Compositions and methods for treating mycobacterial infection

Abstract

Tuberculosis (TB) remains a leading cause of death from infectious disease worldwide, in part due to the limited efficacy of currently available vaccine. Disclosed herein are compositions and methods for providing immunogenic protection against TB.

Description

[0001] COMPOSITIONS AND METHODS FOR TREATING MYCOBACTERIAL INFECTION SEQUENCE LISITNG The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on November 19, 2024, is named “01948-292WO2_Sequence_Listing_11_19_24” and is 1,604,995 bytes in size. BACKGROUND Tuberculosis (TB) remains a leading cause of death from infectious disease worldwide with more than 1.5 million deaths in 2020. TB burden has increased in recent years due to the economic and public health sequelae of COVID-19, reversing decades of modest improvement. The burden of TB is particularly high in low- and middle-income countries, where TB is a primary driver of all-cause morbidity and mortality with little change in recent decades. This is in part due to the limited efficacy of the Bacillus Calmette–Guérin (BCG) vaccine. Therefore, there remains a need in the field for developing next-generation compositions suitable for vaccination against TB. SUMMARY OF THE DISCLOSURE The present disclosure features compositions and methods useful for vaccinating a subject against a mycobacterial infection and for treating tuberculosis (TB) and other diseases and symptoms caused by mycobacterial infection. In a first aspect, the disclosure provides an immunogenic composition including: (I)(a) at least one polypeptide or at least two different polypeptides, wherein each said polypeptide includes at least 12 contiguous amino acids of a polypeptide selected from the group consisting of: PPE family protein PPE20 (PPE20), ESAT-6 like protein EsxG (EsxG), PE family protein PE18 (PE18), secreted antigen 85-B FbpB (fbpB), PPE family protein PPE51 (PPE51), secreted ESAT-6 like protein EsxR (EsxR), ESX conserved component EccD3 (eccD3), PPE family protein PPE2 (PPE2), PPE family protein PPE3 (PPE3), ESAT-6 like protein EsxS (EsxS), PPE family protein PPE46 (PPE46), PPE family protein PPE30 (PPE30), PPE family protein PPE11 (PPE11), PPE family protein PPE4 (PPE4), major secreted immunogenic protein Mpt70 (Mpt70), and PE family protein PE19 (PE19); (b) a nucleic acid molecule encoding the at least two different polypeptides; and / or (c) at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides, and (II) a pharmaceutically acceptable vehicle, diluent, excipient and / or adjuvant. In some embodiments of the first aspect, the immunogenic composition includes: (a) 2 to 8 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 2 to 8 said polypeptides; or (c) 2 to 8 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, fbpB, EsxG, fbpA, PPE3, EsxS, PE18, and PPE2. In some embodiments of the first aspect, the immunogenic composition includes: (a) 2 to 4 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 2 to 4 said polypeptides; or (c) 2 to 4 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, EsxG, PE18, and fbpB. In an embodiment, the immunogenic composition includes the polypeptides PPE20, EsxG, PE18, and fbpB. In an embodiment of the first aspect, the immunogenic composition includes a nucleic acid molecule that encodes PPE20, EsxG, PE18, and fbpB. In an embodiment of the first aspect, the immunogenic composition is an mRNA composition that includes an mRNA molecule encoding each of PPE20, EsxG, PE18, and fbpB. In some embodiments of the first aspect, the immunogenic composition includes: (a) 3 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 3 said polypeptides; or (c) 3 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, EsxG, and PE18. In an embodiment of the first aspect, the immunogenic composition includes the polypeptides PPE20, EsxG, and PE18. In an embodiment of the first aspect, the immunogenic composition includes a nucleic acid molecule that encodes PPE20, EsxG, and PE18. In an embodiment of the first aspect, the immunogenic composition is an mRNA composition that includes an mRNA molecule encoding each of PPE20, EsxG, and PE18. In some embodiments of the first aspect, the nucleic acid molecule of (I)(b) (e.g., the nucleic acid molecule encoding the at least two different polypeptides) or the at least two nucleic acid molecules of (I)(c) (e.g., at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides) includes a nucleotide sequence including 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) or all nucleotides of a nucleic acid molecule encoding a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, and PE19. In some embodiments of the first aspect, the at least two different polypeptides include 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) or all amino acids of a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, PE19. In some embodiments of the first aspect, the immunogenic composition includes or encodes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); and (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). In some embodiments of the first aspect, the immunogenic composition includes or encodes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788); and (d) the fbpB polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25- 75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 4; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807-809, 827-836, 842-846, 862- 869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). In some embodiments of the first aspect: (a) the PPE20 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 1; (b) the EsxG polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (c) the PE18 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (d) the fbpB polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (e) the PPE51 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 5; (f) the EsxR polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 6; (g) the eccD3 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 7; (h) the PPE2 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 8; (i) the PPE3 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 9; (j) the EsxS polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 10; (k) the PPE46 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 11; (l) the PPE30 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 12; (m) the PPE11 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 13; (n) the PPE4 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 14; (o) the Mpt70 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 15; and / or (p) the PE19 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 16. In some embodiments of the first aspect: (a) the PPE20 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to any one or more of SEQ ID NOs: 421-526; (b) the EsxG polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 742-758; (c) the PE18 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 776-793; (d) the fbpB polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 807-869; (e) the PPE2 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 633-741; (f) the PPE3 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 527-632; (g) the ESXs polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 575 and 759-775; (h) the PE19 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 783, 784, and 793-806; and / or (i) the fbpA polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 870-935. In some embodiments of the first aspect, the PPE20 polypeptide can include one, two, three, four, five, six, seven, eight, nine, ten, or eleven mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1. In some embodiments of the first aspect, the PPE20 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or all eleven of the following positions (e.g., to block glycosylation): position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1. In some embodiments of the first aspect, the EsxG polypeptide can include one or two mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 66 and 75 of SEQ ID NO: 2. In some embodiments of the first aspect, the EsxG polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or both of the following positions: position 66 and 75 of SEQ ID NO: 2. In some embodiments of the first aspect, the PE18 polypeptide can include one, two, three, or four mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 26, 29, 78, and 94 of SEQ ID NO: 3. In some embodiments of the first aspect, the PE18 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, or all four of the following positions: position 26, 29, 78, and 94 of SEQ ID NO: 3. In some embodiments of the first aspect, the fbpB polypeptide can include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, or eighteen mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO: 4. In some embodiments of the first aspect, the fbpB polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more or all eighteen of the following positions: position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO: 4.In some embodiments of the first aspect, the nucleic acid molecule of (I)(b) (e.g., the nucleic acid molecule encoding the at least two different polypeptides) or each of the at least two nucleic acid molecules of (I)(c) (e.g., at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides) includes a DNA molecule, and wherein each said DNA molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 43-90. In some embodiments of the first aspect, the nucleic acid molecule of (I)(b) (e.g., the nucleic acid molecule encoding the at least two different polypeptides) or each of the at least two nucleic acid molecules of (I)(c) (e.g., at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides) includes an RNA molecule, and wherein each said RNA molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 169-264. In some embodiments of the first aspect, the immunogenic composition further includes at least one additional polypeptide or a nucleic acid molecule encoding the at least one additional polypeptide, wherein the additional polypeptide includes at least 12 contiguous amino acids of a polypeptide selected from the group consisting of: PPE family protein PPE18 (PPE18), secreted antigen 85-a FbpA (fbpA), low molecular weight protein antigen 7 EsxH (EsxH), and probable serine protease PepA (pepA). In some embodiments of the first aspect, the nucleic acid molecule encoding the additional polypeptide includes a nucleotide sequence with 36-291 contiguous nucleotides (e.g., 36-291, 50- 250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) or all nucleotides of a nucleic acid molecule encoding a polypeptide selected from the group consisting of: PPE18, fbpA, EsxH, and pepA. In some embodiments of the first aspect, the additional polypeptide includes 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) or all amino acids of a polypeptide selected from the group consisting of: PPE18, fbpA, EsxH, and pepA. In some embodiments of the first aspect: (a) the PPE18 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 17; (b) the fbpA polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 18; (c) the EsxH polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 19; and / or (d) the pepA polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 20. In some embodiments of the first aspect, the nucleic acid molecule encoding the at least one additional polypeptide is composed of a DNA molecule, and wherein each said DNA molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 91-102. In some embodiments of the first aspect, the nucleic acid molecule encoding the at least one additional polypeptide is composed of an RNA molecule, and wherein each said RNA molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 265-288. In some embodiments of the first aspect, the immunogenic composition includes one or more DNA expression vectors, and wherein each said DNA expression vector includes the nucleotide sequences of each said DNA molecule (e.g., any one or more of SEQ ID NOs: 43-102 or a variant thereof with at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity thereto). In some embodiments of the first aspect, the immunogenic composition includes one or more mRNA molecules, and wherein each said mRNA molecule includes the nucleotide sequence of each said RNA molecule (e.g., any one or more of SEQ ID NOs: 169-288 or a variant thereof with at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity thereto). In some embodiments of the first aspect, the mRNA molecule is a self-replicating mRNA molecule. In some embodiments of the first aspect, the nucleic acid molecule (e.g., the mRNA molecule (e.g., self-replicating mRNA molecule) or DNA molecule (e.g., DNA expression vector)) is formulated in a lipid nanoparticle (LNP), an exosome, or a liposome. In some embodiments, the mRNA molecule is formulated into an LNP. In some embodiments of the first aspect, the self-replicating mRNA molecule is formulated into an LNP. In some embodiments of the first aspect, the immunogenic composition further includes one or more live attenuated vaccines including: BCG, MTBVAC, VPM1002, DAR-901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72, RUTI, H107, or CysVac2 / Advax. In some embodiments of the first aspect, the immunogenic composition includes the BCG vaccine. In a second aspect, the disclosure provides an immunogenic composition including: (I)(a) at least two different polypeptides, wherein each said polypeptide comprises at least 12 contiguous amino acids of a polypeptide selected from the group consisting of: PPE family protein PPE20 (PPE20), ESAT-6 like protein EsxG (EsxG), PE family protein PE18 (PE18), secreted antigen 85-B FbpB (fbpB), PPE family protein PPE51 (PPE51), secreted ESAT-6 like protein EsxR (EsxR), ESX conserved component EccD3 (eccD3), PPE family protein PPE2 (PPE2), PPE family protein PPE3 (PPE3), ESAT-6 like protein EsxS (EsxS), PPE family protein PPE46 (PPE46), PPE family protein PPE30 (PPE30), PPE family protein PPE11 (PPE11), PPE family protein PPE4 (PPE4), major secreted immunogenic protein Mpt70 (Mpt70), PE family protein PE19 (PE19), PPE family protein PPE18 (PPE18), secreted antigen 85-a FbpA (fbpA), low molecular weight protein antigen 7 EsxH (EsxH), and probable serine protease PepA (pepA); (b) a nucleic acid molecule encoding the at least two different polypeptides; or (c) at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides, and (II) a pharmaceutically acceptable vehicle, diluent, excipient and / or adjuvant. In some embodiments of the second aspect, the immunogenic composition includes: (a) 2 to 8 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 2 to 8 said polypeptides; or (c) 2 to 8 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, fbpB, EsxG, fbpA, PPE3, EsxS, PE18, and PPE2. In some embodiments of the second aspect, the immunogenic composition includes: (a) 2 to 4 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 2 to 4 said polypeptides; or (c) 2 to 4 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, EsxG, PE18, and fbpB. In some embodiments of the second aspect, the immunogenic composition includes: (a) 3 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 3 said polypeptides; or (c) 3 of said nucleic acid molecules, wherein, each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, EsxG, and PE18. In some embodiments of the second aspect, the nucleic acid molecule of (I)(b) (e.g., the nucleic acid molecule encoding the at least two different polypeptides) or the at least two nucleic acid molecules of (I)(c) (e.g., at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides) includes a nucleotide sequence including 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) or all nucleotides of a nucleic acid molecule encoding a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, PE19, PPE18, fbpA, EsxH, and pepA. In some embodiments of the second aspect, the at least two different polypeptides include 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) or all amino acids of a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, PE19, PPE18, fbpA, EsxH, and pepA. In some embodiments of the second aspect: (a) the PPE20 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 1; (b) the EsxG polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (c) the PE18 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (d) the fbpB polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (e) the PPE51 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 5; (f) the EsxR polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 6; (g) the eccD3 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 7; (h) the PPE2 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 8; (i) the PPE3 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 9; (j) the EsxS polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 10; (k) the PPE46 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 11; (l) the PPE30 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 12; (m) the PPE11 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 13; (n) the PPE4 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 14; (o) the Mpt70 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 15; and / or (p) the PE19 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 16; (q) the PPE18 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 17; (r) the fbpA polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 18; (s) the EsxH polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 19; and / or (t) the pepA polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 20. In some embodiments of the second aspect, the nucleic acid molecule of (I)(b) (e.g., the nucleic acid molecule encoding the at least two different polypeptides) or each of the at least two nucleic acid molecules of (I)(c) (e.g., at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides) includes a DNA molecule, and wherein each said DNA molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 43-102. In some embodiments of the second aspect, the nucleic acid molecule of (I)(b) (e.g., the nucleic acid molecule encoding the at least two different polypeptides) or each of the at least two nucleic acid molecules of (I)(c) (e.g., at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides) includes an RNA molecule, and wherein each said RNA molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 169-288. In some embodiments of the second aspect, the immunogenic composition includes one or more DNA expression vectors, and wherein each said DNA expression vector includes the nucleotide sequences of each said DNA molecule (e.g., any one or more of SEQ ID NOs: 43-102 or a variant thereof with at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity thereto). In some embodiments of the second aspect, the immunogenic composition includes one or more mRNA molecules, and wherein each said mRNA molecule includes the nucleotide sequence of each said RNA molecule (e.g., any one or more of SEQ ID NOs: 169-288 or a variant thereof with at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity thereto). In some embodiments of the second aspect, the nucleic acid molecule (e.g., the mRNA molecule or DNA molecule (e.g., DNA expression vector)) is formulated in a lipid nanoparticle (LNP), an exosome, or a liposome. In some embodiments of the second aspect, the mRNA molecule is formulated into an LNP. In some embodiments of the second aspect, the immunogenic composition further includes one or more live attenuated vaccines including: BCG, MTBVAC, VPM1002, DAR-901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72, RUTI, H107, or CysVac2 / Advax. In some embodiments of the second aspect, the immunogenic composition includes the BCG vaccine. In a third aspect, the disclosure features an immunogenic composition including: (I) a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide; or (II) (a) a nucleic acid molecule encoding a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide; (b) a first nucleic acid molecule encoding a EsxG polypeptide and an PPE20 polypeptide and a second nucleic acid molecule encoding a PE18 polypeptide; (c) a first nucleic acid molecule encoding a PPE20 polypeptide and a PE18 polypeptide and a second nucleic acid molecule encoding an EsxG polypeptide; (d) a first nucleic acid molecule encoding a PE18 polypeptide and an EsxG polypeptide and a second nucleic acid molecule encoding a PPE20 polypeptide; or (e) a first nucleic acid molecule encoding a PPE20 polypeptide, a second nucleic acid molecule encoding an EsxG polypeptide, and a third nucleic acid molecule encoding a PE18 polypeptide. In some embodiments of the third aspect: (a) the PPE20 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 1; (b) the EsxG polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; and (c) the PE18 polypeptide includes an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3. In some embodiments of the third aspect, the PPE20 polypeptide can include one, two, three, four, five, six, seven, eight, nine, ten, or eleven mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1. In some embodiments of the third aspect, the PPE20 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or all eleven of the following positions (e.g., to block glycosylation): position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1. In some embodiments of the third aspect, the EsxG polypeptide can include one or two mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 66 and 75 of SEQ ID NO: 2. In some embodiments of the third aspect, the EsxG polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or both of the following positions: position 66 and 75 of SEQ ID NO: 2. In some embodiments of the third aspect, the PE18 polypeptide can include one, two, three, or four mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 26, 29, 78, and 94 of SEQ ID NO: 3. In some embodiments of the third aspect, the PE18 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, or all four of the following positions: position 26, 29, 78, and 94 of SEQ ID NO: 3. In some embodiments of the third aspect, the fbpB polypeptide can include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, or eighteen mutations at an asparagine residue at any of the following positions (e.g., to block glycosylation): position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO: 4. In some embodiments of the third aspect, the PE18 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more or all eighteen of the following positions: position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO: 4. In some embodiments of the third aspect, the nucleic acid molecule of any one of (II)(b) through (II)(e) (e.g., the immunogenic composition including the first nucleic acid molecule encoding the EsxG polypeptide and the PPE20 polypeptide and the second nucleic acid molecule encoding the PE18 polypeptide; the immunogenic composition including the first nucleic acid molecule encoding the PPE20 polypeptide and the PE18 polypeptide and the second nucleic acid molecule encoding the EsxG polypeptide; the immunogenic composition including the first nucleic acid molecule encoding the PE18 polypeptide and the EsxG polypeptide and the second nucleic acid molecule encoding the PPE20 polypeptide; or the immunogenic composition including the first nucleic acid molecule encoding the PPE20 polypeptide, the second nucleic acid molecule encoding the EsxG polypeptide, and the third nucleic acid molecule encoding the PE18 polypeptide) is composed of DNA and includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 43-45, 59-61, and 75-77. In some embodiments of the third aspect, the nucleic acid molecule of any one of (II)(b) through (II)(e) (e.g., the immunogenic composition including the first nucleic acid molecule encoding the EsxG polypeptide and the PPE20 polypeptide and the second nucleic acid molecule encoding the PE18 polypeptide; the immunogenic composition including the first nucleic acid molecule encoding the PPE20 polypeptide and the PE18 polypeptide and the second nucleic acid molecule encoding the EsxG polypeptide; the immunogenic composition including the first nucleic acid molecule encoding the PE18 polypeptide and the EsxG polypeptide and the second nucleic acid molecule encoding the PPE20 polypeptide; or the immunogenic composition including the first nucleic acid molecule encoding the PPE20 polypeptide, the second nucleic acid molecule encoding the EsxG polypeptide, and the third nucleic acid molecule encoding the PE18 polypeptide) is composed of RNA (e.g., mRNA) and includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 169-171, 185-187, 201-203, 217-219, 233-235, and 249-251. In some embodiments of the third aspect, the immunogenic composition further includes: (a) an fbpB polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (b) a PPE51 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 5; (c) an EsxR polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 6; (d) an eccD3 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 7; (e) a PPE2 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 8; (f) a PPE3 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 9; (g) an EsxS polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 10; (h) a PPE46 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 11; (i) a PPE30 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 12; (j) a PPE11 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 13; (k) a PPE4 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 14; (l) an Mpt70 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 15; (m) a PE19 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 16; (n) a PPE18 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 17; (o) an fbpA polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 18; (p) an EsxH polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 19; and / or (q) a pepA polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 20. In some embodiments of the third aspect, the immunogenic composition includes or encodes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); and (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). In embodiments in which the immunogenic composition includes a nucleic acid molecule(s) that encodes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, the nucleic acid molecule(s) is mRNA. In another embodiment, the immunogenic composition may be formulated as an mRNA vaccine (e.g., a trivalent vaccine, such as, a self-amplifying mRNA vaccine). In some embodiments of the third aspect, the immunogenic composition includes or encodes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788); and (d) the fbpB polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25- 75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 4; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807-809, 827-836, 842-846, 862- 869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). In embodiments in which the immunogenic composition includes a nucleic acid molecule(s) that encodes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, the nucleic acid molecule(s) is mRNA. In another embodiment, the immunogenic composition may be formulated as an mRNA vaccine (e.g., a quadrivalent vaccine, such as, e.g., a self-amplifying mRNA vaccine). In some embodiments of the third aspect, the immunogenic composition further includes an additional nucleic acid molecule composed of DNA, wherein said additional nucleic acid molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 46-58, 62-74, and 78-102. In some embodiments of the third aspect, the immunogenic composition further includes an additional nucleic acid molecule composed of RNA (e.g., mRNA), wherein said additional nucleic acid molecule includes a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 172-184, 188-200, 204-216, 220-232, 236-248, and 252-288. In some embodiments of the third aspect, the immunogenic composition is a DNA molecule (e.g., a DNA expression vector) including each said nucleic acid molecule (e.g., any one or more of SEQ ID NOs: 43-102 or a variant thereof with at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity thereto). In some embodiments of the third aspect, the immunogenic composition is an RNA molecule (e.g., an mRNA molecule) including each said nucleic acid molecule (e.g., any one or more of SEQ ID NOs: 169-288 or a variant thereof with at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity thereto). In some embodiments of the third aspect, the mRNA molecule is a self- replicating mRNA molecule. In some embodiments of the third aspect, the RNA molecule (e.g., mRNA molecule) is formulated in an LNP, an exosome, or a liposome. In some embodiments of the third aspect, the mRNA molecule is formulated in an LNP. In some embodiments of the third aspect, the self- replicating mRNA molecule is formulated in an LNP. In some embodiments of the third aspect, the immunogenic composition further includes: (a) a pharmaceutically acceptable vehicle, diluent, excipient and / or adjuvant; and / or (b) one or more live attenuated vaccines selected from BCG, MTBVAC, VPM1002, DAR-901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72, RUTI, H107, or CysVac2 / Advax. In some embodiments of the third aspect, the immunogenic composition includes the BCG vaccine. In some embodiments of any of the foregoing aspects, the immunogenic composition is in lyophilized, solid, or liquid form. In some embodiments of any of the foregoing aspects, the immunogenic composition is formulated in liquid form for subcutaneous, intradermal, intravenous, intramuscular, transdermal, parenteral, intranasal, respiratory, perioral, sublingual, or oral, administration. In some embodiments of any of the foregoing aspects, the immunogenic composition is capable of inducing an immune response in a human. In some embodiments of any of the foregoing aspects, the immune response is mediated by major histocompatibility complex (MHC) class II. In some embodiments of any of the foregoing aspects, the immunogenic composition is a vaccine. In yet another aspect of any of the foregoing aspects, the disclosure features a method of inducing an immune response in a subject, the method including administering the immunogenic composition of any one of the foregoing aspects to the subject. In some embodiments of any of the foregoing aspects, the administration of the immunogenic composition treats and / or reduces the symptoms of a disease. In some embodiments of any of the foregoing aspects, the method: (a) reduces the likelihood of reemergence of the disease from latency; (b) reduces sequela of the disease; and / or (c) reduces the transmissibility of the disease. In some embodiments of any of the foregoing aspects, the disease is an infectious disease. In some embodiments of any of the foregoing aspects, the infectious disease is caused by one or more bacteria. In some embodiments of any of the foregoing aspects, the one or more bacteria are Mycobacterium spp. In some embodiments of any of the foregoing aspects, the at least one Mycobacterium spp. is selected from M. tuberculosis, M. leprae, M. bovis, M. africanum, M. avium, M. canetti, M. chelonae, M. fortuitum, M. gordonae, M. hiberniae, M. intracellulare, M. kansasii, M. marinum, M. microti, M. paratuberculosis, M. phlei, M. pinnipedii, M. scrofulaceum, M. simiae, M. smegmatis, M. szulgai, M. ulcerans, M. vacca, and M. xenopi. In some embodiments of any of the foregoing aspects, the at least one Mycobacterium spp. is M. tuberculosis. In some embodiments of any of the foregoing aspects, the disease is tuberculosis. In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as a single dose. In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as two doses. In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as three doses. In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as four doses. In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as five doses. In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as a plurality (e.g., one, two, three, four, five, six, seven, eight, nine, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or more) of doses. In some embodiments of any of the foregoing aspects, the doses are administered at least one day apart. In some embodiments of any of the foregoing aspects, said plurality of doses are administered at least one day, one week, two weeks, four weeks, eight weeks, 12 weeks, 6 month, 12 months, 18 months, or 24 months apart. In some embodiments of any of the foregoing aspects, the immunogenic composition includes one or more said nucleic acid molecules and the dose or plurality of doses are administered to the subject at a fixed dose of about 10 µg to 100 µg, 10 µg to 50 µg, 25 µg to 75 µg, or 50 µg to 100 µg (e.g., 10 µg, 11 µg, 12 µg, 13 µg, 14 µg, 15 µg, 16 µg, 17 µg, 18 µg, 19 µg, 20 µg, 21 µg, 22 µg, 23 µg, 24 µg, 25 µg, 26 µg, 27 µg, 28 µg, 29 µg, 30 µg, 31 µg, 32 µg, 33 µg, 34 µg, 35 µg, 36 µg, 37 µg, 38 µg, 39 µg, 40 µg, 41 µg, 42 µg, 43 µg, 44 µg, 45 µg, 46 µg, 47 µg, 48 µg, 49 µg, 50 µg, 51 µg, 52 µg, 53 µg, 54 µg, 55 µg, 56 µg, 57 µg, 58 µg, 59 µg, 60 µg, 61 µg, 62 µg, 63 µg, 64 µg, 65 µg, 66 µg, 67 µg, 68 µg, 69 µg, 70 µg, 71 µg, 72 µg, 73 µg, 74 µg, 75 µg, 76 µg, 77 µg, 78 µg, 79 µg, 80 µg, 81 µg, 82 µg, 83 µg, 84 µg, 85 µg, 86 µg, 87 µg, 88 µg, 89 µg, 90 µg, 91 µg, 92 µg, 93 µg, 94 µg, 95 µg, 96 µg, 97 µg, 98 µg, 99 µg, or 100 µg) of the immunogenic composition (e.g., the immunogenic composition containing the DNA molecule and / or the mRNA molecule, or multiple difference DNA and / or RNA molecules). In some embodiments of any of the foregoing aspects, the immunogenic composition includes one or more said nucleic acid molecules and the dose or plurality of doses are administered to the subject at a weight-based dose of about 0.01 µg / kg to 3 µg / kg (e.g., 0.01 µg / kg, 0.02 µg / kg, 0.03 µg / kg, 0.04 µg / kg, 0.05 µg / kg, 0.06 µg / kg, 0.07 µg / kg, 0.08 µg / kg, 0.09 µg / kg, 0.1 µg / kg, 0.2 µg / kg, 0.3 µg / kg, 0.4 µg / kg, 0.5 µg / kg, 0.6 µg / kg, 0.7 µg / kg, 0.8 µg / kg, 0.9 µg / kg, 1 µg / kg, 1.1 µg / kg, 1.2 µg / kg, 1.3 µg / kg, 1.4 µg / kg, 1.5 µg / kg, 1.6 µg / kg, 1.7 µg / kg, 1.8 µg / kg, 1.9 µg / kg, 2 µg / kg, 2.5 µg / kg, or 3 µg / kg) of the immunogenic composition (e.g., the immunogenic composition containing the DNA molecule and / or the mRNA molecule, or multiple different DNA and / or RNA molecules). In some embodiments of any of the foregoing aspects, the immunogenic composition includes one or more said polypeptides and the dose or plurality of doses are administered to the subject at a fixed dose of about 1 mg to 5000 mg (e.g., 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95 mg, 96 mg, 97 mg, 98 mg, 99 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, 2500 mg, 2600 mg, 2700 mg, 2800 mg, 2900 mg, 3000 mg, 3100 mg, 3200 mg, 3300 mg, 3400 mg, 3500 mg, 3600 mg, 3700 mg, 3800 mg, 3900 mg, 4000 mg, 4100 mg, 4200 mg, 4300 mg, 4400 mg, 4500 mg, 4600 mg, 4700 mg, 4800 mg, 4900 mg, or 5000 mg) of the immunogenic composition (e.g., the immunogenic composition containing the polypeptide, or a combination of the polypeptides). In some embodiments of any of the foregoing aspects, the immunogenic composition includes one or more said polypeptides and the dose or plurality of doses are administered to the subject at a weight-based dose of about 0.01 µg / kg to 100 mg / kg of the immunogenic composition (e.g., 0.01 mg / kg, 0.05 mg / kg, 0.10 mg / kg, 0.25 mg / kg, 0.50 mg / kg, 0.75 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, 50 mg / kg, 51 mg / kg, 52 mg / kg, 53 mg / kg, 54 mg / kg, 55 mg / kg, 56 mg / kg, 57 mg / kg, 58 mg / kg, 59 mg / kg, 60 mg / kg, 61 mg / kg, 62 mg / kg, 63 mg / kg, 64 mg / kg, 65 mg / kg, 66 mg / kg, 67 mg / kg, 68 mg / kg, 69 mg / kg, 70 mg / kg, 71 mg / kg, 72 mg / kg, 73 mg / kg, 74 mg / kg, 75 mg / kg, 76 mg / kg, 77 mg / kg, 78 mg / kg, 79 mg / kg, 80 mg / kg, 81 mg / kg, 82 mg / kg, 83 mg / kg, 84 mg / kg, 85 mg / kg, 86 mg / kg, 87 mg / kg, 88 mg / kg, 89 mg / kg, 90 mg / kg, 91 mg / kg, 92 mg / kg, 93 mg / kg, 94 mg / kg, 95 mg / kg, 96 mg / kg, 97 mg / kg, 98 mg / kg, 99 mg / kg, or 100 mg / kg of the immunogenic composition, e.g., the immunogenic composition containing the polypeptide, or a combination of polypeptides). In some embodiments of any of the foregoing aspects, the immunogenic composition includes (i) a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, or (ii) a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and an fbpB polypeptide, and the dose or plurality of doses are administered to the subject at a weight-based dose of about 0.01 µg / kg to 100 mg / kg of the immunogenic composition (e.g., 0.01 mg / kg, 0.05 mg / kg, 0.10 mg / kg, 0.25 mg / kg, 0.50 mg / kg, 0.75 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, 50 mg / kg, 51 mg / kg, 52 mg / kg, 53 mg / kg, 54 mg / kg, 55 mg / kg, 56 mg / kg, 57 mg / kg, 58 mg / kg, 59 mg / kg, 60 mg / kg, 61 mg / kg, 62 mg / kg, 63 mg / kg, 64 mg / kg, 65 mg / kg, 66 mg / kg, 67 mg / kg, 68 mg / kg, 69 mg / kg, 70 mg / kg, 71 mg / kg, 72 mg / kg, 73 mg / kg, 74 mg / kg, 75 mg / kg, 76 mg / kg, 77 mg / kg, 78 mg / kg, 79 mg / kg, 80 mg / kg, 81 mg / kg, 82 mg / kg, 83 mg / kg, 84 mg / kg, 85 mg / kg, 86 mg / kg, 87 mg / kg, 88 mg / kg, 89 mg / kg, 90 mg / kg, 91 mg / kg, 92 mg / kg, 93 mg / kg, 94 mg / kg, 95 mg / kg, 96 mg / kg, 97 mg / kg, 98 mg / kg, 99 mg / kg, or 100 mg / kg of the immunogenic composition). In some embodiments of any of the foregoing aspects, the immunogenic composition is administered as either a priming component or a boosting component in a prime-boost regimen, or both. In some embodiments of any of the foregoing aspects, the prime-boost regimen is a homologous prime-boost regimen including a priming step and a boosting step, wherein the priming step and the boosting step includes administration of the immunogenic composition. In some embodiments of any of the foregoing aspects, the prime-boost regimen is a heterologous prime-boost regimen including a priming step and a boosting step, wherein the priming step includes administration of the immunogenic composition. In some embodiments of any of the foregoing aspects, the boosting step includes administration of a second, different immunogenic composition. In some embodiments of any of the foregoing aspects, the prime-boost regimen is a heterologous prime- boost regimen including a priming step and a boosting step, wherein the boosting step includes administration of the pharmaceutical composition. In some embodiments of any of the foregoing aspects, the priming step includes administration of a second, different immunogenic composition. In a fourth aspect, the disclosure features an LNP, an exosome, or a liposome including the immunogenic composition of any one of the foregoing aspects. In a fifth aspect, the disclosure features a kit including the immunogenic composition, the LNP, the exosome, or the liposome of any one of the foregoing aspects. In some embodiments, the kit is used in the method of any of the foregoing aspects. