AAV 5'-ITRs, coding sequencesand arbitrary control sequences, as well as AAV 3'-ITRs. However, other arrangements of theseelements may be appropriate. A shortened version of the 5'-ITR called ΔITR, which lacks the Dsequence and the terminal resolution site (trs), has been described. In other embodiments, the fulllength AAV 5'-ITR and 3'-ITR are used.The expression cassette usually contains, for example, a promoter sequence as part of anexpression control sequence located between the selected 5'-ITR sequence and the codingsequence.In addition to promoters, expression cassettes and / or vectors include one or more othersuitable transcription initiation, termination, enhancer sequences, efficient RNA processingsignals such as splicing and polyadenylation (polyA) signals. It may contain a sequence thatstabilizes mRNA; a sequence that enhances translation efficiency (i.e., a Kozak consensussequence); a sequence that enhances protein stability; and, if desired, a sequence that enhancesthe secretion of the encoding product.Examples of suitable poly A sequences include, for example, SV40, SV50, bovinegrowth hormone (bGH), human growth hormone, and synthetic poly A.Examples of suitable enhancers include, for example, α-fetoprotein enhancer, TTRminimum promoter / enhancer, LSP (TH-binding globulin promoter / α-microglobulin / bikuninenhancer). In certain embodiments, the expression cassette comprises one or more expression52406514.1 - 53 -Attorney Docket No. 375836-7000WO1(00007)enhancers. In certain embodiments, the expression cassette contains two or more expressionenhancers. These enhancers may be the same or different from each other. The enhancer can bepresent in two copies located adjacent to each other. Alternatively, the dual copy of the enhancercan be separated by one or more sequences. In yet another embodiment, the expression cassettefurther contains an intron, such as a Promega intron. Other suitable introns include those knownin the art, such as those described in International Patent Application No. WO 2011 / 126808,which is incorporated herein by reference in its entirety for all purposes.Recombinant AAV viral vectors are well suited for delivery of the coding sequencesdescribed herein. Such AAV vectors are ITRs derived from the same AAV source as the capsid.Alternatively, the AAV ITR may be derived from an AAV source different from that supplyingthe capsid.Yet other promoters, including tissue-specific promoters, may be selected. Methods formaking and isolating AAV viral vectors suitable for delivery to subjects are known in the art. Forexample, U.S. Patent Application Publication No. US2007 / 0036760 (February 15, 2007), U.S.Patent Nos. 7,790,449; 7,282,199; 7,588,772; and International Publication Nos.WO2003 / 042397; WO2005 / 033321; WO2006 / 11689; all of which are incorporated herein byreference in their entireties for all purposes. The sequence of AAV8 and the method forproducing a vector based on AAV8 capsid are described in U.S. Patent Nos. 7,282,199;7,790,449; and 8,318,480; all of which are incorporated herein by reference in their entireties. Incertain embodiments, the vector is based on a AAV9 capsid.In certain embodiments, the vector is a bacterial expression vector. In certainembodiments, the bacterial expression vector comprises E. coli. In certain embodiments, thebacterial expression vector comprises a pET E. coli T7 expression vector. In certainembodiments, the pET E. coli T7 expression vector comprises pET29b (Novagen).CompositionsIn one aspect, the present disclosure provides a polypeptide comprising o instances of B,p instances of T, q instances of L, wherein:each occurrence of B, if present, independently comprises an immunogenic fragment of abacterial surface protein,wherein each instance of B has a C-terminus and a N-terminus;52406514.1 - 54 -Attorney Docket No. 375836-7000WO1(00007)each occurrence of T, if present, independently comprises an immunogenic fragment of aniron receptor protein,wherein each instance of T has a C-terminus and a N-terminus;each occurrence of L independently comprises a polypeptide of 1 to 40 amino acids,wherein each instance of L has a C-terminus and a N-terminus;each instance of B is covalently linked to one or two independent instances of L by acovalent peptide bond between the C-terminus of the B and the N-terminus of the L and / or theN-terminus of the B and the C-terminus of the L;each instance of T is covalently linked to one or two independent instances of L by acovalent peptide bond between the C-terminus of the T and the N-terminus of the L and / or theN-terminus of the T and the C-terminus of the L;o is an integer ranging from 0 to 15;p is an integer ranging from 0 to 15;q is an integer ranging from 5 to 30; andwherein o + p ≥ 6.In certain embodiments, the C-terminus of the polypeptide may comprise one or moreamino acids associated with polypeptide synthesis and / or purification (e.g., poly-His tag orHHHHHH). It is understood by those of ordinary skill in the art that the design of poly-His tags(i.e., terminal position and relatively short length of 6-10 residues) does not confer any biologicalactivity (e.g., immunogenicity) to the polypeptides to which they are covalently linked. It isfurther understood by those of ordinary skill in the art that the design of poly-His tags minimizesand / or eliminates interference with the biological activity of the polypeptides to which they arecovalently linked. As one of ordinary skill in the art would recognize, particularly in view of theapplication disclosure, the disclosure is not limited to the exemplary polypeptides describedherein which comprise a poly-His tag (e.g., SEQ ID NOs:127-145), but further encompassesanalogues thereof which lack poly-His functionalization (e.g., SEQ ID NOs:223-241).In certain embodiments, the N-terminus of a polypeptide of the disclosure may compriseone or more amino acids associated with polypeptide synthesis and / or purification (e.g.,methionine). In certain embodiments, certain exemplary polypeptides of the disclosure comprisean N-terminal methionine residue. As one of ordinary skill in the art appreciates, the N-terminalmethionine residue present in certain exemplary polypeptides is an artifact of the method by52406514.1 - 55 -Attorney Docket No. 375836-7000WO1(00007)which the polypeptides are synthetized, wherein the AUG start codon of the mRNA transcript(i.e., adenine-uracil-guanine) encodes methionine. Accordingly, as one of ordinary skill in the artwould recognize, particularly in view of the application disclosure, the disclosure is not limitedto the exemplary polypeptides described herein which comprise an N-terminal methionineresidue (e.g., SEQ ID NOs:127-145 and SEQ ID NOs:223-241), but further encompassesanalogues thereof which lack an N-terminal methionine residue (e.g., SEQ ID NOs:242-260).Further, one of ordinary skill in the art is apprised of the methods by which N-terminalmethionine residues are post-translationally removed (i.e., N-terminal methionine excision orcleavage). In certain embodiments, N-terminal methionine excision and / or cleavage is catalyzedby methionine aminopeptidase (MetAP).In certain embodiments, each occurrence of L independently comprises a polypeptide of1 to 10 amino acids. In certain embodiments, each occurrence of L independently comprises apolypeptide of 3 to 10 amino acids. In certain embodiments, each occurrence of L independentlycomprises a polypeptide of 3 to 25 amino acids. In certain embodiments, multiple occurrences ofL may be positioned adjacent to one another.In certain embodiments, each occurrence of L independently comprises a polypeptidehaving an amino acid sequence selected from the group consisting of SEQ ID NO:124 (GSGS),SEQ ID NO:125 (GPGP), SEQ ID NO:126 (LLSVGG), SEQ ID NOs:146-155 ((SGSG)1-10),SEQ ID NO:156 (SSSS), SEQ ID NO:157 (GGGS), SEQ ID NO:158 (GGC), SEQ ID NO:159(GGS), SEQ ID NO:160 ((GGC)8), SEQ ID NO:161 ((GGGGS)3), and SEQ ID NO:162(GGAAY). In certain embodiments, each occurrence of L may be cleavable by a protease.In certain embodiments, B is absent. In certain embodiments, 1 to 15 instances of B aredenoted as B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, B13, B14, and B15, respectively. Incertain embodiments, each instance of B is independently denoted B1, B2, B3, B4, B5, B6, B7, B8,B9, B10, B11, B12, B13, B14, or B15.In certain embodiments, T is absent. In certain embodiments, 1 to 15 instances of T aredenoted as T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, and T15, respectively. In certainembodiments, each instance of T is independently denoted T1, T2, T3, T4, T5, T6, T7, T8, T9, T10,T11, T12, T13, T14, or T15.In certain embodiments, 5 to 30 instances of L are denoted as L1, L2, L3, L4, L5, L6, L7,L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L29,52406514.1 - 56 -Attorney Docket No. 375836-7000WO1(00007)and L30, respectively. In certain embodiments, each instance of L is independently denoted L1,L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24,L25, L26, L27, L28, L29, or L30.In certain embodiments, the polypeptide has a structure of B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13-L25-T13-L26-B14-L27-T14-L28-B15-L29-T15.In certain embodiments, the polypeptide may comprise an instance of L which is notadjacent to two instances of B, two instances of T, or one instance of each of B and T (i.e., aterminal L), as represented in the following non-limiting embodiment: B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13-L25-T13-L26-B14-L27-T14-L28-B15-L29-T15-L30.The present disclosure encompasses any arrangement of any instance of B and anyinstance of T.In certain embodiments, the polypeptide may be initiated (i.e., N-terminus of thepolypeptide) by an instance of T, as represented in the following non-limiting embodiment: T1-L1-B1-L2-T2-L3-B2-L4-T3-L5-B3-L6-T4-L7-B4-L8-T5-L9-B5-L10-T6-L11-B6-L12-T7-L13-B7-L14-T8-L15-B8-L16-T9-L17-B9-L18-T10-L19-B10-L20-T11-L21-B11-L22-T12-L23-B12-L24-T13-L25-B13-L26-T14-L27-B14-L28-T15-L29-B15.In certain embodiments, two instances of B and / or two instances of T may be separatedby an instance of L (e.g., B1-L1-B2 and / or T1-L2-T2), as represented in the following non-limitingembodiments: B1-L1-B2-L2-T1-L3-T2-L4-B3-L5-B4-L6-T3-L7-T4-L8-B5-L9-B6-L10-T5-L11-T6-L12-B7-L13-B8-L14-T7-L15-T8-L16-B9-L17-B10-L18-T9-L19-T10-L20-B11-L21-B12-L22-T11-L23-T12-L24-B13-L25-B14-L26-T13-L27-T14-L28-B15-L29-T15; B1-L1-B2-L2-B3-L3-B4-L4-B5-L5-B6-L6-B7-L7-B8-L8-B9-L9-B10-L10-B11-L11-B12-L12-B13-L13-B14-L14-B15-L15-T1-L16-T2-L17-T3-L18-T4-L19-T5-L20-T6-L21-T7-L22-T8-L23-T9-L24-T10-L25-T11-L26-T12-L27-T13-L28-T14-L29-T15; or many other embodiments inwhich the arrangement of instances of B and T are interchanged, all of which are contemplatedherein.In certain embodiments, any of B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, B13, B14,B15, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, T15, L1, L2, L3, L4, L5, L6, L7, L8, L9,L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L29, or L30 52406514.1Attorney Docket No. 375836-7000WO1(00007)may be present or absent, such that at least 5 instances of L are present, and at a total of 6instances of B and / or T are present, as represented in the following non-limiting embodiments:B1-L1-B2-L2-B3-L3-B4-L4-B5-L5-B6; T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6; B1-L1-B2-L2-B3-L3-B4-L4-B5-L5-T1; T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-B1; B1-L1-B2-L2-B3-L3-B4-L4-T1-L5-T2; T1-L1-T2-L2-T3-L3-T4-L4-B1-L5-B2; B10-L11-B11-L12-B12-L13-B13-L14-B14-L15-T25; or many otherembodiments of truncated polypeptides in which at least 5 instances of L are present, and a totalof 6 instances among B and T are present, all of which are contemplated herein.In certain embodiments, wherein the identity of each of B1, B2, B3, B4, B5, B6, B7, B8, B9,B10, B11, B12, B13, B14, B15, T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14, and T15 aredefined, the position of any two identical or unidentical instances of B (e.g., B1 and B2) and / orany two identical or unidentical instances of T (e.g., T1 and T2) can be substituted, as representedin the following pairs of non-limiting embodiments:B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12 and B2-L1-T1-L2-B1-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12 (e.g., the position of B1 and B2 aresubstituted); andB1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12 and B1-L1-T2-L2-B2-L3-T1-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12 (e.g., the position of T1 and T2 aresubstituted).In certain embodiments, the polypeptide is a polypeptide of structure B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12.In certain embodiments, the polypeptide is a polypeptide of structure B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9.In certain embodiments, the polypeptide is a polypeptide of structure T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12.In certain embodiments, the polypeptide is a polypeptide of structure T1-L1-T2-L2-T3-L3- 52406514.1Attorney Docket No. 375836-7000WO1(00007)T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9.In certain embodiments, the polypeptide is a polypeptide of structure B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13-L25-T13.structure T1-L1-T2-L2 3 3 -T -L -T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12-L12-T13.In certain embodiments, the polypeptide is a polypeptide of structure B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13.In certain embodiments, the polypeptide is a polypeptide of structure B1-L1-B2-L2-B3-L3-B4-L4-T1-L5-T2-L6-T3-L7-T4-L8-B5-L9-B6-L10-B7-L11-B8-L12-T5-L13-T6-L14-T7-L15-T8-L16-B9-L17-B10-L18-B11-L19-B12-L20-T9-L21-T10-L22-T11-L23-T12.In certain embodiments, the polypeptide is a polypeptide of structure T1-L1-T2-L2-T3-L3-T4-L4-B1-L5-B2-L6-B3-L7-B4-L8-T5-L9-T6-L10-T7-L11-T8-L12-B5-L13-B6-L14-B7-L15-B8-L16-T9-L17-T10-L18-T11-L19-T12-L20-B9-L21-B10-L22-B11-L23-B12.One skilled in the art would appreciate that the present disclosure is not limited to theembodiments explicitly disclosed herein.In certain embodiments, the polypeptide comprises a polypeptide of formula (I), or a saltor solvate thereof:B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6n (I),wherein:each occurrence T3 can be present or absent;each occurrence of B1, B2, and B3, if present, independently comprise an immunogenicfragment of a bacterial surface protein;each occurrence of T1, T2, and T3, if present, independently comprise an immunogenicfragment of an iron receptor protein,wherein at least two of T1, T2, and T3 are present or at least one of T1, T2 and T3 ispresent and n is at least 2;each occurrence of L1, L2, L3, L4, L5, and L6, if present, independently comprise apolypeptide of 1-10 amino acids,52406514.1 - 59 -Attorney Docket No. 375836-7000WO1(00007)wherein at least one of L1, L2, L3, L4, L5, and L6 is present, andwherein each occurrence of B1, B2, B3, T1, T2, and T3 are separated from oneanother by at least one of L1, L2, L3, L4, L5, and L6; andn is an integer selected from the group consisting of 1, 2, 3, 4, and 5.In certain embodiments, the polypeptide of formula (I) comprises n (i.e., 1, 2, 3, 4, or 5)independent occurrences of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 . In certain non-limitingembodiments, wherein n is 2, a first independent occurrence ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 is covalently linked to a second independent occurrenceof B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 via an amide (peptide) bond. In certain embodiments,the covalent linkage comprises a linear arrangement of each occurrence ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6. For example, in certain embodiments, a terminal B1, B2,B3, T1, T2, or T3 of a first occurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 is covalentlylinked to a terminal L1, L2, L3, L4, L5, or L6 of a second occurrence ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6. For example, in one non-limiting embodiment, wherein nis 2 and each of B1, B2, B3, L1, L2, L3, L4, L5, L6, T1, T2, and T3 are present in both occurrences ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 , the polypeptide of formula (I) has the following structure(e.g., wherein a terminal L6 of a first occurrence is covalently bound to a terminal B1 of a secondoccurrence):B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 .That said, whether any one of B1, B2, B3, L1, L2, L3, L4, L5, L6, T1, T2, or T3 is present orabsent in a given occurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 , the number ofoccurrences of which is defined by n, is independent of each group’s presence or absence in anyother occurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6. For example, in one non-limitingembodiment, wherein n is 2, a first occurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 maycomprise only B1, occurrence ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 may comprise only T1, L5, and T3 ( T1 L5 T3 ). In theaforementioned non-limiting embodiment, the polypeptide of formula (I) has the followingstructure: B1 L1 T1 L2 T1 L5 T3 . Thus, in the aforementioned non-limiting embodiment, B1, L1,52406514.1 - 60 -Attorney Docket No. 375836-7000WO1(00007)and L2 are present only in the first occurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 , L5 andT3 are present only in the second occurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 , and T1 ispresent in both the first and second occurrences of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 .Further, the identity of each of B1, B2, B3, L1, L2, L3, L4, L5, L6, T1, T2, and T3 in eachoccurrence of B1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 , the number of occurrences of which isdefined by n, are independent from one another. For example, in the aforementioned non-limiting embodiment, wherein n is 2 and T1 is present in both occurrences ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 , T1 in the first occurrence ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 may comprise an immunogenic fragment of the ironreceptor protein defined by SEQ ID NO:10, and T1 in the second occurrence ofB1 L1 T1 L2 B2 L3 T2 L4 B3 L5 T3 L6 may comprise an immunogenic fragment of the ironreceptor protein defined by SEQ ID NO:12.In the polypeptide of formula (I), each occurrence of B1, B2, and B3, if present,independently comprises an immunogenic fragment of a bacterial surface protein. In certainembodiments, each occurrence of B1, B2, and / or B3 is independently present or absent. In certainembodiments, each occurrence of B1, B2, and B3, may comprise an identical immunogenicfragment of a bacterial surface protein. In certain embodiments, each occurrence of B1, B2, andB3, may comprise a different immunogenic fragment of a bacterial surface protein. Thus, incertain non-limiting embodiments, wherein a single occurrence of each of B1 and B2 are present,and the bacterial surface protein of both B1 and B2 may correspond to SEQ ID NO:1, theimmunogenic fragment of the bacterial surface protein in B1 may comprise SEQ ID NO:16, andthe immunogenic fragment of the bacterial surface protein in B2 may comprise SEQ ID NO:17.Additionally, the identity of the bacterial surface protein need not be the same in each occurrenceof B1, B2, and B3. In certain embodiments, each occurrence of B1, B2, and B3, may compriseimmunogenic fragments of different bacterial surface proteins. For example, in certain non-limiting embodiments, wherein a single occurrence of each of B1 and B2 are present, the bacterialsurface protein of B1 may comprise SEQ ID NO:1 and the bacterial surface protein of B2 maycomprise SEQ ID NO:2. Similarly, in certain non-limiting embodiments, wherein thepolypeptide of formula (I) comprises two occurrences of B1, the first occurrence of B1 maycomprise bacterial surface protein SEQ ID NO:1 and the second occurrence of B1 may comprise52406514.1 - 61 -Attorney Docket No. 375836-7000WO1(00007)bacterial surface protein SEQ ID NO:2. Alternatively, in certain non-limiting embodiments,wherein the polypeptide of formula (I) comprises two occurrences of B1, the first and secondoccurrences of B1 may both comprise bacterial surface protein SEQ ID NO:1.In the polypeptide of formula (I), each occurrence of T1, T2, and T3, if present,independently comprises an immunogenic fragment of an iron receptor protein. In certainembodiments, each occurrence of T1, T2, and / or T3 is independently present or absent. In certainembodiments, each occurrence of T1, T2, and T3, may comprise an identical immunogenicfragment of an iron receptor protein. In certain embodiments, each occurrence of T1, T2, and T3,may comprise a different immunogenic fragment of an iron receptor protein. Thus, in certainnon-limiting embodiments, wherein a single occurrence of each of T1 and T2 are present, and theiron receptor protein of both T1 and T2 may correspond to SEQ ID NO:10, the immunogenicfragment of the iron receptor protein in T1 may comprise SEQ ID NO:42, and the immunogenicfragment of the iron receptor protein in T2 may comprise SEQ ID NO:43. Additionally, theidentity of the iron receptor protein need not be the same in each occurrence of T1, T2, and T3. Incertain embodiments, each occurrence of T1, T2, and T3, may comprise immunogenic fragmentsof different iron receptor proteins. For example, in certain non-limiting embodiments, wherein asingle occurrence of each of T1 and T2 are present, the iron receptor protein of T1 may compriseSEQ ID NO:10 and the iron receptor protein of T2 may comprise SEQ ID NO:12. Similarly, incertain non-limiting embodiments, wherein the polypeptide of formula (I) comprises twooccurrences of T1, the first occurrence of T1 may comprise iron receptor protein SEQ ID NO:10and the second occurrence of T1 may comprise iron receptor protein SEQ ID NO:12.Alternatively, in certain non-limiting embodiments, wherein the polypeptide of formula (I)comprises two occurrences of T1, the first and second occurrences of T1 may both comprise ironreceptor protein SEQ ID NO:10.In the polypeptide of formula (I), each occurrence of L1, L2, L3, L4, L5, and L6, if present,independently comprise a polypeptide of 1-10 amino acids. In certain embodiments, eachoccurrence of L1, L2, L3, L4, L5, and / or L6 is independently present or absent. In certainembodiments, each occurrence of L1, L2, L3, L4, L5, and / or L6, may comprise a different 1-10amino acid polypeptide. Thus, in certain non-limiting embodiments, wherein a single occurrenceof each of L1 and L2 are present, L1 may comprise SEQ ID NO:124 and L2 may comprise SEQID NO:125. Alternatively, in certain non-limiting embodiments, wherein a single occurrence of52406514.1 - 62 -Attorney Docket No. 375836-7000WO1(00007)each of L1 and L2 are present, L1 and L2 may both comprise SEQ ID NO:124. Similarly, incertain non-limiting embodiments, wherein n is 2 and the polypeptide of formula (I) comprisestwo occurrences of L1, the first occurrence of L1 may comprise SEQ ID NO:124 and the secondoccurrence of L1 may comprise SEQ ID NO:125. Alternatively, in certain non-limitingembodiments, wherein n is 2 and the polypeptide of formula (I) comprises two occurrences ofL1, both the first and second occurrences of L1 may comprise SEQ ID NO:124.In certain embodiments, at least one of B1, B2, and B3 is present.In certain embodiments, each bacterial surface protein shares at least 85%, 90%, 95%,96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptide independently selectedfrom the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.In certain embodiments, each immunogenic fragment of the bacterial surface proteinshares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with apolypeptide independently selected from the group consisting of SEQ ID NO:16, SEQ IDNO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ IDNO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQID NO:39, SEQ ID NO:40, and SEQ ID NO:41.In certain embodiments, each immunogenic fragment of the bacterial surface proteinshares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with apolypeptide independently selected from the group consisting of SEQ ID NO:16, SEQ IDNO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:23, SEQID NO:25, SEQ ID NO:27, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39,and SEQ ID NO:40.In certain embodiments, each of B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, B13, B14,and B15, if present, shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequencehomology with a polypeptide independently selected from the group consisting of SEQ IDNO:16, SEQ ID NO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26,SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID52406514.1 - 63 -Attorney Docket No. 375836-7000WO1(00007)NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, and SEQ ID NO:41.In certain embodiments, each iron receptor protein shares at least 85%, 90%, 95%, 96%,97%, 98%, 99%, or 100% sequence homology with a polypeptide independently selected fromthe group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQID NO:14, and SEQ ID NO:15.In certain embodiments, each immunogenic fragment of the iron receptor protein sharesat least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideindependently selected from the group consisting of SEQ ID NO:42, SEQ ID NO:43, SEQ IDNO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55,SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ IDNO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72,SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ IDNO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89,SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ IDNO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ IDNO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ IDNO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ IDNO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ IDNO:121, SEQ ID NO:122, and SEQ ID NO:123.In certain embodiments, each immunogenic fragment of the iron receptor protein sharesat least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideindependently selected from the group consisting of SEQ ID NO:42, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQID NO:58, SEQ ID NO:62, SEQ ID NO:67, SEQ ID NO:85, and SEQ ID NO:88.In certain embodiments, each of T1, T2, T3, T4, T5, T6, T7, T8, T9, T10, T11, T12, T13, T14,and T15, if present, shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence52406514.1 - 64 -Attorney Docket No. 375836-7000WO1(00007)homology with a polypeptide independently selected from the group consisting of SEQ IDNO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53,SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ IDNO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70,SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ IDNO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87,SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ IDNO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ IDNO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ IDNO:109, SEQ ID NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ IDNO:114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ IDNO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, and SEQ ID NO:123.In certain embodiments, each of L1, L2, L3, L4, L5, and L6, if present, independentlycomprise a polypeptide wherein each amino acid residue side chain comprises a neutral (i.e.,non-charged) substituent.In certain embodiments, each of L1, L2, L3, L4, L5, and L6, if present, independentlycomprise a polypeptide of 4 amino acids. In certain embodiments, each of L1, L2, L3, L4, L5, andL6, if present, independently comprise a polypeptide of 5 amino acids. In certain embodiments,each of L1, L2, L3, L4, L5, and L6, if present, independently comprise a polypeptide of 6 aminoacids.In certain embodiments, each of L1, L2, L3, L4, L5, and L6, if present, is independentlyselected from the group consisting of GSGS (SEQ ID NO:124), GPGP (SEQ ID NO:125),LLSVGG (SEQ ID NO:126), (SGSG)1-2 (SEQ ID NOs:146-147), SSSS (SEQ ID NO:156),GGGS (SEQ ID NO:157), GGC (SEQ ID NO:158), GGS (SEQ ID NO:159), (GGC)8 (SEQ IDNO:160), (GGGGS)3 (SEQ ID NO:161), and GGAAY (SEQ ID NO:162).In certain embodiments, n is 1. In certain embodiments, n is 2. In certain embodiments, nis 3. In certain embodiments, n is 4. In certain embodiments, n is 5.52406514.1 - 65 -Attorney Docket No. 375836-7000WO1(00007)In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with a polypeptide selected from the group consisting of SEQID NO:130 and SEQ ID NO:129.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with a polypeptide selected from the group consisting of SEQID NO:127, SEQ ID NO:128, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ IDNO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:143, SEQ IDNO:144, SEQ ID NO:145, SEQ ID NO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ IDNO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ IDNO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ IDNO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ IDNO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ IDNO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ IDNO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID NO:253, SEQ ID NO:254, SEQ IDNO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ ID NO:258, SEQ ID NO:259, and SEQ IDNO:260.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:135.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:225.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:226.In certain embodiments, the polypeptide comprises a polypeptide selected from the groupconsisting of:(a) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12;(b) T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12;(c) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9;(d) T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9;(e) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T1-L10-B6-L11-T2-L12-B7-L13-52406514.1 - 66 -Attorney Docket No. 375836-7000WO1(00007)T3-L14-B8-L15-T4-L16-B9-L17-T1-L18-B10-L19-T2-L20-B11-L21-T3-L22-B12-L23-T4;(f) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13-L25-T13;(g) T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12-L12-T13;(h) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13;(i) and(j) T1-L1-T2-L2-T3-L3-T4-L4-B1-L5-B2-L6-B3-L7-B4-L8-T5-L9-T6-L10-T7-L11-T8-L12-B5-L13-B6-L14-B7-L15-B8-L16-T9-L17-T10-L18-T11-L19-T12-L20-B9-L21-B10-L22-B11-L23-B12;wherein:each occurrence of B, if present, independently comprises an immunogenic fragmentof a bacterial surface protein,wherein each instance of B has a C-terminus and a N-terminus;each occurrence of T independently comprises an immunogenic fragment of an ironreceptor protein,wherein each instance of T has a C-terminus and a N-terminus;each occurrence of L independently comprises a polypeptide of 1-10 amino acids,wherein each instance of L has a C-terminus and a N-terminus;each instance of B is covalently linked to one or two independent instances of L by acovalent peptide bond between the C-terminus of the B and the N-terminus of the Land / or the N-terminus of the B and the C-terminus of the L; andeach instance of T is covalently linked to one or two independent instances of L by acovalent peptide bond between the C-terminus of the T and the N-terminus of the Land / or the N-terminus of the T and the C-terminus of the L;or a salt or solvate thereof.In certain embodiments, each immunogenic fragment of the bacterial surface proteinshares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with apolypeptide independently selected from the group consisting of SEQ ID NO:16, SEQ IDNO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ52406514.1 - 67 -Attorney Docket No. 375836-7000WO1(00007)ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ IDNO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQID NO:39, SEQ ID NO:40, and SEQ ID NO:41.In certain embodiments, each immunogenic fragment of the bacterial surface proteinshares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with apolypeptide independently selected from the group consisting of SEQ ID NO:16, SEQ IDNO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:23, SEQID NO:25, SEQ ID NO:27, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37, SEQ ID NO:39,and SEQ ID NO:40.In certain embodiments, each iron receptor protein shares at least 85%, 90%, 95%, 96%,97%, 98%, 99%, or 100% sequence homology with a polypeptide independently selected fromthe group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQID NO:14, and SEQ ID NO:15.In certain embodiments, each immunogenic fragment of the iron receptor protein sharesat least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideindependently selected from the group consisting of SEQ ID NO:42, SEQ ID NO:43, SEQ IDNO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55,SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ IDNO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72,SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ IDNO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89,SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ IDNO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ IDNO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ IDNO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ IDNO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID52406514.1 - 68 -Attorney Docket No. 375836-7000WO1(00007)NO:121, SEQ ID NO:122, and SEQ ID NO:123.In certain embodiments, each immunogenic fragment of the iron receptor protein sharesat least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideindependently selected from the group consisting of SEQ ID NO:42, SEQ ID NO:46, SEQ IDNO:47, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQID NO:58, SEQ ID NO:62, SEQ ID NO:67, SEQ ID NO:85, and SEQ ID NO:88.In certain embodiments, each of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14,L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, and L25, if present, independently comprise apolypeptide wherein each amino acid residue side chain comprises a neutral (i.e., non-charged)substituent.In certain embodiments, each of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14,L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, and L25, if present, independently comprise apolypeptide of 4 to 6 amino acids.In certain embodiments, each of L1, L2, L3, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14,L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, and L25, if present, is independently selected from thegroup consisting of GSGS (SEQ ID NO:124), GPGP (SEQ ID NO:125), LLSVGG (SEQ IDNO:126), (SGSG)1-2 (SEQ ID NOs:146-147), SSSS (SEQ ID NO:156), GGGS (SEQ IDNO:157), GGC (SEQ ID NO:158), GGS (SEQ ID NO:159), (GGC)8 (SEQ ID NO:160),(GGGGS)3 (SEQ ID NO:161), and GGAAY (SEQ ID NO:162).In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with a polypeptide selected from the group consisting of SEQID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ IDNO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ IDNO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ IDNO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:223, SEQ IDNO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ IDNO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ IDNO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ IDNO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ IDNO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ IDNO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ ID52406514.1 - 69 -Attorney Docket No. 375836-7000WO1(00007)NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ IDNO:258, SEQ ID NO:259, and SEQ ID NO:260.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:225.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:226.MethodsIn another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one polypeptide of the present disclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one isolated mRNA of the presentdisclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one isolated DNA of the presentdisclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one isolated polynucleotide of the presentdisclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one vector of the present disclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one LNP of the present disclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, the52406514.1 - 70 -Attorney Docket No. 375836-7000WO1(00007)method comprises administering to the subject at least one the pharmaceutical composition of thepresent disclosure.In another aspect, the present disclosure provides a method of treating, preventing, and / orameliorating a bacterial infection in a subject in need thereof. In certain embodiments, themethod comprises administering to the subject at least one vaccine composition of the presentdisclosure.In certain embodiments, the bacterial infection is a urinary tract infection. In certainembodiments, the bacterial infection comprises a urinary tract infection and sepsis. In certainembodiments, the bacterial infection is sepsis. In certain embodiments, the sepsis is neonatalsepsis. In certain embodiments, the bacterial infection is pneumonia.In another aspect, the present disclosure provides a method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one polypeptide of the present disclosure.In another aspect, the present disclosure provides a method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one isolated mRNA of the present disclosure. Incertain embodiments, the method comprises administering to the subject at least one isolatedDNA of the present disclosure.In another aspect, the present disclosure provides a method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one isolated polynucleotide of the presentdisclosure.In another aspect, the present disclosure provides a method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one vector of the present disclosure.In another aspect, the present disclosure provides method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one LNP of the present disclosure.In another aspect, the present disclosure provides a method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one the pharmaceutical composition of the present52406514.1 - 71 -Attorney Docket No. 375836-7000WO1(00007)disclosure.In another aspect, the present disclosure provides a method of generating immunity toinfection by one or more pathogenic bacteria in a subject. In certain embodiments, the methodcomprises administering to the subject at least one vaccine composition of the present disclosure.In certain embodiments, the one or more pathogenic bacteria comprises at least oneselected from the group consisting of Escherichia coli, Klebsiella pneumoniae, Proteusmirabilis, Shigella dysenteriae, Salmonella enterica, Streptococcus pneumoniae, Haemophilusinfluenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Staphylococcus aureus,Moraxella catarrhalis, and Legionella pneumophila, Streptococcus pyogenes, and Pseudomonasaeruginosa, and Salmonella bongori.In certain embodiments, the immunity prevents a bacterial infection.In certain embodiments, the bacterial infection is a urinary tract infection (UTI). Incertain embodiments, the bacterial infection comprises a urinary tract infection and sepsis. Incertain embodiments, the bacterial infection is sepsis. In certain embodiments, the sepsis isneonatal sepsis. In certain embodiments, the bacterial infection is pneumonia.In certain embodiments, the subject is administered one or more additional doses of thepolypeptide of the present disclosure after initial administration. In certain embodiments, thesubject is administered a second, third, or fourth dose of the polypeptide of the present disclosureafter initial administration.In certain embodiments, the subject is administered one or more additional doses of theisolated mRNA of the present disclosure after initial administration. In certain embodiments, thesubject is administered a second, third, or fourth dose of the isolated mRNA of the presentdisclosure after initial administration.In certain embodiments, the subject is administered one or more additional doses of theisolated polynucleotide of the present disclosure after initial administration. In certainembodiments, the subject is administered a second, third, or fourth dose of the isolatedpolynucleotide of the present disclosure after initial administration.In certain embodiments, the subject is administered one or more additional doses of thevector of the present disclosure after initial administration. In certain embodiments, the subject isadministered a second, third, or fourth dose of the vector of the present disclosure after initialadministration.52406514.1 - 72 -Attorney Docket No. 375836-7000WO1(00007)In certain embodiments, the subject is administered one or more additional doses of theLNP of the present disclosure after initial administration. In certain embodiments, the subject isadministered a second, third, or fourth dose of the LNP of the present disclosure after initialadministration.In certain embodiments, the subject is administered one or more additional doses of thepharmaceutical composition of the present disclosure after initial administration. In certainembodiments, the subject is administered a second, third, or fourth dose of the pharmaceuticalcomposition of the present disclosure after initial administration.In certain embodiments, the subject is administered one or more additional doses of thevaccine composition of the present disclosure after initial administration. In certainembodiments, the subject is administered a second, third, or fourth dose of the vaccinecomposition of the present disclosure after initial administration.In certain embodiments, each additional dose is administered with an interval rangingfrom about 1 to about 365 days. In certain embodiments, the interval between doseadministrations is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66,67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92,93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113,114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132,133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151,152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189,190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208,209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226, 227,228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245, 246,247, 248, 249, 250, 251, 252, 253, 254, 255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265,266, 267, 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284,285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301, 302, 303,304, 305, 306, 307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322,323, 324, 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341,52406514.1 - 73 -Attorney Docket No. 375836-7000WO1(00007)342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359, 360,361, 362, 363, 364, and 365 days apart.In certain embodiments, the subject is a mammal. In certain embodiments, the mammal isa human.In certain embodiments, the administration comprises maternal immunization.In certain embodiments, subject is pregnant with a fetus.In certain embodiments, the bacterial infection is treated, prevented, and / or amelioratedin at least one of the subject and the fetus, or a neonate thereof. In certain embodiments, thebacterial infection is treated, prevented, and / or ameliorated in both the subject and the fetus, or aneonate thereof. In certain embodiments, the bacterial infection is treated, prevented, and / orameliorated in the neonate or infant after birth of the fetus.In certain embodiments, the immunity to infection by one or more pathogenic bacteria isgenerated in at least one of the subject and the fetus, or a neonate thereof. In certainembodiments, the immunity to infection by one or more pathogenic bacteria is generated in boththe subject and the fetus, or a neonate thereof. In certain embodiments, the immunity to infectionby one or more pathogenic bacteria is generated in the neonate or infant after birth of the fetus.Pharmaceutical Compositions and FormulationsIn another aspect, the present disclosure provides a vaccine composition comprising thepolypeptide of the present disclosure and at least one pharmaceutically acceptable excipient.In another aspect, the present disclosure provides a vaccine composition comprising atleast one LNP of the present disclosure and a pharmaceutically acceptable excipient.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with a polypeptide selected from the group consisting of SEQID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ IDNO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ IDNO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ ID NO:141, SEQ IDNO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:223, SEQ IDNO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ IDNO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ IDNO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ ID52406514.1 - 74 -Attorney Docket No. 375836-7000WO1(00007)NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ IDNO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ IDNO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ IDNO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ IDNO:258, SEQ ID NO:259, and SEQ ID NO:260.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:225.In certain embodiments, the polypeptide shares at least 85%, 90%, 95%, 96%, 97%, 98%,99%, or 100% sequence homology with SEQ ID NO:226.In certain embodiments, the vaccine composition further comprises an adjuvant. Incertain embodiments, the adjuvant is at least one selected from the group consisting of aluminumhydroxide (AlOH), double mutant heat labile toxin (dmLt), CpG, AddaS03™, AddaVaxTM,MF59®, W205EC and / or W805EC (NanoBio®), Matrix-MTM, Quil-A®, monophosphoryl lipid A(MPLA; e.g., PHAD® (synthetic) or E. coli derived), monophosphoryl lipid A SalmonellaMinnesota (MPLA-SM; e.g., MPLA-SM VacciGradeTM), Alhydrogel®, aluminum phosphate(ALPO4; e.g., Imject® Alum Adjuvant), chitosan, Class A CpG adjuvant (e.g., OND 1585, ODN2216, and ODN 2336), Class B CpG adjuvant (e.g., ODN 1018, ODN 1668, ODN 1826, ODN2006, ODN 2007, ODN BW006, ODN D-SL01, and ODN 7909), Class C CpG adjuvant (e.g.,ODN 2395, ODN M362, and ODN D-SL03), cCpG, compositions comprising one or morecationic liposomes and / or one or more immunomodulators (e.g., CAF01), AS01b, gardisiladjuvant, AS02, AS03®, AS04, GLA-SE (i.e., glucopyranosyl lipid adjuvant; synthetic TLR4agonist), IC31®, MontanideTM ISA-51 VG, MontamideTM ISA-70 VG, immune stimulatingcomplexes (ISCOMs) (e.g., H5N1), cholera toxin (CT), cholera toxin subunit B (CTB), subunitB of heat-labile enterotoxin (LTB), imiquimod, resiquimod (R848), double stranded RNA(dsRNA) hairpin(s) (e.g., polyinosinic:polycytidylic acid (i.e., poly I:C)), Riboxxim®,rintatolimod (Ampligen®), poly ICLC (e.g., Hiltonol®), AF03, polyphosphazene (PCEP and / orPCPP), cyclic diguanylate monophosphate (c-di-GMP or CDG), CAF01, CAF05, CAF09,trehalose dibehenate (TDB), furfurman, curdlan, retinoic acid, protollin, proteosomes (IDBiomedical), EndocineTM (L3B), N30A, N30ASq, NanoVax (NanoBio®), inulin, delta inulin(e.g., AdvaxTM), Advax-CpG55.2, polyactin and / or alpha-polyactin, mannatide, β-glucosylceramide, α-galactosylceramide, cholesterol, IFN-α, flagellin, MALT chemokines (e.g.,52406514.1 - 75 -Attorney Docket No. 375836-7000WO1(00007)CCL25, CCL27, and CCL28), glucosylpyranosyl lipid adjuvant, ADP ribosylating toxins,trehalose, and hydroxypropyl methacrylamide (HPMA) co-polymers.In certain embodiments, the adjuvant comprises aluminum hydroxide. In certainembodiments, the adjuvant comprises dmLT. In certain embodiments, the adjuvant comprisesCpG. In certain embodiments, the adjuvant comprises AddaS03™. In certain embodiments, theadjuvant comprises AS03®.In certain embodiments, the adjuvant comprises AlOH and CpG. In certain embodiments,the adjuvant comprises AddaS03™ and / or AS03® and CpG. In certain embodiments, theadjuvant comprises AddaS03™ and CpG. In certain embodiments, the adjuvant comprisesAS03® and CpG.In certain embodiments, the adjuvant in compositions of the disclosure suitable fortreatment and / or prevention of a urinary tract infection in a subject comprise AddaS03™ and / orAS03® and CpG. In certain embodiments, the adjuvant in compositions of the disclosuresuitable for treatment and / or prevention of a urinary tract infection in a subject compriseAddaS03™ and CpG. In certain embodiments, the adjuvant in compositions of the disclosuresuitable for treatment and / or prevention of a urinary tract infection in a subject comprise AS03®and CpG.In certain embodiments, the adjuvant in compositions of the disclosure suitable fortreatment and / or prevention of neonatal sepsis in a subject comprises AlOH. In certainembodiments, the adjuvant in compositions of the disclosure suitable for treatment and / orprevention of neonatal sepsis in a subject comprises AlOH and CpG.In certain embodiments, the compositions of the disclosure comprise about 10, 11, 12, 13,14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39,40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65,66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91,92, 93, 94, 95, 96, 97, 98, 99, or about 100 µg of the polypeptide.In certain embodiments, the compositions of the disclosure comprise about 10, 20, 30, 40,50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180,190, 200, 210, 220, 230, 240, 250,260, 270, 280, 290, 300, 310, 320, 330, 340, 350, 360, 370, 380, 390, 400, ,410, 420, 430, 440,450, 460, 470, 480, 490, or about 500 µg of the polypeptide.In certain embodiments, the vaccine composition has a concentration of the polypeptide52406514.1 - 76 -Attorney Docket No. 375836-7000WO1(00007)of about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0,2.1, 2.2, 2.32.4, 2.5, 2.6, 2.7, 2.8, 2.9, 3.0, 3.1, 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 4.0, 4.1, 4.2,4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9, or about 5.0 µg / µL.In certain embodiments, the is administered with a volume selectedfrom the group consisting of about 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140,150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 310, 320, 330,340, 350, 360, 370, 380, 390, 400, 410, 420, 430, 440, 450, 460, 470, 480, 490, or about 500 µL.In certain embodiments, the compositions of the disclosure comprise about 100, 200, 300,400, 500, 600, 700, 800, 900, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900,2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000, 