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings are included to illustrate embodiments of the disclosure and further an understanding of its implementations. FIG.1 are graphs showing the results of a confirmatory in vivo screen of candidate CD4 T cell vaccine antigens, as measured by lung CFU. Antigens demonstrating ≥2.5-fold protection in the primary in vivo screen were selected for a secondary confirmatory screen. CB6F1 females underwent 50 μg prime-boost IM immunization followed by 50-100 CFU aerosol challenge and lung bacterial load quantification by agar outgrowth assay. * P<0.05, ** P<0.01, *** P<0.001, **** P<0.0001. FIG.2 is a graph showing the quantification of CD4 IFN-γ response after an mRNA-LNP vaccination with the indicated antigens. Groups of CB6F1 mice were primed at week 0 and boosted at week 4 followed by splenocyte ICS with overlapping peptide pools at week 6 to measure CD4 IFN-γ response. Bars are group medians. P values represent Mann-Whitney U tests compared to naïve groups. * P<0.05, ** P<0.01. FIG.3A is a graph showing the quantification of CD4 TNF-α response after an mRNA-LNP vaccination. Groups of CB6F1 mice were primed at week 0 and boosted at week 4 followed by splenocyte ICS with overlapping peptide pools at week 6 to measure CD4 TNF-α response. FIG.3B is a graph showing the quantification of CD4 IL-2 response after an mRNA-LNP vaccination with the indicated antigens. Groups of CB6F1 mice were primed at week 0 and boosted at week 4 followed by splenocyte ICS with overlapping peptide pools at week 6 to measure CD4 IL-2 responses. FIG.3C is a graph showing the quantification of CD8 IFN-γ response after an mRNA-LNP vaccination with the indicated antigens. Groups of CB6F1 mice were primed at week 0 and boosted at week 4 followed by splenocyte ICS with overlapping peptide pools at week 6 to measure CD8 IFN-γ response. FIG.3D is a graph showing the quantification of lung protection in a second cohort of mice that underwent 50-100 CFU H37Rv aerosol challenge at week 6 for lung harvest and bacterial load quantification at week 10. FIG.4 is a graph showing the quantification CD4 IFN-γ response after a single or multivalent antigen mRNA-LNP vaccination with the indicated antigens. Groups of CB6F1 mice were primed at week 0 and boosted at week 4 followed by splenocyte ICS with overlapping peptide pools at week 6 to measure CD4 IFN-γ response. Bars are group medians. P values represent Mann-Whitney U tests compared to naïve groups. * P<0.05, ** P<0.01. FIG.5 is a graph showing the quantification of lung protection in a second cohort of mice that underwent 50-100 CFU H37Rv aerosol challenge at week 6 for lung harvest and bacterial load quantification at week 10. Total mRNA-LNP vaccine dose was 20 μg for all mRNA-LNP groups. FIG 6. is a graph showing the quantification of immunogenicity of a tetravalent mRNA-LNP vaccine alone or in combination with BCG. In brief, groups of CB6F1 mice were primed at week 0 with BCG, tetravalent mRNA-LNP vaccine, or both and boosted at week 4 followed by splenocyte ICS with overlapping peptide pools and PPD at week 6 to measure CD4 IFN-γ responses. Bars are group medians. P values represent Mann-Whitney U tests compared to naïve groups. * P<0.05, ** P<0.01. FIG.7A is a bar graph of 42 antigens screened and their fold reduction in lung CFU, relative to control. These data show the protective efficacy of LTB CD4 and selected clinical antigens. Briefly, groups of CB6F1 mice were primed and boosted 50 μg of DNA followed by 100 CFU H37Rv aerosol challenge, lung harvest, and bacterial load quantification. Dots represent individual mice and histograms represent the median fold reduction in lung CFU per vaccine antigen group relative to an internal naïve control. LTB CD4 antigens are shown in order of decreasing immunodominance. At least eight protective antigens (e.g., Rv1387, Rv1886c, Rv0287, Rv3804c, Rv0280, Rv3020c, Rv1788, and Rv0256c) were identified. FIG.7B is a graph showing the protective efficacy of screened antigens. Dots represent the median fold reduction in lung CFU for individual antigens relative to naïve. P value represents a Mann-Whitney U test. ** represents P<0.01. FIG.7C is a graph showing splenocyte Th1 responses to the 8 protective antigens from FIG. 7A after 50 μg DNA prime-boost immunization and ex vivo stimulation with overlapping peptide pools. FIG.7D is a graph showing splenocyte CD8 IFN-γ responses to the 8 protective antigens described in FIG.7A. FIG.7E is a boolean analysis of Th1 responses described in FIG.7C. FIG.7F is a graph showing splenocyte Th1 responses to selected non-protective antigens described in FIG.7A. FIG.8A is a schematic of in vivo screening pipeline strategy. Briefly, 42 codon-optimized ORFs were cloned in pcDNA3.1(+) mammalian expression plasmids followed by 50 μg prime-boost immunization in CB6F1 mice, 100 CFU H37Rv aerosol challenge, lung harvest, and bacterial load quantification by agar outgrowth assay at the indicated timepoints. FIG.8B is a graph of the DNA vaccine screen of the eight protective outliers identified as having ≥2.5-fold (0.40 log10) bacterial load reduction in the primary screen. Briefly, groups of mice underwent the same immunization, challenge and harvest scheme as in FIG.8A. P values represent Mann Whitney U tests. * represents P<0.05, ** represents P<0.01, *** represents P<0.001, and **** represents P<0.0001. FIG.8C are images showing the flow cytometry gating strategy for ICS data shown in FIGS. 7B-E. FIG 9A is a phylogenetic analysis using a Tamura-Nei genetic distance model of screened antigens showing clustering of protective outliers. Eight protective antigens (e.g., Rv1387, Rv1886c, Rv0287, Rv3804c, Rv0280, Rv3020c, Rv1788, and Rv0256c) are segregated into four phylogenetic clusters. FIG.9B shows a series of graphs quantifying splenocyte CD4 Th1 (IFN-γ, TNF-α, and IL-2) responses in CB6F1 mice vaccinated with the indicated antigen followed by ex vivo stimulation with overlapping peptide pools from autologous and heterologous antigens from each cluster identified in FIG.9A. FIG.9C shows a series of graphs quantifying splenocyte CD4 Th1 (IFN-γ, TNF-α, and IL-2) responses in CB6F1 mice vaccinated with the indicated antigen followed by ex vivo stimulation with overlapping peptide pools from autologous and heterologous antigens from each cluster identified in FIG.9A. FIG.9D shows a series of graphs quantifying splenocyte CD4 Th1 (IFN-γ, TNF-α, and IL-2) responses in CB6F1 mice vaccinated with the indicated antigen followed by ex vivo stimulation with overlapping peptide pools from autologous and heterologous antigens from each cluster identified in FIG.9A. FIG.9E shows a series of graphs quantifying splenocyte CD4 Th1 (IFN-γ, TNF-α, and IL-2) responses in CB6F1 mice vaccinated with the indicated antigen followed by ex vivo stimulation with overlapping peptide pools from autologous and heterologous antigens from each cluster identified in FIG.9A. FIG.9F is a sequence alignment of the two most immunodominant and conserved regions from the given phylogenetic cluster identified in FIG.9A. Black boxes represent amino acid positions with 100% sequence homology, grey boxes represent positions with partial homology, and white boxes represent positions with 0% homology. Bars below sequence alignments represent the position of the most immunodominant CD4 peptide for each antigen region. FIG.9G is a sequence alignment of the two most immunodominant and conserved regions from the given phylogenetic cluster identified in FIG.9A. Black boxes represent amino acid positions with 100% sequence homology, grey boxes represent positions with partial homology, and white boxes represent positions with 0% homology. Bars below sequence alignments represent the position of the most immunodominant CD4 peptide for each antigen region. FIG.9H is a sequence alignment of the two most immunodominant and conserved regions from the given phylogenetic cluster identified in FIG.9A. Black boxes represent amino acid positions with 100% sequence homology, grey boxes represent positions with partial homology, and white boxes represent positions with 0% homology. Bars below sequence alignments represent the position of the most immunodominant CD4 peptide for each antigen region. FIG.9I is a sequence alignment of the two most immunodominant and conserved regions from the given phylogenetic cluster identified in FIG.9A. Black boxes represent amino acid positions with 100% sequence homology, grey boxes represent positions with partial homology, and white boxes represent positions with 0% homology. Bars below sequence alignments represent the position of the most immunodominant CD4 peptide for each antigen region. FIG.10A is a graph showing a 10-peptide subpool CD4 T cell reactivity analysis of the given antigen from the high molecular weight Rv1387-Rv0280-Rv0256c phylogenetic cluster in CB6F1 mice. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10B is a graph showing a 10-peptide subpool CD4 T cell reactivity analysis of the given antigen from the high molecular weight Rv1387-Rv0280-Rv0256c phylogenetic cluster in CB6F1 mice. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10C is a graph showing a 10-peptide subpool CD4 T cell reactivity analysis of the given antigen from the high molecular weight Rv1387-Rv0280-Rv0256c phylogenetic cluster in CB6F1 mice. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10D is a graph showing a single peptide (Rv1387) deconvolution for subpool 1 from the Rv1387-Rv0280-Rv0256c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10E is a graph showing a single peptide (Rv0280) deconvolution for subpool 1 from the Rv1387-Rv0280-Rv0256c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10F is a graph showing a single peptide (Rv0256c) deconvolution for subpool 1 from the Rv1387-Rv0280-Rv0256c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10G is a graph showing a single peptide (Rv1387) deconvolution for subpool 3 from the Rv1387-Rv0280-Rv0256c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10H is a graph showing a single peptide (Rv0280) deconvolution for subpool 3 from the Rv1387-Rv0280-Rv0256c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10I is a graph showing a single peptide (Rv0256c) deconvolution for subpool 3 from the Rv1387-Rv0280-Rv0256c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10J is a graph showing a single peptide CD4 T cell reactivity analysis of the given antigen from the low molecular weight Rv0287-Rv3020c protective antigen phylogenetic cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10K is a graph showing a single peptide CD4 T cell reactivity analysis of the given antigen from the low molecular weight Rv0287-Rv3020c protective antigen phylogenetic cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10L is a graph showing a single peptide CD4 T cell reactivity analysis of the given antigen from the low molecular weight Rv1788-Rv1791 protective antigen phylogenetic cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10M is a graph showing a single peptide CD4 T cell reactivity analysis of the given antigen from the low molecular weight Rv1788-Rv1791 protective antigen phylogenetic cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10N is a graph showing a 5-peptide subpool CD4 T cell reactivity analysis of the given antigen from the high molecular weight Rv1886c-Rv3804c protective antigen phylogenetic cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10O is a graph showing a 5-peptide subpool CD4 T cell reactivity analysis of the given antigen from the high molecular weight Rv3804c-Rv3804c protective antigen phylogenetic cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10P is a graph showing a single peptide deconvolution of the given antigen for subpools 6 and 13 from the Rv1886c-Rv3804c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.10Q is a graph showing a single peptide deconvolution of the given antigen for subpools 6 and 13 from the Rv3804c protective antigen cluster. “Pool” stimulation refers to overlapping peptides spanning the entire matching antigen. FIG.11A is a graph showing splenocyte CD4 Th1 responses after 5 μg mRNA-LNP prime- boost immunization in CB6F1 mice and ex vivo splenocyte overlapping peptide stimulation for each given antigen. FIG.11B is a boolean analysis of splenocyte CD4 Th1 responses after 5 μg mRNA-LNP prime-boost immunization in CB6F1 mice and ex vivo splenocyte overlapping peptide stimulation for each given antigen. FIG.11C is a graph showing splenocyte CD8 IFN-γ responses after 5 μg mRNA-LNP prime- boost immunization in CB6F1 mice and ex vivo splenocyte overlapping peptide stimulation for each given antigen. FIG.11D is a graph comparing the CD4 non-IFN-γ+ / IFN-γ+ratio after DNA or mRNA-LNP vaccine delivery of the given antigens. P values represent Mann-Whitney U tests. ** represents P<0.01. FIG.11E is a graph comparing the IFN-γ+fraction of total Th1 response after DNA or mRNA- LNP vaccine delivery of the given antigens. P values represent Mann-Whitney U tests. * represents p<0.05; ** represents P<0.01. FIG.11F is a graph showing the protective efficacy of CD4 antigens after 5 μg mRNA-LNP prime-boost immunization, 100 CFU H37Rv aerosol challenge, and lung harvest for bacterial load quantification. P values represent Mann-Whitney U tests for comparisons relative to the naïve group. *** represents P<0.001 and **** represents P<0.0001. FIG.11G is a graph comparing the protective efficacy of eight CD4 antigens delivered with the DNA of mRNA-LNP vaccine platform. P value represents a Wilcoxon matched-pairs rank test. ** represents P<0.01. FIG.11H is a graph showing splenocyte CD4 IFN-γ+responses after prime-boost trivalent or tetravalent mRNA-LNP immunization (aggregate 20 μg dose divided evenly among antigens). P values represent Mann-Whitney U tests for comparisons relative to the matched antigen in the naïve group. ** represents P<0.01. FIG.11I is a graph showing the protective efficacy of CD4 antigens after prime-boost trivalent or tetravalent mRNA-LNP immunization (aggregate 20 μg dose divided evenly among antigens), 100 CFU H37Rv aerosol challenge, and lung harvest for bacterial load quantification. P values represent Mann-Whitney U tests for comparisons relative to the naïve group. **** represents P<0.0001. FIG.12A shows the experimental design for splenocyte ICS studies with monovalent mRNA- LNP vaccine studies with selected CD4 antigens. FIG.12B is a graph comparing TNF-α+ fractions after DNA or mRNA-LNP vaccine delivery of CD4 antigens. P values represent Mann-Whitney U tests. ** represents P<0.01. FIG.12C is a graph comparing TNF-α+IL-2+ fractions after DNA or mRNA-LNP vaccine delivery of CD4 antigens. P values represent Mann-Whitney U tests. ** represents P<0.01. FIG.12D shows the experimental design for 100 CFU aerosol challenge studies with monovalent mRNA-LNP vaccine studies with selected CD4 antigens. FIG.12E is a graph showing the protective efficacy of CD4 antigens after 5 μg mRNA-LNP prime-boost immunization, 100 CFU H37Rv aerosol challenge, and lung harvest for bacterial load quantification. P values represent Mann-Whitney U tests for comparisons relative to the naïve group. * represents P<0.05 and ** represents P<0.01. FIG.12F is a graph showing splenocyte CD4 IFN-γ+responses after prime-boost mRNA-LNP immunization (aggregate 20 μg dose divided evenly among antigens for all groups). P values represent Mann-Whitney U tests for comparisons relative to the matched antigen in the naïve group. ** represents P<0.01. FIG.12G is a graph showing splenocyte CD8 IFN-γ+responses after prime-boost mRNA-LNP immunization (aggregate 20 μg dose divided evenly among antigens for all groups). P values represent Mann-Whitney U tests for comparisons relative to the matched antigen in the naïve group. ** represents P<0.01. FIG.12H is a graph showing the protective efficacy of CD4 antigens after prime-boost mRNA- LNP immunization (aggregate 20 μg dose divided evenly among antigens for all groups), 100 CFU H37Rv aerosol challenge, and lung harvest for bacterial load quantification. P values represent Mann- Whitney U tests for comparisons relative to the naïve group. **** represents P<0.0001. FIG.13A is a graph showing antigen-specific, splenocyte CD4 IFN-γ+responses after BCG prime (“BCG”) or BCG in combination with 15 μg trivalent mRNA-LNP prime-boost (“+RNA”) immunization. P values represent Mann-Whitney U tests for antigen-specific comparisons between the BCG and combination groups. ** represents P<0.01. FIG.13B is a graph of lung CD4 IFN-γ+responses in the same animals described in FIG. 13A. FIG.13C is a graph showing the protective efficacy of BCG prime (“BCG”) or BCG prim with 15 μg trivalent mRNA-LNP prime-boost (“+RNA”) immunization after 100 CFU H37Rv aerosol challenge and lung harvest for bacterial load quantification. P values represent Mann-Whitney U tests. *** represents P<0.001 and **** represents P<0.0001. FIG.13D is a graph showing left and right lung lobe bacterial loads in naïve mice followed by 1 MID50 H37Rv aerosol challenge and lung lobe harvest for bacterial load quantification. FIG.13E is a graph showing left and right lung lobe bacterial loads after BCG prime followed by 1 MID50 H37Rv aerosol challenge and lung lobe harvest for bacterial load quantification. FIG.13F is a graph showing left and right lung lobe bacterial loads after BCG prime with 15 μg trivalent mRNA-LNP prime-boost followed by 1 MID50 H37Rv aerosol challenge and lung lobe harvest for bacterial load quantification. FIG.13G is a graph comparing the infection rates between the given vaccine groups after 1-3 CFU H37Rv aerosol challenge. P values represent Fisher’s exact tests. * represents P<0.05. BCG prime immunization = “BCG”; a combination of BCG prime immunization and 15 μg trivalent mRNA- LNP prime-boost immunization = “+RNA.” FIG.13H is a graph comparing the bilateral lung lobe dissemination rates among infected mice between the given vaccine groups after 1-3 CFU H37Rv aerosol challenge. P values represent Fisher’s exact tests. * represents P<0.05. BCG prime immunization = “BCG”; a combination of BCG prime immunization and 15 μg trivalent mRNA-LNP prime-boost immunization = “+RNA.” FIG.13I is a graph comparing the bacterial loads between the given vaccine groups after 1-3 CFU H37Rv aerosol challenge. P values represent mixed effects negative binomial models for each vaccine group relative to the naïve group. **** represents P<0.0001. BCG prime immunization = “BCG”; a combination of BCG prime immunization and 15 μg trivalent mRNA-LNP prime-boost immunization = “+RNA.” FIG.13J is a graph comparing left and right lung lobe bacterial loads after BCG prime followed by four weekly 0.3 MID50 H37Rv aerosol challenges and lung lobe harvest for bacterial load quantification. FIG.13K is a graph comparing left and right lung lobe bacterial loads after 15 μg trivalent mRNA-LNP prime-boost followed by four weekly 0.3 MID50 H37Rv aerosol challenges and lung lobe harvest for bacterial load quantification. FIG.13L is a graph comparing the infection rate of BCG and trivalent mRNA-LNP vaccination in mice. FIG.13M is a graph comparing the dissemination rate of BCG and trivalent mRNA-LNP vaccination in mice. FIG.14A shows the experimental design for splenocyte ICS studies after BCG prime (“BCG”) or a combination os BCG and 15 μg trivalent mRNA-LNP prime-boost (“+RNA”) immunization. FIG.14B is a graph showing splenocyte CD4 T cells responses to the immunodominant BCG antigen Rv0288 following the immunization scheme described in FIG.14A. FIG.14C is a graph showing antigen-specific, splenocyte CD8 IFN-γ responses following the immunization scheme described in FIG.14A. FIG.14D is a graph showing antigen-specific, lung CD8 IFN-γ responses following the immunization scheme described in FIG.14A. FIG.14E shows the experimental design for 100 CFU aerosol challenge after BCG prime (“BCG”) or a combination of BCG and 15 μg trivalent mRNA-LNP prime-boost (“+RNA”) immunization. FIG.14F shows the experimental design for 1 MID50 aerosol challenge after BCG prime (“BCG”) or a combination of BCG and 15 μg trivalent mRNA-LNP prime-boost (“+RNA”) immunization, and pre-challenge PBMC ICS for correlates of protection. FIG.14G is a graph showing PBMC CD4 IFN-γ responses following the immunization scheme described in FIG.14F and ex vivo stimulation with an aggregate peptide pool of Rv1387, Rv0287, and Rv1788. P values represents a Mann-Whitney U test. **** represents P<0.0001. FIG.14H is a graph showing PBMC CD8 IFN-γ responses following the immunization scheme described in FIG.14F and ex vivo stimulation with an aggregate peptide pool of Rv1387, Rv0287, and Rv1788. FIG.14I is a graph showing PBMC CD4 IL-17 responses following the immunization scheme described in FIG.14F and ex vivo stimulation with an aggregate peptide pool of Rv1387, Rv0287, and Rv1788. P values represent Mann-Whitney U tests. * represents P<0.05 and **** represents P<0.0001. FIG.14J is a graph showing spleen CD4 IL-17 responses following the immunization scheme in FIG.14A. FIG.14K is a graph showing lung CD4 IL-17 responses following the immunization scheme described in FIG.14A. FIG.14L shows the experimental design for repeated 0.3 MID50 challenge studies after BCG prime or 15 μg trivalent mRNA-LNP prime-boost immunization. FIG.15 is a correlogram showing Spearman correlations between post-immunization, pre- challenge PBMC CD4 T cell subsets and bacterial loads among infected animals after 1-3 CFU aerosol challenge. DEFINTIONS Unless otherwise defined herein, scientific, and technical terms used herein have the meanings that are commonly understood by those of ordinary skill in the art. In the event of any latent ambiguity, definitions provided herein take precedent over any dictionary or extrinsic definition. Unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The use of "or" means "and / or" unless stated otherwise. The use of the term "including," as well as other forms, such as "includes" and "included," is not limiting. As used herein, the term "about," as applied to one or more values of interest, refers to a value that falls within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of a stated reference value, unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value). The term “adjuvant” refers to a pharmacological or immunological agent that modifies the effect of other agents (e.g., vaccines) while having few if any direct effects when given by itself. They are often included in vaccines to enhance the recipient's immune response to a supplied antigen while keeping the injected foreign material at a minimum. As used herein, by “administering” is meant a method of giving a dosage of a composition (e.g., a pharmaceutical composition (e.g., an immunogenic composition (e.g., a vaccine))) to a subject. The compositions utilized in the methods described herein can be administered, for example, intramuscularly, intravenously, intradermally, percutaneously, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intranasally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subcutaneously, subconjunctivally, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularly, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion bathing target cells directly, by catheter, by lavage, by gavage, in cremes, or in lipid compositions. The method of administration can vary depending on various factors (e.g., the components of the composition being administered and the severity of the condition being treated). An “antigen” refers to any agent, generally a macromolecule (e.g., a polypeptide of Table 2), which can elicit an immunological response in an individual. As used herein, “antigen” is generally used to refer to a polypeptide molecule or portion thereof (e.g., at least 12 contiguous amino acids thereof) which contains one or more epitopes. Furthermore, for the purposes of the present disclosure, an “antigen” also includes a polypeptide having modifications, such as deletions, additions, and substitutions (generally conservative in nature) to the native sequence, so long as the polypeptide maintains sufficient immunogenicity. These modifications may be deliberate, for example through site-directed mutagenesis, or may be accidental, such as through mutations of hosts which produce the antigens. As used herein, the term “epitope” generally refers to a site on a target antigen that is recognized by an immune receptor, such as a T-cell receptor and / or an antibody. An epitope may be a contiguous epitope, where the site recognized is a conformation of contiguous amino acid residues of a polypeptide, or a discontiguous epitope, where the site recognized is a portion of a folded polypeptide where the amino acid residues interacting with the immune receptor are not consecutive amino acids. The epitope may also include glycopeptides and carbohydrate epitopes. A single antigenic molecule may include several different epitopes. The term “immunogenic composition” as used herein, is defined as material used to provoke an immune response and may confer immunity after administration of the immunogenic composition (e.g., a vaccine) to a subject (e.g., human subject). An “immune response” against an antigen of interest is the development in a mammalian subject (e.g., a human subject) of a humoral and / or a cellular immune response to that antigen. For purposes of the present disclosure, a “humoral immune response” refers to an immune response mediated by antibody molecules, a “cellular immune response” is one mediated by T-lymphocytes and / or other white blood cells. In addition, “sufficient immunogenicity,” as referred to herein, means a magnitude of an immune response that is sufficient to treat disease (e.g., a Mycobacterium tuberculosis (Mtb) infection), prevent or reduce the chance of an infection (e.g., Mtb infection), to alleviate one or more symptoms of a disease (e.g., Mtb infection, e.g., tuberculosis (TB)), and / or to reduce a period of time during which a subject is suffering from a disease (e.g., Mtb infection, e.g., TB). A mammalian subject to be administered an immunogenic composition (e.g., a vaccine) disclosed herein may be any member of the subphylum cordata, including, without limitation, humans and other primates, including non-human primates, such as chimpanzees and other apes and monkey species; farm animals, such as cattle, sheep, pigs, goats, and horses; domestic mammals, such as dogs and cats; laboratory animals including rodents, such as mice, rats and guinea pigs; birds, including domestic, wild, and game birds, such as chickens, turkeys and other gallinaceous birds, ducks, geese, and the like. The terms do not denote a particular age. Thus, both adult and newborn individuals are intended to be covered. The methods described herein can be intended for use in any of the above vertebrate species, since the immune systems of all of these vertebrates operate similarly. The subject is preferably a human. “Percent (%) sequence identity” with respect to a reference polynucleotide or polypeptide sequence is defined as the percentage of nucleic acids or amino acids in a candidate sequence that are identical to the nucleic acids or amino acids in the reference polynucleotide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid or amino acid sequence identity can be achieved in various ways that are within the capabilities of one of skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, or Megalign software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For example, percent sequence identity values may be generated using the sequence comparison computer program BLAST. As an illustration, the percent sequence identity of a given nucleic acid or amino acid sequence, A, to, with, or against a given nucleic acid or amino acid sequence, B, (which can alternatively be phrased as a given nucleic acid or amino acid sequence, A that has a certain percent sequence identity to, with, or against a given nucleic acid or amino acid sequence, B) is calculated as follows: 100 multiplied by (the fraction X / Y) where X is the number of nucleotides or amino acids scored as identical matches by a sequence alignment program (e.g., BLAST) in that program’s alignment of A and B, and where Y is the total number of nucleic acids in B. It will be appreciated that where the length of nucleic acid or amino acid sequence A is not equal to the length of nucleic acid or amino acid sequence B, the percent sequence identity of A to B will not equal the percent sequence identity of B to A. As used herein, the term “polynucleotide” refers to a polymer of nucleosides. Typically, a polynucleotide is composed of nucleosides that are naturally found in DNA or RNA (e.g., adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine) joined by phosphodiester bonds. The term encompasses molecules comprising nucleosides or nucleoside analogs (e.g., pseudouridine (ψ)) containing chemically or biologically modified bases, modified backbones, etc., whether or not found in naturally occurring nucleic acids, and such molecules may be preferred for certain applications. Where this application refers to a polynucleotide it is understood that both DNA, RNA, and in each case both single- and double- stranded forms (and complements of each single-stranded molecule) are provided. "Polynucleotide sequence" as used herein can refer to the polynucleotide material itself and / or to the sequence information (i.e., the succession of letters used as abbreviations for bases) that biochemically characterizes a specific nucleic acid. A polynucleotide sequence presented herein is presented in a 5' to 3' direction unless otherwise indicated. By “pharmaceutically acceptable diluent, excipient, carrier, or adjuvant” is meant a diluent, excipient, carrier, or adjuvant that is physiologically acceptable to the subject while retaining the therapeutic properties of the immunogenic composition with which it is administered. One exemplary pharmaceutically acceptable carrier is physiological saline. Other physiologically acceptable diluents, excipients, carriers, or adjuvants and their formulations are known to one skilled in the art (see, e.g., U.S. Pub. No.2012 / 0076812). As used herein, the term “polypeptide” means a polymer of amino acid residues linked together by peptide bonds. The term, as used herein, refers to proteins, polypeptides, and peptides of any size, structure, or function. A polypeptide may be a single molecule or may be a multi-molecular complex such as a dimer, trimer or tetramer. The term polypeptide may also apply to amino acid polymers in which one or more amino acid residues are an artificial chemical analogue of a corresponding naturally occurring amino acid. As used herein, the term “prophylactically or therapeutically effective dose” means a dose in an amount sufficient to elicit an immune response to one or more epitopes of a polypeptide of the disclosure and / or to alleviate, reduce, cure or at least partially arrest symptoms and / or complications from a disease or infection. A “subject” is a vertebrate, such as a mammal (e.g., a primate and a human, in particular a human). Mammals also include, but are not limited to, farm animals (such as cows), sport animals (e.g., horses), pets (such as cats, and dogs), mice, rats, bats, civets, and raccoon dogs. A subject to be treated according to the methods described herein (e.g., a subject in need of protection from an Mtb infection or having an Mtb infection) may be one who has been diagnosed by a medical practitioner as having such a need or infection. Diagnosis may be performed by any suitable means. A subject in whom the development of an infection is being prevented may or may not have received such a diagnosis. One skilled in the art will understand that a subject to be treated according to the present invention may have been subjected to standard tests or may have been identified, without examination, as one with a suspected infection or at high risk of infection due to the presence of one or more risk factors (e.g., exposure to Mtb, for example, due to travel to an area where Mtb infection is prevalent). As used herein, the term “treatment,” in the context of treating subjects with or at risk of developing and / or transmitting disease, means an action taken that can eliminate, reduce, alleviate one or more symptoms or signs of disease; prevent, delay, or reduce a course of disease; prevent or reduce the likelihood of disease transmission; and / or prevent, eliminate, reduce, alleviate, or delay sequelae. Preferably, the action taken includes the compositions or methods described herein either alone or in combination with other known compositions or methods. The term “vaccine” as used herein, is defined as material used to provoke an immune response and that confers immunity for a period of time after administration of the vaccine to a subject. DETAILED DESCRIPTION The present disclosure provides therapeutic and prophylactic compositions, methods, and articles of manufacture for treating and / or preventing infectious disease, such as treating and / or reducing the likelihood of developing an infection with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). The compositions and methods described herein utilize an immunogenic composition (e.g., a vaccine) containing one or more polypeptides (e.g., antigens) and / or polynucleotides (e.g., vectors or mRNA molecules encoding an antigen) described herein. The invention is based, at least in part, on the discovery of several antigens that, when administered as a vaccine, provide improved protection from an Mtb infection. These antigens, whether administered as a polypeptide or encoded in a DNA expression vector or an mRNA molecule, are capable of inducing a robust immunological response (e.g., inducing the production of antigen-specific cytokine-secreting CD4+T cells) and provide improved protective efficacy from TB over other commercially available immunogenic compositions, such as the century-old Bacillus Calmette–Guérin (BCG) vaccine. I. IMMUNOGENIC COMPOSITIONS The present disclosure provides immunogenic compositions containing one or more of the polypeptides (e.g., antigens) and / or nucleic acid molecules (e.g., DNA and / or RNA encoding an antigen, e.g., a DNA vector and / or mRNA molecule encoding an antigen, or a portion thereof) described below. The immunogenic compositions of the disclosure may further include, or may be administered in combination with, one or more live attenuated vaccines (e.g., the BCG vaccine). The immunogenic compositions may be used for inducing an immune response in a subject, thereby providing a subject with a therapeutic or prophylactic effect against a bacterial (e.g., Mtb) infection and diseases caused thereby, such as TB. The present disclosure describes the following 42 antigens: PPE family protein PPE20 (PPE20), ESAT-6 like protein EsxG (EsxG), PE family protein PE18 (PE18), secreted antigen 85-B FbpB (fbpB), PPE family protein PPE51 (PPE51), secreted ESAT-6 like protein EsxR (EsxR), ESX conserved component EccD3 (eccD3), PPE family protein PPE2 (PPE2), PPE family protein PPE3 (PPE3), ESAT-6 like protein EsxS (EsxS), PPE family protein PPE46 (PPE46), PPE family protein PPE30 (PPE30), PPE family protein PPE11 (PPE11), PPE family protein PPE4 (PPE4), major secreted immunogenic protein Mpt70 (Mpt70), PE family protein PE19 (PE19), PPE family protein PPE18 (PPE18), secreted antigen 85-a FbpA (fbpA), low molecular weight protein antigen 7 EsxH (EsxH), and probable serine protease PepA (pepA). Any one or more of these antigens, either as a polypeptide or a nucleic acid molecule (e.g., DNA or mRNA molecule, e.g., a DNA vector) encoding said polypeptide (e.g., see Tables 2-4), may be formulated into a single composition of matter described herein, such as a pharmaceutical composition and / or a vaccine (e.g., a multivalent vaccine a self-amplifying RNA vaccine). Any number and any combination of the 42 antigens may be formulated into a pharmaceutical composition or a vaccine described herein. Exemplary combinations of antigens are provided in Table 1 below. While all possible bivalent, trivalent, quadrivalent, and pentavalent antigen combinations are provided in Table 1 (each box represents a vaccine combination), all other hexavalent, heptavalent, octovalent, enneavalent, decavalent, and 10+ valency vaccines are envisioned. Table 1. Exemplary Multi-valent Antigen Combinations

[0002]

[0003]

[0004]

[0005]

[0006]

[0007]

[0008]

[0009]

[0010]

[0011]

[0012]

[0013]

[0014]

[0015]

[0016]

[0017] A. Polypeptides The immunogenic composition may include at least one of the polypeptides listed in Table 2, or a portion thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide, such as at least 16 contiguous amino acids of the polypeptide). For example, the immunogenic composition may include at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or all 42 of the polypeptides listed in Table 2 or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. The immunogenic composition may include any number or combination of the 42 polypeptides listed in Table 2 (e.g., 1-35, 1-30, 1-25, 1-20, or 1-15 polypeptides, e.g., 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, or 42 of the polypeptides listed in Table 2), or a portion thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). The immunogenic composition may include any number or combination of up to 20 of the polypeptides listed in Table 2 (e.g., 1-19, 1-18, 1-17, 1-16, 1-15, 1-14, 1-13, 1-12, 1-11, 1-10, 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, or 1-2 of the polypeptides listed in Table 2) or a portion thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). The immunogenic composition may include any number or combination of up to 16 polypeptides of the polypeptides listed in Table 2 (e.g., 1-15, 1-14, 1-13, 1-12, 1-11, 1-10, 1-9, 1-8, 1- 7, 1-6, 1-5, 1-4, 1-3, or 1-2 of the polypeptides) or a portion thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). The immunogenic composition may include 1-4 polypeptides of the polypeptides listed in Table 2 (e.g., 1-2, 1-3, 2-3, or 2-4 of the polypeptides, e.g., 1, 2, 3, or 4 of the polypeptides) or a portion thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). The immunogenic composition may include 1-3 of the polypeptides, 1-2 of the polypeptides, or 1 polypeptide listed in Table 2, or a portion thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). In some embodiments, each polypeptide of the immunogenic composition may contain a portion of a polypeptide listed in Table 2 (e.g., see Tables 8A-8D), such as 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 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, or 96 contiguous amino acids, or all of the amino acids) of a polypeptide listed in Table 2 or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. This portion of the polypeptide may be an epitope capable of eliciting an immune response in a subject (e.g., see Table 8A-8D). For example, any one or more of SEQ ID NOs: 421-935 may be included in one or more polypeptides of the immunogenic composition or encoded by one or more nucleic acids (e.g., an mRNA) of the immunogenic composition. By way of example, and immunogenic composition can include a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, wherein the PPE20 polypeptide includes one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449), the EsxG polypeptide includes one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757), and the PE18 polypeptide includes one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). This immunogenic composition can further include an fbpB polypeptide, wherein the fbpB polypeptide includes one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807-809, 827-836, 842-846, 862-869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). Alternatively, the immunogenic composition can include one or more nucleic acid molecules encoding these polypeptides (e.g., an mRNA). In some embodiments, the immunogenic composition includes at least two different polypeptides (e.g., at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 different polypeptides), in which each of the at least two different polypeptides comprises at least 12 contiguous amino acids (at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83, at least 84, at least 85, at least 86, at least 87, at least 88, at least 89, at least 90, at least 91, at least 92, at least 93, at least 94, at least 95, or 96 contiguous amino acids, or all amino acids) of a polypeptide selected from the group consisting of: PPE family protein PPE20 (PPE20), ESAT-6 like protein EsxG (EsxG), PE family protein PE18 (PE18), secreted antigen 85-B FbpB (fbpB), PPE family protein PPE51 (PPE51), secreted ESAT-6 like protein EsxR (EsxR), ESX conserved component EccD3 (eccD3), PPE family protein PPE2 (PPE2), PPE family protein PPE3 (PPE3), ESAT-6 like protein EsxS (EsxS), PPE family protein PPE46 (PPE46), PPE family protein PPE30 (PPE30), PPE family protein PPE11 (PPE11), PPE family protein PPE4 (PPE4), major secreted immunogenic protein Mpt70 (mpt70), PE family protein PE19 (PE19), PPE family protein PPE18 (PPE18), secreted antigen 85-a FbpA (fbpA), low molecular weight protein antigen 7 EsxH (EsxH), probable serine protease PepA (pepA), cell surface lipoprotein Mpt83 (mpt83), PPE family protein PPE68 (PPE68), probable transposase for insertion sequence element IS1081 (Rv2666), PPE family protein PPE49 (PPE49), PPE family protein PPE47 (PPE47), PPE family protein PPE37 (PPE37), probable transposase (Rv1047), probable transposase (Rv1199c), probable tRNA (5-methylaminomethyl-2-thiouridylate)-methyltransferase TrmU (trmU), ESX-1 secretion-associated protein EspC (espC), ESX-3 secretion-associated protein EspG3 (espG3), probable penicillin-binding protein DacB1 (dacB1), PPE family protein PPE32 (PPE32), secreted antigen 85-C FbpC (fbpC), BCG-a heat shock protein (groES), 6 kDa early secretory antigenic target EsxA (esxA), 10 kDa culture filtrate antigen EsxB (esxB), hypothetical protein (Rv2660c), conserved hypothetical protein (Rv1813c), PPE family protein PPE42 (PPE42), putative ESAT-6 like protein EsxV (esxV), and putative ESAT-6 like protein EsxW (esxW). Exemplary amino acid sequences for these polypeptides are provided in Table 2. In some embodiments, the immunogenic composition includes at least two different polypeptides (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, or 16 different polypeptides), in which each of the at least two different polypeptides comprises at least 12 contiguous amino acids (at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, at least 42, at least 43, at least 44, at least 45, at least 46, at least 47, at least 48, at least 49, at least 50, at least 51, at least 52, at least 53, at least 54, at least 55, at least 56, at least 57, at least 58, at least 59, at least 60, at least 61, at least 62, at least 63, at least 64, at least 65, at least 66, at least 67, at least 68, at least 69, at least 70, at least 71, at least 72, at least 73, at least 74, at least 75, at least 76, at least 77, at least 78, at least 79, at least 80, at least 81, at least 82, at least 83, at least 84, at least 85, at least 86, at least 87, at least 88, at least 89, at least 90, at least 91, at least 92, at least 93, at least 94, at least 95, or 96 (or all) contiguous amino acids) of a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, and PE19. Optionally, the immunogenic composition may further include one or more additional polypeptides having at least 12 contiguous amino acids (e.g., 12-96, or all, contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of one or more polypeptides selected from the group consisting of: PPE18, fbpA, EsxH, and pepA. Exemplary amino acid sequences for these polypeptides are provided in Table 2. Table 2. Antigen Polypeptide Sequences