3100, 3200, 3300, 3400,3500, 3600, 3700, 3800, 3900, 4000, 4100, 4200, 4300, 4400, 4500, 4600, 4700, 4800, 4900,5000, 5100, 5200, 5300, 5400, 5500, 5600, 5700, 5800, 5900, or about 6000 µg of CpG.In certain embodiments, the compositions of the disclosure comprise about 250, 300, 350,400, 450, 500, 550, 600, 650, 700, or about 750 µg of AlOH.In certain embodiments, the compositions of the disclosure comprise about 1, 2, 3, 4, 5, 6,7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or about 25 µg of dmLT.In certain embodiments, the polypeptide and CpG have a mass ratio in the pharmaceuticalor vaccine composition of about 10:6000, 15:6000, 20:6000, 25:6000, 30:6000, 35:6000,40:6000, 45:6000, 50:6000, 55:6000, 60:6000, 65:6000, 70:6000, 75:6000, 80:6000, 85:6000,90:6000, 95:6000, 100:6000, 10:5750, 15:5750, 20:5750, 25:5750, 30:5750, 35:5750, 40:5750,45:5750, 50:5750, 55:5750, 60:5750, 65:5750, 70:5750, 75:5750, 80:5750, 85:5750, 90:5750,95:5750, 100:5750, 10:5500, 15:5500, 20:5500, 25:5500, 30:5500, 35:5500, 40:5500, 45:5500,50:5500, 55:5500, 60:5500, 65:5500, 70:5500, 75:5500, 80:5500, 85:5500, 90:5500, 95:5500,100:5500, 10:5250, 15:5250, 20:5250, 25:5250, 30:5250, 35:5250, 40:5250, 45:5250, 50:5250,55:5250, 60:5250, 65:5250, 70:5250, 75:5250, 80:5250, 85:5250, 90:5250, 95:5250, 100:5250,10:5000, 15:5000, 20:5000, 25:5000, 30:5000, 35:5000, 40:5000, 45:5000, 50:5000, 55:5000,60:5000, 65:5000, 70:5000, 75:5000, 80:5000, 85:5000, 90:5000, 95:5000, 100:5000, 10:4750,15:4750, 20:4750, 25:4750, 30:4750, 35:4750, 40:4750, 45:4750, 50:4750, 55:4750, 60:4750,65:4750, 70:4750, 75:4750, 80:4750, 85:4750, 90:4750, 95:4750, 100:4750, 10:4500, 15:4500,20:4500, 25:4500, 30:4500, 35:4500, 40:4500, 45:4500, 50:4500, 55:4500, 60:4500, 65:4500,70:4500, 75:4500, 80:4500, 85:4500, 90:4500, 95:4500, 100:4500, 10:4250, 15:4250, 20:4250,52406514.1 - 77 -Attorney Docket No. 375836-7000WO1(00007)25:4250, 30:4250, 35:4250, 40:4250, 45:4250, 50:4250, 55:4250, 60:4250, 65:4250, 70:4250,75:4250, 80:4250, 85:4250, 90:4250, 95:4250, 100:4250, 10:4000, 15:4000, 20:4000, 25:4000,30:4000, 35:4000, 40:4000, 45:4000, 50:4000, 55:4000, 60:4000, 65:4000, 70:4000, 75:4000,80:4000, 85:4000, 90:4000, 95:4000, 100:4000, 10:3750, 15:3750, 20:3750, 25:3750, 30:3750,35:3750, 40:3750, 45:3750, 50:3750, 55:3750, 60:3750, 65:3750, 70:3750, 75:3750, 80:3750,85:3750, 90:3750, 95:3750, 100:3750, 10:3500, 15:3500, 20:3500, 25:3500, 30:3500, 35:3500,40:3500, 45:3500, 50:3500, 55:3500, 60:3500, 65:3500, 70:3500, 75:3500, 80:3500, 85:3500,90:3500, 95:3500, 100:3500, 10:3250, 15:3250, 20:3250, 25:3250, 30:3250, 35:3250, 40:3250,45:3250, 50:3250, 55:3250, 60:3250, 65:3250, 70:3250, 75:3250, 80:3250, 85:3250, 90:3250,95:3250, 100:3250, 10:3000, 15:3000, 20:3000, 25:3000, 30:3000, 35:3000, 40:3000, 45:3000,50:3000, 55:3000, 60:3000, 65:3000, 70:3000, 75:3000, 80:3000, 85:3000, 90:3000, 95:3000,100:3000, 10:2750, 15:2750, 20:2750, 25:2750, 30:2750, 35:2750, 40:2750, 45:2750, 50:2750,55:2750, 60:2750, 65:2750, 70:2750, 75:2750, 80:2750, 85:2750, 90:2750, 95:2750, 100:2750,10:2500, 15:2500, 20:2500, 25:2500, 30:2500, 35:2500, 40:2500, 45:2500, 50:2500, 55:2500,60:2500, 65:2500, 70:2500, 75:2500, 80:2500, 85:2500, 90:2500, 95:2500, 100:2500, 10:2250,15:2250, 20:2250, 25:2250, 30:2250, 35:2250, 40:2250, 45:2250, 50:2250, 55:2250, 60:2250,65:2250, 70:2250, 75:2250, 80:2250, 85:2250, 90:2250, 95:2250, 100:2250, 10:2000, 15:2000,20:2000, 25:2000, 30:2000, 35:2000, 40:2000, 45:2000, 50:2000, 55:2000, 60:2000, 65:2000,70:2000, 75:2000, 80:2000, 85:2000, 90:2000, 95:2000, 100:2000, 10:1750, 15:1750, 20:1750,25:1750, 30:1750, 35:1750, 40:1750, 45:1750, 50:1750, 55:1750, 60:1750, 65:1750, 70:1750,75:1750, 80:1750, 85:1750, 90:1750, 95:1750, 100:1750, 10:1500, 15:1500, 20:1500, 25:1500,30:1500, 35:1500, 40:1500, 45:1500, 50:1500, 55:1500, 60:1500, 65:1500, 70:1500, 75:1500,80:1500, 85:1500, 90:1500, 95:1500, 100:1500, 10:1250, 15:1250, 20:1250, 25:1250, 30:1250,35:1250, 40:1250, 45:1250, 50:1250, 55:1250, 60:1250, 65:1250, 70:1250, 75:1250, 80:1250,85:1250, 90:1250, 95:1250, 100:1250, 10:1000, 15:1000, 20:1000, 25:1000, 30:1000, 35:1000,40:1000, 45:1000, 50:1000, 55:1000, 60:1000, 65:1000, 70:1000, 75:1000, 80:1000, 85:1000,90:1000, 95:1000, 100:1000, 10:750, 15:750, 20:750, 25:750, 30:750, 35:750, 40:750, 45:750,50:750, 55:750, 60:750, 65:750, 70:750, 75:750, 80:750, 85:750, 90:750, 95:750, 100:750,10:500, 15:500, 20:500, 25:500, 30:500, 35:500, 40:500, 45:500, 50:500, 55:500, 60:500,65:500, 70:500, 75:500, 80:500, 85:500, 90:500, 95:500, 100:500, 10:250, 15:250, 20:250,25:250, 30:250, 35:250, 40:250, 45:250, 50:250, 55:250, 60:250, 65:250, 70:250, 75:250,52406514.1 - 78 -Attorney Docket No. 375836-7000WO1(00007)80:250, 85:250, 90:250, 95:250, 100:250, 10:100, 15:100, 20:100, 25:100, 30:100, 35:100,40:100, 45:100, 50:100, 55:100, 60:100, 65:100, 70:100, 75:100, 80:100, 85:100, 90:100,95:100, or about 100:100 (polypeptide:CpG).In certain embodiments, the pharmaceutical composition comprises about 0.4% AlOH(w / w%). In certain embodiments, the polypeptide and AlOH have a mass ratio in thepharmaceutical or vaccine composition of about 10:750, 15:750, 20:750, 25:750, 30:750, 35:750,40:750, 45:750, 50:750, 55:750, 60:750, 65:750, 70:750, 75:750, 80:750, 85:750, 90:750,95:750, 100:750, 10:700, 15:700, 20:700, 25:700, 30:700, 35:700, 40:700, 45:700, 50:700,55:700, 60:700, 65:700, 70:700, 75:700, 80:700, 85:700, 90:700, 95:700, 100:700, 10:650,15:650, 20:650, 25:650, 30:650, 35:650, 40:650, 45:650, 50:650, 55:650, 60:650, 65:650,70:650, 75:650, 80:650, 85:650, 90:650, 95:650, 100:650, 10:600, 15:600, 20:600, 25:600,30:600, 35:600, 40:600, 45:600, 50:600, 55:600, 60:600, 65:600, 70:600, 75:600, 80:600,85:600, 90:600, 95:600, 100:600, 10:550, 15:550, 20:550, 25:550, 30:550, 35:550, 40:550,45:550, 50:550, 55:550, 60:550, 65:550, 70:550, 75:550, 80:550, 85:550, 90:550, 95:550,100:550, 10:500, 15:500, 20:500, 25:500, 30:500, 35:500, 40:500, 45:500, 50:500, 55:500,60:500, 65:500, 70:500, 75:500, 80:500, 85:500, 90:500, 95:500, 100:500, 10:450, 15:450,20:450, 25:450, 30:450, 35:450, 40:450, 45:450, 50:450, 55:450, 60:450, 65:450, 70:450,75:450, 80:450, 85:450, 90:450, 95:450, 100:450, 10:400, 15:400, 20:400, 25:400, 30:400,35:400, 40:400, 45:400, 50:400, 55:400, 60:400, 65:400, 70:400, 75:400, 80:400, 85:400,90:400, 95:400, 100:400, 10:350, 15:350, 20:350, 25:350, 30:350, 35:350, 40:350, 45:350,50:350, 55:350, 60:350, 65:350, 70:350, 75:350, 80:350, 85:350, 90:350, 95:350, 100:350,10:300, 15:300, 20:300, 25:300, 30:300, 35:300, 40:300, 45:300, 50:300, 55:300, 60:300,65:300, 70:300, 75:300, 80:300, 85:300, 90:300, 95:300, 100:300, 10:250, 15:250, 20:250,25:250, 30:250, 35:250, 40:250, 45:250, 50:250, 55:250, 60:250, 65:250, 70:250, 75:250,80:250, 85:250, 90:250, 95:250, or about 100:250 (polypeptide:AlOH).In certain embodiments, the pharmaceutical composition comprises about 50%AddaS03™.In certain embodiments, polypeptide and dmLT have a mass ratio in the pharmaceuticalor vaccine composition of about 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1,65:1, 70:1, 75:1, 80:1, 85:1, 90:1, 95:1, 100:1, 10:2, 15:2, 20:2, 25:2, 30:2, 35:2, 40:2, 45:2, 50:2,55:2, 60:2, 65:2, 70:2, 75:2, 80:2, 85:2, 90:2, 95:2, 100:2, 10:3, 15:3, 20:3, 25:3, 30:3, 35:3, 40:3,52406514.1 - 79 -Attorney Docket No. 375836-7000WO1(00007)45:3, 50:3, 55:3, 60:3, 65:3, 70:3, 75:3, 80:3, 85:3, 90:3, 95:3, 100:3, 10:4, 15:4, 20:4, 25:4, 30:4,35:4, 40:4, 45:4, 50:4, 55:4, 60:4, 65:4, 70:4, 75:4, 80:4, 85:4, 90:4, 95:4, 100:4, 10:5, 15:5, 20:5,25:5, 30:5, 35:5, 40:5, 45:5, 50:5, 55:5, 60:5, 65:5, 70:5, 75:5, 80:5, 85:5, 90:5, 95:5, 100:5,10:10, 15:10, 20:10, 25:10, 30:10, 35:10, 40:10, 45:10, 50:10, 55:10, 60:10, 65:10, 70:10, 75:10,80:10, 85:10, 90:10, 95:10, 100:10, 10:15, 15:15, 20:15, 25:15, 30:15, 35:15, 40:15, 45:15,50:15, 55:15, 60:15, 65:15, 70:15, 75:15, 80:15, 85:15, 90:15, 95:15, 100:15, 10:20, 15:20,20:20, 25:20, 30:20, 35:20, 40:20, 45:20, 50:20, 55:20, 60:20, 65:20, 70:20, 75:20, 80:20, 85:20,90:20, 95:20, 100:20, 10:25, 15:25, 20:25, 25:25, 30:25, 35:25, 40:25, 45:25, 50:25, 55:25,60:25, 65:25, 70:25, 75:25, 80:25, 85:25, 90:25, 95:25, or about 100:25 (polypeptide:dmLT).In certain embodiments, the oil-in-water emulsion adjuvant comprises about 0.5, 1.0, 1.5,2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or about 10.0 mgpolysorbate 80. In certain embodiments, the oil-in-water emulsion adjuvant comprises about 2.43mg polysorbate 80. In certain embodiments, the oil-in-water emulsion adjuvant comprises about4.86 mg polysorbate 80. In certain embodiments, the oil-in-water emulsion adjuvant comprisesabout 9.72 mg polysorbate 80.In certain embodiments, the oil-in-water emulsion adjuvant comprises about 0.5, 1.0, 1.5,2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, 12.0,12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5,21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, or about 25.0 mg squalene. In certain embodiments,the oil-in-water emulsion adjuvant comprises about 5.35 mg squalene. In certain embodiments,the oil-in-water emulsion adjuvant comprises about 10.69 mg squalene. In certain embodiments,the oil-in-water emulsion adjuvant comprises about 21.38 mg squalene.In certain embodiments, the oil-in-water emulsion adjuvant comprises about 0.5, 1.0, 1.5,2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, 10.0, 10.5, 11.0, 11.5, 12.0,12.5, 13.0, 13.5, 14.0, 14.5, 15.0, 15.5, 16.0, 16.5, 17.0, 17.5, 18.0, 18.5, 19.0, 19.5, 20.0, 20.5,21.0, 21.5, 22.0, 22.5, 23.0, 23.5, 24.0, 24.5, or about 25.0 mg α-tocopherol (e.g., racemic α-tocopherol). In certain embodiments, the oil-in-water emulsion adjuvant comprises about 5.93 α-tocopherol. In certain embodiments, the oil-in-water emulsion adjuvant comprises about 11.86mg α-tocopherol. In certain embodiments, the oil-in-water emulsion adjuvant comprises about23.72 mg α-tocopherol.In certain embodiments, the oil-in-water emulsion adjuvant comprises about 25%, 26%,52406514.1 - 80 -Attorney Docket No. 375836-7000WO1(00007)27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%,43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%,59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, orabout 75% (v / v) of the vaccine composition of the disclosure.In certain embodiments, the disclosure provides a vaccine composition comprising:(a) a polypeptide which shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or100% sequence homology with SEQ ID NO:225, wherein the vaccinecomposition comprises about 10 µg to about 100 µg of the polypeptide;(b) α-tocopherol, wherein the α-tocopherol comprises about 2.5% (v / v) of the vaccinecomposition;(c) squalene, wherein the squalene comprises about 2.5% (v / v) of the vaccinecomposition; and(d) polysorbate 80, wherein the polysorbate 80 comprises about 0.9% (v / v) of thevaccine composition;wherein the polypeptide, α-tocopherol, squalene, and polysorbate are dissolved orsuspended in a phosphate buffered saline (PBS) solution.In certain embodiments, the disclosure provides a vaccine composition comprising:(a) a polypeptide which shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or100% sequence homology with SEQ ID NO:225, wherein the vaccinecomposition comprises about 10 µg to about 100 µg of the polypeptide;(b) α-tocopherol, wherein the α-tocopherol comprises about 2.5% (v / v) of the vaccinecomposition;(c) squalene, wherein the squalene comprises about 2.5% (v / v) of the vaccinecomposition;(d) polysorbate 80, wherein the polysorbate 80 comprises about 0.9% (v / v) of thevaccine composition;(e) CpG, wherein the vaccine comprises about 100 µg to about 6000 µg of the CpG;wherein the polypeptide, α-tocopherol, squalene, polysorbate, and CpG aredissolved or suspended in a phosphate buffered saline (PBS) solution.In certain embodiments, the disclosure provides a vaccine composition comprising:(a) a polypeptide which shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or52406514.1 - 81 -Attorney Docket No. 375836-7000WO1(00007)100% sequence homology with SEQ ID NO:226, wherein the vaccinecomposition comprises about 10 µg to about 100 µg of the polypeptide;(b) α-tocopherol, wherein the α-tocopherol comprises about 2.5% (v / v) of the vaccinecomposition;(c) squalene, wherein the squalene comprises about 2.5% (v / v) of the vaccinecomposition; and(d) polysorbate 80, wherein the polysorbate 80 comprises about 0.9% (v / v) of thevaccine composition;wherein the polypeptide, α-tocopherol, squalene, and polysorbate are dissolved orsuspended in a phosphate buffered saline (PBS) solution.In certain embodiments, the disclosure provides a vaccine composition comprising:(a) a polypeptide which shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or100% sequence homology with SEQ ID NO:226, wherein the vaccinecomposition comprises about 10 µg to about 100 µg of the polypeptide;(b) α-tocopherol, wherein the α-tocopherol comprises about 2.5% (v / v) of the vaccinecomposition;(c) squalene, wherein the squalene comprises about 2.5% (v / v) of the vaccinecomposition;(d) polysorbate 80, wherein the polysorbate 80 comprises about 0.9% (v / v) of thevaccine composition;(e) CpG, wherein the vaccine comprises about 100 µg to about 6000 µg of the CpG;wherein the polypeptide, α-tocopherol, squalene, polysorbate, and CpG aredissolved or suspended in a phosphate buffered saline (PBS) solution.In another aspect, the present disclosure provides a pharmaceutical compositioncomprising at least one LNP of the present disclosure and a pharmaceutically acceptableexcipient.The invention provides pharmaceutical compositions comprising at least one polypeptideor compound of the invention or a salt or solvate thereof, which are useful to practice methods ofthe invention. Such a pharmaceutical composition may consist of at least one polypeptide orcompound of the invention or a salt or solvate thereof, in a form suitable for administration to asubject, or the pharmaceutical composition may comprise at least one polypeptide or compound52406514.1 - 82 -Attorney Docket No. 375836-7000WO1(00007)of the invention or a salt or solvate thereof, and one or more pharmaceutically acceptablecarriers, one or more additional ingredients, or any combinations of these. At least onepolypeptide or compound of the invention may be present in the pharmaceutical composition inthe form of a physiologically acceptable salt, such as in combination with a physiologicallyacceptable cation or anion, as is well known in the art.In certain embodiments, the pharmaceutical compositions useful for practicing themethod of the invention may be administered to deliver a dose of between 1 ng / kg / day and 1mg / kg / day. In other embodiments, the pharmaceutical compositions useful for practicing theinvention may be administered to deliver a dose of between 100 ng / kg / day and 1 mg / kg / day.The relative amounts of the active ingredient, the pharmaceutically acceptable carrier,and any additional ingredients in a pharmaceutical composition of the invention will vary,depending upon the identity, size, and condition of the subject treated and further dependingupon the route by which the composition is to be administered. By way of example, thecomposition may comprise between 0.1% and 100% (w / w) active ingredient.Pharmaceutical compositions that are useful in the methods of the invention may besuitably developed for nasal, inhalational, oral, rectal, vaginal, pleural, peritoneal, parenteral,topical, transdermal, pulmonary, intranasal, buccal, ophthalmic, epidural, intrathecal,intravenous, or another route of administration. A composition useful within the methods of theinvention may be directly administered to the brain, the brainstem, or any other part of thecentral nervous system of a mammal or bird. Other contemplated formulations include projectednanoparticles, microspheres, liposomal preparations, coated particles, polymer conjugates,resealed erythrocytes containing the active ingredient, and immunologically-based formulations.In certain embodiments, the compositions of the invention are part of a pharmaceuticalmatrix, which allows for manipulation of insoluble materials and improvement of thebioavailability thereof, development of controlled or sustained release products, and generationof homogeneous compositions. By way of example, a pharmaceutical matrix may be preparedusing hot melt extrusion, solid solutions, solid dispersions, size reduction technologies,molecular complexes (e.g., cyclodextrins, and others), microparticulate, and particle andformulation coating processes. Amorphous or crystalline phases may be used in such processes.The route(s) of administration will be readily apparent to the skilled artisan and willdepend upon any number of factors including the type and severity of the disease being treated,52406514.1 - 83 -Attorney Docket No. 375836-7000WO1(00007)the type and age of the veterinary or human patient being treated, and the like.The formulations of the pharmaceutical compositions described herein may be preparedby any method known or hereafter developed in the art of pharmacology and pharmaceutics. Ingeneral, such preparatory methods include the step of bringing the active ingredient intoassociation with a carrier or one or more other accessory ingredients, and then, if necessary ordesirable, shaping or packaging the product into a desired single-dose or multi-dose unit.As used herein, a “unit dose” is a discrete amount of the pharmaceutical compositioncomprising a predetermined amount of the active ingredient. The amount of the active ingredientis generally equal to the dosage of the active ingredient that would be administered to a subjector a convenient fraction of such a dosage such as, for example, one-half or one-third of such adosage.Although the descriptions of pharmaceutical compositions provided herein are principallydirected to pharmaceutical compositions suitable for ethical administration to humans, it will beunderstood by the skilled artisan that such compositions are generally suitable for administrationto animals of all sorts. Modification of pharmaceutical compositions suitable for administrationto humans in order to render the compositions suitable for administration to various animals iswell understood, and the ordinarily skilled veterinary pharmacologist can design and performsuch modification with merely ordinary, if any, experimentation. Subjects to whichadministration of the pharmaceutical compositions of the invention is contemplated include, butare not limited to, humans and other primates, mammals including commercially relevantmammals such as cattle, pigs, horses, sheep, cats, dogs, and rodents.In certain embodiments, the compositions of the invention are formulated using one ormore pharmaceutically acceptable excipients or carriers. In certain embodiments, thepharmaceutical compositions of the invention comprise a therapeutically effective amount of atleast one polypeptide or compound of the invention and a pharmaceutically acceptable carrier.Pharmaceutically acceptable carriers, which are useful, include, but are not limited to, glycerol,water, saline, ethanol, recombinant human albumin (e.g., RECOMBUMIN®), solubilized gelatins(e.g., GELOFUSINE®), and other pharmaceutically acceptable salt solutions such as phosphatesand salts of organic acids. Examples of these and other pharmaceutically acceptable carriers aredescribed in Remington’s Pharmaceutical Sciences (1991, Mack Publication Co., New Jersey).The carrier may be a solvent or dispersion medium containing, for example, water,52406514.1 - 84 -Attorney Docket No. 375836-7000WO1(00007)ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and thelike), recombinant human albumin, solubilized gelatins, suitable mixtures thereof, and vegetableoils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin,by the maintenance of the required particle size in the case of dispersion and by the use ofsurfactants. Prevention of the action of microorganisms may be achieved by various antibacterialand antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal,and the like. In many cases, isotonic agents, for example, sugars, sodium chloride, orpolyalcohols such as mannitol and sorbitol, are included in the composition. Prolongedabsorption of the injectable compositions may be brought about by including in the compositionan agent that delays absorption, for example, aluminum monostearate or gelatin.Formulations may be employed in admixtures with conventional excipients, i.e.,pharmaceutically acceptable organic or inorganic carrier substances suitable for parenteral,intravenous, subcutaneous, transdermal enteral, or any other suitable mode of administration,known to the art. The pharmaceutical preparations may be sterilized and if desired mixed withauxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts forinfluencing osmotic pressure buffers, coloring, flavoring, and / or fragrance-conferring substancesand the like. They may also be combined where desired with other active agents, e.g., otheranalgesic, anxiolytics or hypnotic agents. As used herein, “additional ingredients” include, butare not limited to, one or more ingredients that may be used as a pharmaceutical carrier.The composition of the invention may comprise a preservative from about 0.005% to2.0% by total weight of the composition. The preservative is used to prevent spoilage in the caseof exposure to contaminants in the environment. Examples of preservatives useful in accordancewith the invention include but are not limited to those selected from the group consisting ofbenzyl alcohol, sorbic acid, parabens, imidurea and any combinations thereof. One suchpreservative is a combination of about 0.5% to 2.0% benzyl alcohol and 0.05-0.5% sorbic acid.The composition may include an antioxidant and a chelating agent that inhibit thedegradation of the polypeptide or compound. Antioxidants for some polypeptide or compoundsare BHT, BHA, alpha-tocopherol and ascorbic acid in the exemplary range of about 0.01% to0.3%, or BHT in the range of 0.03% to 0.1% by weight by total weight of the composition. Thechelating agent may be present in an amount of from 0.01% to 0.5% by weight by total weight ofthe composition. Exemplary chelating agents include edetate salts (e.g. disodium edetate) and52406514.1 - 85 -Attorney Docket No. 375836-7000WO1(00007)citric acid in the weight range of about 0.01% to 0.20%, or in the range of 0.02% to 0.10% byweight by total weight of the composition. The chelating agent is useful for chelating metal ionsin the composition that may be detrimental to the shelf life of the formulation. While BHT anddisodium edetate are exemplary antioxidant and chelating agent, respectively, for somepolypeptides or compounds, other suitable and equivalent antioxidants and chelating agents maybe substituted therefore as would be known to those skilled in the art.Liquid suspensions may be prepared using conventional methods to achieve suspensionof the active ingredient in an aqueous or oily vehicle. Aqueous vehicles include, for example,water, and isotonic saline. Oily vehicles include, for example, almond oil, oily esters, ethylalcohol, vegetable oils such as arachis, olive, sesame, or coconut oil, fractionated vegetable oils,and mineral oils such as liquid paraffin. Liquid suspensions may further comprise one or moreadditional ingredients including, but not limited to, suspending agents, dispersing or wettingagents, emulsifying agents, demulcents, preservatives, buffers, salts, flavorings, coloring agents,and sweetening agents. Oily suspensions may further comprise a thickening agent. Knownsuspending agents include, but are not limited to, sorbitol syrup, hydrogenated edible fats,sodium alginate, polyvinylpyrrolidone, gum tragacanth, gum acacia, and cellulose derivativessuch as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethyl cellulose.Known dispersing or wetting agents include, but are not limited to, naturally-occurringphosphatides such as lecithin, condensation products of an alkylene oxide with a fatty acid, witha long chain aliphatic alcohol, with a partial ester derived from a fatty acid and a hexitol, or witha partial ester derived from a fatty acid and a hexitol anhydride (e.g., polyoxyethylene stearate,heptadecaethyleneoxycetanol, polyoxyethylene sorbitol monooleate, and polyoxyethylenesorbitan monooleate, respectively). Known emulsifying agents include, but are not limited to,lecithin, acacia, and ionic or non-ionic surfactants. Known preservatives include, but are notlimited to, methyl, ethyl, or n-propyl para-hydroxybenzoates, ascorbic acid, and sorbic acid.Known sweetening agents include, for example, glycerol, propylene glycol, sorbitol, sucrose,and saccharin.Liquid solutions of the active ingredient in aqueous or oily solvents may be prepared insubstantially the same manner as liquid suspensions, the primary difference being that the activeingredient is dissolved, rather than suspended in the solvent. As used herein, an “oily” liquid isone which comprises a carbon-containing liquid molecule and which exhibits a less polar52406514.1 - 86 -Attorney Docket No. 375836-7000WO1(00007)character than water. Liquid solutions of the pharmaceutical composition of the invention maycomprise each of the components described with regard to liquid suspensions, it beingunderstood that suspending