[0018] In some embodiments, the immunogenic composition includes any number or combination of different polypeptides, each of which includes an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 1-42. The composition may include a plurality of each different polypeptide. In some embodiments, the immunogenic composition includes any number or combination of different polypeptides, each of which includes an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 1-35. The composition may include a plurality of each different polypeptide. In some embodiments, the immunogenic composition includes any number or combination of different polypeptides, each of which includes an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 1-20. The composition may include a plurality of each different polypeptide. In some embodiments, the immunogenic composition includes any number or combination of different polypeptides, each of which includes an amino acid sequence having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 1-16. The composition may include a plurality of each different polypeptide. In some embodiments, the immunogenic composition includes two, three, or four different polypeptides, each of the polypeptides having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 1-4. The composition may include a plurality of each different polypeptide. In some embodiments, the immunogenic composition contains a PPE20 polypeptide, or a portion thereof, and an EsxG polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1 and 2, respectively. Optionally, the immunogenic composition can further include a PE18 polypeptide, or a portion thereof, and / or an fbpB polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 3 and / or 4, respectively. In some embodiments, the immunogenic composition contains a PPE20 polypeptide, or a portion thereof, and an PE18 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1 and 3, respectively. Optionally, the immunogenic composition can further include a EsxG polypeptide, or a portion thereof, and / or an fbpB polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 2 and / or 4, respectively. In some embodiments, the immunogenic composition contains a PPE20 polypeptide, or a portion thereof, and an fbpB polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1 and 4, respectively. Optionally, the immunogenic composition can further include an EsxG polypeptide, or a portion thereof, and / or a PE18 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 2 and / or 3, respectively. In some embodiments, the immunogenic composition contains an EsxG polypeptide, or a portion thereof, and an PE18 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 2 and 3, respectively. Optionally, the immunogenic composition can further include a PPE20 polypeptide, or a portion thereof, and / or an fbpB polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1 and / or 4, respectively. In some embodiments, the immunogenic composition contains an EsxG polypeptide, or a portion thereof, and an fbpB polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 2 and 4, respectively. Optionally, the immunogenic composition can further include a PPE20 polypeptide, or a portion thereof, and / or an PE18 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1 and 3, respectively. In some embodiments, the immunogenic composition contains a PE18 polypeptide, or a portion thereof, and an fbpB polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 3 and 4, respectively. Optionally, the immunogenic composition can further include a PPE20 polypeptide, or a portion thereof, and / or an EsxG polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1 and 2, respectively. In some embodiments, the immunogenic composition contains a PPE20 polypeptide, or a portion thereof, an EsxG polypeptide, or a portion thereof, and a PE18 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 1-3, respectively. Optionally, the immunogenic composition can further include an fbpB polypeptide or a portion thereof, a PPE51 polypeptide or a portion thereof, an EsxR polypeptide or a portion thereof, an eccD3 polypeptide or a portion thereof, a PPE2 polypeptide or a portion thereof, a PPE3 polypeptide or a portion thereof, an EsxS polypeptide or a portion thereof, a PPE46 polypeptide or a portion thereof, a PPE30 polypeptide or a portion thereof, a PPE11 polypeptide or a portion thereof, a PPE4 polypeptide or a portion thereof, an mpt70 polypeptide or a portion thereof, a PE19 polypeptide or a portion thereof, a PPE18 polypeptide or a portion thereof, an fbpA polypeptide or a portion thereof, an EsxH polypeptide or a portion thereof, a pepA polypeptide or a portion thereof, an mpt83 polypeptide or a portion thereof, a PPE68 polypeptide or a portion thereof, an Rv2666 polypeptide or a portion thereof, a PPE49 polypeptide or a portion thereof, a PPE47 polypeptide or a portion thereof, a PPE37 polypeptide or a portion thereof, an Rv1047 polypeptide or a portion thereof, an Rv1199c polypeptide or a portion thereof, a trmU polypeptide or a portion thereof, an espC polypeptide or a portion thereof, an espG3 polypeptide or a portion thereof, a dacB1 polypeptide or a portion thereof, a PPE32 polypeptide or a portion thereof, an fbpC polypeptide or a portion thereof, a groES polypeptide or a portion thereof, an esxA polypeptide or a portion thereof, an esxB polypeptide or a portion thereof, an Rv2660c polypeptide or a portion thereof, an Rv1813c polypeptide or a portion thereof, a PPE42 polypeptide or a portion thereof, an esxV polypeptide or a portion thereof, and / or an esxW polypeptide or a portion thereof having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to SEQ ID NOs: 4-42, respectively. In some embodiments, the immunogenic composition includes one or more of the following polypeptides, or a nucleic acid sequence (e.g., DNA, RNA, or mRNA) encoding said polypeptide: (a) a PPE20 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to any one or more of SEQ ID NOs: 421-526; (b) a EsxG polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 742-758; (c) a PE18 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 776-793; (d) a fbpB polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 807-869; (e) a PPE2 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 633-741; (f) a PPE3 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 527-632; (g) a ESXs polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 575 and 759-775; (h) a PE19 polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 783, 784, and 793-806; and / or (i) a fbpA polypeptide including an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one or more of SEQ ID NOs: 870-935. In some embodiments, the immunogenic composition includes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412- 450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); and (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12- 60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). In embodiments in which the immunogenic composition includes a nucleic acid molecule(s) that encodes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, the nucleic acid molecule(s) is mRNA. In another embodiment, the immunogenic composition may be formulated as an mRNA vaccine (e.g., a quadrivalent vaccine, such as, e.g., a self-amplifying mRNA vaccine). In some embodiments, the immunogenic composition includes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786- 788); and (d) the fbpB polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 4; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807-809, 827-836, 842-846, 862-869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). In embodiments in which the immunogenic composition includes a nucleic acid molecule(s) that encodes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, the nucleic acid molecule(s) is mRNA. In another embodiment, the immunogenic composition may be formulated as an mRNA vaccine (e.g., a quadrivalent vaccine, such as, e.g., a self-amplifying mRNA vaccine). Exemplary antigenic polypeptide sequences for use in the immunogenic compositions of the disclosure are provided in Table 2 and Tables 8A-8D. In some embodiments, one or more polypeptides of the immunogenic composition may contain a mutation (e.g., a substitution mutation) at an asparagine (N) such that the residue cannot be glycosylated (e.g., via N-linked glycosylation). For example, the PPE20 polypeptide can include one, two, three, four, five, six, seven, eight, nine, ten, or eleven mutations at an asparagine residue at any of the following positions to remove the possibility of an N-linked glycan: position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1. In some embodiments , the PPE20 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, or all eleven of the following positions (e.g., to block glycosylation): position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1. As another example, the EsxG polypeptide can include one or two mutations at an asparagine residue at any of the following positions to remove the possibility of an N-linked glycan: position 66 and 75 of SEQ ID NO: 2. In some embodiments , the EsxG polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or both of the following positions: position 66 and 75 of SEQ ID NO: 2. As yet another example, the PE18 polypeptide can include one, two, three, or four mutations at an asparagine residue at any of the following positions to remove the possibility of an N-linked glycan: position 26, 29, 78, and 94 of SEQ ID NO: 3. In some embodiments , the PE18 polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, or all four of the following positions: position 26, 29, 78, and 94 of SEQ ID NO: 3. As yet another example, the fbpB polypeptide can include one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, or eighteen mutations at an asparagine residue at any of the following positions to remove the possibility of an N- linked glycan: position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO: 4. In some embodiments , the fbpB polypeptide includes a substitution mutation of asparagine to serine, asparagine to threonine, or asparagine to glutamine at one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more or all eighteen of the following positions: position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO: 4. B. Nucleic Acid Molecules Nucleic acid molecules of the disclosure may be composed of DNA, such as a DNA molecule or DNA vector, that encodes a polypeptide of Table 2 or a portion of a polypeptide thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). Additionally, or alternatively, the nucleic acid molecules of the disclosure may be composed of RNA, such as an mRNA molecule (e.g., an isolated mRNA molecule), and encodes a polypeptide of Table 2 or a portion of a polypeptide thereof (e.g., an epitope including at least about 12 contiguous amino acids of the polypeptide). Nucleic acid molecules (e.g., DNA and / or RNA molecules) of the disclosure are described further below. i. DNA molecules The immunogenic composition may include at least one nucleic acid molecule (or multiple different nucleic acid molecules) composed of DNA that encodes at least one polypeptide described herein, such as a polypeptide described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. The immunogenic composition may include at least one nucleic acid molecule composed of DNA that encodes at least two different polypeptides described herein, such as any two or more of the polypeptides described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. For example, the immunogenic composition may include one single nucleic acid molecule or multiple different nucleic acid molecules, each of which has a nucleotide sequence encoding only a single polypeptide described herein (see, e.g., Table 2) (e.g., the nucleic acid molecule(s) is / are monocistronic). Alternatively, the immunogenic composition may include one single nucleic acid molecule or multiple different nucleic acid molecules, each of which can have a nucleotide sequence encoding at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or all 42 of the polypeptides described herein (see, e.g., Table 2) in any order or combination (e.g., the nucleic acid molecule(s) is / are polycistronic). One to 21 nucleic acid molecules (e.g., polycistronic nucleic acid molecules), each encoding a different set (e.g., two or more) of polypeptides, may be used in the immunogenic composition. For example, the immunogenic composition may include 1 to 21 nucleic acid molecules (e.g., 1 to 21, 1 to 20, 1 to 19, 1 to 18, 1 to 17, 1 to 16, 1 to 15, 1 to 14, 1 to 13, 1 to 12, 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 nucleic acid molecules) composed of DNA, wherein each nucleic acid molecule contains at least two different nucleotide sequences (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleic acid molecule encoding a polypeptide listed in Table 2, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Alternatively, each nucleic acid molecule may contain at least two different nucleotide sequence having at least 36-291 (or all) contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleotide sequence listed in Table 3, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In other embodiments, each nucleic acid molecule may contain at least two nucleotide sequences (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) listed in Table 3, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. The immunogenic composition may include at least one (e.g., at least two) nucleic acid molecule composed of DNA, wherein each nucleic acid molecule encodes a single one of the polypeptides described herein, such as a polypeptide described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. For example, the immunogenic composition can include at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleic acid molecules each having a nucleotide sequence encoding a single, different polypeptide described herein (e.g., each of the nucleic acid molecules are monocistronic). The immunogenic composition may include at least 1 to 42 (e.g., 2-42) nucleic acid molecules (e.g., monocistronic nucleic acid molecules), each encoding one different polypeptide. For example, the immunogenic composition may include 2 to 42 nucleic acid molecules (e.g., 2 to 41, 2 to 40, 2 to 39, 2 to 38, 2 to 37, 2 to 36, 2 to 35, 2 to 34, 2 to 33, 2 to 32, 2 to 31, 2 to 30, 2 to 29, 2 to 28, 2 to 27, 2 to 26, 2 to 25, 2 to 24, 2 to 23, 2 to 22, 2 to 21, 2 to 20, 2 to 19, 2 to 18, 2 to 17, 2 to 16, 2 to 15, 2 to 14, 2 to 13, 2 to 12, 2 to 11, 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, 2 to 4, 2 to 3, or 2 nucleic acid molecules), composed of DNA, wherein each nucleic acid molecule contains one different nucleotide sequence having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125- 225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleic acid molecule encoding a polypeptide listed in Table 2, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Alternatively, each nucleic acid molecule may contain at least one different nucleotide sequence having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200- 250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleotide sequence listed in Table 3, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In other embodiments, each nucleic acid molecule may contain one nucleotide sequence listed in Table 3, or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Table 3. DNA Sequences Encoding Antigens

[0019] In some embodiments, each nucleic acid molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) composed of DNA, wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-168. For example, each nucleic acid molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each nucleic acid molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-168. Alternatively, each nucleic acid molecule may have a single, different nucleotide sequence (e.g., each nucleic acid molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43- 168. In some embodiments, each nucleic acid molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or 20 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-102. For example, each nucleic acid molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each nucleic acid molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-102. Alternatively, each nucleic acid molecule may have a single, different nucleotide sequence (e.g., each nucleic acid molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-102. In some embodiments, each nucleic acid molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, or 15 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43- 90. For example, each nucleic acid molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each nucleic acid molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-90. Alternatively, each nucleic acid molecule may have a single, different nucleotide sequence (e.g., each nucleic acid molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-90. In some embodiments, each nucleic acid molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, or four nucleotide sequences), wherein each nucleotide sequence has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-46, 59-62, and 75-78. For example, each nucleic acid molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each nucleic acid molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-46, 59-62, and 75-78. Alternatively, each nucleic acid molecule may have a single, different nucleotide sequence (e.g., each nucleic acid molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-46, 59-62, and 75-78. In some embodiments, each nucleic acid molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least or three nucleotide sequences), wherein each nucleotide sequence has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 75-78. For example, each nucleic acid molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each nucleic acid molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 75-78. Alternatively, each nucleic acid molecule may have a single, different nucleotide sequence (e.g., each nucleic acid molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 75- 78. In some embodiments, the immunogenic composition contains a nucleic acid molecule including a nucleotide sequence encoding a PPE20 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43, 59, and 75. Optionally, the immunogenic composition contains a nucleic acid molecule including a nucleotide sequence encoding an EsxG polypeptide, or a portion thereof, and / or a PE18 polypeptide, or a portion thereof. The nucleotide sequence encoding the EsxG polypeptide, or portion thereof, may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 44, 60, and 76. The nucleotide sequence encoding the PE18 polypeptide, or portion thereof, may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 45, 61, and 77. For example, the immunogenic composition may include a first nucleic acid molecule encoding a EsxG polypeptide (or a portion thereof) and an PPE20 polypeptide (or a portion thereof) and a second nucleic acid molecule encoding a PE18 polypeptide (or a portion thereof). In another example the immunogenic composition may include a first nucleic acid molecule encoding a PPE20 polypeptide (or a portion thereof) and a PE18 polypeptide (or a portion thereof) and a second nucleic acid molecule encoding an EsxG polypeptide (or a portion thereof). In yet another example, the immunogenic may include a first nucleic acid molecule encoding a PE18 polypeptide (or a portion thereof) and an EsxG polypeptide (or a portion thereof) and a second nucleic acid molecule encoding a PPE20 polypeptide (or a portion thereof). In yet another example, the immunogenic composition may include a first nucleic acid molecule encoding a PPE20 polypeptide (or a portion thereof) , a second nucleic acid molecule encoding an EsxG polypeptide (or a portion thereof), and a third nucleic acid molecule encoding a PE18 polypeptide (or a portion thereof). Optionally, the immunogenic composition also contains a nucleic acid molecule having a nucleotide sequence encoding an fbpB polypeptide (or a portion thereof), a PPE51 polypeptide (or a portion thereof), an EsxR polypeptide (or a portion thereof), an eccD3 polypeptide (or a portion thereof), a PPE2 polypeptide (or a portion thereof), a PPE3 polypeptide (or a portion thereof), an EsxS polypeptide (or a portion thereof), a PPE46 polypeptide (or a portion thereof), a PPE30 polypeptide (or a portion thereof), a PPE11 polypeptide (or a portion thereof), a PPE4 polypeptide (or a portion thereof), an mpt70 polypeptide (or a portion thereof), a PE19 polypeptide (or a portion thereof), a PPE18 polypeptide (or a portion thereof), an fbpA polypeptide (or a portion thereof), an EsxH polypeptide (or a portion thereof), a pepA polypeptide (or a portion thereof), an mpt83 polypeptide (or a portion thereof), a PPE68 polypeptide (or a portion thereof), an Rv2666 polypeptide (or a portion thereof), a PPE49 polypeptide (or a portion thereof), a PPE47 polypeptide (or a portion thereof), a PPE37 polypeptide (or a portion thereof), an Rv1047 polypeptide (or a portion thereof), an Rv1199c polypeptide (or a portion thereof), a trmU polypeptide (or a portion thereof), an espC polypeptide (or a portion thereof), an espG3 polypeptide (or a portion thereof), a dacB1 polypeptide (or a portion thereof), a PPE32 polypeptide (or a portion thereof), an fbpC polypeptide (or a portion thereof), a groES polypeptide (or a portion thereof), an esxA polypeptide (or a portion thereof), an esxB polypeptide (or a portion thereof), an Rv2660c polypeptide (or a portion thereof), an Rv1813c polypeptide (or a portion thereof), a PPE42 polypeptide (or a portion thereof), an esxV polypeptide (or a portion thereof), and / or an esxW polypeptide (or a portion thereof). The nucleic acid molecule having the nucleotide sequence encoding the fbpB polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 46, 62, and 78. The nucleic acid molecule having the nucleotide sequence encoding the PPE51 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 47, 63, and 79. The nucleic acid molecule having the nucleotide sequence encoding the EsxR polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 48, 64, and 80. The nucleic acid molecule having the nucleotide sequence encoding the eccD3 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 49, 65, and 81. The nucleic acid molecule having the nucleotide sequence encoding the PPE2 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 50, 66, and 82. The nucleic acid molecule having the nucleotide sequence encoding the PPE3 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 51, 67, and 83. The nucleic acid molecule having the nucleotide sequence encoding the EsxS polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 52, 68, and 84. The nucleic acid molecule having the nucleotide sequence encoding the PPE46 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 53, 69, and 85. The nucleic acid molecule having the nucleotide sequence encoding the PPE30 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 54, 70, and 86. The nucleic acid molecule having the nucleotide sequence encoding the PPE11 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 55, 71, and 87. The nucleic acid molecule having the nucleotide sequence encoding the PPE4 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 56, 72, and 88. The nucleic acid molecule having the nucleotide sequence encoding the mpt70 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 57, 73, and 89. The nucleic acid molecule having the nucleotide sequence encoding the PE19 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 58, 74, and 90. The nucleic acid molecule having the nucleotide sequence encoding the PPE18 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 91, 95, and 99. The nucleic acid molecule having the nucleotide sequence encoding the fbpA polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 92, 96, and 100. The nucleic acid molecule having the nucleotide sequence encoding the EsxH polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 93, 97, and 101. The nucleic acid molecule having the nucleotide sequence encoding the pepA polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 94, 98, and 102. In some embodiments, the immunogenic composition includes a nucleic acid molecule that encodes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); and (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). In some embodiments, the immunogenic composition includes a nucleic acid molecule that encodes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25- 50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788); and (d) the fbpB polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25- 50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 4; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807-809, 827-836, 842-846, 862-869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). ii. Vectors The immunogenic composition may include at least one DNA vector, wherein each vector encodes at least two different polypeptides described herein, such as any two or more of the polypeptides described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. For example, each of the vectors may have a nucleotide sequence encoding at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 of the polypeptides described herein in any order or combination (e.g., the vector is polycistronic). One to 21 vectors (e.g., polycistronic vectors), each encoding a different set (e.g., two or more) of polypeptides, may be used in the immunogenic composition. For example, the immunogenic composition may include 1 to 21 vectors (e.g., 1 to 21, 1 to 20, 1 to 19, 1 to 18, 1 to 17, 1 to 16, 1 to 15, 1 to 14, 1 to 13, 1 to 12, 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 vectors) composed of DNA, wherein each vector contains at least two different nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleic acid molecule encoding a polypeptide listed in Table 2, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Alternatively, each vector may contain at least two different nucleotide sequence having at least 36- 291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleotide sequence listed in Table 3, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In other embodiments, each vector may contain at least two nucleotide sequences (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) listed in Table 3, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. The immunogenic composition may include at least one (e.g., at least two) vector composed of DNA, wherein each vector encodes a single one of the polypeptides described herein, such as a polypeptide described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. For example, the immunogenic composition can include at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 vectors each having a nucleotide sequence encoding a single, different polypeptide described herein (e.g., each of the vectors are monocistronic). The immunogenic composition may include at least 1 to 42 (e.g., 2-42) vectors (e.g., monocistronic vectors), each encoding one different polypeptide. For example, the immunogenic composition may include 2 to 42 vectors (e.g., 2 to 41, 2 to 40, 2 to 39, 2 to 38, 2 to 37, 2 to 36, 2 to 35, 2 to 34, 2 to 33, 2 to 32, 2 to 31, 2 to 30, 2 to 29, 2 to 28, 2 to 27, 2 to 26, 2 to 25, 2 to 24, 2 to 23, 2 to 22, 2 to 21, 2 to 20, 2 to 19, 2 to 18, 2 to 17, 2 to 16, 2 to 15, 2 to 14, 2 to 13, 2 to 12, 2 to 11, 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, 2 to 4, 2 to 3, or 2 vectors), composed of DNA, wherein each vector contains one different nucleotide sequence having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleic acid molecule encoding a polypeptide listed in Table 2, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Alternatively, each vector may contain at least one different nucleotide sequence having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleotide sequence listed in Table 3, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In other embodiments, each vector may contain one nucleotide sequence listed in Table 3, or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In some embodiments, each vector of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) composed of DNA, wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-168. For example, each vector may include multiple (e.g., two or more) different nucleotide sequences (e.g., each vector is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-168. Alternatively, each vector may have a single, different nucleotide sequence (e.g., each vector is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-168. In some embodiments, each vector of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or 20 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-102. For example, each vector may include multiple (e.g., two or more) different nucleotide sequences (e.g., each vector is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-102. Alternatively, each vector may have a single, different nucleotide sequence (e.g., each vector is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-102. In some embodiments, each vector of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, or 15 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-90. For example, each vector may include multiple (e.g., two or more) different nucleotide sequences (e.g., each vector is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-90. Alternatively, each vector may have a single, different nucleotide sequence (e.g., each vector is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-90. In some embodiments, each vector of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, or four nucleotide sequences), wherein each nucleotide sequence has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-46, 59-62, and 75-78. For example, each vector may include multiple (e.g., two or more) different nucleotide sequences (e.g., each vector is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43-46, 59-62, and 75-78. Alternatively, each vector may have a single, different nucleotide sequence (e.g., each vector is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 43-46, 59-62, and 75-78. In some embodiments, each vector of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least or three nucleotide sequences), wherein each nucleotide sequence has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 75-78. For example, each vector may include multiple (e.g., two or more) different nucleotide sequences (e.g., each vector is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 75-78. Alternatively, each vector may have a single, different nucleotide sequence (e.g., each vector is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 75-78. In some embodiments, the immunogenic composition contains a vector including a nucleotide sequence encoding a PPE20 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 43, 59, and 75. Optionally, the immunogenic composition contains a vector including a nucleotide sequence encoding an EsxG polypeptide, or a portion thereof, and / or a PE18 polypeptide, or a portion thereof. The nucleotide sequence encoding the EsxG polypeptide, or portion thereof, may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 44, 60, and 76. The nucleotide sequence encoding the PE18 polypeptide, or portion thereof, may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 45, 61, and 77. For example, the immunogenic composition may include a first vector encoding a EsxG polypeptide (or a portion thereof) and an PPE20 polypeptide (or a portion thereof) and a second vector encoding a PE18 polypeptide (or a portion thereof). In another example the immunogenic composition may include a first vector encoding a PPE20 polypeptide (or a portion thereof) and a PE18 polypeptide (or a portion thereof) and a second vector encoding an EsxG polypeptide (or a portion thereof). In yet another example, the immunogenic may include a first vector encoding a PE18 polypeptide (or a portion thereof) and an EsxG polypeptide (or a portion thereof) and a second vector encoding a PPE20 polypeptide (or a portion thereof). In yet another example, the immunogenic composition may include a first vector encoding a PPE20 polypeptide(or a portion thereof) , a second vector encoding an EsxG polypeptide (or a portion thereof), and a third vector encoding a PE18 polypeptide (or a portion thereof). Further optionally, the immunogenic composition contains a vector having a nucleotide sequence encoding an fbpB polypeptide (or a portion thereof), a PPE51 polypeptide (or a portion thereof), an EsxR polypeptide (or a portion thereof), an eccD3 polypeptide (or a portion thereof), a PPE2 polypeptide (or a portion thereof), a PPE3 polypeptide (or a portion thereof), an EsxS polypeptide (or a portion thereof), a PPE46 polypeptide (or a portion thereof), a PPE30 polypeptide (or a portion thereof), a PPE11 polypeptide (or a portion thereof), a PPE4 polypeptide (or a portion thereof), an mpt70 polypeptide (or a portion thereof), a PE19 polypeptide (or a portion thereof), a PPE18 polypeptide (or a portion thereof), an fbpA polypeptide (or a portion thereof), an EsxH polypeptide (or a portion thereof), a pepA polypeptide (or a portion thereof), an mpt83 polypeptide (or a portion thereof), a PPE68 polypeptide (or a portion thereof), an Rv2666 polypeptide (or a portion thereof), a PPE49 polypeptide (or a portion thereof), a PPE47 polypeptide (or a portion thereof), a PPE37 polypeptide (or a portion thereof), an Rv1047 polypeptide (or a portion thereof), an Rv1199c polypeptide (or a portion thereof), a trmU polypeptide (or a portion thereof), an espC polypeptide (or a portion thereof), an espG3 polypeptide (or a portion thereof), a dacB1 polypeptide (or a portion thereof), a PPE32 polypeptide (or a portion thereof), an fbpC polypeptide (or a portion thereof), a groES polypeptide (or a portion thereof), an esxA polypeptide (or a portion thereof), an esxB polypeptide (or a portion thereof), an Rv2660c polypeptide (or a portion thereof), an Rv1813c polypeptide (or a portion thereof), a PPE42 polypeptide (or a portion thereof), an esxV polypeptide (or a portion thereof), and / or an esxW polypeptide (or a portion thereof). The vector having the nucleotide sequence encoding the fbpB polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 46, 62, and 78. The vector having the nucleotide sequence encoding the PPE51 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 47, 63, and 79. The vector having the nucleotide sequence encoding the EsxR polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 48, 64, and 80. The vector having the nucleotide sequence encoding the eccD3 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 49, 65, and 81. The vector having the nucleotide sequence encoding the PPE2 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 50, 66, and 82. The vector having the nucleotide sequence encoding the PPE3 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 51, 67, and 83. The vector having the nucleotide sequence encoding the EsxS polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 52, 68, and 84. The vector having the nucleotide sequence encoding the PPE46 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 53, 69, and 85. The vector having the nucleotide sequence encoding the PPE30 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 54, 70, and 86. The vector having the nucleotide sequence encoding the PPE11 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 55, 71, and 87. The vector having the nucleotide sequence encoding the PPE4 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 56, 72, and 88. The vector having the nucleotide sequence encoding the mpt70 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 57, 73, and 89. The vector having the nucleotide sequence encoding the PE19 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 58, 74, and 90. The vector having the nucleotide sequence encoding the PPE18 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 91, 95, and 99. The vector having the nucleotide sequence encoding the fbpA polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 92, 96, and 100. The vector having the nucleotide sequence encoding the EsxH polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 93, 97, and 101. The vector having the nucleotide sequence encoding the pepA polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 94, 98, and 102. Any suitable viral vector system can be used including, e.g., adenoviruses (e.g., Ad2, Ad5, Ad9, Ad15, Ad17, Ad19, Ad20, Ad22, Ad26, Ad27, Ad28, Ad30, or Ad39), rhabdoviruses (e.g., vesicular stomatitis virus), retroviruses, adeno-associated vectors, poxviruses, herpes viral vectors, and Sindbis viral vectors. iii. mRNA molecules The immunogenic composition may include at least one nucleic acid molecule composed of mRNA, wherein each mRNA molecule encodes at least two different polypeptides described herein, such as any two or more of the polypeptides described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. For example, each of the mRNA molecules may have a nucleotide sequence encoding at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 of the polypeptides described herein in any order or combination (e.g., the mRNA molecule is polycistronic). One to 21 mRNA molecules (e.g., polycistronic mRNA molecules), each encoding a different set (e.g., two or more) of polypeptides, may be used in the immunogenic composition. For example, the immunogenic composition may include 1 to 21 mRNA molecules (e.g., 1 to 21, 1 to 20, 1 to 19, 1 to 18, 1 to 17, 1 to 16, 1 to 15, 1 to 14, 1 to 13, 1 to 12, 1 to 11, 1 to 10, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, or 1 to 2 mRNA molecules), wherein each mRNA molecule contains at least two different nucleotide sequences (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) having at least 36-291 contiguous nucleotides (e.g., 36- 291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleic acid molecule encoding a polypeptide listed in Table 2, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Alternatively, each mRNA molecule may contain at least two different nucleotide sequence having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleotide sequence listed in Table 4, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In other embodiments, each mRNA molecule may contain at least two nucleotide sequences (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences) listed in Table 4, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. The immunogenic composition may include at least one (e.g., at least two) mRNA molecule that encodes a single one of the polypeptides described herein, such as a polypeptide described in Table 2 or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. For example, the immunogenic composition can include at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 mRNA molecules each having a nucleotide sequence encoding a single, different polypeptide described herein (e.g., each of the mRNA molecules are monocistronic). The immunogenic composition may include at least 1 to 42 (e.g., 2-42) mRNA molecules (e.g., monocistronic mRNA molecules), each encoding one different polypeptide. For example, the immunogenic composition may include 2 to 42 mRNA molecules (e.g., 2 to 41, 2 to 40, 2 to 39, 2 to 38, 2 to 37, 2 to 36, 2 to 35, 2 to 34, 2 to 33, 2 to 32, 2 to 31, 2 to 30, 2 to 29, 2 to 28, 2 to 27, 2 to 26, 2 to 25, 2 to 24, 2 to 23, 2 to 22, 2 to 21, 2 to 20, 2 to 19, 2 to 18, 2 to 17, 2 to 16, 2 to 15, 2 to 14, 2 to 13, 2 to 12, 2 to 11, 2 to 10, 2 to 9, 2 to 8, 2 to 7, 2 to 6, 2 to 5, 2 to 4, 2 to 3, or 2 mRNA molecules), wherein each mRNA molecule contains one different nucleotide sequence having at least 36-291 contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleic acid molecule encoding a polypeptide listed in Table 2, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. The immunogenic composition may contain multiple copies of each of the different mRNA molecules. Alternatively, each mRNA molecule may contain at least one different nucleotide sequence having at least 36-291 (or all) contiguous nucleotides (e.g., 36-291, 50-250, 75-200, 100-200, 125-225, 200-250, or 225-291 contiguous nucleotides, e.g., 48, 96, 144, 192, 240, or 288 contiguous nucleotides) of a nucleotide sequence listed in Table 4, or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. In other embodiments, each mRNA molecule may contain one nucleotide sequence listed in Table 4, or a variant thereof with at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto. Table 4. mRNA Sequences Encoding Antigens