agents will not necessarily aid dissolution of the active ingredient inthe solvent. Aqueous solvents include, for example, water, and isotonic saline. Oily solventsinclude, for example, almond oil, oily esters, ethyl alcohol, vegetable oils such as arachis, olive,sesame, or coconut oil, fractionated vegetable oils, and mineral oils such as liquid paraffin.Powdered and granular formulations of a pharmaceutical preparation of the inventionmay be prepared using known methods. Such formulations may be administered directly to asubject, used, for example, to form tablets, to fill capsules, or to prepare an aqueous or oilysuspension or solution by addition of an aqueous or oily vehicle thereto. Each of theseformulations may further comprise one or more of dispersing or wetting agent, a suspendingagent, ionic and non-ionic surfactants, and a preservative. Additional excipients, such as fillersand sweetening, flavoring, or coloring agents, may also be included in these formulations.A pharmaceutical composition of the invention may also be prepared, packaged, or soldin the form of oil-in-water emulsion or a water-in-oil emulsion. The oily phase may be avegetable oil such as olive or arachis oil, a mineral oil such as liquid paraffin, or a combinationof these. Such compositions may further comprise one or more emulsifying agents such asnaturally occurring gums such as gum acacia or gum tragacanth, naturally-occurringphosphatides such as soybean or lecithin phosphatide, esters or partial esters derived fromcombinations of fatty acids and hexitol anhydrides such as sorbitan monooleate, andcondensation products of such partial esters with ethylene oxide such as polyoxyethylenesorbitan monooleate. These emulsions may also contain additional ingredients including, forexample, sweetening or flavoring agents.Methods for impregnating or coating a material with a chemical composition are knownin the art, and include, but are not limited to methods of depositing or binding a chemicalcomposition onto a surface, methods of incorporating a chemical composition into the structureof a material during the synthesis of the material (i.e., such as with a physiologically degradablematerial), and methods of absorbing an aqueous or oily solution or suspension into an absorbentmaterial, with or without subsequent drying. Methods for mixing components include physicalmilling, the use of pellets in solid and suspension formulations and mixing in a transdermalpatch, as known to those skilled in the art.52406514.1 - 87 -Attorney Docket No. 375836-7000WO1(00007)Administration / DosingIn clinical settings, delivery systems for the compositions described herein can beintroduced into a subject by any of a number of methods, each of which is familiar in the art. Forinstance, a pharmaceutical formulation of the composition can be administered by intravenousinjection.The regimen of administration may affect what constitutes an effective amount. Thetherapeutic formulations may be administered to the subject either prior to or after themanifestation of symptoms associated with the disease or condition (i.e., to prevent, treat, and / orameliorate infection in a subject, or symptoms thereof, and / or to prevent recurrence of infectionin a subject, or symptoms thereof).Administration of the composition of the present invention to a subject, preferably amammal, more preferably a human and / or laboratory mammal (e.g., rodent), may be carried outusing known procedures, at dosages and for periods of time effective to treat, prevent, and / orameliorate a disease or condition in the subject. An effective amount of the compositionnecessary to achieve a therapeutic effect may vary according to factors such as the time ofadministration; the duration of administration; other drugs, polypeptides, compounds or materialsused in combination with the composition; the state of the disease or disorder; age, sex, weight,condition, general health and prior medical history of the subject being treated; and like factorswell-known in the medical arts. Dosage regimens may be adjusted to provide the optimumtherapeutic response. For example, doses may be annually or semi-annually, or the dose may beproportionally reduced as indicated by the exigencies of the therapeutic situation. One ofordinary skill in the art would be able to study the relevant factors and make the determinationregarding the effective amount of the composition without undue experimentation. Formulationsmay be employed in admixtures with conventional excipients, i.e., pharmaceutically acceptableorganic or inorganic carrier substances suitable for oral, parenteral, nasal, intravenous,subcutaneous, enteral, or any other suitable mode of administration, known to the art. Thepharmaceutical preparations may be sterilized and if desired mixed with auxiliary agents, e.g.,lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmoticpressure buffers, coloring, flavoring and / or aromatic substances and the like. They may also becombined where desired with other active agents, e.g., other analgesic agents.52406514.1 - 88 -Attorney Docket No. 375836-7000WO1(00007)Routes of administration of any of the compositions of the invention include oral, nasal,rectal, intravaginal, parenteral, buccal, sublingual or topical. The polypeptides for use in theinvention may be formulated for administration by any suitable route, such as for oral orparenteral, for example, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal,(trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal and (trans)rectal),intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous,intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topicaladministration.In certain preferred embodiments, compositions of the present invention are administeredintramuscularly.Suitable compositions and dosage forms include, for example, tablets, capsules, caplets,pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, transdermalpatches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs,suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolizedformulations for inhalation, compositions and formulations for intravesical administration andthe like. It should be understood that the formulations and compositions that would be useful inthe present invention are not limited to the particular formulations and compositions that aredescribed herein.Oral AdministrationFor oral application, particularly suitable are tablets, dragees, liquids, drops,suppositories, or capsules, caplets and gelcaps. The compositions intended for oral use may beprepared according to any method known in the art and such compositions may contain one ormore agents selected from the group consisting of inert, non-toxic pharmaceutically excipientsthat are suitable for the manufacture of tablets. Such excipients include, for example an inertdiluent such as lactose; granulating and disintegrating agents such as cornstarch; binding agentssuch as starch; and lubricating agents such as magnesium stearate. The tablets may be uncoatedor they may be coated by known techniques for elegance or to delay the release of the activeingredients. Formulations for oral use may also be presented as hard gelatin capsules wherein theactive ingredient is mixed with an inert diluent.For oral administration, the polypeptides or compounds of the invention may be in the52406514.1 - 89 -Attorney Docket No. 375836-7000WO1(00007)form of tablets or capsules prepared by conventional means with pharmaceutically acceptableexcipients such as binding agents (e.g., polyvinylpyrrolidone, hydroxypropylcellulose orhydroxypropyl methylcellulose); fillers (e.g., cornstarch, lactose, microcrystalline cellulose orcalcium phosphate); lubricants (e.g., magnesium stearate, talc, or silica); disintegrates (e.g.,sodium starch glycollate); or wetting agents (e.g., sodium lauryl sulphate). If desired, the tabletsmay be coated using suitable methods and coating materials such as OPADRY™ film coatingsystems available from Colorcon, West Point, Pa. (e.g., OPADRY™ OY Type, OYC Type,Organic Enteric OY-P Type, Aqueous Enteric OY-A Type, OY-PM Type and OPADRY™White, 32K18400). Liquid preparation for oral administration may be in the form of solutions,syrups or suspensions. The liquid preparations may be prepared by conventional means withpharmaceutically acceptable additives such as suspending agents (e.g., sorbitol syrup, methylcellulose or hydrogenated edible fats); emulsifying agent (e.g., lecithin or acacia); non-aqueousvehicles (e.g., almond oil, oily esters or ethyl alcohol); and preservatives (e.g., methyl or propylp-hydroxy benzoates or sorbic acid).Parenteral AdministrationFor parenteral administration, the polypeptides or compounds of the invention may beformulated for injection or infusion, for example, intravenous, intramuscular or subcutaneousinjection or infusion, or for administration in a bolus dose and / or continuous infusion.Suspensions, solutions or emulsions in an oily or aqueous vehicle, optionally containing otherformulatory agents such as suspending, stabilizing and / or dispersing agents may be used.Controlled Release Formulations and Drug Delivery SystemsIn certain embodiments, the formulations of the present invention may be, but are notlimited to, short-term, rapid-offset, as well as controlled, for example, sustained release, delayedrelease and pulsatile release formulations.The term sustained release is used in its conventional sense to refer to a drug formulationthat provides for gradual release of a drug over an extended period of time, and that may,although not necessarily, result in substantially constant blood levels of a drug over an extendedtime period. The period of time may be as long as a month or more and should be a release that islonger that the same amount of agent administered in bolus form.52406514.1 - 90 -Attorney Docket No. 375836-7000WO1(00007)For sustained release, the polypeptides or compounds may be formulated with a suitablepolymer or hydrophobic material that provides sustained release properties to the polypeptides orcompounds. As such, the polypeptides or compounds for use the method of the invention may beadministered in the form of microparticles, for example, by injection or in the form of wafers ordiscs by implantation.In certain embodiments, the polypeptides or compounds of the invention are administeredto a patient, alone or in combination with another pharmaceutical agent, using a sustained releaseformulation.The term delayed release is used herein in its conventional sense to refer to a drugformulation that provides for an initial release of the drug after some delay following drugadministration, which may include a delay of from about 10 minutes up to about 12 hours.The term pulsatile release is used herein in its conventional sense to refer to a drugformulation that provides release of the drug in such a way as to produce pulsed plasma profilesof the drug after drug administration.The term immediate release is used in its conventional sense to refer to a drugformulation that provides for release of the drug immediately after drug administration.As used herein, short-term refers to any period of time up to and including about 8 hours,about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours, about 1hour, about 40 minutes, about 20 minutes, or about 10 minutes and any or all whole or partialincrements thereof after drug administration after drug administration.As used herein, rapid-offset refers to any period of time up to and including about 8hours, about 7 hours, about 6 hours, about 5 hours, about 4 hours, about 3 hours, about 2 hours,about 1 hour, about 40 minutes, about 20 minutes, or about 10 minutes, and any and all whole orpartial increments thereof after drug administration.DosingThe therapeutically effective amount or dose of a polypeptide, compound, and / orcomposition of the present invention depends on the age, sex and weight of the patient, thecurrent medical condition of the patient and the progression of a disease or disordercontemplated herein in the patient being treated. The skilled artisan is able to determineappropriate dosages depending on these and other factors.52406514.1 - 91 -Attorney Docket No. 375836-7000WO1(00007)A suitable dose of a polypeptide, compound and / or composition of the present inventionmay be in the range of from about 1 ng to about 1 mg per dosage, such as from about 100 ng toabout 1 mg, for example, from about 100 ng to about 500 ng per dosage. In certain embodiments,the suitable dose of a polypeptide, compound and / or composition of the present invention maybe in the range of from about 10 µg to about 100 µg. The dose may be administered in a singledosage or in multiple dosages, for example from 1 to 4 or more times. When multiple dosagesare used, the amount of each dosage may be the same or different.In certain embodiments, the composition may be administered to the subject as one tofour doses. In certain embodiments, the subject is administered a single dose. In certainembodiments, the subject is administered two doses. In certain embodiments, the subject isadministered three doses. In certain embodiments, the subject is administered four doses. Incertain embodiments, the subject is administered more than four doses.In certain embodiments, each dose is administered with an intervening period of about 1week. In certain embodiments, each dose is administered with an intervening period of about 1week or less. In certain embodiments, each dose is administered with an intervening period ofapproximately 1 week or more. In certain embodiments, each dose is administered with anintervening period of about 2 weeks. In certain embodiments, each dose is administered with anintervening period of about 2 weeks or less. In certain embodiments, each dose is administeredwith an intervening period of approximately 2 weeks or more. In certain embodiments, each doseis administered with an intervening period of about 3 weeks. In certain embodiments, each doseis administered with an intervening period of about 3 weeks or less. In certain embodiments,each dose is administered with an intervening period of approximately 3 weeks or more. Incertain embodiments, each dose is administered with an intervening period of about 4 weeks. Incertain embodiments, each dose is administered with an intervening period of about 4 weeks orless. In certain embodiments, each dose is administered with an intervening period ofapproximately 4 weeks or more.In certain embodiments, the subject is administered two doses, wherein each dose isadministered with an intervening period of about 2 weeks between doses. In certainembodiments, the subject is administered two doses, wherein each dose is administered with anintervening period of about 3 weeks between doses. In certain embodiments, the subject isadministered two doses, wherein each dose is administered with an intervening period of about 452406514.1 - 92 -Attorney Docket No. 375836-7000WO1(00007)weeks between doses. In certain embodiments, the subject is administered two doses, whereineach dose is administered with an intervening period of about 5 weeks between doses. In certainembodiments, the subject is administered two doses, wherein each dose is administered with anintervening period of about 6 weeks between doses. In certain embodiments, the subject isadministered two doses, wherein each dose is administered with an intervening period of about 7weeks between doses. In certain embodiments, the subject is administered two doses, whereineach dose is administered with an intervening period of about 8 weeks between doses.In certain embodiments, the subject is administered three doses, wherein each dose isadministered with an intervening period of about 2 weeks between doses. In certainembodiments, the subject is administered three doses, wherein each dose is administered with anintervening period of about 3 weeks between doses. In certain embodiments, the subject isadministered three doses, wherein each dose is administered with an intervening period of about4 weeks between doses. In certain embodiments, the subject is administered three doses, whereineach dose is administered with an intervening period of about 5 weeks between doses. In certainembodiments, the subject is administered three doses, wherein each dose is administered with anintervening period of about 6 weeks between doses. In certain embodiments, the subject isadministered three doses, wherein each dose is administered with an intervening period of about7 weeks between doses. In certain embodiments, the subject is administered three doses, whereineach dose is administered with an intervening period of about 8 weeks between doses.In certain embodiments, the subject is administered four doses, wherein each dose isadministered with an intervening period of about 2 weeks between doses. In certainembodiments, the subject is administered four doses, wherein each dose is administered with anintervening period of about 3 weeks between doses. In certain embodiments, the subject isadministered four doses, wherein each dose is administered with an intervening period of about 4weeks between doses. In certain embodiments, the subject is administered four doses, whereineach dose is administered with an intervening period of about 5 weeks between doses. In certainembodiments, the subject is administered four doses, wherein each dose is administered with anintervening period of about 6 weeks between doses. In certain embodiments, the subject isadministered four doses, wherein each dose is administered with an intervening period of about 7weeks between doses. In certain embodiments, the subject is administered four doses, whereineach dose is administered with an intervening period of about 8 weeks between doses.52406514.1 - 93 -Attorney Docket No. 375836-7000WO1(00007)In certain preferred, non-limiting embodiments, the subject is administered four doseswith an intervening period of about 2 weeks between doses (i.e., first dose on day 0, second doseon about day 14, third dose on about day 28, and fourth dose on about day 42).In certain preferred, non-limiting embodiments, the subject is administered two doseswith an intervening period of about 3 weeks between doses (i.e., first dose on day 0 and seconddose on about day 21). In certain preferred, non-limiting embodiments, the subject isadministered two doses with an intervening period of about 4 weeks between doses (i.e., firstdose on day 0 and second dose on about day 28). In certain preferred, non-limiting embodiments,the subject is administered two doses with an intervening period of about 8 weeks between doses(i.e., first dose on day 0 and second dose on about day 56).Actual dosage levels of the cells in the pharmaceutical formulations of this invention maybe varied so as to obtain an amount of the composition that are effective to achieve the desiredtherapeutic response for a particular subject, composition, and mode of administration, withoutbeing toxic to the subject.Toxicity and therapeutic efficacy of such therapeutic regimens are optionally determinedin cell cultures or experimental animals, including, but not limited to, the determination of theLD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effectivein 50% of the population). The dose ratio between the toxic and therapeutic effects is thetherapeutic index, which is expressed as the ratio between LD50 and ED50. The data obtainedfrom cell culture assays and animal studies are optionally used in formulating a range of dosagefor use in human. The dosage of such polypeptides, compounds and / or compositions liespreferably within a range of circulating concentrations that include the ED50 with minimaltoxicity. The dosage optionally varies within this range depending upon the dosage formemployed and the route of administration utilized.EXAMPLESVarious embodiments of the present application can be better understood by reference tothe following Examples which are offered by way of illustration. The scope of the presentapplication is not limited to the Examples given herein.Preparation of antigens52406514.1 - 94 -Attorney Docket No. 375836-7000WO1(00007)In certain embodiments, the polypeptides described herein were prepared utilizing one ormore bacterial expression vectors (e.g., E. coli), according to methods known to those skilled inthe art (Front. Microbiol. 2014, 5:172). In one aspect, the construction of such recombinationDNA molecules comprises the steps of: (a) producing a single-stranded DNA copy (cDNA) of apurified messenger RNA (mRNA) as a template for the desired protein; (b) converting the cDNAinto double-stranded DNA; (c) binding the DNA to a suitable point in a suitable clone carrier toform a recombination DNA molecule; and (d) transforming a suitable host with thisrecombination DNA molecule. Such a transformation allows the host to produce the desiredprotein.An expression vector has features that any vector may have, such as an origin ofreplication, a selectable marker, and a suitable site for the insertion of a gene like the multiplecloning site. The cloned gene may be transferred from a specialized cloning vector to anexpression vector, although it is possible to clone directly into an expression vector. The cloningprocess can be performed in E. coli. Vectors used for protein production in organisms other thanE. coli may have, in addition to a suitable origin of replication for its propagation in E. coli,elements that allow them to be maintained in another organism (i.e., shuttle vectors).HLA-DR4 miceHLA-DR4 allele is associated with the development of autoimmune diseases such asrheumatoid arthritis and multiple sclerosis. In an attempt to provide a mouse model for thesediseases, a hybrid MHC class II molecule between the peptide binding domains of human HLA-DRA and HLA-DRB*0401 and the membrane proximal domains of mouse I-E (H2-E) wasengineered and co-injected into C57BL / 6 fertilized eggs. The transgenic offspring were bred to amouse incapable of expressing other MHC class II molecules (Abb knockout on B6background). By preserving the alpha 2 and beta 2 domains of mouse MHC class II, interactionswith CD4 co-receptors on T cells were preserved. This mouse is healthy and breeds normally.Immunization with a peptide from a proteolipid protein known to bind to HLA-DR4, provoked astrong T cell proliferative response, caused inflammatory lesions in CNS white matter, andsymptoms of experimental allergic encephalomyelitis (Ito K, et al. J. Exp. Med. 1996,183(6):2635-2644).52406514.1 - 95 -Attorney Docket No. 375836-7000WO1(00007)Immunization of HLA-DR4 miceHLA-DR4 transgenic mice, each of an age within one week of all other mice within thestudy, were used in the experiments described herein. HLA-DR4 mice were divided intotreatment groups and control groups (e.g., naïve and / or placebo). Mice were immunized twicevia the route of administration indicated elsewhere herein (e.g., subcutaneously orintramuscularly) on the specified days with vaccine compositions having a total volume of 50 µLor 100 µL, wherein the vaccine compositions comprise 100 µg of antigen (e.g., SEQ ID NO:127,SEQ ID NO:128, SEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135) and an adjuvant (e.g.,AlOH, dmLT, CpG, and / or AddaS03™), and diluted to the total volume with a phosphatebuffered saline (PBS) solution. In certain embodiments, HLA-DR4 mice were immunized asdescribed in Tables 1-7 (i.e., Experiment Nos. 1-7). Sera and urine samples were obtained fromthe mice at specified timepoints, as described elsewhere herein.Table 1. Immunization of HLA-DR4 micea (Exp. No. 1)Group Antigen Adjuvant1 -b -bddeem Table 2. Immunization of HLA-DR4 micea (Exp. No. 2)Group Antigen AdjuvantA -b 0.4% AlOHc + 10 µg CpGdB SEQ ID NO:127 04% AlOHc + 10 µg CpGdddd Attorney Docket No.375836-7000WO1(00007)F SEQ ID NO:135 0.4% AlOHc + 10 µg CpGd su cuaneousyb, an mce age - mcon s a rs vaccna odn (approxmaey wee s eweenvaccinations); placebo control group; aluminum hydroxide; CpG ODN 2395.Table 3. Immunization of HLA-DR4 micea (Exp. No.3)Group Antigen Adjuvant envaccinations); bCpG ODN 2395.Table 4. Immunization of HLA-DR4 micea (Exp. No.4)Group Antigen AdjuvantA -b 50% AddaS03™ + 10 µg CpGc100 Table 5. Immunization of HLA-DR4 micea (Exp. No.5)Group Antigen AdjuvantA -b 0.4% AlOHc + 10 µg CpGdB SEQ ID NO:136 04% AlOHc + 10 C Gdd Attorney Docket No. 375836-7000WO1(00007)intramuscularlyb, and mice aged 9 -10 wceeks at first vaccinatiodn (approximately 3 weeks betweenvaccinations); placebo control group; aluminum hydroxide; CpG ODN 2395.Table 6. Immunization of HLA-DR4 micea (Exp. No. 6)Group Antigen Adjuvant nvaccinations); placebo control group; CpG ODN 2395.Table 7. Immunization of HLA-DR4 micea (Exp. No. 7)Group Antigen AdjuvantA -b 50% AddaS03™ + 10 µg CpGct, (20 mM Na2PO4, 300 mM urea, 300 mM NaCl, pH 9.5); fbuffer conditions (20 mM Na2PO, 300mM NaCl, pH 9.5).CD1 miceCD1 IGS (i.e., Crl:CD1(ICR)) is an albino outbred strain of mouse model frequently usedin toxicology and pharmacological research. A notable feature of CD1 IGS mice is their largegenetic diversity, which is similar to that found within and between human populations. CD152406514.1 - 98 -Attorney Docket No. 375836-7000WO1(00007)mice were immunized in a manner analogous to that which is described for HLA-DR4 mice. Adetailed description of experiments performed utilizing