[0020] Modified mRNA sequences above may include a pseudouridine (ψ) in place of a uracil (U). In some embodiments, each mRNA molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22, at least 23, at least 24, at least 25, at least 26, at least 27, at least 28, at least 29, at least 30, at least 31, at least 32, at least 33, at least 34, at least 35, at least 36, at least 37, at least 38, at least 39, at least 40, at least 41, or 42 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-420. For example, each mRNA molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each mRNA molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-420. Alternatively, each mRNA molecule may have a single, different nucleotide sequence (e.g., each mRNA molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 169-420. In some embodiments, each mRNA molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or 20 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-288. For example, each mRNA molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each mRNA molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-288. Alternatively, each mRNA molecule may have a single, different nucleotide sequence (e.g., each mRNA molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 169-288. In some embodiments, each mRNA molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, or 16 nucleotide sequences), wherein each nucleotide sequence is different and has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-264. For example, each mRNA molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each mRNA molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-264. Alternatively, each mRNA molecule may have a single, different nucleotide sequence (e.g., each mRNA molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 169-264. In some embodiments, each mRNA molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, at least three, or four nucleotide sequences), wherein each nucleotide sequence has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-172, 185-188, 201-204, 217-220, 233-236, and 249-252. For example, each mRNA molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each mRNA molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-172, 185-188, 201-204, 217-220, 233-236, and 249-252. Alternatively, each mRNA molecule may have a single, different nucleotide sequence (e.g., each mRNA molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 169-172, 185- 188, 201-204, 217-220, 233-236, and 249-252. In some embodiments, each mRNA molecule of the immunogenic composition may include at least one nucleotide sequence (e.g., at least two, or at least three nucleotide sequences), wherein each nucleotide sequence has at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-171, 185-187, 201-203, 217-219, 233-235, and 249-251. For example, each mRNA molecule may include multiple (e.g., two or more) different nucleotide sequences (e.g., each mRNA molecule is polycistronic), each having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169-171, 185-187, 201- 203, 217-219, 233-235, and 249-251. Alternatively, each mRNA molecule may have a single, different nucleotide sequence (e.g., each mRNA molecule is monocistronic) having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to one of SEQ ID NOs: 169-171, 185-187, 201- 203, 217-219, 233-235, and 249-251. In some embodiments, the immunogenic composition contains a mRNA molecule including a nucleotide sequence encoding a PPE20 polypeptide, or a portion thereof, having at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 169, 185, 201, 217, 233, and 249. Optionally, the immunogenic composition contains a mRNA molecule including a nucleotide sequence encoding an EsxG polypeptide, or a portion thereof, and / or a PE18 polypeptide, or a portion thereof. The nucleotide sequence encoding the EsxG polypeptide, or portion thereof, may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 170, 186, 202, 218, 234, and 250. The nucleotide sequence encoding the PE18 polypeptide, or portion thereof, may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 171, 187, 203, 219, 235, and 251. For example, the immunogenic composition may include a first mRNA molecule encoding a EsxG polypeptide (or a portion thereof) and an PPE20 polypeptide (or a portion thereof) and a second mRNA molecule encoding a PE18 polypeptide (or a portion thereof). In another example the immunogenic composition may include a first mRNA molecule encoding a PPE20 polypeptide (or a portion thereof) and a PE18 polypeptide (or a portion thereof) and a second mRNA molecule encoding an EsxG polypeptide (or a portion thereof). In yet another example, the immunogenic may include a first mRNA molecule encoding a PE18 polypeptide (or a portion thereof) and an EsxG polypeptide (or a portion thereof) and a second mRNA molecule encoding a PPE20 polypeptide (or a portion thereof). In yet another example, the immunogenic composition may include a first mRNA molecule encoding a PPE20 polypeptide (or a portion thereof) , a second mRNA molecule encoding an EsxG polypeptide (or a portion thereof), and a third mRNA molecule encoding a PE18 polypeptide (or a portion thereof). Optionally, the immunogenic composition also contains an mRNA molecule having a nucleotide sequence encoding an fbpB polypeptide (or a portion thereof), a PPE51 polypeptide (or a portion thereof), an EsxR polypeptide (or a portion thereof), an eccD3 polypeptide (or a portion thereof), a PPE2 polypeptide (or a portion thereof), a PPE3 polypeptide (or a portion thereof), an EsxS polypeptide (or a portion thereof), a PPE46 polypeptide (or a portion thereof), a PPE30 polypeptide (or a portion thereof), a PPE11 polypeptide (or a portion thereof), a PPE4 polypeptide (or a portion thereof), an mpt70 polypeptide (or a portion thereof), a PE19 polypeptide (or a portion thereof), a PPE18 polypeptide (or a portion thereof), an fbpA polypeptide (or a portion thereof), an EsxH polypeptide (or a portion thereof), a pepA polypeptide (or a portion thereof), an mpt83 polypeptide (or a portion thereof), a PPE68 polypeptide (or a portion thereof), an Rv2666 polypeptide (or a portion thereof), a PPE49 polypeptide (or a portion thereof), a PPE47 polypeptide (or a portion thereof), a PPE37 polypeptide (or a portion thereof), an Rv1047 polypeptide (or a portion thereof), an Rv1199c polypeptide (or a portion thereof), a trmU polypeptide (or a portion thereof), an espC polypeptide (or a portion thereof), an espG3 polypeptide (or a portion thereof), a dacB1 polypeptide (or a portion thereof), a PPE32 polypeptide (or a portion thereof), an fbpC polypeptide (or a portion thereof), a groES polypeptide (or a portion thereof), an esxA polypeptide (or a portion thereof), an esxB polypeptide (or a portion thereof), an Rv2660c polypeptide (or a portion thereof), an Rv1813c polypeptide (or a portion thereof), a PPE42 polypeptide (or a portion thereof), an esxV polypeptide (or a portion thereof), and / or an esxW polypeptide (or a portion thereof). The mRNA molecule having the nucleotide sequence encoding the fbpB polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 172, 188, 204, 220, 236, 252. The mRNA molecule having the nucleotide sequence encoding the PPE51 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 173, 189, 205, 221, 237, 253. The mRNA molecule having the nucleotide sequence encoding the EsxR polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 174, 190, 206, 222, 238, 254. The mRNA molecule having the nucleotide sequence encoding the eccD3 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 175, 191, 207, 223, 239, 255. The mRNA molecule having the nucleotide sequence encoding the PPE2 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 176, 192, 208, 224, 240, 256. The mRNA molecule having the nucleotide sequence encoding the PPE3 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 177, 193, 209, 225, 241, 257. The mRNA molecule having the nucleotide sequence encoding the EsxS polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 178, 194, 210, 226, 242, 258. The mRNA molecule having the nucleotide sequence encoding the PPE46 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 179, 195, 211, 227, 243, 259. The mRNA molecule having the nucleotide sequence encoding the PPE30 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 180, 196, 212, 228, 244, 260. The mRNA molecule having the nucleotide sequence encoding the PPE11 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 181, 197, 213, 229, 245, 261. The mRNA molecule having the nucleotide sequence encoding the PPE4 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 182, 198, 214, 230, 246, 262. The mRNA molecule having the nucleotide sequence encoding the mpt70 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 183, 199, 215, 231, 247, 263. The mRNA molecule having the nucleotide sequence encoding the PE19 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 184, 200, 216, 232, 248, 264. The mRNA molecule having the nucleotide sequence encoding the PPE18 polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 265, 269, 273, 277, 281, 285. The mRNA molecule having the nucleotide sequence encoding the fbpA polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 266, 270, 274, 278, 282, 286. The mRNA molecule having the nucleotide sequence encoding the EsxH polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 267, 271, 275, 279, 283, 287. The mRNA molecule having the nucleotide sequence encoding the pepA polypeptide (or a portion thereof) may have at least 70% (e.g., at least 75%, at least 80%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%) sequence identity to any one of SEQ ID NOs: 268, 272, 276, 280, 284, 288. In some embodiments, the mRNA molecule of an immunogenic composition encodes a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757); and (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). In some embodiments, the mRNA molecule of an immunogenic compostion includes a nucleic acid molecule that encodes a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and a fbpB polypeptide, wherein: (a) the PPE20 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449); (b) the EsxG polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751- 753 and 757); (c) the PE18 polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788); and (d) the fbpB polypeptide includes (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 4; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807- 809, 827-836, 842-846, 862-869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). In some embodiments, mRNA molecule(s) in the immunogenic composition of the invention is a self-amplifying mRNA molecule, also known as a replicon. Self-amplifying mRNA molecules are known to induce potent immunity responses, even with a single dose, and present few adverse effects in humans. Self-amplifying mRNA molecules are described in, for example International Patent Application Nos. WO2022137128, WO2023081935, and WO2021255270, each of which is incorporated herein by reference in its entirety. In some embodiments, the self-amplifying mRNA molecule is derived from a positive-strand RNA virus. In some embodiments, the self-amplifying mRNA is derived from a negative-strand RNA virus. In some embodiments, the self-amplifying mRNA is an alphavirus-based replicon. In some embodiments, the self-amplifying mRNA is a flavivirus-based replicon. C. Live Attenuated Vaccines Any of the polypeptide or polynucleotide compositions described above may further include, or may be administered in combination with, a live attenuated vaccine. Bacille Calmette-Guerin (BCG) is an attenuated whole cell vaccine based on Mycobacterium bovis. Having some, albeit suboptimal, efficacy to protect against tuberculosis (TB). BCG is currently the only approved TB vaccine for use in humans and provides, albeit suboptimal, some protection against tuberculosis (TB). Thus, it is contemplated that any of the compositions described herein may further include, or may be administered in combination with, the BCG vaccine, or any other live attenuated vaccine (e.g., MTBVAC, VPM1002, DAR-901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72, RUTI, H107, or CysVac2 / Advax ). For example, the immunogenic compositions of the disclosure may be administered at the same time as, prior to, or after administration of a BCG vaccine or other live attenuated vaccine. In particular, the immunogenic composition may be administered as part of a prime-boost regimen in combination with the BCG vaccine or other live attenuated vaccine. The immunogenic composition could be administered as either the prime, the boost, or as both a prime and a boost. Similarly, the BCG vaccine or other live attenuated vaccine could be administered as either the prime, the boost, or as both a prime and a boost. D. Formulations The immunogenic compositions described herein may be formulated into liposomes. Liposomes are artificially-prepared vesicles which may primarily be composed of a lipid bilayer and may be used as a delivery vehicle for the administration of the inhibitory nucleic acids described herein, and compositions thereof. Liposomes can be of different sizes such as, but not limited to, a multilamellar vesicle (MLV) which may be hundreds of nanometers in diameter and may contain a series of concentric bilayers separated by narrow aqueous compartments, a small unicellular vesicle (SUV) which may be smaller than 50 nm in diameter, and a large unilamellar vesicle (LUV) which may be between 50 and 500 nm in diameter. Liposome design may include, but is not limited to, opsonins or ligands in order to improve the attachment of liposomes to unhealthy tissue or to activate events such as, but not limited to, endocytosis. Liposomes may contain a low or a high pH in order to improve the delivery of the pharmaceutical composition. For example, one or more immunogenic DNA molecules (e.g., a vector(s)) described herein (e.g., DNA molecules including a nucleotide sequence of any one or more of SEQ ID NOs: 43-168, or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) maybe be formulated into a liposome. In another example, one or more immunogenic RNA molecules (e.g., mRNA molecules) described herein (e.g., mRNA molecules including a nucleotide sequence of any one or more of SEQ ID NOs: 169-420, or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) maybe be formulated into a liposome. In yet another example, one or more (e.g., one, two, three, or four) mRNA molecules described herein may include one or more (e.g., one, two, three, or four) nucleotide sequences selected from SEQ ID NOs: 169-172, 185-188, 201-204, 217-220, 233-236, and 249-252 (or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) and may be formulated into a liposome. The immunogenic compositions described herein may be formulated into exosomes. Exosomes produced from cells can be collected from cell culture medium by any suitable method. Typically, a preparation of exosomes can be prepared from cell culture or tissue supernatant by centrifugation, filtration or combinations of these methods. For example, using standard methods, exosomes can be prepared by differential centrifugation, that is low speed (<20000 g) centrifugation to pellet larger particles followed by high speed (>100000 g) centrifugation to pellet exosomes, size filtration with appropriate filters (for example, 0.22 micrometer filter), gradient ultracentrifugation (for example, with sucrose gradient) or a combination of these methods. For example, one or more immunogenic DNA molecules (e.g., a vector(s)) described herein (e.g., DNA molecules including a nucleotide sequence of any one or more of SEQ ID NOs: 43-168, or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) maybe be formulated into an exosome. In another example, one or more immunogenic RNA molecules (e.g., mRNA molecules) described herein (e.g., mRNA molecules including a nucleotide sequence of any one or more of SEQ ID NOs: 169-420, or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) maybe be formulated into an exosome. In yet another example, one or more (e.g., one, two, three, or four) mRNA molecules described herein may include one or more (e.g., one, two, three, or four) nucleotide sequences selected from SEQ ID NOs: 169-172, 185-188, 201-204, 217-220, 233-236, and 249-252 (or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) and may be formulated into an exosome. The immunogenic compositions described herein may be formulated into lipid nanoparticles (LNPs). Exemplary LNPs are described in International Publication No. WO2012170930, herein incorporated by reference in its entirety. As a non-limiting example, LNP formulations may contain cationic lipids, distearoylphosphatidylcholine (DSPC), cholesterol, polyethylene glycol (PEG), R-3-[(ω- methoxy poly(ethylene glycol)2000)carbamoyl)]-1,2-dimyristyloxl-propyl-3-amine (PEG-c-DOMG), distearoyl-rac-glycerol (DSG) and / or dimethylaminobutanoate (DMA). As a non-limiting example, 1- 5% of the lipid molar ratio of PEG-c-DOMG as compared to the cationic lipid, DSPC and cholesterol. In another embodiment the PEG-c-DOMG may be replaced with a PEG lipid such as, but not limited to, PEG-DSG (1,2-Distearoyl-sn-glycerol, methoxypoly ethylene glycol) or PEG-DPG (1,2-Dipalmitoyl- sn-glycerol, methoxypolyethylene glycol). The cationic lipid may be selected from any lipid known in the art such as, but not limited to, (6Z,9Z,28Z,31Z)-heptatriacont-6,9,28,31-tetraene-19-yl 4- (dimethylamino)butanoate (Dlin-MC3-DMA), 1,2-dilinoleyloxy-n,n-dimethyl-3-aminopropane (Dlin- DMA), C 12-200, and N,N-dimethyl-2,2-di-(9Z,12Z)-9,12-octadecadien-1-yl-1,3-dioxolane-4- ethanamine (Dlin-KC2-DMA). For example, one or more immunogenic DNA molecules (e.g., a vector(s)) described herein (e.g., DNA molecules including a nucleotide sequence of any one or more of SEQ ID NOs: 43-168, or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) maybe be formulated into an LNP. In another example, one or more immunogenic RNA molecules (e.g., mRNA molecules) described herein (e.g., mRNA molecules including a nucleotide sequence of any one or more of SEQ ID NOs: 169-420, or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) maybe be formulated into an LNP. In yet another example, one or more (e.g., one, two, three, or four) mRNA molecules described herein may include one or more (e.g., one, two, three, or four) nucleotide sequences selected from SEQ ID NOs: 169-172, 185-188, 201-204, 217-220, 233-236, and 249-252 (or a portion or variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto) and may be formulated into an LNP. Exemplary commercial reagents useful for formulating lipid-based compositions, but not limited to, TRANSIT-TKO™ (Mirus, Catalog No. MIR 2150), TRANSMESSENGER™ (Qiagen, Catalog No.301525), OLIGOFECTAMINE™ and LIPOFECTAMINE™ (Invitrogen, Catalog No. MIR 12252-011 and Catalog No.13778-075), SIPORT™ (Ambion, Catalog No.1631), and DHARMAFECT™ (Fisher Scientific, Catalog No. T-2001-01). The immunogenic compositions described herein may be formulated with a pharmaceutically acceptable carrier to form a pharmaceutical composition. Therapeutic formulations of compositions of the disclosure can be prepared using standard methods known in the art, such as by mixing the composition with optional physiologically acceptable carriers, excipients or stabilizers (Remington’s Pharmaceutical Sciences (20thedition), ed. A. Gennaro, 2000, Lippincott, Williams & Wilkins, Philadelphia, PA). Acceptable carriers include saline and / or buffers, such as phosphate, citrate and other organic acids. Other components can include, e.g., antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone, amino acids such as glycine, glutamine, asparagine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and / or nonionic surfactants such as TWEEN™, PLURONICS™, or PEG. The carrier can be sufficiently pure to be administered therapeutically to a human subject. Those of relevant skill in the art are well able to prepare suitable solutions using, e.g., isotonic vehicles such as Sodium Chloride Injection, Ringer’s Injection, or Lactated Ringer’s Injection. Optionally, the formulations of the disclosure can contain a pharmaceutically acceptable preservative. In some embodiments the preservative concentration can range from 0.1 to 2.0%, typically v / v. Suitable preservatives include those known in the pharmaceutical arts. Benzyl alcohol, phenol, m-cresol, methylparaben, and propylparaben are preferred preservatives. Optionally, the formulations of the disclosure can include a pharmaceutically acceptable surfactant at a concentration of 0.005 to 0.02%. Stabilizers, buffers, antioxidants and / or other additives may be included, as required. The immunogenic compositions described herein may be incorporated into microparticles or microcapsules to prolong the exposure of the immunogenic material to the subject and hence protect the subject against infection for long periods of time. The microparticles and capsules may be formed from a variety of well-known inert, biocompatible matrix materials using techniques conventional in the art. Suitable matrix materials include, e.g., natural or synthetic polymers such as alginates, poly(lactic acid), poly(lactic / glycolic acid), poly(caprolactone), polycarbonates, polyamides, polyanhydrides, polyortho esters, polyacetals, polycyanoacrylates, polyurethanes, ethytlenevinyl acetate copolymers, polystyrenes, polyvinyl chloride, polyvinyl fluoride, poly(vinyl imidazole), chlorosulphonated polyolefϊns, polyethylene oxide, and particularly agar and polyacrylates. The compositions described herein may be contained in small particles suspended in the water or saline. Immunogenicity of the composition of the disclosure may be significantly improved if it is co- administered with an immunostimulatory agent, adjuvant, antibacterial agent, or other pharmaceutically active agent as are conventional in the art. Adjuvants may include but are not limited to salts, emulsions (including oil / water compositions), saponins, liposomal formulations, virus particles, polypeptides, pathogen-associated molecular patterns (PAMPS), nucleic acid-based compounds or other formulations utilizing certain antigens. Suitable adjuvants include, e.g., aluminum phosphate, aluminum hydroxide, OS21, Quil A (and derivatives and components thereof), calcium phosphate, calcium hydroxide, zinc hydroxide, glycolipid analogs, vegetable oils, alum, Freund’s incomplete adjuvant, or Freund’s incomplete adjuvant, octodecyl esters of an amino acid, muramyl dipeptides, polyphosphazene, lipoproteins, DC-Chol, DDA, cytokines, and other adjuvants and derivatives thereof. Other adjuvants include agents such as immunestimulating complexes (ISCOMs), synthetic polymers of sugars (CARBOPOL®), aggregation of the protein in the vaccine by heat treatment, aggregation by reactivating with pepsin treated (Fab) antibodies to albumin, endotoxins or lipopolysaccharide components of gram-negative bacteria, emulsion in physiologically acceptable oil vehicles such as mannide mono-oleate (Aracel A) or emulsion with 20 percent solution of a perfluorocarbon (Fluosol-DA) used as a block substitute may also be employed. The immunogenic compositions described herein can be formulated, e.g., for administration subcutaneously, intranasally, intrapulmonarally, intramuscularly, intravenously, intradermally, percutaneously, intraarterially, intraperitoneally, intralesionally, intracranially, intraarticularly, intraprostatically, intrapleurally, intratracheally, intravitreally, intravaginally, intrarectally, topically, intratumorally, peritoneally, subconjunctivally, intravesicularlly, mucosally, intrapericardially, intraumbilically, intraocularly, orally, topically, locally, by inhalation, by injection, by infusion, by continuous infusion, by localized perfusion bathing target cells directly, by catheter, by lavage, by gavage, in cremes, or in lipid compositions. Immunogenic compositions may be sterilized by conventional sterilization techniques or may be sterile filtered. The resulting aqueous solutions may be packaged for use as is, or lyophilized, the lyophilized preparation may be administered in powder form or combined with a sterile aqueous carrier prior to administration. The pH of the preparations typically will be between 3 and 11, more preferably between 5 and 9 or between 6 and 8, and most preferably between 7 and 8, such as 7 to 7.5. The resulting compositions in solid form may be packaged in multiple single dose units, each containing a fixed amount of the composition and, if desired, one or more immunomodulatory agents, such as in a sealed package of tablets or capsules, or in a suitable dry powder inhaler (DPI) capable of administering one or more doses. II. METHODS The present disclosure provides methods of inducing an immune response in a subject, the method including administering any one or more of the immunogenic compositions described herein. The immunogenic compositions described herein are useful, e.g., as a vaccine, for the treatment and / or prophylaxis of a subject (e.g., a human) having or at risk of having an infection (e.g., an Mtb infection) or a disease (e.g., TB). Upon its administration, the immunogenic composition may treat the disease, reduce the symptoms of a disease, reduce the likelihood of any reemergence of the disease from latency, reduce sequela of the disease and / or reduce the transmissibility of the disease. The disease may be an infectious disease (e.g., TB), such as a disease caused by one or more bacteria (e.g., Mycobaterium spp.). Exemplary bacterial species include Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium avium, Mycobacterium bovis, Mycobacterium canetti, Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium gordonae, Mycobacterium hiberniae, Mycobacterium intracellulare, Mycobacterium leprae, Mycobacterium kansasii, Mycobacterium marinum, Mycobacterium microti, Mycobacterium paratuberculosis, M. phlei, Mycobacterium pinnipedii, Mycobacterium scrofulaceum, Mycobacterium simiae, Mycobacterium smegmatis, Mycobacterium szulgai, Mycobacterium ulcerans, Mycobacterium vacca, or Mycobacterium xenopi. Exemplary symptoms that can be treated include fever, muscle aches, coughing, sneezing, runny nose, sore throat, headache, chills, diarrhea, vomiting, rash, weakness, dizziness, bleeding under the skin, in internal organs, or from body orifices like the mouth, eyes, or ears, shock, nervous system malfunction, delirium, seizures, renal (kidney) failure, personality changes, neck stiffness, dehydration, seizures, lethargy, paralysis of the limbs, confusion, back pain, loss of sensation, impaired bladder and bowel function, and sleepiness that can progress into coma or death. These symptoms, and their resolution during treatment, may be measured by, for example, a physician during a physical examination or by other tests and methods known in the art. Immunogenic compositions (e.g., vaccines) of the disclosure can be administered to a subject (e.g., a human), pre- or post-exposure to an infective agent (e.g., Mtb) or pre- or post-diagnosis of a disease (e.g., TB) to treat, prevent, ameliorate, inhibit the progression of, or reduce the severity of one or more symptoms of the disease in the subject. Immunogenic compositions of the disclosure may be administered, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 35, 40, 45, 50, 55, or 60 minutes, 2, 4, 6, 10, 15, or 24 hours, 2, 3, 5, or 7 days, 2, 4, 6 or 8 weeks, or even 3, 4, or 6 months pre-exposure or pre-diagnosis, or may be administered to the subject 1-30 minutes or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 20, 24, 48, or 72 hours, 3, 5, or 7 days, 2, 4, 6 or 8 weeks, 3, 4, 6, or 9 months, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 years or longer post-diagnosis or post-exposure to the infective agent (e.g., Mtb). Immunogenic compositions of the disclosure may be administered to the subject either before the occurrence of symptoms or a definitive diagnosis or after diagnosis or symptoms become evident. For example, a composition may be administered, e.g., immediately after diagnosis or the clinical recognition of symptoms or 2, 4, 6, 10, 15, or 24 hours, 2, 3, 5, or 7 days, 2, 4, 6 or 8 weeks, or even 3, 4, or 6 months after diagnosis or detection of symptoms. A skilled person in the field familiar with the protocols, formulations, dosages and clinical practice associated with the administration of an immunogenic composition, such as a vaccine (e.g., MTBVAC or BCG) can readily adapt known administration protocols for use with an immunogenic composition of the present disclosure. The immunogenic compositions described herein can be administered in a manner compatible with the dosage and / or formulation, and in such amount as will be therapeutically effective and immunogenic. The quantity to be administered may depend on the subject to be treated (e.g., the age, body weight, the capacity of the subject’s immune system to mount an immune response, the degree of protection desired, and general health of the subject being treated), the form of administration (e.g., as a solid or liquid), the manner of administration (e.g., by injection, inhalation, dry powder propellant), and the cells targeted (e.g., epithelial cells, such as blood vessel epithelial cells, nasal epithelial cells, or pulmonary epithelial cells). A single dose or a plurality (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or more) of doses of one or more immunogenic compositions described here may be given (pre- or post-exposure and / or pre- or post- diagnosis) to a subject (e.g., one administration or administration two or more times). For example, subjects who are particularly susceptible to a bacterial infection may require a plurality of doses to establish and / or maintain protection against the virus. In some embodiments, the plurality of doses (e.g., two doses, three doses, four doses, five doses, six doses, or more) are administered at least one day, two weeks, 12 weeks, 6 month, 12 months, 18 months, or 24 months apart. In some instances, an immune response triggered by a single administration of a composition of the disclosure may not be sufficiently potent and / or persistent to provide effective protection. Accordingly, the methods of inducing an immune response may include repeated administration of one or more immunogenic compositions of the disclosure; thus, immunogenic compositions of the disclosure may be administered as either a priming component or a boosting component in a prime- boost regimen, or both. This can significantly enhance the subject’s immune response to the immunogenic compositions of the disclosure. For example, the prime-boost regimen may be a homologous prime-boost regimen having a priming step and a boosting step, wherein the priming step and the boosting step includes administration of the immunogenic composition. Alternatively, prime-boost regimen may be a heterologous prime-boost regimen comprising a priming step and a boosting step, wherein the priming step comprises administration of the immunogenic composition and the boosting step comprises administration of a second, different immunogenic composition. The dose of an immunogenic composition or the number of treatments with the immunogenic composition of the disclosure may be increased or decreased based on the severity of, occurrence of, or progression of, the disease in the subject (e.g., based on the severity of one or more symptoms of TB). A pharmaceutical composition of the disclosure can be administered in a therapeutically effective amount that induces an immune response in the subject and / or provides a protective effect against an infective agent (e.g., Mtb). Doses of the immunogenic composition may be administered as a fixed dose or a weight-based dose. For example, the subject can be administered at least about 10 µg to 100 µg (e.g., 10 µg, 11 µg, 12 µg, 13 µg, 14 µg, 15 µg, 16 µg, 17 µg, 18 µg, 19 µg, 20 µg, 21 µg, 22 µg, 23 µg, 24 µg, 25 µg, 26 µg, 27 µg, 28 µg, 29 µg, 30 µg, 31 µg, 32 µg, 33 µg, 34 µg, 35 µg, 36 µg, 37 µg, 38 µg, 39 µg, 40 µg, 41 µg, 42 µg, 43 µg, 44 µg, 45 µg, 46 µg, 47 µg, 48 µg, 49 µg, 50 µg, 51 µg, 52 µg, 53 µg, 54 µg, 55 µg, 56 µg, 57 µg, 58 µg, 59 µg, 60 µg, 61 µg, 62 µg, 63 µg, 64 µg, 65 µg, 66 µg, 67 µg, 68 µg, 69 µg, 70 µg, 71 µg, 72 µg, 73 µg, 74 µg, 75 µg, 76 µg, 77 µg, 78 µg, 79 µg, 80 µg, 81 µg, 82 µg, 83 µg, 84 µg, 85 µg, 86 µg, 87 µg, 88 µg, 89 µg, 90 µg, 91 µg, 92 µg, 93 µg, 94 µg, 95 µg, 96 µg, 97 µg, 98 µg, 99 µg, or 100 µg), 10 µg to 50 µg, 25 µg to 75 µg, or 50 µg to 100 µg of a fixed does of the immunogenic composition (e.g., an immunogenic composition containing a DNA molecule and / or an mRNA molecule described herein (or multiple different DNA and / or RNA molecules as described herein)). In another example, the subject can be administered at least about 0.01 µg per kilogram (kg) to 3 µg / kg (e.g., 0.01 µg / kg, 0.02 µg / kg, 0.03 µg / kg, 0.04 µg / kg, 0.05 µg / kg, 0.06 µg / kg, 0.07 µg / kg, 0.08 µg / kg, 0.09 µg / kg, 0.1 µg / kg, 0.2 µg / kg, 0.3 µg / kg, 0.4 µg / kg, 0.5 µg / kg, 0.6 µg / kg, 0.7 µg / kg, 0.8 µg / kg, 0.9 µg / kg, 1 µg / kg, 1.1 µg / kg, 1.2 µg / kg, 1.3 µg / kg, 1.4 µg / kg, 1.5 µg / kg, 1.6 µg / kg, 1.7 µg / kg, 1.8 µg / kg, 1.9 µg / kg, 2 µg / kg, 2.5 µg / kg, or 3 µg / kg) of the subjects weight (e.g., a weight-based dose) of the immunogenic composition (e.g., an immunogenic composition containing a DNA molecule and / or an mRNA molecule described herein (or multiple difference DNA and / or RNA molecules as described herein)). In yet another example, the subject can be administered at least 1 mg to 5000 mg (e.g., 1 mg, 2 mg, 3 mg, 4 mg, 5 mg, 6 mg, 7 mg, 8 mg, 9 mg, 10 mg, 11 mg, 12 mg, 13 mg, 14 mg, 15 mg, 16 mg, 17 mg, 18 mg, 19 mg, 20 mg, 21 mg, 22 mg, 23 mg, 24 mg, 25 mg, 26 mg, 27 mg, 28 mg, 29 mg, 30 mg, 31 mg, 32 mg, 33 mg, 34 mg, 35 mg, 36 mg, 37 mg, 38 mg, 39 mg, 40 mg, 41 mg, 42 mg, 43 mg, 44 mg, 45 mg, 46 mg, 47 mg, 48 mg, 49 mg, 50 mg, 51 mg, 52 mg, 53 mg, 54 mg, 55 mg, 56 mg, 57 mg, 58 mg, 59 mg, 60 mg, 61 mg, 62 mg, 63 mg, 64 mg, 65 mg, 66 mg, 67 mg, 68 mg, 69 mg, 70 mg, 71 mg, 72 mg, 73 mg, 74 mg, 75 mg, 76 mg, 77 mg, 78 mg, 79 mg, 80 mg, 81 mg, 82 mg, 83 mg, 84 mg, 85 mg, 86 mg, 87 mg, 88 mg, 89 mg, 90 mg, 91 mg, 92 mg, 93 mg, 94 mg, 95 mg, 96 mg, 97 mg, 98 mg, 99 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 280 mg, 290 mg, 300 mg, 310 mg, 320 mg, 330 mg, 340 mg, 350 mg, 360 mg, 370 mg, 380 mg, 390 mg, 400 mg, 410 mg, 420 mg, 430 mg, 440 mg, 450 mg, 460 mg, 470 mg, 480 mg, 490 mg, 500 mg, 525 mg, 550 mg, 575 mg, 600 mg, 625 mg, 650 mg, 675 mg, 700 mg, 725 mg, 750 mg, 775 mg, 800 mg, 825 mg, 850 mg, 875 mg, 900 mg, 925 mg, 950 mg, 975 mg, 1000 mg, 1100 mg, 1200 mg, 1300 mg, 1400 mg, 1500 mg, 1600 mg, 1700 mg, 1800 mg, 1900 mg, 2000 mg, 2100 mg, 2200 mg, 2300 mg, 2400 mg, 2500 mg, 2600 mg, 2700 mg, 2800 mg, 2900 mg, 3000 mg, 3100 mg, 3200 mg, 3300 mg, 3400 mg, 3500 mg, 3600 mg, 3700 mg, 3800 mg, 3900 mg, 4000 mg, 4100 mg, 4200 mg, 4300 mg, 4400 mg, 4500 mg, 4600 mg, 4700 mg, 4800 mg, 4900 mg, or 5000 mg) of a fixed dose of the immunogenic composition (e.g., an immunogenic composition containing a polypeptide (or a combination of polypeptides) described herein). In yet another example, the subject can be administered at least 0.01 mg / kg to 100 mg / kg (e.g., 0.01 mg / kg, 0.05 mg / kg, 0.10 mg / kg, 0.25 mg / kg, 0.50 mg / kg, 0.75 mg / kg, 1 mg / kg, 2 mg / kg, 3 mg / kg, 4 mg / kg, 5 mg / kg, 6 mg / kg, 7 mg / kg, 8 mg / kg, 9 mg / kg, 10 mg / kg, 11 mg / kg, 12 mg / kg, 13 mg / kg, 14 mg / kg, 15 mg / kg, 16 mg / kg, 17 mg / kg, 18 mg / kg, 19 mg / kg, 20 mg / kg, 21 mg / kg, 22 mg / kg, 23 mg / kg, 24 mg / kg, 25 mg / kg, 26 mg / kg, 27 mg / kg, 28 mg / kg, 29 mg / kg, 30 mg / kg, 31 mg / kg, 32 mg / kg, 33 mg / kg, 34 mg / kg, 35 mg / kg, 36 mg / kg, 37 mg / kg, 38 mg / kg, 39 mg / kg, 40 mg / kg, 41 mg / kg, 42 mg / kg, 43 mg / kg, 44 mg / kg, 45 mg / kg, 46 mg / kg, 47 mg / kg, 48 mg / kg, 49 mg / kg, 50 mg / kg, 51 mg / kg, 52 mg / kg, 53 mg / kg, 54 mg / kg, 55 mg / kg, 56 mg / kg, 57 mg / kg, 58 mg / kg, 59 mg / kg, 60 mg / kg, 61 mg / kg, 62 mg / kg, 63 mg / kg, 64 mg / kg, 65 mg / kg, 66 mg / kg, 67 mg / kg, 68 mg / kg, 69 mg / kg, 70 mg / kg, 71 mg / kg, 72 mg / kg, 73 mg / kg, 74 mg / kg, 75 mg / kg, 76 mg / kg, 77 mg / kg, 78 mg / kg, 79 mg / kg, 80 mg / kg, 81 mg / kg, 82 mg / kg, 83 mg / kg, 84 mg / kg, 85 mg / kg, 86 mg / kg, 87 mg / kg, 88 mg / kg, 89 mg / kg, 90 mg / kg, 91 mg / kg, 92 mg / kg, 93 mg / kg, 94 mg / kg, 95 mg / kg, 96 mg / kg, 97 mg / kg, 98 mg / kg, 99 mg / kg, or 100 mg / kg) of a weight-based dose of the immunogenic composition (e.g., an immunogenic composition containing a polypeptide (or a combination of polypeptides) described herein). An immunogenic composition (e.g., a vaccine) of the present disclosure may be administered in a single dose or in a plurality of doses (e.g., 2, 3, 4, 5, or more doses). Doses may be administered concurrently or about 1-30 minutes or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 20, 24, 48, or 72 hours, or about 3, 5, or 7 days, or about 2, 4, 6 or 8 weeks, or about 3, 4, 6, or 9 months, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 years or longer. In one embodiment, an immunogenic composition (e.g., a vaccine) of the present disclosure may be administered in two doses about 1-12 months apart. The subject may be vaccinated at any time, although it may be preferred to administer an immunogenic composition (e.g., a vaccine) of the present disclosure shortly (optimally about 10 days to two weeks) before anticipated exposure to an infected individual. An immunogenic composition of the disclosure may be administered alone or in combination with other treatments (e.g., other vaccines, such as BCG, MTBVAC, VPM1002, DAR-901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72 (e.g., M72 / AS01E (GSK)), RUTI, H107, or CysVac2 / Advax), either simultaneously or sequentially (e.g., as a prime-boost) dependent upon the condition to be treated. The composition can be administered after vaccination with, e.g., BCG or another vaccine, and therefore may act as a boosting TB vaccine. III. KITS Also featured herein are kits that include one or more immunogenic compositions described herein, such as one or more polypeptides or nucleic acid molecules (e.g., DNA molecules, mRNA molecules, or DNA vectors) alone or in combination with a live attenuated vaccine (e.g., BCG), and a pharmaceutically acceptable vehicle, diluent, excipient and / or adjuvant, in a therapeutically effective amount for treating and / or reducing the symptoms of a disease (e.g., TB). The kits can include instructions directing a clinician (e.g., a physician or nurse) in methods for administering the composition contained therein. The kits may include packages of single-doses or multiple doses of the immunogenic compositions. Optionally, instruments or devices necessary for administering the pharmaceutical composition(s) may be included in the kits. For instance, a kit of this invention may provide one or more pre-filled syringes containing an effective amount of the immunogenic composition. Furthermore, the kits may also include additional components, such as instructions or schedules for administration of the immunogenic composition. The following are examples of the methods of the disclosure. It is understood that various other aspects may be practiced, given the general descriptions provided above. EXAMPLES Example 1. Mining the CD4 T cell antigen repertoire for next-generation tuberculosis vaccine design Introduction In the following example, we leveraged a versatile murine aerosol challenge model and a DNA vaccine platform to perform a large-scale in vivo screen of the human latent tuberculosis (LTB) cluster of differentiation 4 (CD4) T cell antigen repertoire. This approach identified several vaccine antigens not previously described in preclinical or clinical vaccine development. We show that these antigens exhibit robust immunogenicity and protection when delivered as individual or multivalent vaccines. Finally, we show that when combined with the live attenuated Bacillus Calmette–Guérin (BCG) vaccine, these novel vaccines exhibit a co-adjuvant effect with enhanced antigen-specific immunogenicity. Results Development of an in vivo TB CD4 T cell vaccine antigen screening platform In order to undertake a large-scale screen of CD4 T cell antigens in the murine aerosol challenge model, we first selected a vaccine platform and a mouse model. We selected a DNA vaccine platform because it exhibits two key features well suited to tuberculosis (TB) CD4 T cell vaccine antigen screening, namely rapid synthesis and stimulation of a balanced adaptive immune response that includes robust CD4 T cell responses. In addition, we selected the CB6F1 mouse strain, a first filial generation (F1) cross between BALB / c females and C57BL / 6 males that achieves increased major histocompatibility complex class two (MHC II) diversity by incorporating both the H-2 Ib and H-2 Id MHC II alleles. Our screening pipeline incorporated 50 μg of a prime-boost DNA vaccine immunization in female CB6F1 mice via the intramuscular (IM) route followed by 50-100 colony forming unit (CFU) H37Rv aerosol challenge and lung bacterial load quantification four weeks post- infection by agar outgrowth assay (FIG.8A). Large-scale screening of LTB CD4 T cell antigens and selected clinical candidates with DNA vaccines in CB6F1 mice Having established the DNA vaccine-based pipeline, we proceeded with screening of 42 select vaccine candidates (FIG.7A). Overall, we observed a broad distribution of bacterial load reductions that ranged from no protection to a maximum 4.1-fold (0.6 log10) reduction. A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain (RBD) served as a negative control and conferred no protection in our screen. Notably, Rv1196 and Rv0129, the two antigens that comprise a current clinical trial vaccine, the M72 / AS01E (M72) vaccine, showed some protection (1.8-fold and 2.0-fold, respectively) but, surprisingly, were not among the most protective antigens in our screen, ranking 16thand 19thby protection, respectively. To focus on antigens demonstrating the greatest protection, we selected a ≥2.5-fold (0.4 log10) reduction in bacterial load threshold. Notably, only two of the eight top vaccine antigens from our screen, Rv1886c and Rv3804 (also known as Ag85B and Ag85A, respectively), are in clinical development. Interestingly, phylogenetic analysis showed broad segregation of the screened CD4 T cell antigen repertoire into clusters with varying degrees of DNA sequence homology (FIG.9A). Indeed, seven of the top eight antigens from our screen clustered into three groups of homologous antigens (FIG.9A). Moreover, the eighth antigen, Rv1788, clustered with Rv1791, an antigen that did not meet the stringent ≥2.5- fold (0.4 log10) threshold but demonstrated a 1.9-fold (0.3 log10) reduction (FIG.7A). We next performed a second, fully independent screen to confirm the reproducibility of the DNA vaccine protection observed our primary screen described above. We again used a 50 μg prime- boost DNA vaccine immunization schedule in female CB6F1 mice via the IM route followed by 50-100 CFU H37Rv aerosol challenge and lung bacterial load quantification four weeks post-infection by agar outgrowth assay. Overall, seven of the eight antigens showed ≥1.8-fold protection in this second, independent DNA vaccine study (FIG.1). Novel antigens identified in our DNA vaccine screen are immunogenic and protective when delivered with the mRNA-LNP platform as single or multivalent vaccines To deliver our antigens in a vaccine platform with both a proven clinical profile and scalability, we initiated studies with mRNA packaged into lipid nanoparticles (LNPs) (mRNA-LNPs). The sequences from our DNA vaccine screen were delivered with 5’ and 3’ untranslated regions (UTRs), polyadenylated (polyA) tail, and LNP components. Based on our screen results showing robust protection for antigens in phylogenetic groups (FIG.8A), we selected the most protective antigen from each group for delivery (e.g., Rv1387, Rv0287, Rv1886c, and Rv1788). CB6F1 mice received 5 μg of vaccine at weeks 0 and 4, and T cell responses were assessed by intracellular cytokine staining (ICS) among splenocytes after ex vivo stimulation with matched overlapping peptide pools at week 6. We observed that all four antigens stimulated CD4 T cells responses with secretion of IFN-γ (FIG.2), TNF-α (FIG.3A), and IL-2 (FIG.3B). Interestingly, Rv1387 and Rv1886c also stimulated CD8 T cell responses (FIG.3C). Additional mice were aerosol challenged on week 6 with 50-100 CFU of H37Rv, and all four vaccines showed approximately 5-fold (0.7 log10) reductions in bacterial loads (FIG.3D). We next assessed the immunogenicity and protection of our novel antigen mRNA-LNPs as individual vaccines compared to multivalent vaccines. CB6F1 mice received a total mRNA-LNP dose of 20 μg of vaccine at weeks 0 and 4 for all vaccine groups, and T cell responses were assessed by ICS among splenocytes after ex vivo stimulation with matched overlapping peptide pools at week 6. We observed the expected antigen-specific responses for all tested vaccines (FIG.4). An additional cohort of mice was immunized and underwent aerosol challenge on week 6 with 50-100 CFU of H37Rv. Lung bacterial loads were quantified at week 10. We observed incremental increases in protection and a multivalent vaccine consisting of Rv1387, Rv0287, and Rv1788 showed 14-fold protection (FIG.5). Notably, antigens in the M72 vaccine only showed 0.4-0.6 log10 (2.5-4 fold) reductions in bacterial loads in mice when combined with an AS01 adjuvant. mRNA-LNP vaccines both exceed and enhance antigen-specific responses to BCG Finally, we performed immunogenicity studies comparing our multivalent mRNA-LNP vaccine to BCG alone or in combination with BCG. At week 0 CB6F1 mice received BCG at a dose of 1x106CFU administered subcutaneously, 20 μg of mRNA-LNP administered intramuscularly, or a combination. At week four, mice that were primed with mRNA-LNP received a mRNA-LNP boost. Splenocytes were isolated at week 6 for ICS after stimulation with antigen-specific overlapping peptide pools as well as purified protein derivative (PPD). As expected, BCG stimulated low-level CD4 T cell IFN-γ responses to PPD (FIG.6, P = 0.0079, Mann-Whitney U test). Compared to BCG, a tetravalent mRNA-LNP vaccine showed greater antigen-specific responses to three of four antigens, and a combination of BCG with a tetravalent mRNA-LNP vaccine showed greater antigen-specific responses to all antigens (FIG.6). Conclusion In conclusion, we developed a pipeline and performed a large-scale in vivo screen to classify the protective efficacy of the LTB immunodominant CD4 T cell antigen repertoire. We observed a broad range of protection ranging from negligible to significant efficacy in a number of previously uncharacterized vaccine antigens. We further demonstrate the immunogenicity and protective efficacy of these antigens as individual and multivalent mRNA vaccines. Finally, we show that combining BCG with a multivalent mRNA vaccine enhances antigen-specific responses. Materials and Methods DNA and mRNA-LNP vaccines All native vaccine nucleic sequences were obtained from the H37Rv genome on Mycobrowser (e.g., see Kapopoulou et al., Tuberculosis (Edinb) 91:8-13, 2011). For DNA vaccines, native sequences were codon optimized and cloned into plasmid cloning (pcDNA) mammalian expression plasmids (GeneArt, Thermo Fisher). A 5’ Kozak sequence was added and antigens with non-canonical start codons were changed to methionine for mammalian translation. For mRNA-LNP vaccines, the same codon optimized sequences were In-Fusion cloned (Takara Bio) into a pVax1 plasmid (Thermo Fisher) containing 5’ UTR, 3’ UTR, and polyA sequences. N-1-methylpseudouridine (m1Ψ-5′)-triphosphate (TriLink BioTechnologies) was used to substitute UTP to generate modified nucleoside-containing mRNAs, and capping of in vitro transcribed mRNAs was performed in a one- pot-reaction using CLEANCAP®Reagent AG – 3’ Ome (Trilink BioTechnologies). mRNAs were purified by cellulose purification to obtain dsRNA-free mRNA molecules. To synthesize mRNA-LNP vaccines, mRNAs were encapsulated in LNPs using an aqueous solution of mRNA at acidic pH 4.0 and mixed with a solution of lipids, consisting of an ionizable cationic lipid / phospholipid / cholesterol / PEG-lipid (50:10:38.5:1.5 mol / mol). After mixing, mRNA-LNPs were dialyzed in 2L of 1×PBS overnight and concentrated and stored using cryoprotectants. The diameter (z-average) and polydispersity index (PDI) of the mRNA-LNPs was measured by dynamic light scattering (DLS) using a Zetasizer Nano (Malvern Instruments). Quantification of encapsulated mRNAs was performed using QUANT-IT™ RiboGreen RNA Assay Kit (Thermo Fisher). Mycobacterial challenge and vaccine strains H37Rv challenge strain was obtained from the Rubin laboratory (Harvard School of Public Health). BCG vaccine strain was obtained from the Urdahl laboratory (University of Washington). All challenge and vaccine strains were grown in media consisting of Middlebrook 7H9 (BD Difco) containing 10% Middlebrook OADC (BD BBL), 0.5% glycerol (Sigma Aldrich), and 0.05% tween 80 (Sigma Aldrich). For preparation of vaccine stocks, vaccine strains were grown in complete growth medium as above additionally supplemented with 0.05% tyloxapol (Sigma Aldrich). Cells were pelleted twice with resuspension in PBS containing 0.05% tyloxapol and then pelleted a third time with resuspension in PBS containing 0.05% tyloxapol and 15% glycerol. Mouse strains, immunizations, and aerosol challenges 6-8 old female CB6F1 mice were obtained from Jackson Laboratory (strain 100007) and stored in sterile conditions at the Harvard School of Public Health. All mouse procedures were performed in accordance with Institutional Animal Care and Use Committee (IACUC) guidelines. BCG immunizations were performed subcutaneously with 1x106CFU of tittered vaccine strain. DNA and mRNA vaccines were administered intramuscularly in the bilateral quadriceps in 100 μl of PBS. For 100 CFU challenge, a Glas-Col instrument was used and challenge stocks were titrated to result in a day 1 lung bacterial load of approximately 100 CFU. Lung processing and CFU quantification Mice were euthanized 4 weeks following 100 CFU challenge and both lung lobes were dissected en bloc. Tissues were placed into GENTLEMACS™ M Tubes (Miltenyi Biotec, catalog # 130-096-335) containing 5 ml of PBS and mechanically dissociated using a GENTLEMACS™ Dissociator (Miltenyi Biotec). Lysates were then plated in serial log10 dilutions onto 100x15mm Middlebrook 7H10 plates (Hardy Diagnosatics). CFU were counted after a 3 week incubation at 37°C. Splenocyte flow cytometry For immunological studies spleens were mechanically dissociated followed by passage through 100 μm then 30 μm filters in R10 media consisting of RPMI supplemented with 10% FBS (Gibco) and 1% penicillin-streptomycin (Fisher Scientific). Cells were then quantified by trypan blue staining and distributed on 96-well plates at a density of 2x106cells in 100 μl of R10. Splenocytes were then stimulated with antigen-specific peptide pools (21stCentury Biochemicals) and PPD (Cedarlane) at 400 ng of peptide per test or media control for 1 hour followed by GolgiStop / GolgiPlug (BD Biosciences) overlay for 6 hours at 37°C and then rested overnight 4°C. PBMCs were then stained with live / dead and cell surface markers in MACS solution (Miltenyi) supplemented with 2% BSA (Miltenyi) prior to permeabilization with Cytofix / Cytoperm (BD Biosciences) and staining with intracellular markers in Perm / Wash (BD Biosciences). Splenocytes were then fixed in 2% formaldehyde and stored at 4°C until flow cytometry on an LSR II flow cytometer (BD Biosciences). Cell surface markers included cluster of differentiation (CD) 3 (CD3) (clone 17A2, BD Biosciences), CD19 (clone 6D5, BioLegend), CD4 (clone RM4-5, BioLegend), CD8a (clone 53-6.7, BD Biosciences), CD44 (clone IM7, BD Biosciences), and CD62L (clone MEL-14, BioLegend). Intracellular markers included IFN-γ (clone XMG1.2, BioLegend), IL-2 (clone JES6-5H4, BioLegend), TNF-α (clone MP6-XT22, BioLegend) , IL17-A (clone TC11-18H10.1, BioLegend), and IL-4 (clone 11B11, BD Biosciences). Data were analyzed using FloJo 10.8.1 software. Example 2. Use of an immunogenic composition to treat an infection An infection (e.g., a bacterial infection, such as an infection with Mtb) in a subject (e.g., a human) may not induce an immune response to a level sufficient to clear the infection in a timely manner or at all. For instance, a course of an infection may range from 1 to 72 hours, 3 to 7 days, 1 to 8 weeks, 2 to 12 months, 1 to 10 years or longer, or it may persist for the lifetime of the subject. In this instance, an immunogenic composition described in Section I can be administered to the subject to treat or reduce the term of the infection, as described in Section II. Example 3. Use of an immunogenic composition in a prime-boost immunization Protective immune responses induced by immunogenic compositions often wane to below a protective level over time. As a result, re-administration of an immunogenic composition or administration of a different immunogenic composition is necessary to maintain a protective immune response. An immunogenic composition described in Section I can be administered to a subject which has previously been administered an immunogenic composition containing one or more polypeptides listed in Table 2 (or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto), or polynucleotide sequences listed in Tables 2 and / or Table 4 (or a variant thereof at least 70% or more (e.g., 80%, 95%, 90%, 95%, 99%, or 100%) sequence identity thereto). In this instance, the immunogenic composition is administered as a boost immunization in a prime-boost immunization strategy. The timing of administration of the boost immunization can be a pre-set time (e.g., 1, 2, 3, or more weeks, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or more months, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more years after administration of the prime immunization). For example, a boost immunization of an immunogenic composition described herein may be administered to a subject soon (e.g., 1, 2, or 3 weeks, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or 11 months, or 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 years) after a prime immunization. Example 4. Mining the CD4 antigen repertoire for next-generation tuberculosis vaccines Introduction In this example, we show the results of an in vivo vaccine efficacy screening pipeline in mice and compared several antigens that represent targets of CD4 T cell responses in humans with latent TB. We found striking heterogeneity in vaccine efficacy among the antigens tested, and most of the identified protective antigens are not currently in clinical vaccine development. We further observed significant immunologic cross-reactivity among groups of phylogenetically clustered antigens, reflecting common CD4 T cell epitopes. Finally, we developed a trivalent mRNA-LNP vaccine consisting of the lead candidates PPE20 (Rv1387), EsxG (Rv0287), and PE18 (Rv1788), resulting in a vaccine strategy that exceeded BCG in multiple murine challenge models. These data advance our understanding of vaccine immunity to TB and identify a next-generation TB vaccine candidate for clinical evaluation (e.g., trivalent mRNA-LNP vaccine that augments BCG protection). Results In vivo antigen screening To develop an in vivo screening pipeline of candidate TB antigens and analyzed their efficacy, we utilized the DNA vaccine platform described in FIG.8A to evaluate emergent pathogens. We screened antigens recognized by CD4 T cells in LTB. We prioritized the 36 CD4 T cell antigens that were detected most frequently among LTB individuals, reasoning that a high rate of recognition during natural infection is an important criterion for vaccine antigen selection. We cloned codon-optimized reference genes for these 36 antigens as well as 6 additional antigens that were already in clinical development (e.g., esxV, PPE42, pepA, Rv1813c, Rv2660c, and esxW) into DNA vaccines. Thus, our screen included 42 TB antigens (Table 5) as well as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike receptor binding domain (RBD) negative control. Table 5. Mycobacterium tuberculosis (Mtb) Antigens Included in the DNA Vaccine Protection Screen in Mice

[0021] * %LTB Response reported in Lindestam Arlehamn et al. Gene locus, name, and alias of n=36 genes identified as targets of CD4 T cells responses in human LTB, as well as n=6 additional genes in clinical development vaccine development. We selected the CB6F1 mouse strain, a first filial generation (F1) cross between BALB / c females and C57BL / 6 males that achieves increased major histocompatibility complex (MHC II) diversity. Mice were immunized twice via the intramuscular (IM) route and then received a 100 colony forming unit (CFU) H37Rv by aerosol challenge. Protection was measured as fold reduction in bacterial load relative to sham controls. We observed a spectrum of vaccine efficacy for the DNA vaccines tested, ranging from no protection (1-fold reduction) to a maximum of 4.1-fold reduction (0.61 log10, FIG.7A and Table 6). DNA vaccines expressing SARS-CoV-2 Spike RBD did not reduce bacterial loads. To focus subsequent studies on the most protective antigens, we prioritized the 8 antigens that demonstrated ≥2.5-fold (0.40 log10) protection: Rv1387, Rv1886c, Rv0287, Rv3804c, Rv0280, Rv3020c, Rv1788, and Rv0256c. With the exception of Rv1886c and Rv3804c (also called Ag85B and Ag85A, respectively), none of these protective antigens have previously been in clinical vaccine development. Moreover, these protective antigens were more protective than those currently in clinical trials in this model (P=0.0024, Mann-Whitney U test, FIG.7B). Table 6. Protective Efficacy of Individual Antigens Included in the DNA Vaccine Protection Screen in Mice Fold reduction in lung bacterial loads relative to naïve mice for n=42 Mtb genes following two DNA vaccine immunizations followed by 100 CFU H37Rv aerosol challenge and lung bacterial load quantification. We assessed the reproducibility of our initial screen data with a second focused DNA vaccine study that confirmed protection for the 8 lead antigens (Rv1387, Rv1886c, Rv0287, Rv3804c, Rv0280, Rv3020c, Rv1788, and Rv0256c; range 0.28 to 0.67 log10 reduction in lung CFU; FIG.8B). To characterize the T cell responses among vaccinated mice, we performed splenocyte intracellular cytokine staining (ICS) assays after ex vivo stimulation with overlapping peptide pools. We observed that all 8 antigens yielded robust CD4 Th1 responses with secretion of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin 2 (IL-2; FIG.7C and FIG.8C). In addition, we observed CD8 responses with Rv1387, Rv1886c, Rv3804c, Rv0280, and Rv0256c, but not Rv0287, Rv3020c, or Rv1788 in these mice (FIG.7D). Boolean analysis further demonstrated that the CD4 responses were primarily polyfunctional with secretion of ≥2 cytokines (FIG.7E). We also observed robust T cell responses among five selected non-protective antigens (showing ≤1.5-fold protection; Table 6 and FIG.7F), suggesting that protection vs. lack of protection was due to antigen biology rather than antigen presentation and immunogenicity. Phylogenetic and epitope analyses of protective antigens To further investigate the characteristics of the protective antigens from our screen, we performed phylogenetic analysie as well as structural and functional annotation. The 8 protective antigens (e.g., Rv1387, Rv1886c, Rv0287, Rv3804c, Rv0280, Rv3020c, Rv1788, and Rv0256c) segregated into four phylogenetic clusters with distinct structural and functional properties (FIG.9A and Table 7). Rv1387, Rv0280, and Rv0256c formed a cluster of structurally related proline-proline- glutamic acid (PPE) family proteins implicated in various aspects of immune evasion and nutrient stress adaptation. Rv0287 and Rv3020c formed a cluster belonging to a family of type VII secretion (Esx) proteins that are critical virulence factors in mycobacteria. Rv1788 belongs to the structurally related proline-glutamic acid (PE) family proteins that share overlapping functions with the PPE family. Rv1788 also clustered with Rv1791, another PE family protein that demonstrated 1.9-fold (0.28 log10) protection in our screen, slightly below the stringent ≥2.5-fold (0.40 log10) cut-off (FIG.7A and Table 6). Finally, Rv1886c and Rv3804c formed a cluster of related Ag85 family proteins, a group of mycolyl transferases with essential roles in Mtb cell wall homeostasis and intracellular survival. Table 7. Structural and Functional Annotation of Protective Antigens from the DNA Vaccine Protection Screen in Mice