CD1 mice is provided herein (Table 8).Table 8. Immunization of CD1 micea (Exp. No. 8)Group Antigen Adjuvantice cn=4 mice; dplacebo control group; ealuminum hydroxide.C57BL / 6 miceC57BL / 6 mice are the most used inbred strain in research and are commonly used asmodels of human disease. C57BL / 6 mice were immunized in a manner analogous to that whichis described for HLA-DR4 mice. A detailed description of experiments performed utilizingC57BL / 6 mice is provided herein (Tables 9-11).Table 9. Immunization of C57BL / 6a (Exp. No. 9)Group Antigen AdjuvantA -b 50% AddaS03™ + 10 µg CpGcGccccn Table 10. Immunization of C57BL / 6 micea (Exp. No. 10)Group Antigen AdjuvantA -b 50% AddaS03™ + 10 µg CpGc Attorney Docket No. 375836-7000WO1(00007)B SEQ ID NO:225 50% AddaS03™ + 10 µg CpGc , nvaccinations)b, immunological samples harvested at approximately 14ebo control group; c days post secondvaccination; plac CpG ODN 2395; daluminum hydroxide.Table 11. Immunization of C57BL / 6 micea (Exp. No. 11)Group Antigen AdjuvantA SE ID NO 225 -cc vaccination; placebo control group; cCpG ODN 2395; aluminum hydroxide.C3H / HeN miceC3H / HeN mice are homozygous for the Pde6brd1 allele and have an early onset severeretinal degeneration that causes blindness at weaning age. Despite an atherogenic diet, C3H / HeNmice do not develop aortic atherosclerosis, in contrast to the C57BL / 6J. There is a geneticallymediated difference between the C3H / HeN and the C3H / HeJ regarding their response tobacterial endotoxin (LPS). This response is linked to the TL4 protein (Toll-like receptor 4).C3H / HeN are Tlr4lps-n (toll-like receptor 4; normal LPS response). This strain has a normalresponse to an LPS challenge and is endotoxin-sensitive. Per contra, the C3H / HeJ strain isTlr4lps-d, and said to be endotoxin-resistant. C3H / HeN mice were immunized in a manneranalogous to that which is described for HLA-DR4 mice. A detailed description of experiments52406514.1 - 100 -Attorney Docket No. 375836-7000WO1(00007)performed utilizing C3H / HeN mice is provided herein (Table 12).Table 12. Immunization of C3H / HeN micea (Exp. No. 12)Group Antigen Adjuvantcc vaccinations), immunological samples harvested at approximately 14 days post secondvaccination; bplacebo control group; cCpG ODN 2395; daluminum hydroxide.Cytometric Bead Array (CBA)Cytometric Bead Array (CBA) assay (BD Biosciences) provides a method of capturing asoluble analyte or set of analytes with beads of known size and fluorescence, enabling detectionof analytes using flow cytometry. Each capture bead in the CBA kit has a distinct fluorescenceand is coated with an antibody specific for a soluble protein. The detection reagent is a mixtureof phycoerythrin (PE)-conjugated antibodies, which provides a fluorescent signal in proportionto the amount of bound analyte.When capture beads and detection reagent are incubated with standards or unknownsamples containing recognized analytes, sandwich complexes are formed (e.g., capture bead +analyte + detection reagent). These complexes are measured using flow cytometry to identifyparticles with fluorescence characteristics of both the bead and the detector, enablingidentification of analyte.The immunological response to the compositions described herein was determined bymeasuring cytokine levels (e.g., IL-6, IL-17A, IL-2, TNF-α, IFN-γ, IL-4, and / or IL-10) by CBA.Enzyme-Linked Immunoassay (ELISA)The immunological response to the compositions described herein was determined bymeasuring sample optical density and / or antibody, antigen, protein, and / or glycoprotein titers(e.g., IgG1, IgG2b, IgA, and / or GTxMS IgG) by standard ELISA and / or peptide-based ELISA.52406514.1 - 101 -Attorney Docket No. 375836-7000WO1(00007)Experimental protocols for standard ELISA and / or peptide ELISA are known to those skilled inthe art. The following example is offered by way of illustration. It is understood that the scope ofthe present application is not limited to the example provided herein.In brief, 100 µL of polypeptide at 2 pg / mL, solubilized in 5 M urea, was added to eachwell of a 96-well EIA / RIA plate (Coming / Costar 3590) and incubated overnight at 4 °C. Allremaining steps were performed at room temperature. The plate was washed three times withPBS wash buffer (PBS containing 0.05% Tween 20) followed by the addition of 200 µL / wellsample buffer consisting of PBS containing 0.05% Tween 20 and 1% bovine serum albumin.After 90 minutes, the sample buffer was replaced with 100 µL / well PBS sample buffer. Serial1:3 dilutions of the primary antisera were performed in the plate by the addition of 50 µL to thefirst row, mixing 10 times, and transfer of 50 µL to the next row. The plate was incubated for 90minutes followed by three washes and addition of 100 µL / well of the antibody, antigen, protein,and / or glycoprotein response to be measured. After a 90 minute incubation period the plate waswashed four times followed by the addition of 100 pl TMB (BioFx; Surmodics, Eden Prairie,MN) / well.Color was allowed to develop for 30 minutes, and the reaction was stopped by theaddition of 100 pl stop reagent (BioFx). The absorbance was measured at a wavelength of 450nm, and the titer was calculated as the inverse of the dilution corresponding to an absorbance of1.0. Controls included a standardized primary serum included on each plate to monitor assayvariability and wells that were uncoated to subtract background. The limit of detection for theassay was the inverse of the initial serum dilution.Evaluation of secreted cytokines by MILLIPLEX® multiplex immunoassayThe MILLIPLEX® multiplex immunoassay (Millipore Sigma), based on the Luminex®xMAP® bead-based multiplex assay platform, provides a method of capturing a soluble analyteor set of analytes with magnetic microspheres of known size and fluorescence, enablingdetection of analytes using a Luminex® Detection System. Briefly, each magnetic MagPlex®microsphere bead is fluorescently coded with one of 500 specific ratios of two fluorophores andis coated with analyte-specific capture antibodies. These microspheres are incubated withsample, washed, and are then incubated with a detection reagent comprised of a mixture of abiotinylated analyte-specific detection antibody and a R-Phycoerythrin-conjugated streptavidin52406514.1 - 102 -Attorney Docket No. 375836-7000WO1(00007)reagent which provides a fluorescent signal in proportion to the amount of bound analyte. Whencapture microspheres and detection reagent are incubated with standards or unknown samplescontaining recognized analytes, sandwich complexes are formed (e.g., capture microsphere +analyte + detection reagent). These complexes are measured using a Luminex MAGPIX®detection system to identify particles with fluorescence characteristics of both the bead and thedetector, enabling identification of analyte.The immunological response to the compositions described herein was determined bymeasuring cytokine levels (e.g., IL-6, IL-17A, IL-2, TNF-α, IFN-γ, IL-4, IL-22, and / or IL-10) byMILLIPLEX® multiplex immunoassay.For the assays described herein, splenic lymphocytes (1 x 106 cells in 0.2 mL) andbladder lymphocytes (2 x 105 cells in 0.2 mL) were cultured with 12.5 pg of antigen at 37°C for48 hours. At the end of the culture period, culture plates were briefly centrifuged to pellet thecells after which the culture supernatants were removed. Samples were acquired on a LuminexMAGPIX® analyzer using Luminex® acquisition software, and data were analyzed by Belysa®Immunoassay Curve Fitting software.Splenocyte StudiesMice used for T cell studies were euthanized, and their spleens were removed andprocessed to lyse red blood cells. Splenic lymphocytes (1 x 106 cells in 0.2 mL RPMI-1640containing 10% fetal bovine serum) were cultured with 12.5 pg of antigen for 48 hours, and therelease of cytokines into cell supernatants was measured according to the manufacturer’sprotocol (BD Cytometric Bead Array (CBA), BD Biosciences, San Jose, CA).Dissociation of bladder and spleen tissueBladders were dissected, pooled by group (3-5 bladders per group), cut into small pieces,and digested using the Multi Tissue Dissociation Kit 1 (Miltenyi) per the manufacturer’sprotocol at 37 °C for 1 hour with robust manual agitation every 15 min. Digestion was stoppedby adding an equal volume of RPMI-1640 containing 10% fetal bovine serum. Remaining tissuewas disrupted using the plunger from a 3cc syringe and was passed through 70 µm filters(Greiner Bio-One). Cells obtained from pooled bladders preparations were resuspended at a finalconcentration of 2 x 106 cells / mL of RPMI-1640 containing 10% fetal bovine serum.52406514.1 - 103 -Attorney Docket No. 375836-7000WO1(00007)Individual spleens were dissected, disrupted using the plunger from a 3cc syringe andwere passed through 70 µm filters before being processed to remove red blood cells and beingresuspended in RPMI-1640 containing 10% fetal bovine serum. Cells obtained from individualspleen preparations were resuspended at a final concentration of 1 x 107 cells / mL of RPMI-1640 containing 10% fetal bovine serum.Evaluation of activation induced markers (AIM) on restimulated lymphocytes by flow cytometryActivation induced marker (AIM) proteins are a group of proteins that become expressedon immune cells when those immune cells have contacted and / or bound their cognate antigenand have become activated. AIM proteins are not expressed, or are expressed only at low levels,on resting, inactivated immune cells. In the experiments described herein, the combination ofCD49d and CD11a was used to identify effector / memory CD4+ and CD8+ T cells induced byvaccination. The combination of CD49d and CD80 was used to identify effector / memory B cellsinduced by vaccination. The combination of the AIM proteins OX40 and PD-L1 wassubsequently used to identify CD4+ T cells activated in vitro by protein antigen; the combinationof the AIM proteins CD69 and PD-L1 was subsequently used to identify CD8+ T cells activatedin vitro by protein antigen; combination of the AIM proteins CD69 and PD-L1 or CD69 andCD86 was subsequently used to identify B cells activated in vitro by protein antigen.Splenic lymphocytes (1 x 106 cells in 0.2 mL) and bladder lymphocytes (2 x 105 cells in0.2 mL) were cultured with 12.5 pg of antigen at 37°C for 24 - 48 hours. At the end of theculture period, cells were washed in PBS and resuspended in an amine-reactive Live / Dead dyesolution to exclude dead cells and with anti-mouse CD16 / CD32 antibodies to block Fc receptors.Cells were incubated at 4°C for 25 to 30 min protected from light. Cells were then washed inFACS buffer (PBS supplemented with 2% fetal bovine serum and 0.095% Sodium Azide) andstained with combinations of fluorescent antibodies to identify T cells (CD3, CD4, CD8), B cells(CD19, HLA-DR) and to determine the expression of activation induced marker (AIM) proteins(CD11a, CD25, CD49d, OX40, PD-L1, CD69 CD80 and CD86) on these cells followingrestimulation with protein antigen. Antibodies were purchased from BD, BioLegend, andThermoFisher and optimal staining concentrations were determined empirically based on themanufacturers recommended concentrations. Cells were stained with fluorescent antibodies for25 to 30 min at 4°C. Samples were acquired on an Agilent NovoCyte Quanteon Flow Cytometer52406514.1 - 104 -Attorney Docket No. 375836-7000WO1(00007)using NovoExpress software, and data were analyzed by FlowJo (Treestar) software. Expressionof AIM proteins was evaluated on live, single cells.Example 1: Immunized mice demonstrate an innate immune responseExp. No. 1HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 1. Serum samples were obtained from mice 24 h after the second vaccinationand analyzed for serum IL-6 concentration. Comparable levels of IL-6 were observed across alltreatment groups (i.e., groups 2-5 of Table 1), whereas serum IL-6 levels of naïve mice werebelow the lower limit of quantification (FIG. 1). Thus, the data indicates that immunizationelicits an innate immune response.Example 2: Immunized mice demonstrate an adaptive immune response (B cell mediatedantibody production)Exp. No. 1HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 1.Serum samples were obtained from mice of groups 1-2 and 4 (i.e., SEQ ID NO:127 witheither AlOH + dmLT or AlOH + CpG adjuvants) approximately 14 days after the secondvaccination (i.e., approximately day 35) and analyzed by ELISA for serum IgG1 (FIG. 2A),serum IgG2b (FIG. 2B), serum IgA (FIG. 2C), and urine IgG(H) (FIG. 2D). The results indicatethat SEQ ID NO:127 immunization induces both IgG1 and IgG2b production in HLA-DR4 mice.Serum samples were obtained from mice from of groups 1, 3, and 5 (i.e., SEQ IDNO:128 with either AlOH + dmLT or AlOH + CpG adjuvants) approximately 14 days after thesecond vaccination (i.e., day 35) and analyzed by ELISA for serum IgG1 (FIG. 3A) and serumIgG2b (FIG. 3B). The results indicate that SEQ ID NO:128 immunization induces both IgG1 andIgG2b production in HLA-DR4 mice.Serum and urine samples were obtained from mice from of groups 1, 3, and 5 (i.e., SEQID NO:128 with either AlOH + dmLT or AlOH + CpG adjuvants) approximately 14 days afterthe second vaccination (i.e., day 35) and analyzed by ELISA for serum IgA (FIG. 4A), urine IgA(FIG. 4B), and urine IgG(H) (FIG. 4C). The results indicate that SEQ ID NO:128 immunization52406514.1 - 105 -Attorney Docket No. 375836-7000WO1(00007)induces IgA and IgG(H) production in HLA-DR4 mice, as evidenced by urine and / or serumsamples.Serum samples were obtained from mice from groups 1, 2, and 4 (i.e., SEQ ID NO:127with either AlOH +dmLT or AlOH + CpG adjuvants) approximately 14 days after the secondvaccination (i.e., day 35) and analyzed by peptide ELISA, wherein wells were coated withcertain polypeptides and / or antigen fragments (e.g., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182, 188-192, 200-202, 206-207, 213-215, and 218-219); antigens (e.g., SEQ IDNO:127 and SEQ ID NO:128), and controls (i.e., tetanus toxin, serum albumin only and no coat).Antibody production was not substantially observed in unvaccinated subjects (i.e., signal belowor minimally over serum albumin only control in Group 1), whereas significant peptide specificantibody production was observed for many of the antigens, or antigen fragments thereof,evaluated in this study (FIG. 5).Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of several antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp No. 2HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 2.Serum samples were obtained from mice from each of groups A and D-F approximately14 days after the second vaccination (i.e., day 28) and analyzed by ELISA for serum IgG1 (FIG.9A, FIG. 10A, FIG. 11A) and serum IgG2b (FIG. 9B, FIG. 10B, and FIG. 11B). The resultsindicate that immunization with each of SEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135induces both IgG1 and IgG2b production in HLA-DR4 mice.Serum samples were obtained from mice from groups A (i.e., placebo) and D (i.e., SEQID NO:132) approximately 14 days after the second vaccination (i.e., day 28) and analyzed bypeptide ELISA, wherein wells were coated with certain polypeptides and / or antigen fragments(e.g., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182, 188-192, 200-202, 206-207, 213-215, and 218-219), antigens (i.e., SEQ ID NO:132, SEQ ID NO:133, and SEQ ID NO:135), andcontrols (i.e., tetanus toxin, serum albumin only and no coat). Antibody production was not52406514.1 - 106 -Attorney Docket No. 375836-7000WO1(00007)substantially observed in subjects administered placebo (i.e., signal below or minimally overserum albumin only control in Group A), whereas significant peptide specific antibodyproduction was observed for many of the antigens, or antigen fragments thereof, evaluated in thisstudy (FIG. 12).Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of several antibodies, non-limiting examples including IgG1 and IgG2b.Exp. No. 3HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 3.Serum samples were obtained from mice from the treatment group (i.e., group A) on days0 (i.e., day of first vaccination; sample taken before vaccination), 21 (i.e., day of secondvaccination), 28, and 41 (i.e., approximately 20 days after second vaccination) and analyzed byELISA for serum IgG1 (FIG. 16A) and IgG2b (FIG. 16B). The results indicate thatimmunization with SEQ ID NO:132 induces both IgG1 and IgG2b production in HLA-DR4mice.Serum and urine samples were obtained from mice from the treatment group (i.e., groupA) on day 0 (i.e., day of first vaccination; sample taken before vaccination), and approximatelyeach of days 21 (i.e., day of second vaccination), 28, and 41 (i.e., 20 days after secondvaccination) and analyzed by ELISA for serum IgA (FIG. 17A), urine IgA (FIG. 17B), and urineIgG(H) (FIG. 17C). The results indicate that SEQ ID NO:132 immunization induces IgA andIgG(H) production in HLA-DR4 mice, as evidenced by urine and / or serum samples.Serum samples were obtained from mice from the treatment group (i.e., group A)approximately on days 21 and 41 analyzed by peptide ELISA, wherein wells were coated withcertain polypeptides and / or antigen fragments (e.g., SEQ ID NOs: 17, 20, 24, 40, 197-199, 163-168, 176-182, 188-192, 200-202, 206-207, 213-215, and 218-219), antigens (i.e., SEQ IDNO:132), and controls (i.e., tetanus toxin, serum albumin only and no coat). Generally, antibodyproduction was greater on approximately day 41 than on approximately day 21 (FIG. 18).Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated by52406514.1 - 107 -Attorney Docket No. 375836-7000WO1(00007)elevated levels of several antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 4HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 4.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B-F) and a control group (i.e., Group A) at several time points after initial vaccinationand analyzed by ELISA for serum IgG1, serum IgG2b, serum IgA, urine IgA, and urine IgG(H)in wells coated with SEQ ID NO:136 (FIGs. 28A-28E), SEQ ID NO:137 (FIGs. 29A-29E), SEQID NO:138 (FIGs. 30A-30E), SEQ ID NO:139 (FIGs. 31A-31E), and SEQ ID NO:140 (FIGs.32A-32E).In certain embodiments, the results indicate that all evaluated immunizations induceIgG1, IgG2b, and IgA production in HLA-DR4 mice sera approximately 5 weeks after initialvaccination, as compared to the control. In certain embodiments, the results indicate that mostevaluated immunizations induce IgG1, IgG2b, and IgA production in HLA-DR4 mice seraapproximately 2 weeks after second vaccination, as compared to the control. In certainembodiments, the results indicate that most evaluated immunizations induce IgG1, IgG2b, andIgA production in HLA-DR4 mice sera approximately 2 weeks after initial vaccination, ascompared to the control.In certain embodiments, the results indicate that all evaluated immunizations induce IgAand IgG(H) production in the urine of HLA-DR4 mice approximately 5 weeks after initialvaccination, as compared to the control.Serum samples were obtained from mice from the control group (i.e., Group A) and eachof the treatment groups B (FIG. 33A), D (FIG. 33B), and F (FIG. 33C) on day 36 after firstvaccination (approximately 2 weeks after second vaccination) and analyzed by peptide ELISA,wherein wells were coated with certain polypeptides and / or antigen fragments (e.g., SEQ IDNOs: 17, 20, 25, 27, 195, 197-199, 163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203,and 136-140) and controls (i.e., tetanus toxin, serum albumin only and no coat). The data depictantibody production in wells containing each antigen utilized in Groups B-F and certainexemplary antigenic fragments.52406514.1 - 108 -Attorney Docket No. 375836-7000WO1(00007)Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 5HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 5.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B-C and E-F) and a control group (i.e., Groups A and D) 33 days after initial vaccination(approximately 2 weeks after second vaccination) and analyzed by ELISA for serum IgG1,serum IgG2b, serum IgA, urine IgA, and urine IgG(H) in wells coated with SEQ ID NO:136(FIG. 36A-36E) or SEQ ID NO:138 (FIG. 37A-37E).In certain embodiments, the results indicate that all evaluated immunizations induceIgG1, IgG2b, and IgA production in HLA-DR4 mice sera 33 days after initial vaccination(approximately 2 weeks after second vaccination), as compared to the control. In certainembodiments, the results indicate that most evaluated immunizations induce IgA and IgG(H)production in the urine of HLA-DR4 mice 33 days after initial vaccination (approximately 2weeks after second vaccination), as compared to the control.Serum samples were obtained from mice from the treatment groups B and D (FIG. 38A)and treatment groups E and F (FIG. 38B) on day 33 after first vaccination (approximately 2weeks after second vaccination) and analyzed by peptide ELISA, wherein wells were coated withcertain polypeptides and / or antigen fragments (e.g., SEQ ID NOs: 16-17, 20, 25, 27, 195, 197-199, 163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203, 136 and 138) and controls(i.e., tetanus toxin, serum albumin only and no coat). The data depict antibody production inwells containing each antigen utilized in exemplary vaccine antigens and / or fragments thereof.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).52406514.1 - 109 -Attorney Docket No. 375836-7000WO1(00007)Exp. No. 6HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 6.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B-F) and a control group (i.e., Group A) 34 days after initial vaccination (approximately2 weeks after second vaccination) and analyzed by ELISA for serum IgG1, serum IgG2b, serumIgA, urine IgA, and urine IgG(H) (FIG. 41A-41E).In certain embodiments, the results indicate that the evaluated immunizations induceIgG1, IgG2b, and IgA production in HLA-DR4 mice sera 34 days after initial vaccination(approximately 2 weeks after second vaccination), as compared to the control. In certainembodiments, the results indicate that the evaluated immunizations induce IgA and IgG(H)production in the urine of HLA-DR4 mice 34 days after initial vaccination (approximately 2weeks after second vaccination), as compared to the control.Serum samples were obtained from mice from the control (Group A) and each oftreatment groups B (FIG. 42A), C (FIG. 42B), D (FIG. 42C), and E (FIG. 42D) on day 34 afterfirst vaccination (approximately 2 weeks after second vaccination) and analyzed by peptideELISA, wherein wells were coated with certain polypeptides and / or antigen fragments (e.g., SEQID Nos: 16-17, 20, 25, 27, 195, 197-199, 163-168, 176-182, 188-192, 207, 213-215, 218-219,200-203, and 141-145) and controls (i.e., tetanus toxin, serum albumin only and no coat). Thedata depict antibody production in wells containing each antigen utilized in exemplary vaccineantigens and / or fragments thereof.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 7HLA-DR4 mice were immunized as described herein using the vaccine compositionsindicated in Table 7.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B-C, E, and G) and each control group (i.e., Groups A, D, and F) 35 days after initial52406514.1 - 110 -Attorney Docket No. 375836-7000WO1(00007)vaccination (approximately 2 weeks after second vaccination) and analyzed by ELISA for serumIgG1, serum IgG2b, serum IgA, urine IgA, and urine IgG(H) in wells coated with SEQ IDNO:138 (1) or (2), wherein (1) and (2) vary with respect to buffer conditions, as described inTable 7 (FIGs. 45A-45E).In certain embodiments, the results indicate that certain evaluated immunizations induceIgG1, IgG2b, and IgA production in HLA-DR4 mice sera 35 days after initial vaccination(approximately 2 weeks after second vaccination), as compared to the control. In certainembodiments, the results indicate that certain evaluated immunizations induce IgA and IgG(H)production in the urine of HLA-DR4 mice 35 days after initial vaccination (approximately 2weeks after second vaccination).Serum samples were obtained from mice from the control (Group A) and each oftreatment groups B-C (FIG. 46) on day 35 after first vaccination (approximately 2 weeks aftersecond vaccination) and analyzed by peptide ELISA, wherein wells were coated with certainpolypeptides and / or antigen fragments (e.g., SEQ ID NOs: 16-17, 20, 25, 27, 195, 197-199, 163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203, 138(1), and 138(2), wherein (1) and (2)vary with respect to buffer conditions, as described in Table 7) and controls (i.e., tetanus toxin,serum albumin only and no coat). The data depict antibody production in wells containing eachantigen utilized in exemplary vaccine antigens and / or fragments thereof.