[0022] Gene locus, name, and alias as well as protein product, amino acid length, and function if known for n=8 protective antigens from the DNA vaccine protection screen in mice. We hypothesized that the protective efficacy of TB vaccine antigens within each phylogenetic cluster is associated with conserved CD4 T cell epitopes. We immunized mice using DNA vaccines with individual protective antigens and assessed whether the resulting CD4 T cell responses could be stimulated by heterologous peptide pools from other antigens within each phylogenetic cluster. For the PPE antigens, vaccination with Rv1387 stimulated the greatest response to the autologous Rv1387 peptide pool, but we also observed cross-reactive responses to the Rv0280 and Rv0256c pools (FIG.9B). Similarly, vaccination with Rv0280 yielded cross-reactive responses to Rv0256c, and vaccination with Rv0256c yielded cross-reactive responses to Rv0280 (FIG.9B). In contrast, similar experiments with the Rv0287-Rv3020c and Rv1788-Rv1791 clusters showed that stimulation with either the homologous or cross-reactive peptide pools yielded responses that were nearly indistinguishable (FIG.9C and FIG.9D, respectively). Finally, the Rv1886c-Rv3804c cluster demonstrated cross-reactive responses (FIG.9E). These studies demonstrated substantial cross- reactivity of CD4 T cell responses within each antigen phylogenetic cluster. We next performed epitope mapping to further characterize the CD4 T cell responses. Given the larger size of the PPE family antigens (536-556 amino acids), we immunized mice using DNA vaccines and stimulated splenocytes ex vivo with subpools of 10 overlapping peptides (Tables 8A-D). We observed a multitude of responses ranging between 4 and 8 subpools (FIGS.10A-C). We selected two subpools that demonstrated both immunodominance and shared responses among the three antigens for deconvolution, and we observed overlapping regions of CD4 T cell recognition among both subpools (FIG.9 and FIGS.10D-I). Table 8A. Rv1387-Rv0280-Rv0256 Cluster – Amino Acid Sequences for Peptides and Peptide Pools Used in T cell Epitope Mapping Studies

[0023] Given the small size of the Esx and PE family antigens (97-100 amino acids), we performed single-round mapping experiments (FIGS.10J-K and FIGS.10L-M, respectively; Table 8B and Table 8C, respectively). For both antigen families, we observed two regions of overlapping CD4 reactivity (FIG.9G and FIG.9H). Table 8B. Rv0287-Rv3020c Cluster – Amino Acid Sequences for Peptides and Peptide Pools Used in T cell Epitope Mapping Studies Table 8C. Rv1788-Rv1791 Cluster – Amino Acid Sequences for Peptides and Peptide Pools Used in T cell Epitope Mapping Studies Finally, for the intermediate sized (325-338 amino acids) Ag85 protein family, we performed subpool analysis and observed responses in 6 to 7 subpools (FIG.10N and FIG.10O; Table 8C). We again selected two subpools that demonstrated immunodominance and shared responses among the two antigens for deconvolution, and we similarly observed overlapping regions of CD4 T cell recognition among both subpools (FIG.9I, FIG.10P, and FIG.10Q). These data demonstrate significant immunologic cross-reactivity of protective antigens in each phylogenetic cluster associated with overlapping CD4 T cell recognition. Table 8C. Rv1886c-Rv3804c Cluster – Amino Acid Sequences for Peptides and Peptide Pools Used in T cell Epitope Mapping Studies

[0024] Multivalent mRNA-LNP vaccine We next evaluated the immunogenicity and protective efficacy of our top protective antigens delivered as mRNA-LNP vaccines. Given the observed cross-reactivity in CD4 epitopes (FIGS.9B-E), we selected the most protective antigen from each cluster (i.e. Rv1387, Rv0287, Rv1788, and Rv1886c) for these studies. The ORFs were cloned into constructs containing a 5’ cap, 5’ untranslated region (UTR), 3’ UTR, and polyadenylation (polyA) signal, subjected to in vitro transcription (IVT) using N1-methylpseudouridine, and encapsulated in four-component LNPs. Following immunization with mRNA-LNPs expressing single antigens and ex vivo splenocyte stimulation with overlapping peptide pools, we observed robust secretion of the Th1 cytokines IFN-γ, TNF-α, and IL-2 (FIG.11A and FIG.12A) and a substantial subset with secretion of ≥2 cytokines (FIG.12B and FIG.12C). Similar to our DNA vaccine studies, we observed CD8 T cell responses with Rv1387 and Rv1886c but not with Rv0287 or Rv1788 in these mice (FIG.11C). An increased ratio of non-IFN-γ+to IFN-γ+Th1 responses has previously been associated with increased protection in studies of both natural infection and vaccine protection. Boolean analysis showed that the ratio of non-IFN-γ+to IFN-γ+Th1 responses was higher for Rv1387, Rv1788, and Rv1886c when delivered as mRNA-LNP compared with to DNA (FIG.11D). This was primarily attributable to substantially higher IL-2+cells with the mRNA-LNP vaccines (FIG.11E) and to a lesser extent TNF-α+and TNF-α+IL-2+subsets (FIG.11B and FIG.11C). These phenotypic differences were associated with reductions in lung bacterial loads in the 100 CFU aerosol challenge model with mRNA-LNP vaccines expressing the single antigens Rv1387, Rv0287, Rv1788, and Rv1886c in two independent experiments (range 0.62 to 0.86 log10 reduction in lung CFU, FIG.11F and FIG.12D). Rv0280, Rv0256c, Rv3020c, and Rv3804c were also protective as monovalent mRNA-LNP vaccines (range 0.54 to 0.73 log10 reduction in lung CFU, FIG.12E). Overall, the 0.54-0.86 log10 reductions in lung CFU with mRNA-LNP vaccines were greater than the corresponding 0.26-0.67 log10 reductions with DNA (FIG.11G). To assess the protective efficacy of a multivalent cocktail of mRNA-LNP vaccines, we combined monovalent mRNA-LNP vaccines while maintaining a fixed total mRNA dose. Iterative multiplexing caused no significant reductions in CD4 (FIG.12F) or CD8 (FIG.12G) T cell responses, and both trivalent (Rv1387, Rv0287, and Rv1788) and tetravalent (Rv1387, Rv0287, Rv1788, and Rv1886c) vaccines showed robust Th1 responses to all component antigens (FIG.11H). Complementary studies in the 100 CFU aerosol challenge model showed incremental increases in vaccine protection (FIG.12H) including 0.91-1.00 log10 reductions in lung bacterial loads with the trivalent and tetravalent mRNA-LNPs (P<0.0001 for both vaccines compared with sham; p-value was not significant for trivalent vaccine compared to tetravalent vaccine; FIG.11I). These data show that the protective antigens from our DNA vaccine screen demonstrated enhanced immunogenicity and protection as monovalent mRNA-LNP vaccines and that protection was increased with a multivalent mRNA-LNP vaccine combinations. Trivalent mRNA-LNP vaccine augments BCG immunity Early childhood BCG vaccination is widespread in endemic regions, and therefore next- generation TB subunit vaccines will be administered with BCG. To explore whether our mRNA-LNP vaccines augment BCG immunity, we performed experiments in which mice received BCG with or without the trivalent mRNA-LNP. We first performed immunogenicity studies to characterize the effect of trivalent mRNA-LNP co-administration with BCG (FIG.14A). BCG alone stimulated CD4 T cell IFN- γ responses in spleen (FIG.13A) and lung (FIG.13B) to Rv0287 and Rv1788 but not Rv1387, suggesting that Rv0287 and Rv1788 are immunodominant BCG antigens. In contrast, co- administration of BCG with the trivalent mRNA-LNP vaccine significantly augmented the CD4 T cell IFN-γ response to all three vaccine antigens in both spleen (FIG.13A) and lung (FIG.13B). There was no effect on the immunodominant BCG antigen Rv0288 (also called TB10.4; FIG.14B), suggesting increased responses in the combination group are antigen-specific. We did not observe antigen-specific CD8 T cells responses in the BCG group (FIG.14C and FIG.14D), although as expected mice receiving the trivalent mRNA-LNP vaccine showed robust CD8 T cells responses to Rv1387 (FIG.14D). Importantly, the increased antigen-specific CD4 T cell responses in the combination group were associated with a significantly greater reduction in lung bacterial load compared to BCG after 100 CFU H37Rv aerosol challenge (1.86 vs 1.32 log10 reduction compared with controls; P=0.0002, FIG.13C and FIG.14E). Mtb transmission in humans likely occurs with low bacterial doses. We have shown that low- dose (1-3 CFU) infection in mice may better recapitulate these transmission dynamics and yield additional measures of vaccine protection including prevention of detectable infection and bilateral lung dissemination, in addition to conventional lung bacterial load measurements. We next performed low-dose challenge studies with BCG with or without the trivalent mRNA-LNP vaccine as well as pre- challenge peripheral blood mononuclear cell (PBMC) ICS for correlates of protection analyses (FIG. 14F). For the pre-challenge immunogenicity study, we performed ex vivo stimulation with a combined Rv1387, Rv0287, and Rv1788 overlapping peptide pool given cell limitations in mouse PBMC. The combination group exhibited greater antigen-specific CD4 T cell responses relative to BCG alone (FIG.14G), and CD8 T cell responses were only observed in groups receiving the trivalent mRNA- LNP vaccine (FIG.14H). Interestingly, we observed low but detectable Th17 responses in PBMC (FIG.14I), which had not been apparent in the spleens or lungs of mice receiving the same vaccines (FIGS.14J-M). In the low-dose challenge study, naïve animals showed an infection rate of 18 / 30 (60%), a bilateral lung dissemination rate of 10 / 18 (56%), and a median infected lung bacterial load of 126,250 CFU (FIG.13D and FIGS.13G-I). BCG modestly reduced the infection rate to 8 / 20 (40%) and the bilateral dissemination rate to 1 / 8 (13%), respectively (FIG.13E, FIG.13G, and FIG.13H). In contrast, the addition of the mRNA-LNP vaccine yielded an increased reduction in the infection rate to 5 / 19 (26%, P=0.039, Fisher’s exact test, FIG.13F and FIG.13G) as well as a 100% reduction in the rate of bilateral dissemination to 0 / 5 (0%, P=0.046, Fisher’s exact test, FIG.13F and FIG.13H). Both vaccine groups significantly reduced lung bacterial loads (P<0.0001, negative binomial model, FIG.13I). Moreover, multiple post-vaccination PBMC CD4 subsets correlated with aggregate bacterial loads among post-challenge infected animals (FIG.15). The strongest correlations were observed with aggregate IFN-γ (Spearman ρ=-0.57, P=0.0006) and TNF-α (ρ=-0.56, P=0.0008) CD4 T cell responses, followed by IFN-γ+TNF-α+IL-2+triple-positive and IFN-γ+TNF-α+double-positive CD4 T cell subsets, among others. Moreover, in a repeated low-dose challenge model, BCG provided a 11 / 20 (55%) infection rate, whereas the mRNA-LNP vaccine alone provided an 8 / 20 (40%) infection rate (FIGS.13J-M and FIG.14I). Taken together, these data show that the trivalent mRNA-LNP vaccine augmented vaccine protection compared with BCG in both high and low dose challenge models, and protection correlated with antigen-specific CD4 T cell responses. Conclusion Rational antigen selection is an enduring challenge in TB vaccine development. We developed a screening pipeline in mice to define the protective efficacy of candidate antigens recognized by CD4 T cell responses, identified several protective antigens, and developed a trivalent mRNA-LNP vaccine that showed efficacy in mouse challenge models. Our findings provide insight into TB vaccine immunity and identify a next-generation TB vaccine candidate. We observed significant differences in vaccine protection among the screened antigens (FIG. 7A). Moreover, we observed substantial phylogenetic clustering and immunologic cross-reactivity among antigens that were associated with shared CD4 epitopes (FIG.9). Systematic antigen selection, rather than a strategy relying on empirically selected antigens, may therefore be important for the design of next-generation TB vaccines. We developed a trivalent vaccine consisting of highly most protective antigen from our screen that represented different phylogenetic clusters: Rv1387 (i.e., PPE20), as well as Rv0287 (i.e., EsxG), and Rv1788 (i.e., PE18). We show that mRNA-LNP vaccines stimulate strong polyfunctional Th1 responses to TB antigens. Moreover, multivalent vaccines yielded robust log10-scale reductions in bacterial loads in the conventional murine aerosol challenge model. Finally, our data provide proof-of-concept that a trivalent mRNA-LNP vaccine with BCG increases antigen-specific responses and protection relative to BCG alone, including increased prevention of infection and dissemination in the low-dose challenge model. Materials and Methods Mouse strains and immunizations Eight week-old female CB6F1 / J mice (strain #100007) and C3HeB / FeJ (strain #000658) were obtained from Jackson Laboratory and housed in pathogen-free conditions at Beth Israel Deaconess Medical Center and the Harvard School of Public Health. All mouse procedures were performed in accordance with Institutional Animal Care and Use Committee (IACUC) guidance. DNA vaccine immunizations were performed by diluting 50 μg vaccine in 100 μL of phosphate buffered saline (PBS) followed by IM injection of 50 μL of vaccine into each of the bilateral quadriceps. Monovalent mRNA-LNP immunizations were performed by diluting 5 μg of vaccine by mRNA into 100 μL of PBS followed by IM injection of 50 μL into each of the bilateral quadriceps. For mRNA-LNP iterative multiplexing studies, up to four monovalent mRNA-LNP vaccines were mixed with a uniform aggregate dose of 20 μg. The trivalent vaccine used in BCG combination strategies contained a combination of 5 μg of each monovalent vaccine for an aggregate vaccine dose of 15 μg. For BCG immunizations an aggregate 1x106CFU of tittered vaccine strain was diluted into 200 μL of PBS followed by subcutaneous (SC) injection of 100 μL into each of the bilateral lower flanks. Challenge and vaccine strains H37Rv challenge strain was a gift from the Rubin laboratory (Harvard School of Public Health). BCG vaccine strain was a gift from the Urdahl laboratory (University of Washington). Both challenge and vaccine strains were grown in media consisting of Middlebrook 7H9 (BD Difco) containing 10% Middlebrook OADC (BD BBL), 0.5% glycerol (Sigma Aldrich), and 0.05% tween 80 (Sigma Aldrich). For preparation of conventional H37Rv challenge stock, H37Rv was propagated in growth media to an optical density (OD) of 0.8-1.0, frozen in growth media, and tittered. For low dose challenge studies, H37Rv culture was grown to an OD of 0.8-1.0 followed by passaging through a 5 μm filter to generate a single-cell suspension, resulting in an approximately 2-log10 reduction in titer as measured by agar outgrowth assay. For preparation of BCG vaccine stock, vaccine strain was grown in complete growth medium as above additionally supplemented with 0.05% tyloxapol (Sigma Aldrich). Cells were pelleted twice with resuspension in PBS containing 0.05% tyloxapol and then pelleted a third time with resuspension in PBS containing 0.05% tyloxapol and 15% glycerol. Cells were then passaged though a 40 μm filter followed by a 20 μm filter for clump removal, followed by storage at −80°C and titering by agar outgrowth assay. Mtb aerosol challenge For 100 CFU H37Rv challenge, a Glas-Col instrument was used and challenge stocks were titrated to result in a day 1 lung bacterial load of approximately 100 CFU. For low-dose challenge, the same instrument was used and singe-cell suspension challenge stocks were titrated to result in a week 4 infection rate of approximately 63% in accordance with the Poisson distribution. For repeated low-dose challenge, the same instrument and singe-cell suspension challenge stocks were used at four one-week intervals. CB6F1 / J mice were used for all single-challenge studies and C3HeB / FeJ were used for the repeated challenge study. Lung bacterial load quantifications Mice were euthanized 4 weeks following both 100 CFU challenge or low-dose challenge. For 100 CFU challenge, both lung lobes were dissected en bloc whereas for low dose challenge right and left lung lobes were dissected separately. Tissues were placed into GENTLEMACSTMM Tubes (Miltenyi) containing 5 mL of PBS and mechanically dissociated using a GENTLEMACSTMDissociator (Miltenyi) according to manufacturer’s instructions. Lysates were then plated in serial log10 dilutions on 100 mm Middlebrook 7H10 plates (Hardy Diagnostics). In order to achieve an LOD of 5 CFU in low dose challenge studies, we additionally plated 1 mL of lysate onto 150 mm plates containing Middlebrook 7H10 agar (BD Difco), 10% Middlebrook OADC (BD BBL), 0.5% glycerol (Sigma Aldrich), and cycloheximide (Sigma Aldrich) at 100 mg / mL. CFU were counted after a 3 week incubation at 37ºC. DNA vaccine library and screening Antigens demonstrating >20% CD4 T cell responses in a clinical dataset of LTB were selected for screening. Among the 39 candidate antigens, Rv1047, Rv3023c, and Rv3115 showed identical primary sequences. Similarly, Rv1199c and Rv2512c showed identical primary sequences. Therefore, these 5 genes were consolidated into 2 sequences (Table 5), resulting in 36 distinct candidate antigen sequences. We further identified 6 other antigens (Rv3619c, Rv2608, Rv0125, Rv1813c, Rv2660c, and Rv3620c) which were in clinical development at the time the screen was performed in 2022. Finally, a SARS-CoV-2 Spike RBD sequence was obtained as a negative control, resulting in a total of 43 screened antigens. H37Rv reference sequences were obtained from Mycobrowser, codon-optimized for expression in Homo sapiens, and cloned into pcDNA3.1(+) expression plasmids (GENEARTTM, Thermo Fisher Scientific). A subset of ORFs with a valine (V) start codon were replaced with methionine (M) for mammalian expression, and no other modifications were made to the reference primary sequence. To facilitate screening of large numbers of antigens while accounting for potential variations between individual aerosol experiments, the screen was performed in groups of 20 mice distributed equally into subgroups of 4-5 animals including a naïve group in every individual aerosol challenge. To calculate fold reduction in lung CFU for each vaccinated mouse, the lung bacterial load was divided by the median bacterial load of the naïve subgroup within each individual aerosol challenge. mRNA-LNP design and fabrication We created a custom mRNA expression vector with non-coding backbone elements that included the regions from the T7 promoter compatible with CleanCap®AG-3’OMe (TriLink BioTechnologies) to the 5′ and 3′ UTR plus a 110-nucleotide polyA tail interrupted by a linker (A30LA70, 10 nucleotides). mRNA constructs were cloned for Rv1387, Rv0280, Rv0256c, Rv0287, Rv3020c, Rv1788, Rv1791, Rv1886c, and Rv3804c using the same codon-optimized sequences from our DNA vaccine studies. The DNA was linearized, purified, and in-vitro transcribed to make mRNAs. N-1-methylpseudouridine (m1Ψ-5′)-triphosphate (TriLink®BioTechnologies) was used to substitute UTP to generate modified nucleoside-containing mRNAs, and capping of in vitro transcribed mRNAs was performed in a one-pot-reaction using CleanCap®Reagent AG - 3' OMe (Trilink®BioTechnologies). mRNAs were purified by cellulose purification to obtain dsRNA-free mRNA molecules. To synthesize mRNA-LNP vaccines, mRNAs were encapsulated in LNPs using an aqueous solution of mRNA at acidic pH 4.0 mixed with an ethanolic lipid solution at a ratio of 3:1 (aqueous:ethanol) using a NanoAssemblr Ignite+(Cytiva Lifesciences) at a flow rate of 12 mL / min. The lipid solution consisted of ALC-0315 (Avanti), 18:1 (Δ9-Cis) PE (DOPE, Avanti), cholesterol (Avanti), and 14:0 PEG2000 PE (Avanti) at a ratio of 50:10:38.5:1.5 mol. After microfluidic mixing, mRNA-LNPs were dialyzed against PBS overnight, concentrated using Amicon®ultracentrifugal filters (EMD Millipore), reconstituted using 10% sucrose, and stored at -80°C until further use. All formulations underwent quality control for particle size by dynamic light scattering (DLS) using a Zetasizer Nano (Malvern Instruments). The diameter (z-average) and polydispersity index (PDI) of the mRNA-LNPs was measured, with sizes ranging from 70-100 nm. Quantification of encapsulated mRNAs was performed using QUANT-IT™ RIBOGREENTMRNA Assay Kit (ThermoFisher), and all mRNA-LNPs were confirmed to have >95% encapsulation. Spleen, lung, and PBMC harvesting for immunogenicity studies CB6F1 mice were used for all immunogenicity studies. For spleen harvest, mice were euthanized and spleens were transferred into R10 medium containing RPMI supplemented with 10% FBS (Gibco) and 1% penicillin-streptomycin (Fisher Scientific). Tissues were mechanically dissociated through a 100 μm filter and red blood cells were lysed with ACK Lysing Buffer (Gibco). Splenocytes were then filtered out through a 30 μm filter, pelleted, and resuspended in R10. For lung harvest, mice were euthanized and lungs were thoroughly perfused with 10 mL ice cold PBS via the right ventricle. Lungs were transferred into Gentle MACS C tubes (Miltenyi) containing 4 mL of R10. This was supplemented with 5X digestion buffer consisting of R10 supplemented with 5 mg of type I collagenase (Worthington Biochemicals) and 0.5 mg of DNAse I (Sigma). Lung tissue was then mechanically dissociated using a GentlleMACS instrument according to manufacturer instructions (Miltenyi) following by passaging through a 70 μm filter. The solution then underwent red blood cells lysis with ACK Lysing Buffer (Gibco) and lung cells were then filtered out through a 30 μm filter. For PBMC harvesting, mice were bled via the submandibular route into RPMI (Gibco) containing 5% EDTA (Invitrogen) in accordance with IACUC protocols. The buffy layer containing PBMCs was isolated via Ficoll (GE Healthcare) centrifugation and transferred into R10. Following lymphocyte isolation, viable cell counts were quantified by trypan blue exclusion using a Countess 3 instrument (Thermo Fisher Scientific). Flow cytometry Lymphocytes were stimulated with peptide of interest (21st Century Bio) or purified protein derivative (PPD; Cedarlane) at 400 ng of peptide per test or DMSO control for 1 hour followed by GOLGISTOPSTOPTM / GOLGIPLUGTM(BD Biosciences) overlay for 6 hours at 37°C. Lymphocytes were then stained with live / dead (Aqua) and cell surface markers in MACS solution (Miltenyi) supplemented with 2% BSA (Miltenyi) and 1.5% penicillin-streptomycin (Fisher Scientific) prior to permeabilization with CYTOFIX / PERMTM(BD Biosciences) and staining with intracellular markers in PERM / WASHTM(BD Biosciences). Cells were then fixed in 2% formaldehyde and stored at 4°C until flow cytometry on an LSR II flow cytometer (BD Biosciences). PMBC and splenocyte cell surface markers included CD3 (clone 17A2, BD Biosciences), CD19 (clone 6D5, BioLegend), CD4 (clone RM4-5, BioLegend), CD8a (clone 53-6.7, BD Biosciences), CD44 (clone IM7, BD Biosciences), and CD62L (clone MEL-14, BioLegend). PMBC and splenocyte intracellular markers included IFN-γ (cloneXMG1.2, BioLegend), TNF-α (clone MP6-XT22, BioLegend), IL-2 (clone JES6-5H4, BioLegend), IL17-A (clone TC11-18H10.1, BioLegend), and IL-4 (clone 11B11, BD Biosciences). Lung cell surface markers included CD3 (clone 17A2, BD Biosciences), CD4 (clone GK1.5, BD Biosciences), CD8a (clone 53-6.7, BD Biosciences), CD44 (clone IM7 BD, Biosciences), CD62L (clone MEL-14, BioLegend), TCRg / d (clone GL3, BioLegend), CD45 (clone 30-F11, BioLegend), CD103 (clone 2E.7, BioLegend), PD-1 (clone 29F.1A12, BioLegend), CD11b (clone M1 / 70, BioLegend), and NK-1.1 (clone PK136, BD Biosciences). Lung intracellular markers included IFN-γ (clone XMG1.2, BioLegend), TNF-α (clone MP6-XT22, BioLegend), IL-2 (clone JES6-5H4, BioLegend), IL-17A (clone TC11-18H10.1, BioLegend), IL-4 (clone 11B11, BD Biosciences), and CD69 (clone H1.2P3, BD Biosciences). Data and statistical analyses Flow cytometry data were analyzed using FLOJOTM10.10.0 software. Statistical comparisons between groups for immunogenicity and 100 CFU challenge studies were performed using GraphPad Prism 9.4.0 software. Between-group differences in bacterial loads for low-dose challenge studies were analyzed using mixed effects negative binomial regression models while controlling for lobe side (right vs. left). Heatmaps were generated using the R package pheatmap. The correlation of CD4 T cell phenotypes with lung CFU was performed using the R package corrplot and Spearman’s method. Statistical evaluation was assessed using a t-test distribution implemented in the R cor.test function. Example 5. Use of a Trivalent Immunogenic Composition An Mtb infection in a subject may range from 1 to 72 hours, 3 to 7 days, 1 to 8 weeks, 2 to 12 months, 1 to 10 years or longer, or it may persist for the lifetime of the subject. In this instance, an immunogenic composition that contains (or that includes a nucleic acid molecule(s) that encodes, e.g., in the case of composition that contains one or more mRNA molecules (e.g., an mRNA vaccine)) a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide is administered to the subject. The PPE20 polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449). The EsxG polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751-753 and 757). The PE18 polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). An effective amount of the immunogenic composition is administered 2, 4, 6, 10, 15, or 24 hours; 2, 3, 5, or 7 days; 2, 4, 6 or 8 weeks; 3, 4, or 6 months; or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 years or more post-exposure to an Mtb infection. The immunogenic composition may be administered to the subject once a week, once a month, every other month, once every three, four, five, or six months, once a year, or once every other year, for example, as and when needed. Example 6. Use of a Quadrivalent Immunogenic Composition An Mtb infection in a subject may range from 1 to 72 hours, 3 to 7 days, 1 to 8 weeks, 2 to 12 months, 1 to 10 years or longer, or it may persist for the lifetime of the subject. In this instance, an immunogenic composition that contains (or that includes a nucleic acid molecule(s) that encodes, e.g., in the case of composition that contains one or more mRNA molecules (e.g., an mRNA vaccine)) a PPE20 polypeptide, an EsxG polypeptide, a PE18 polypeptide, and an fbpB polypeptide is administered to the subject. The PPE20 polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 1; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25- 75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 1; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 421-526 (e.g., one or more of SEQ ID NOs: 412-450 and 491-500, e.g., one or more of SEQ ID NOs: 421, 422, 429, 430, 448, and 449). The EsxG polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 2; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 742-758 (e.g., one or more of SEQ ID NOs: 751- 753 and 757). The PE18 polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 3; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 3; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 776-793 (e.g., one or more of SEQ ID NOs: 786-788). The fbpB polypeptide can include (i) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4; (ii) 12-96 contiguous amino acids (e.g., 12-60, 25-50, 25-75, 50-75, 50-96, or 75-96 contiguous amino acids, e.g., 16, 32, 48, 64, 80, or 96 contiguous amino acids) of SEQ ID NO: 4; and / or (iii) 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to one or more of SEQ ID NOs: 807-869 (e.g., one or more of SEQ ID NOs: 807- 809, 827-836, 842-846, 862-869, e.g., one or more of SEQ ID NOs: 835, 836, 867, and 868). An effective amount of the immunogenic composition is administered 2, 4, 6, 10, 15, or 24 hours; 2, 3, 5, or 7 days; 2, 4, 6 or 8 weeks; 3, 4, or 6 months; or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 years or more post- exposure to an Mtb infection. The immunogenic composition may be administered to the subject once a week, once a month, every other month, once every three, four, five, or six months, once a year, or once every other year, for example, Other Embodiments A...