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 8CD1 mice were immunized as described herein using the vaccine compositions indicatedin Table 8.Serum samples were obtained from mice from each of groups A-C approximately 14days after the second vaccination (i.e., approximately day 28) and analyzed by ELISA for serumIgG1 (FIG. 19A and FIG. 21A) and serum IgG2b (FIG. 19B and FIG. 21B). The results indicatethat immunization with each of SEQ ID NO:132 and SEQ ID NO:135 induces both IgG1 andIgG2b production in CB1 mice.52406514.1 - 111 -Attorney Docket No. 375836-7000WO1(00007)Serum samples were obtained from mice from each of groups A-C approximately 14days after the second vaccination (i.e., approximately day 28) and analyzed by ELISA for serumIgA (FIG. 20A and FIG. 22A), urine IgA (FIG. 20B and FIG. 22B), and urine IgG(H) (FIG. 20Cand FIG. 22C). The results indicate that SEQ ID NO:132 immunization induces IgA and IgG(H)production in CB1 mice, as evidenced by urine and / or serum samples.Serum samples were obtained from mice from groups A (i.e., placebo) and B (i.e., SEQID NO:132) on day 28 (i.e., approximately 14 days after the second vaccination) and analyzed bypeptide ELISA, wherein wells were coated with certain polypeptides and / or antigen fragments(e.g., SEQ ID NOs:17-20, 23-25, 27, 32, 35, 37, 39-40), antigens (i.e., SEQ ID NO:132 and SEQID NO:135), and controls (i.e., tetanus toxin, serum albumin only and no coat). Antibodyproduction was not substantially observed in subjects administered placebo (i.e., signal below orminimally over serum albumin only control in Group A), whereas significant peptide specificantibody production was observed for many of the antigens, or antigen fragments thereof,evaluated in this study (FIG. 23).Serum samples were obtained from mice from groups A (i.e., placebo) and C (i.e., SEQID NO:135) on day 28 (i.e., approximately 14 days after the second vaccination) and analyzed bypeptide ELISA, wherein wells were coated with certain polypeptides and / or antigen fragments(e.g., SEQ ID NOs:17-20, 23-25, 27, 32, 35, 37, 39-40), antigens (i.e., SEQ ID NO:132 and SEQID NO:135), and controls (i.e., tetanus toxin, serum albumin only and no coat). Antibodyproduction was not substantially observed in subjects administered placebo (i.e., signal below orminimally over serum albumin only control in Group A), whereas significant peptide specificantibody production was observed for many of the antigens, or antigen fragments thereof,evaluated in this study (FIG. 24).Exp. No. 9C57BL / 6 mice were immunized as described herein using the vaccine compositionsindicated in Table 9.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B-E) and the control group (i.e., Groups A) 34 days after initial vaccination(approximately 2 weeks after second vaccination) and analyzed by ELISA for serum IgG1,serum IgG2b, serum IgA, urine IgA, and urine IgG(H) (FIGs. 51A-51E).52406514.1 - 112 -Attorney Docket No. 375836-7000WO1(00007)In certain embodiments, the results indicate that certain evaluated immunizations induceIgG1, IgG2b, and IgA production in C57BL / 6 mice sera 34 days after initial vaccination(approximately 2 weeks after second vaccination), as compared to the control. In certainembodiments, the results indicate that certain evaluated immunizations induce IgA and IgG(H)production in the urine of HLA-DR4 mice 34 days after initial vaccination (approximately 2weeks after second vaccination).Serum samples were obtained from mice from the control (Group A) and each oftreatment groups B and D (FIG. 52A) and treatment groups C and E (FIG. 52B) on day 34 afterfirst vaccination (approximately 2 weeks after second vaccination) and analyzed by peptideELISA, wherein wells were coated with certain polypeptides and / or antigen fragments (e.g., SEQID NOs: 17, 20, 25, 27, 195, 197-199, 163-168, 176-182, 188-192, 207, 213-215, 218-219, 200-203, and 136-139) and controls (i.e., tetanus toxin, serum albumin only and no coat). The datadepict antibody production in wells containing each antigen utilized in exemplary vaccineantigens and / or fragments thereof.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 10C57BL / 6 mice were immunized as described herein using the vaccine compositionsindicated in Table 10.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B and D) and the control group (i.e., Groups A and C) 33 days after initial vaccination(approximately 12 days after second vaccination) and analyzed by ELISA for serum IgG1, serumIgG2b, serum IgA, urine IgA, and urine IgG(H) (FIGs. 59A-59E).In certain embodiments, the results indicate that certain evaluated immunizations induceIgG1, IgG2b, and IgA production in C57BL / 6 mice sera 33 days after initial vaccination(approximately 12 days after second vaccination), as compared to the control. In certainembodiments, the results indicate that certain evaluated immunizations induce IgA and IgG(H)production in the urine of HLA-DR4 mice 33 days after initial vaccination (approximately 252406514.1 - 113 -Attorney Docket No. 375836-7000WO1(00007)weeks after second vaccination).Serum samples were obtained from mice from the control Group A and treatment GroupB (FIG. 60A), and control Group C and treatment Group D (FIG. 60B) on day 33 after firstvaccination (approximately 12 days after second vaccination) and analyzed by peptide ELISA,wherein wells were coated with certain polypeptides and / or antigen fragments (e.g., SEQ IDNOs: 17, 20, 25, 27, 40, 163-168, 176-182, 188-192, 195, 197-202, 207, 213-215, 218-219, and225) and controls (i.e., tetanus toxin, serum albumin only and no coat). The data depict antibodyproduction in wells containing each antigen utilized in exemplary vaccine antigens and / orfragments thereof.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 11C57BL / 6 mice were immunized as described herein using the vaccine compositionsindicated in Table 11.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups A, C, E, G, and I) and control / placebo groups (i.e., Groups B, D, F, and H) 12 days aftersecond vaccination (i.e., 33 days post first vaccination) and analyzed by ELISA for serum IgG1,serum IgG2b, serum IgA, urine IgA, and urine IgG(H) (FIGs. 62A-62E).In certain embodiments, the results indicate that the evaluated immunizations induceIgG1, IgG2b, and IgA production in C57BL / 6 mice sera 12 days after second vaccination, ascompared to the control. In certain embodiments, the results indicate that the evaluatedimmunizations induce IgA and IgG(H) production in the urine of C57BL / 6 mice 12 days afterinitial vaccination, as compared to the control. In certain embodiments, the results indicate theuse of an adjuvant, when administering the antigen parenterally (e.g., intramuscularly), is criticalfor stimulating IgG1, IgG2b, IgA, and / or IgG(H) production (cf. Group A and any of groups C,E, G, and I).Serum samples were obtained from C57BL / 6 mice from each treatment group (i.e.,Groups A, C, E, G, and I) and control / placebo groups (i.e., Groups B, D, F, and H) 12 days after52406514.1 - 114 -Attorney Docket No. 375836-7000WO1(00007)second vaccination (i.e., 33 days post first vaccination) and analyzed by peptide ELISA, whereinwells were coated with certain polypeptides and / or antigen fragments (i.e., SEQ ID NOs: 17, 20,25, 27, 40, 163-168, 176-182, 188-192, 195, 197-202, 207, 213-215, 218-219, and 225) andcontrols (i.e., tetanus toxin, serum albumin only, and no coat). The data depict antibodyproduction in wells containing each antigen and / or fragments thereof utilized in exemplaryvaccine compositions of the disclosure.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2b, IgA, andIgG(H).Exp. No. 12C3H / HeN mice were immunized as described herein using the vaccine compositionsindicated in Table 12.Serum and urine samples were obtained from mice from each treatment group (i.e.,Groups B and D) and the control group (i.e., Groups A and C) 33 days after initial vaccination(approximately 12 days after second vaccination) and analyzed by ELISA for serum IgG1, serumIgG2a, serum IgA, urine IgA, and urine IgG(H) (FIGs. 56A-56E).In certain embodiments, the results indicate that certain evaluated immunizations induceIgG1, IgG2a, and IgA production in C3H / HeN mice sera 33 days after initial vaccination(approximately 12 days after second vaccination), as compared to the control. In certainembodiments, the results indicate that certain evaluated immunizations induce IgA and IgG(H)production in the urine of HLA-DR4 mice 33 days after initial vaccination (approximately 2weeks after second vaccination).Serum samples were obtained from mice from the control Group A and treatment GroupB (FIG. 57A), and control Group C and treatment Group D (FIG. 57B) on day 33 after firstvaccination (approximately 12 days after second vaccination) and analyzed by peptide ELISA,wherein wells were coated with certain polypeptides and / or antigen fragments (e.g., SEQ IDNOs: 17, 20, 25, 27, 40, 163-168, 176-182, 188-192, 195, 197-202, 207, 213-215, 218-219, and225) and controls (i.e., tetanus toxin, serum albumin only and no coat). The data depict antibodyproduction in wells containing each antigen utilized in exemplary vaccine antigens and / or52406514.1 - 115 -Attorney Docket No. 375836-7000WO1(00007)fragments thereof.Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by B cell activation, as indicated byelevated levels of certain antibodies, non-limiting examples including IgG1, IgG2a, IgA, andIgG(H).Example 3: Immunized mice demonstrate an adaptive immune response (T cell mediatedantibody production)Exp. No. 1Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from HLA-DR4 mice immunized as described elsewhere herein usingthe vaccine compositions indicated in Table 1.Splenocytes were obtained from mice of groups 1-5 approximately 22 days after secondvaccination and stimulated with SEQ ID NO:127, SEQ ID NO:128, and analyzed for productionof Th1 / 17 / pro-inflammatory cytokines IL-17A (FIG. 6A), IL-2 (FIG. 6B), and IL-6 (FIG. 6C) byCytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Results indicate that astrong response (i.e., high concentration of antibody) was observed in response to stimulationwith antigens SEQ ID NO:127 and SEQ ID NO:128 in splenocytes derived from treatment groupmice (i.e., groups 2-5).Splenocytes were obtained from mice of groups 1-5 approximately 22 days after secondvaccination and stimulated with SEQ ID NO:127 and SEQ ID NO:128, and analyzed forproduction of Th1 / pro-inflammatory cytokines TNF-α (FIG. 7A) and IFN-γ (FIG. 7B) byCytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Results indicate thatTNF-α production was observed in response to stimulation with antigens SEQ ID NO:127 andSEQ ID NO:128 in splenocytes derived from treatment group mice (i.e., groups 2-5).Splenocytes were obtained from mice of groups 1-5 approximately 22 days after secondvaccination and stimulated with SEQ ID NO:127 and SEQ ID NO:128, and analyzed forproduction of Th2 / pro-inflammatory cytokines IL-4 (FIG. 8A) and IL-10 (FIG. 8B) byCytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Generally, the resultsindicate that IL-4 production was observed in response to stimulation with antigens SEQ IDNO:127 and SEQ ID NO:128 in splenocytes derived from treatment group mice (i.e., groups 2-52406514.1 - 116 -Attorney Docket No. 375836-7000WO1(00007)5).Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by T cell activation, as indicated byelevated levels of several antibodies and / or cytokines, non-limiting examples including IL-17A,IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10.Exp. No. 2Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from HLA-DR4 mice immunized as described elsewhere herein usingthe vaccine compositions indicated in Table 2.Splenocytes were obtained from mice of groups A-F approximately 14 days after secondvaccination and stimulated with SEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135, andanalyzed for production of Th1 / Th17 / pro-inflammatory cytokines IL-17A (FIG. 13A), IL-2(FIG. 13B), and IL-6 (FIG. 13C) by Cytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BDBiosciences). Results indicate that a response was observed in response to stimulation withantigens SEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135 in splenocytes derived fromtreatment group mice.Splenocytes were obtained from mice of groups A and D-F approximately 14 days aftersecond vaccination and stimulated with SEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135,and analyzed for production of Th1 / pro-inflammatory cytokines TNF-α (FIG. 14A) and IFN-γ(FIG. 14B) by Cytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Resultsindicate that TNF-α and IFN-γ production was observed in response to stimulation with antigensSEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135 in splenocytes derived from treatmentgroup mice (i.e., groups D-F).Splenocytes were obtained from mice of groups A and D-F 14 approximately days aftersecond vaccination and stimulated with SEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135,and analyzed for production of Th2 / anti-inflammatory cytokines IL-4 (FIG. 15A) and IL-10(FIG. 15B) by Cytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Generally,the results indicate that IL-10 production was observed in response to stimulation with antigensSEQ ID NO:132, SEQ ID NO:133, or SEQ ID NO:135 in splenocytes derived from treatmentgroup mice (i.e., groups D-F).52406514.1 - 117 -Attorney Docket No. 375836-7000WO1(00007)Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by T cell activation, as indicated byelevated levels of several antibodies and / or cytokines, non-limiting examples including IL-17A,IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10.Exp. No. 4Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from HLA-DR4 mice immunized as described elsewhere herein usingthe vaccine compositions indicated in Table 4.Splenocytes were obtained from mice of groups A-F 49 days after first vaccination(approximately 30 days after second vaccination), and approximately 3 days after UPEC25challenge, and stimulated with SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ IDNO:139, SEQ ID NO:140, or no stimulation, and cytokine levels measured using a MagPix®system. Results indicate that a cytokine response was observed in response to stimulation withcertain antigens in mice from treatment groups, with the strongest responses observed for IFN-γ,IL-4, IL-6, IL-22, IL-17a, and IL-10.The combination of the AIM protein markers OX40 and PD-L1, CD69 and PD-L1, andCD25 and PD-L1 were used to identify antigen specific CD4+ T cells, CD8+ T cells, and B cells,respectively, by flow cytometry of splenocytes obtained from HLA-DR4 mice in all treatment(Groups B-F) and control (Group A) groups, which were activated in vitro by exemplaryantigens: SEQ ID NO:136; SEQ ID NO:137; SEQ ID NO:138; SEQ ID NO:139; and SEQ IDNO:140; or no stimulation (FIG. 35A-35C).Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by T cell activation, as indicated by elevated levels of certainexemplary cytokines and / or certain exemplary T cells.Exp. No. 5Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from HLA-DR4 mice immunized as described elsewhere herein usingthe vaccine compositions indicated in Table 5.Splenocytes were obtained from mice of groups A-F 54 days after first vaccination52406514.1 - 118 -Attorney Docket No. 375836-7000WO1(00007)(approximately 30 days after second vaccination), and approximately 7 days after UPEC25challenge, and stimulated with SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ IDNO:139, SEQ ID NO:140, or no stimulation, and cytokine levels measured using a MagPix®system. Results indicate that a response was observed in response to stimulation with certainantigens in mice from treatment groups (FIGs. 39A-39F).The combination of the AIM protein markers OX40 and PD-L1, CD69 and PD-L1, andCD69 and CD86 were used to identify antigen specific CD4+ T cells, CD8+ T cells, and B cells,respectively, by flow cytometry of splenocytes obtained from HLA-DR4 mice in all treatment(Groups B-F) and control (Group A) groups, which were activated in vitro by exemplaryantigens: SEQ ID NO:136; SEQ ID NO:137; SEQ ID NO:138; SEQ ID NO:139; and SEQ IDNO:140; or no stimulation (FIG. 40A-40C).Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by antigen specific T cell activation, as indicated by elevated levelsof certain exemplary cytokines and / or certain exemplary T cells.Exp. No. 6Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from HLA-DR4 mice immunized as described elsewhere herein usingthe vaccine compositions indicated in Table 6.Splenocytes were obtained from mice of groups A-F 47 days after first vaccination(approximately 30 days after second vaccination), and approximately 7 days after UPEC25challenge, and stimulated with SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ IDNO:144, SEQ ID NO:145, and SEQ ID NO:137, and cytokine levels measured using a MagPix®system. Results indicate that a cytokine response was observed in response to stimulation withcertain antigens in mice from treatment groups (FIGs. 43A-43F).The combination of the AIM protein markers OX40 and PD-L1, CD69 and PD-L1, andCD69 and CD86 were used to identify antigen specific CD4+ T cells, CD8+ T cells, and B cells,respectively, by flow cytometry of splenocytes obtained from HLA-DR4 mice in all treatment(Groups B-F) and control (Group A) groups, which were activated in vitro by exemplaryantigens: SEQ ID NO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, and SEQ IDNO:145, or no stimulation (FIG. 44A-44C).52406514.1 - 119 -Attorney Docket No. 375836-7000WO1(00007)Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by antigen specific T cell activation, as indicated by elevated levelsof certain exemplary cytokines and / or certain exemplary T cells.Exp. No. 7Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes and spleen cells obtained from HLA-DR4 mice immunized as describedelsewhere herein using the vaccine compositions indicated in Table 7.Splenocytes (FIGs. 47A-47F) and spleen cells (FIGs. 48A-48F) were obtained from miceof groups A-G 55 days after first vaccination (approximately 30 days after second vaccination),and approximately 7 days after UPEC25 challenge, and stimulated with SEQ ID NO:138(1),SEQ ID NO:138(2), and SEQ ID NO:139, wherein (1) and (2) vary with respect to bufferconditions, as described in Table 7, and cytokine levels measured using a MagPix® system.Results indicate that a cytokine response was observed in response to stimulation with certainantigens in mice from treatment groups.The combination of the AIM protein markers OX40 and PD-L1, CD69 and PD-L1, andCD69 and CD86 were used to identify antigen specific CD4+ T cells, CD8+ T cells, and B cells,respectively, by flow cytometry of splenocytes obtained from HLA-DR4 mice in all treatment(Groups B-E) and control (Group A) groups, which were activated in vitro by exemplaryantigens: SEQ ID NO:138(1), SEQ ID NO:138(2), and SEQ ID NO:139, wherein (1) and (2)vary with respect to buffer conditions, as described in Table 7, or no stimulation (FIG. 49A-49C).The combination of the AIM protein markers OX40 and PD-L1, and CD69 and PD-L1,were used to identify antigen specific CD4+ T cells and CD8+ T cells, respectively, by flowcytometry of bladder cells obtained from HLA-DR4 mice in all treatment (Groups B-C) andcontrol (Group A) groups, which were activated in vitro by exemplary antigens: SEQ IDNO:138(1), SEQ ID NO:138(2), wherein (1) and (2) vary with respect to buffer conditions, asdescribed in Table 7, or no stimulation (FIG. 50A-50B).Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by antigen specific T cell activation, as indicated by elevated levelsof certain exemplary cytokines and / or certain exemplary T cells.52406514.1 - 120 -Attorney Docket No. 375836-7000WO1(00007)Exp. No. 8Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from CB1 mice immunized as described elsewhere herein using thevaccine compositions indicated in Table 8.Splenocytes were obtained from mice of groups A-C approximately 14 days after secondvaccination and stimulated with SEQ ID NO:132 or SEQ ID NO:135, and analyzed forproduction of Th1 / Th17 / pro-inflammatory cytokines IL-17A (FIG. 25A), IL-2 (FIG. 25B), andIL-6 (FIG. 25C) by Cytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences).Results indicate that an IL-2 and IL-6 response was observed in response to stimulation withantigens SEQ ID NO:132 or SEQ ID NO:135 in splenocytes derived from treatment group mice.Splenocytes were obtained from mice of groups A-C approximately 14 days after secondvaccination and stimulated with SEQ ID NO:132 or SEQ ID NO:135, and analyzed forproduction of Th1 / pro-inflammatory cytokines TNF-α (FIG. 26A) and IFN-γ (FIG. 26B) byCytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Results indicate thatTNF-α and IFN-γ production was observed in response to stimulation with antigens SEQ IDNO:132 or SEQ ID NO:135 in splenocytes derived from treatment group mice.Splenocytes were obtained from mice of groups A-C approximately 14 days after secondvaccination and stimulated with SEQ ID NO:132 or SEQ ID NO:135, and analyzed forproduction of Th2 / anti-inflammatory cytokines IL-4 (FIG. 27A) and IL-10 (FIG. 27B) byCytometric Bead Array (CBA) using a Th1 / 2 / 17 kit (BD Biosciences). Generally, the resultsindicate that IL-10 production was observed in response to stimulation with antigens SEQ IDNO:132 or SEQ ID NO:135 in splenocytes derived from treatment group mice (i.e., groups D-F).Thus, in certain embodiments, the antigens and / or antigen fragments of the presentdisclosure elicit an adaptive immune response mediated by T cell activation, as indicated byelevated levels of several antibodies and / or cytokines, non-limiting examples including IL-17A,IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10.Exp. No. 9Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes and spleen cells obtained from C57BL / 6 mice immunized as described elsewhere52406514.1 - 121 -Attorney Docket No. 375836-7000WO1(00007)herein using the vaccine compositions indicated in Table 9.Splenocytes were obtained from mice of groups A-E 52 days after first vaccination(approximately 30 days after second vaccination), and approximately 7 days after UPEC25challenge, and stimulated with SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ IDNO:139, or no stimulation, and cytokine levels measured using a MagPix® system. Resultsindicate that a response was observed in response to stimulation with certain antigens in micefrom treatment groups (FIGs. 53A-53F).The combination of the AIM protein markers OX40 and PD-L1, and CD86 and CD69,were used to identify antigen specific CD4+ T cells and B cells, respectively, by flow cytometryof splenocytes obtained from C57BL / 6 mice in all treatment (Groups B-E) and control (GroupA) groups, which were activated in vitro by exemplary antigens SEQ ID NO:136, SEQ IDNO:137, SEQ ID NO:138, SEQ ID NO:139, or no stimulation (FIGs. 54A-54B).The combination of the AIM protein markers OX40 and PD-L1 was used to identifyantigen specific CD4+ T cells by flow cytometry bladder cells obtained from C57BL / 6 mice inall treatment (Groups B-E) and control (Group A) groups, which were activated in vitro byexemplary antigens SEQ ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, or nostimulation (FIG. 55).Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by antigen specific T cell activation, as indicated by elevated levelsof certain exemplary cytokines and / or certain exemplary T cells.Exp. No. 10Assessment of adaptive immune response mediated by T cells was performed by analysisof cells obtained from the spleen (individual), lymph node (pooled), and bladder (pooled) ofC57BL / 6 mice immunized as described elsewhere herein using the vaccine compositionsindicated in Table 10.Spleen, lymph node, and bladder cells were obtained from mice groups A-D 33 days afterfirst vaccination (approximately 12 days after second vaccination) and subjected to stimulationwith SEQ ID NO:225 or no stimulation, and IFN-γ concentration was measured using aMagPix® system. Results indicate that a response was observed in response to stimulation withcertain antigens in mice from treatment groups (FIG. 61).52406514.1 - 122 -Attorney Docket No. 375836-7000WO1(00007)Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by antigen specific T cell activation, as indicated by elevated levelsof IFN-γ.Exp. No. 11Assessment of adaptive immune response mediated by T cells was performed by analysisof splenocytes obtained from C57BL / 6 mice immunized as described elsewhere herein using thevaccine compositions indicated in Table 11.The combination of AIM protein markers OX40 and PD-L1 was used to identify specificCD4+ T cells by flow cytometry of splenocytes obtained from C57BL / 6 mice in all treatment(i.e., Groups A, C, E, G, and I) and control or placebo (i.e., Groups B, D, F, and H) groups,which were activated in vitro by exemplary antigen SEQ ID NO:225, or unstimulated (FIG. 64).Splenocytes were obtained from mice of groups A-I 12 days post second vaccination(approximately 33 days post first vaccination) and either stimulated with SEQ ID NO:225 orunstimulated (i.e., “Unstim”), and cytokine levels were measured using a MagPix® system.Results indicate that a cytokine response was observed in response to stimulation with SEQ IDNO:225 (FIG. 65).Thus, in certain embodiments, the antigens of the present disclosure elicit an adaptiveimmune response mediated by antigen specific T cell activation, as indicated by elevated levelsof certain exemplary cytokines and / or certain exemplary T cells. In certain embodiments, theresults indicate the use of an adjuvant, when administering the antigen parenterally (e.g.,intramuscularly), is critical for stimulating certain exemplary cytokines and / or certain exemplaryT cells (cf...