Claims

CLAIMS 1. An immunogenic composition comprising: (I) (a) at least two different polypeptides, wherein each said polypeptide comprises at least 12 contiguous amino acids of a polypeptide selected from the group consisting of: PPE family protein PPE20 (PPE20), ESAT-6 like protein EsxG (EsxG), PE family protein PE18 (PE18), secreted antigen 85-B FbpB (fbpB), PPE family protein PPE51 (PPE51), secreted ESAT-6 like protein EsxR (EsxR), ESX conserved component EccD3 (eccD3), PPE family protein PPE2 (PPE2), PPE family protein PPE3 (PPE3), ESAT-6 like protein EsxS (EsxS), PPE family protein PPE46 (PPE46), PPE family protein PPE30 (PPE30), PPE family protein PPE11 (PPE11), PPE family protein PPE4 (PPE4), major secreted immunogenic protein Mpt70 (Mpt70), PE family protein PE19 (PE19), PPE family protein PPE18 (PPE18), secreted antigen 85-a FbpA (fbpA), low molecular weight protein antigen 7 EsxH (EsxH), and probable serine protease PepA (pepA); (b) a nucleic acid molecule encoding the at least two different polypeptides; or (c) at least two nucleic acid molecules, each of which encodes one of the at least two different polypeptides, and (II) a pharmaceutically acceptable vehicle, diluent, excipient and / or adjuvant.

2. The immunogenic composition of claim 1, wherein the immunogenic composition comprises: (a) 2 to 8 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 2 to 8 said polypeptides; or (c) 2 to 8 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, fbpB, EsxG, fbpA, PPE3, EsxS, PE18, and PPE2.

3. The immunogenic composition of claim 2, wherein the immunogenic composition comprises: (a) 2 to 4 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 2 to 4 said polypeptides; or (c) 2 to 4 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide, wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, EsxG, PE18, and fbpB.

4. The immunogenic composition of claim 3, wherein the immunogenic composition comprises: (a) 3 of said polypeptides, wherein each said polypeptide is different; (b) one said nucleic acid molecule that encodes each of the 3 said polypeptides; or (c) 3 of said nucleic acid molecules, wherein each said nucleic acid molecule encodes a single one of said polypeptide,wherein, optionally, the polypeptides are selected from the group consisting of: PPE20, EsxG, and PE18.

5. The immunogenic composition of claim 1, wherein the nucleic acid molecule of (b) or the at least two nucleic acid molecules of (c) comprises a nucleotide sequence comprising 36-291, or all, contiguous nucleotides of a nucleic acid molecule encoding a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, PE19, PPE18, fbpA, EsxH, and pepA.

6. The immunogenic composition of claim 1, wherein the at least two different polypeptides comprise 12-96, or all, contiguous amino acids of a polypeptide selected from the group consisting of: PPE20, EsxG, PE18, fbpB, PPE51, EsxR, eccD3, PPE2, PPE3, EsxS, PPE46, PPE30, PPE11, PPE4, Mpt70, PE19, PPE18, fbpA, EsxH, and pepA.

7. The immunogenic composition of any one of claims 1-6, wherein: (a) the PPE20 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NOs: 1 and 421-526; (b) the EsxG polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 2 and 742-758; (c) the PE18 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 3 and 776-793; (d) the fbpB polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 4 and 807-869; (e) the PPE51 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 5; (f) the EsxR polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 6; (g) the eccD3 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 7; (h) the PPE2 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 8 and 633-741; (i) the PPE3 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 9 and 527-632; (j) the EsxS polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 10, 757, and 759-775; (k) the PPE46 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 11; (l) the PPE30 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 12;(m) the PPE11 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 13; (n) the PPE4 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 14; (o) the Mpt70 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 15; (p) the PE19 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NOs: 16, 783, 784, and 793-806; (q) the PPE18 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 17; (r) the fbpA polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 18; (s) the EsxH polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 19; and / or (t) the pepA polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO:

20.

8. The immunogenic composition of claim 6 or 7, wherein the PPE20 polypeptide, the EsxG polypeptide, the PE18 polypeptide, the fbpB polypeptide, the PPE51 polypeptide, the EsxR polypeptide, the eccD3 polypeptide, the PPE2 polypeptide, the PPE3 polypeptide, the EsxS polypeptide, the PPE46 polypeptide, the PPE30 polypeptide, the PPE11 polypeptide, the PPE4 polypeptide, the Mpt70 polypeptide, the PE19 polypeptide, the PPE18 polypeptide, the fbpA polypeptide, the EsxH polypeptide, and / or the pepA polypeptide comprises at least one glycosylated amino acid.

9. The immunogenic composition of claim 8, wherein: (a) the PPE20 polypeptide comprises one, two, three, four, five, six, seven, eight, nine, ten, or eleven mutations at position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1; (b) the EsxG polypeptide comprises one or two mutations at position 66 and 75 of SEQ ID NO: 2; (c) the PE18 comprises one, two, three, or four mutations at position 26, 29, 78, and 94 of SEQ ID NO: 3; and / or (d) the fbpB comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, or eighteen mutations at position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO:

4.

10. The immunogenic composition of claim 1, wherein the nucleic acid molecule of (b) or each of the at least two nucleic acid molecules of (c) comprises a DNA molecule, and wherein each said DNAmolecule comprises a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 43-102.

11. The immunogenic composition of claim 1, wherein the nucleic acid molecule of (b) or each of the at least two nucleic acid molecules of (c) comprises an RNA molecule, and wherein each said RNA molecule comprises a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 169-288.

12. The immunogenic composition of claim 10, wherein the immunogenic composition comprises one or more DNA expression vectors, and wherein each said DNA expression vector comprises the nucleotide sequence of each said DNA molecule.

13. The immunogenic composition of claim 11, wherein the immunogenic composition comprises one or more mRNA molecules, and wherein each said mRNA molecule comprises the nucleotide sequence of each said RNA molecule.

14. The immunogenic composition of claim 13, wherein the mRNA molecule is a self-replicating mRNA molecule.

15. The immunogenic composition of claim 13, wherein the mRNA molecule is formulated in a lipid nanoparticle (LNP), an exosome, or a liposome.

16. The immunogenic composition of any one of claims 1-15, wherein the immunogenic composition further comprises one or more live attenuated vaccines comprising: BCG, MTBVAC, VPM1002, DAR- 901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72, RUTI, H107, or CysVac2 / Advax.

17. An immunogenic composition comprising: (I) a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide; or (II) (a) a nucleic acid molecule encoding a PPE20 polypeptide, an EsxG polypeptide, and a PE18 polypeptide; (b) a first nucleic acid molecule encoding a EsxG polypeptide and an PPE20 polypeptide and a second nucleic acid molecule encoding a PE18 polypeptide; (c) a first nucleic acid molecule encoding a PPE20 polypeptide and a PE18 polypeptide and a second nucleic acid molecule encoding an EsxG polypeptide; (d) a first nucleic acid molecule encoding a PE18 polypeptide and an EsxG polypeptide and a second nucleic acid molecule encoding a PPE20 polypeptide; or(e) a first nucleic acid molecule encoding a PPE20 polypeptide, a second nucleic acid molecule encoding an EsxG polypeptide, and a third nucleic acid molecule encoding a PE18 polypeptide.

18. The immunogenic composition of claim 17, wherein: (a) the PPE20 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 1; (b) the EsxG polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 2; and (c) the PE18 polypeptide comprises an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO:

3.

19. The immunogenic composition of claim 17 or 18, wherein the PPE20 polypeptide, the EsxG polypeptide, and / or the PE18 polypeptide comprises at least one glycosylated amino acid.

20. The method of claim 19, wherein: (a) the PPE20 polypeptide comprises one, two, three, four, five, six, seven, eight, nine, ten, or eleven mutations at position 18, 33, 115, 126, 131, 138, 196, 211, 231, 235, and 272 of SEQ ID NO: 1; (b) the EsxG polypeptide comprises one or two mutations at position 66 and 75 of SEQ ID NO: 2; (c) the PE18 comprises one, two, three, or four mutations at position 26, 29, 78, and 94 of SEQ ID NO: 3; and / or (d) the fbpB comprises one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, or eighteen mutations at position 71, 72, 89, 94, 152, 231, 243, 244, 253, 257, 263, 271, 277, 285, 291, 295, 299, and 312 of SEQ ID NO:

4.

21. The immunogenic composition of claim 17, wherein the nucleic acid molecule of any one of (b) through (e) is composed of DNA and comprises a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 43-45, 59-61, and 75-77.

22. The immunogenic composition of claim 17, wherein the nucleic acid molecule of any one of (b) through (e) is composed of RNA and comprises a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 169-171, 185-187, 201-203, 217-219, 233-235, and 249-251.

23. The immunogenic composition of any one of claims 14-20, wherein the immunogenic composition further comprises: (a) an fbpB polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 4;(b) a PPE51 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 5; (c) an EsxR polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 6; (d) an eccD3 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 7; (e) a PPE2 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 8; (f) a PPE3 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 9; (g) an EsxS polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 10; (h) a PPE46 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 11; (i) a PPE30 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 12; (j) a PPE11 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 13; (k) a PPE4 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 14; (l) an Mpt70 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 15; (m) a PE19 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 16; (n) a PPE18 polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100%, sequence identity to SEQ ID NO: 17; (o) an fbpA polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 18; (p) an EsxH polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO: 19; and / or (q) a pepA polypeptide comprising an amino acid sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to SEQ ID NO:

20.

24. The immunogenic composition of claim 21, wherein the immunogenic composition further comprises an additional nucleic acid molecule composed of DNA, wherein said additional nucleic acid molecule comprises a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 46-58, 62-74, and 78-102.

25. The immunogenic composition of claim 22, wherein the immunogenic composition further comprises an additional nucleic acid molecule composed of RNA, wherein said additional nucleic acidmolecule comprises a nucleotide sequence having at least 80%, 85%, 90%, 95%, 99%, or 100% sequence identity to any one of SEQ ID NOs: 172-184, 188-200, 204-216, 220-232, 236-248, and 252-288.

26. The immunogenic composition of claim 21 or 24, wherein the immunogenic composition is a DNA expression vector comprising each said nucleic acid molecule.

27. The immunogenic composition of claim 22 or 25, wherein the immunogenic composition is an mRNA molecule comprising each said nucleic acid molecule.

28. The immunogenic composition of claim 27, wherein the mRNA molecule is a self-replicating mRNA molecule.

29. The immunogenic composition of claim 27 or 28, wherein the mRNA molecule is formulated in an LNP, an exosome, or a liposome.

30. The immunogenic composition of any one of claims 17-29 further comprising: (a) a pharmaceutically acceptable vehicle, diluent, excipient and / or adjuvant; and / or (b) one or more live attenuated vaccines comprising BCG, MTBVAC, VPM1002, DAR-901, MVA85A, ChAdOx1.PPE15, TB / FLU-04L, Ad5Ag85A, AERAS-402, M72, RUTI, H107, or CysVac2 / Advax.

31. The immunogenic composition of any one of claims 1-30, wherein the immunogenic composition is in lyophilized, solid, or liquid form.

32. The immunogenic composition of claim 31, wherein the immunogenic composition is in said liquid form and is formulated for subcutaneous, intradermal, intravenous, intramuscular, transdermal, parenteral, intranasal, respiratory, perioral, sublingual, or oral, administration.

33. The immunogenic composition of any one of claims 1-32, wherein the immunogenic composition is capable of inducing an immune response in a human.

34. The immunogenic composition of claim 33, wherein the immune response is mediated by major histocompatibility complex (MHC) class II.

35. The immunogenic composition of any one of claims 1-34, wherein the immunogenic composition is a vaccine.

36. A method of inducing an immune response in a subject, the method comprising administering the immunogenic composition of any one of claims 1-35 to the subject.

37. The method of claim 36, wherein administration of the immunogenic composition treats and / or reduces the symptoms of a disease.

38. The method of claim 37, wherein the method: (a) reduces the likelihood of reemergence of the disease from latency; (b) reduces sequela of the disease; and / or (c) reduces the transmissibility of the disease.

39. The method of claim 37 or 38, wherein the disease is an infectious disease.

40. The method of claim 39, wherein the infectious disease is caused by one or more bacteria.

41. The method of claim 40, wherein one or more bacteria are Mycobacterium spp.

42. The method of claim 41, wherein at least one Mycobacterium spp. is selected from M. tuberculosis, M. leprae, M. bovis, M. africanum, M. avium, M. canetti, M. chelonae, M. fortuitum, M. gordonae, M. hiberniae, M. intracellulare, M. kansasii, M. marinum, M. microti, M. paratuberculosis, M. phlei, M. pinnipedii, M. scrofulaceum, M. simiae, M. smegmatis, M. szulgai, M. ulcerans, M. vacca, and M. xenopi.

43. The method of claim 42, wherein at least one Mycobacterium spp. is M. tuberculosis.

44. The method of any one of claims 37-43, wherein the disease is tuberculosis.

45. The method of any one of claims 36-44, wherein the immunogenic composition is administered as a single dose.

46. The method of any one of claims 36-45, wherein the immunogenic composition is administered as a plurality of doses.

47. The method of claim 46, wherein the doses are administered at least one day apart.

48. The method of claim 46, wherein said plurality of doses are administered at least one day, two weeks, 12 weeks, 6 month, 12 months, 18 months, or 24 months apart.

49. The method of any one of claims 46-48, wherein: (I) the immunogenic composition comprises one or more said nucleic acid molecules and the dose or plurality of doses are administered to the subject at: (a) a fixed dose of about 10 µg to 100 µg of the immunogenic composition;(b) a weight-based dose of about 0.01 µg / kg to 3 µg / kg of the immunogenic composition, or (II) the immunogenic composition comprises one or more said polypeptides and the dose or plurality of doses are administered to the subject at: (a) a fixed dose of about 1 mg to 5000 mg of the immunogenic composition; or (b) a weight-based dose of about 0.01 mg / kg to 100 mg / kg of the immunogenic composition.

50. The method of claim 49, wherein the immunogenic composition is administered in two doses.

51. The method of any one of claims 36-50, wherein the immunogenic composition is administered as either a priming component or a boosting component in a prime-boost regimen, or both.

52. The method of claim 51, wherein the prime-boost regimen is a homologous prime-boost regimen comprising a priming step and a boosting step, wherein the priming step and the boosting step comprise administration of the immunogenic composition.

53. The method of claim 51, wherein the prime-boost regimen is a heterologous prime-boost regimen comprising a priming step and a boosting step, wherein the priming step comprises administration of the immunogenic composition.

54. The method of claim 53, wherein the boosting step comprises administration of a second, different immunogenic composition.

55. The method of claim 51, wherein the prime-boost regimen is a heterologous prime-boost regimen comprising a priming step and a boosting step, wherein the boosting step comprises administration of the immunogenic composition.

56. The method of claim 55, wherein the priming step comprises administration of a second, different immunogenic composition.

57. An LNP, an exosome, or a liposome comprising the immunogenic composition of any one of claims 1-35.

58. A kit comprising the immunogenic composition of any one of claims 1-35 or the LNP, exosome, or liposome of claim 57.

59. The immunogenic composition of claim 9, wherein the mutation is an asparagine to serine, asparagine to threonine, or asparagine to glutamine.

60. The method of claim 20, wherein the mutation is an asparagine to serine, asparagine to threonine, or asparagine to glutamine.

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