Claims

Attorney Docket No. 375836-7000WO1(00007)CLAIMSWhat is claimed is:

1. A polypeptide comprising formula (I), or a salt or solvate thereof:,wherein:each occurrence of B1, B2, B3, L1, L2, L3, L4, L5, L6, T1, T2, and T3 can be present orabsent;each occurrence of B1, B2, and B3, if present, independently comprise an immunogenicfragment of a bacterial surface protein;each occurrence of T1, T2, and T3, if present, independently comprise an immunogenicfragment of an iron receptor protein,wherein at least two of T1, T2, and T3 are present or at least one of T1, T2 and T3 ispresent and n is at least 2;each occurrence of L1, L2, L3, L4, L5, and L6, if present, independently comprise apolypeptide of 1-10 amino acids,wherein at least one of L1, L2, L3, L4, L5, and L6 is present, andwherein each occurrence of B1, B2, B3, T1, T2, and T3 are separated from oneanother by at least one of L1, L2, L3, L4, L5, and L6; andn is an integer selected from the group consisting of 1, 2, 3, 4, and 5.

2. The polypeptide of claim 1, wherein at least one of B1, B2, or B3 is present.

3. The polypeptide of claim 1 or 2, wherein each bacterial surface protein has at least 85%,90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology to a polypeptide independentlyselected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9.

4. The polypeptide of claim 3, wherein each immunogenic fragment of the bacterial surfaceprotein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology witha polypeptide independently selected from the group consisting of SEQ ID NO:16, SEQ IDNO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ52406514.1 - 178 -Attorney Docket No. 375836-7000WO1(00007)ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27,SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ IDNO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQID NO:39, SEQ ID NO:40, and SEQ ID NO:41.

5. The polypeptide of claim 3 or 4, wherein each immunogenic fragment of the bacterialsurface protein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequencehomology with a polypeptide independently selected from the group consisting of SEQ IDNO:16, SEQ ID NO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37,SEQ ID NO:39, and SEQ ID NO:40.

6. The polypeptide of any one of claims 1-5, wherein each iron receptor protein shares atleast 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideindependently selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, and SEQ ID NO:15.

7. The polypeptide of claim 6, wherein each immunogenic fragment of the iron receptorprotein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology witha polypeptide independently selected from the group consisting of SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54,SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ IDNO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71,SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ IDNO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88,SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ IDNO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID52406514.1 - 179 -Attorney Docket No. 375836-7000WO1(00007)NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ IDNO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ IDNO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ IDNO:120, SEQ ID NO:121, SEQ ID NO:122, and SEQ ID NO:123.

8. The polypeptide of claim 6 or 7, wherein each immunogenic fragment of the ironreceptor protein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequencehomology with a polypeptide independently selected from the group consisting of SEQ IDNO:42, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:54, SEQID NO:55, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:67, SEQ ID NO:85,and SEQ ID NO:88.

9. The polypeptide of any one of claims 1-8, wherein each of L1, L2, L3, L4, L5, and L6, ifpresent, independently comprise a polypeptide wherein each amino acid residue side chaincomprises a neutral (i.e., non-charged) substituent.

10. The polypeptide of any one of claims 1-9, wherein each of L1, L2, L3, L4, L5, and L6, ifpresent, independently comprise a polypeptide of 4 to 6 amino acids.

11. The polypeptide of any one of claims 1-10, wherein each of L1, L2, L3, L4, L5, and L6, ifpresent, is independently selected from the group consisting of GSGS (SEQ ID NO:124), GPGP(SEQ ID NO:125), LLSVGG (SEQ ID NO:126), (SGSG)1-2 (SEQ ID NOs:146-147), SSSS (SEQID NO:156), GGGS (SEQ ID NO:157), GGC (SEQ ID NO:158), GGS (SEQ ID NO:159),(GGC)8 (SEQ ID NO:160), (GGGGS)3 (SEQ ID NO:161), and GGAAY (SEQ ID NO:162).

12. The polypeptide of any one of claims 1-11, wherein n is 3.

13. The polypeptide of any one of claims 1-12, wherein the polypeptide shares at least 85%,90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptide selected fromthe group consisting of SEQ ID NO:130 and SEQ ID NO:129.52406514.1 - 180 -Attorney Docket No. 375836-7000WO1(00007)14. The polypeptide of any one of claims 1-11, wherein n is 4.

15. The polypeptide of any one of claims 1-11 and 14, wherein the polypeptide shares at least85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideselected from the group consisting of SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:131, SEQID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ IDNO:137, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ ID NO:223, SEQ IDNO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ ID NO:228, SEQ IDNO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ ID NO:233, SEQ IDNO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ ID NO:238, SEQ IDNO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ ID NO:243, SEQ IDNO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ ID NO:248, SEQ IDNO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ ID NO:253, SEQ IDNO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ ID NO:257, SEQ IDNO:258, SEQ ID NO:259, and SEQ ID NO:260.

16. A polypeptide selected from the group consisting of:(a) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12;(b) T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12;(c) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9;(d) T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9;(e) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T1-L10-B6-L11-T2-L12-B7-L13-T3-L14-B8-L15-T4-L16-B9-L17-T1-L18-B10-L19-T2-L20-B11-L21-T3-L22-B12-L23-T4;(f) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13-L25-T13;(g) T1-L1-T2-L2-T3-L3-T4-L4-T5-L5-T6-L6-T7-L7-T8-L8-T9-L9-T10-L10-T11-L11-T12-L12-T13;(h) B1-L1-T1-L2-B2-L3-T2-L4-B3-L5-T3-L6-B4-L7-T4-L8-B5-L9-T5-L10-B6-L11-T6-L12-B7-L13-T7-L14-B8-L15-T8-L16-B9-L17-T9-L18-B10-L19-T10-L20-B11-L21-T11-L22-B12-L23-T12-L24-B13;52406514.1 - 181 -Attorney Docket No. 375836-7000WO1(00007)(i) B1-L1-B2-L2-B3-L3-B4-L4-T1-L5-T2-L6-T3-L7-T4-L8-B5-L9-B6-L10-B7-L11-B8-L12-T5-L13-T6-L14-T7-L15-T8-L16-B9-L17-B10-L18-B11-L19-B12-L20-T9-L21-T10-L22-T11-L23-T12; and(j) T1-L1-T2-L2-T3-L3-T4-L4-B1-L5-B2-L6-B3-L7-B4-L8-T5-L9-T6-L10-T7-L11-T8-L12-B5-L13-B6-L14-B7-L15-B8-L16-T9-L17-T10-L18-T11-L19-T12-L20-B9-L21-B10-L22-B11-L23-B12;wherein:each occurrence of B, if present, independently comprises an immunogenic fragmentof a bacterial surface protein,wherein each instance of B has a C-terminus and a N-terminus;each occurrence of T independently comprises an immunogenic fragment of an ironreceptor protein,wherein each instance of T has a C-terminus and a N-terminus;each occurrence of L independently comprises a polypeptide of 1-10 amino acids,wherein each instance of L has a C-terminus and a N-terminus;each instance of B is covalently linked to one or two independent instances of L by acovalent peptide bond between the C-terminus of the B and the N-terminus of the Land / or the N-terminus of the B and the C-terminus of the L; andeach instance of T is covalently linked to one or two independent instances of L by acovalent peptide bond between the C-terminus of the T and the N-terminus of the Land / or the N-terminus of the T and the C-terminus of the L;or a salt or solvate thereof.

17. The polypeptide of claim 16, wherein each bacterial surface protein has at least 85%,90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology to a polypeptide independentlyselected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ IDNO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, and SEQ DI NO:9.

18. The polypeptide of claim 17, wherein each immunogenic fragment of the bacterialsurface protein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequencehomology with a polypeptide independently selected from the group consisting of SEQ IDNO:16, SEQ ID NO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26,52406514.1 - 182 -Attorney Docket No. 375836-7000WO1(00007)SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ IDNO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQID NO:38, SEQ ID NO:39, SEQ ID NO:40, and SEQ ID NO:41.

19. The polypeptide of claim 17 or 18, wherein each immunogenic fragment of the bacterialsurface protein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequencehomology with a polypeptide independently selected from the group consisting of SEQ IDNO:16, SEQ ID NO:195, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQID NO:23, SEQ ID NO:25, SEQ ID NO:27, SEQ ID NO:32, SEQ ID NO:35, SEQ ID NO:37,SEQ ID NO:39, and SEQ ID NO:40.

20. The polypeptide of any one of claims 16-19, wherein each iron receptor protein shares atleast 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptideindependently selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ IDNO:12, SEQ ID NO:13, SEQ ID NO:14, and SEQ ID NO:15.

21. The polypeptide of claim 20, wherein each immunogenic fragment of the iron receptorprotein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology witha polypeptide independently selected from the group consisting of SEQ ID NO:42, SEQ IDNO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54,SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ IDNO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71,SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ IDNO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88,SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ IDNO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ IDNO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID52406514.1 - 183 -Attorney Docket No. 375836-7000WO1(00007)NO:110, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:113, SEQ ID NO:114, SEQ IDNO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ IDNO:120, SEQ ID NO:121, SEQ ID NO:122, and SEQ ID NO:123.

22. The polypeptide of claim 20 or 21, wherein each immunogenic fragment of the ironreceptor protein shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequencehomology with a polypeptide independently selected from the group consisting of SEQ IDNO:42, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:54, SEQID NO:55, SEQ ID NO:56, SEQ ID NO:58, SEQ ID NO:62, SEQ ID NO:67, SEQ ID NO:85,and SEQ ID NO:88.

23. The polypeptide of any one of claims 16-22, wherein each of L1, L2, L3, L4, L5, L6, L7, L8,L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, and L25, if present,independently comprise a polypeptide wherein each amino acid residue side chain comprises aneutral (i.e., non-charged) substituent.

24. The polypeptide of any one of claims 16-23, wherein each of L1, L2, L3, L4, L5, L6, L7, L8,L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, and L25, if present,independently comprise a polypeptide of 4 to 6 amino acids.

25. The polypeptide of any one of claims 16-24, wherein each of L1, L2, L3, L4, L5, L6, L7, L8,L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, and L25, if present, isindependently selected from the group consisting of GSGS (SEQ ID NO:124), GPGP (SEQ IDNO:125), LLSVGG (SEQ ID NO:126), (SGSG)1-2 (SEQ ID NOs:146-147), SSSS (SEQ IDNO:156), GGGS (SEQ ID NO:157), GGC (SEQ ID NO:158), GGS (SEQ ID NO:159), (GGC)8(SEQ ID NO:160), (GGGGS)3 (SEQ ID NO:161), and GGAAY (SEQ ID NO:162).

26. The polypeptide of any one of claims 16-25, wherein the polypeptide shares at least 85%,90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with a polypeptide selected fromthe group consisting of SEQ ID NO:127, SEQ ID NO:128, SEQ ID NO:129, SEQ ID NO:130,SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ52406514.1 - 184 -Attorney Docket No. 375836-7000WO1(00007)ID NO:136, SEQ ID NO:137, SEQ ID NO:138, SEQ ID NO:139, SEQ ID NO:140, SEQ IDNO:141, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:144, SEQ ID NO:145, SEQ IDNO:223, SEQ ID NO:224, SEQ ID NO:225, SEQ ID NO:226, SEQ ID NO:227, SEQ IDNO:228, SEQ ID NO:229, SEQ ID NO:230, SEQ ID NO:231, SEQ ID NO:232, SEQ IDNO:233, SEQ ID NO:234, SEQ ID NO:235, SEQ ID NO:236, SEQ ID NO:237, SEQ IDNO:238, SEQ ID NO:239, SEQ ID NO:240, SEQ ID NO:241, SEQ ID NO:242, SEQ IDNO:243, SEQ ID NO:244, SEQ ID NO:245, SEQ ID NO:246, SEQ ID NO:247, SEQ IDNO:248, SEQ ID NO:249, SEQ ID NO:250, SEQ ID NO:251, SEQ ID NO:252, SEQ IDNO:253, SEQ ID NO:253, SEQ ID NO:254, SEQ ID NO:255, SEQ ID NO:256, SEQ IDNO:257, SEQ ID NO:258, SEQ ID NO:259, and SEQ ID NO:260.

27. The polypeptide of any one of claims 1-26, wherein the polypeptide shares at least 85%,90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with SEQ ID NO:225.

28. The polypeptide of any one of claims 1-26, wherein the polypeptide shares at least 85%,90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence homology with SEQ ID NO:226.

29. An isolated messenger ribonucleic acid (mRNA) encoding the polypeptide of any one ofclaims 1-28.

30. The isolated mRNA of claim 29, wherein the mRNA is codon optimized for expressionin:(a) a prokaryote; or(b) a mammal.

31. The isolated mRNA of claim 30, wherein one of the following applies:(a) the prokaryote is E. coli; or(b) the mammal is a human.

32. An isolated deoxyribonucleic acid (DNA) encoding the polypeptide of any one of claims1-28.52406514.1 - 185 -Attorney Docket No. 375836-7000WO1(00007)33. The isolated DNA of claim 32, wherein the DNA is codon optimized for expression in:(a) a prokaryote; or(b) a mammal.

34. The isolated DNA of claim 33, wherein one of the following applies:(a) the prokaryote is E. coli; or(b) the mammal is a human.

35. An isolated polynucleotide encoding the mRNA of any one of claims 29-31, wherein thepolynucleotide comprises one or more promoters and / or a polyadenylation signal operably linkedto a sequence encoding the mRNA.

36. A vector comprising the isolated mRNA of any one of claims 29-31, the isolated DNA ofany one of claims 32-34, and / or the isolated polynucleotide of claim 35.

37. The vector of claim 36, wherein the vector is a viral vector.

38. The vector of claim 37, wherein the viral vector is Adeno-Associated Virus (AAV),optionally wherein the AAV is AAV9.

39. The vector of claim 36, wherein the vector is a bacterial expression vector.

40. The vector of claim 39, wherein the bacterial expression vector is an E. coli vector.

41. A lipid nanoparticle (LNP) composition comprising the isolated mRNA of any one ofclaims 29-31, the isolated DNA of any one of claims 32-34, and / or the isolated polynucleotide ofclaim 35.

42. The LNP of claim 41, wherein at least one of the following applies:(a) the LNP has a ratio of lipid to isolated mRNA or DNA ranging from about 5:1 to52406514.1 - 186 -Attorney Docket No. 375836-7000WO1(00007)about 25:1; and(b) the LNP has a ratio of lipid to isolated polynucleotide ranging from about 5:1 toabout 25:1.

43. The LNP of claim 41 or 42, wherein the LNP comprises:(a) at least one ionizable lipid;(b) at least one helper lipid;(c) cholesterol, or a modified derivative thereof, and any combinations thereof; and(d) at least one conjugated lipid.

44. The LNP of claim 43, wherein the ionizable lipid is at least one selected from the groupconsisting of DLinDMA, DLenDMA, DLin-K-C2-DMA, D Lin-K-C3-D MA, DLin-K-C4-DMA, DLin-K6-DMA, DLin-K-MPZ, DLin-KDMA, D Lin-C-DAP, DLin-DAC, DLin-MA,DLinDAP, DLin-2-DMAP, DLin-TMA.Cl, DLin-TAP.Cl, D Lin-MPZ, D LinAP, DOAP, D Lin-EG-D MA, DODAC, DODMA, DSD MA, DOTMA, DDAB, DOTAP, DC-Chol, DMRIE,DOSPA, DOGS, CLinDMA, CpLinDMA, DMOBA, DOcarbDAP, and DLincarbDAP.

45. The LNP of claim 43 or 44, wherein the at least one ionizable lipid comprises about 50mol% to about 90 mol% of the LNP.

46. The LNP of any one of claims 43-45, wherein the helper lipid is at least one selectedfrom the group consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine (DOPE), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).

47. The LNP of any one of claims 43-46, wherein the at least one helper lipid comprisesabout 1 to about 25 mol% of the LNP.

48. The LNP of any one of claims 43-47, wherein the cholesterol comprises about 20 toabout 60 mol% of the LNP.52406514.1 - 187 -Attorney Docket No. 375836-7000WO1(00007)49. The LNP of any one of claims 43-48, wherein the conjugated lipid is at least one selectedfrom the group consisting of 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000(PEG-DMG), 1,2-Distearoyl-sn-glycerol, methoxypolyethylene glycol (PEG-DSG), 1,2-Dipalmitoyl-sn-glycerol, methoxypolyethylene glycol (PEG-DPG), mPEG-OH, mPEG-AA(mPEG-CM), mPEG-CH2CH2CH2-NH2, mPEG-DMG, mPEG-N,N-Ditetradecylacetamide(ALC-0159), mPEG-DSPE, and mPEG-DPPE.

50. The LNP of any one of claims 43-49, wherein the at least one conjugated lipid comprisesabout 0.1 to about 5 mol% of the LNP.

51. The LNP of any one of claims 41-50, wherein the isolated mRNA, isolated DNA, and / orisolated polynucleotide is at least partially encapsulated in the LNP.

52. A pharmaceutical composition comprising the LNP of any one of claims 41-51 and apharmaceutically acceptable carrier.

53. A vaccine composition comprising the LNP of any one of claims 41-51 and / or thepharmaceutical composition of claim 52.

54. A vaccine composition comprising the polypeptide of any one of claims 1-28 and at leastone pharmaceutically acceptable excipient.

55. The vaccine composition of claim 54, wherein the polypeptide shares at least 85%, 90%,95%, 96%, 97%, 98%, 99%, or 100% sequence homology with SEQ ID NO:225.

56. The vaccine composition of claim 54, wherein the polypeptide shares at least 85%, 90%,95%, 96%, 97%, 98%, 99%, or 100% sequence homology with SEQ ID NO:22657. The vaccine composition of any one of claims 54-56, further comprising an adjuvant.

58. The vaccine composition of claim 57, wherein the adjuvant comprises at least one52406514.1 - 188 -Attorney Docket No. 375836-7000WO1(00007)selected from the group consisting of aluminum hydroxide (AlOH), double mutant heat-labiletoxin (dmLT), CpG, and an oil-in-water emulsion adjuvant.

59. The vaccine composition of claim 58, wherein at least one of the following applies:(a) the vaccine comprises about 10 µg to about 100 µg of the polypeptide;(b) the vaccine comprises about 100 µg to about 6000 µg of the CpG;(c) the vaccine comprises about 250 µg to about 750 µg of the AlOH;(d) the vaccine comprises about 1 µg to about 25 µg of the dmLT; and(e) the vaccine comprises about 25% (v / v) to about 75% (v / v) of the oil-in-wateremulsion adjuvant.

60. A vaccine composition comprising:(a) a polypeptide which shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or100% sequence homology with SEQ ID NO:225 or SEQ ID NO:226, wherein thevaccine composition comprises about 10 µg to about 100 µg of the polypeptide;(b) α-tocopherol, wherein the α-tocopherol comprises about 2.5% (v / v) of the vaccinecomposition;(c) squalene, wherein the squalene comprises about 2.5% (v / v) of the vaccinecomposition; and(d) polysorbate 80, wherein the polysorbate 80 comprises about 0.9% (v / v) of thevaccine composition;wherein the polypeptide, α-tocopherol, squalene, and polysorbate are dissolved orsuspended in a phosphate buffered saline (PBS) solution.

61. A vaccine composition comprising:(a) a polypeptide which shares at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or100% sequence homology with SEQ ID NO:225 or SEQ ID NO:226, wherein thevaccine composition comprises about 10 µg to about 100 µg of the polypeptide;(b) α-tocopherol, wherein the α-tocopherol comprises about 2.5% (v / v) of the vaccinecomposition;(c) squalene, wherein the squalene comprises about 2.5% (v / v) of the vaccine52406514.1 - 189 -Attorney Docket No. 375836-7000WO1(00007)composition;(d) polysorbate 80, wherein the polysorbate 80 comprises about 0.9% (v / v) of thevaccine composition; and(e) CpG, wherein the vaccine comprises about 100 µg to about 6000 µg of the CpG;wherein the polypeptide, α-tocopherol, squalene, polysorbate, and CpG aredissolved or suspended in a phosphate buffered saline (PBS) solution.

62. A method of treating, preventing, and / or ameliorating a bacterial infection in a subject inneed thereof, the method comprising administering to the subject at least one selected from thegroup consisting of:(a) the polypeptide of any one of claims 1-28;(b) the isolated mRNA of any one of claims 29-31;(c) the isolated DNA of any one of claims 32-34;(d) the isolated polynucleotide of claim 35;(e) the vector of any one of claims 36-40;(f) the LNP of any one of claims 41-51;(g) the pharmaceutical composition of claim 52; and(h) the vaccine composition of any one of claims 53-61.

63. The method of claim 62, wherein the bacterial infection is a urinary tract infection (UTI).

64. The method of claim 62, wherein the bacterial infection comprises a urinary tractinfection (UTI) and sepsis.

65. The method of claim 62, wherein the bacterial infection is sepsis.

66. The method of claim 64 or 65, wherein the sepsis is neonatal sepsis.

67. The method of claim 62, wherein the bacterial infection is pneumonia.

68. The method of any one of claims 62-67, wherein the subject is a mammal.52406514.1 - 190 -Attorney Docket No. 375836-7000WO1(00007)69. The method of claim 68, wherein the mammal is a human.

70. The method of any one of claims 62-69, wherein the subject is pregnant with a fetus.

71. The method of claim 70, wherein the bacterial infection is treated, prevented, and / orameliorated in at least one of the subject and the fetus, or a neonate thereof.

72. The method of claim 70, wherein the bacterial infection is treated, prevented, and / orameliorated in both the subject and the fetus, or a neonate thereof.

73. A method of generating immunity to infection by one or more pathogenic bacteria in asubject, the method comprising administering to the subject at least one selected from the groupconsisting of:(a) the polypeptide of any one of claims 1-28;(b) the isolated mRNA of any one of claims 29-31;(c) the isolated DNA of any one of claims 32-34;(d) the isolated polynucleotide of claim 35;(e) the vector of any one of claims 36-40;(f) the LNP of any one of claims 41-51;(g) the pharmaceutical composition of claim 52; and(h) the vaccine composition of any one of claims 53-61.

74. The method of claim 73, wherein the one or more pathogenic bacteria comprises at leastone selected from the group consisting of Escherichia coli, Klebsiella pneumoniae, Proteusmirabilis, Shigella dysenteriae, Salmonella enterica, Streptococcus pneumoniae, Haemophilusinfluenzae, Chlamydophila pneumoniae, Mycoplasma pneumoniae, Staphylococcus aureus,Moraxella catarrhalis, and Legionella pneumophila, Streptococcus pyogenes, and Pseudomonasaeruginosa, and Salmonella bongori.

75. The method of claim 73 or 74, wherein the immunity prevents a bacterial infection.52406514.1 - 191 -Attorney Docket No. 375836-7000WO1(00007)76. The method of claim 75, wherein the bacterial infection is a urinary tract infection (UTI).

77. The method of claim 75, wherein the bacterial infection comprises a urinary tractinfection (UTI) and sepsis.

78. The method of claim 75, wherein the bacterial infection is sepsis.

79. The method of claim 77 or 78, wherein the sepsis is neonatal sepsis.

80. The method of claim 75, wherein the bacterial infection is pneumonia81. The method of any one of claims 73-80, wherein the subject is a mammal.

82. The method of claim 81, wherein the mammal is a human.

83. The method of any one of claims 73-82, wherein the subject is pregnant with a fetus.

84. The method of claim 83, wherein the immunity to infection by one or more pathogenicbacteria is generated in at least one of the subject and the fetus, or a neonate thereof.

85. The method of claim 83 or 84, wherein the immunity to infection by one or morepathogenic bacteria is generated in both the subject and the fetus, or a neonate thereof.52406514.1 - 192 -

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