Lipid nanoparticles for delivery of vaccine for prevention of tuberculosis

Abstract

Aspects of the present disclosure provides for improved mycobacterium tuberculosis vaccine compositions of ionizable lipid nanoparticles for the delivery of immunogenic nucleic acids to cells. Anionic phospholipids, including phosphatidylserine and phosphatidylglycerol are included in the lipid nanoparticles to increase the transfection efficiency in dendritic cells. In some embodiments, the incorporation of mono-unsaturated alkyl chain analogs in dimethylaminopropyl-dioxolane or heterocyclic ketal ionizable lipids in the formulation provided high levels of transfection in human dendritic cells, compared to other ionizable lipids in the same family, and demonstrated good stability to oxidative damage. Other aspects of the present disclosure provide mRNA that encodes for concatenated peptides encoding for multiple MHC-II tuberculosis epitopes, and optionally includes a second mRNA encoding for concatenated MHC-I tuberculosis epitopes.

Description

[0001]Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 LIPID NANOPARTICLES FOR DELIVERY OF NUCLEIC ACIDS AND VACCINE FOR THE PREVENTION OF TUBERCULOSIS OR OTHER MYCOBACTERIAL INFECTIONS RELATED APPLICATIONS This application claims the benefit of and priority to United States Provisional Application Serial No. 63 / 662,752, filed June 21, 2024, and United States Application Serial No. 19 / 244,650, filed June 20, 2025, each of which is incorporated herein by reference in its entirety. SEQUENCE LISTING 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 June 16, 2025, is named 191016-011101_PCT_SL.xml and is 575,078 bytes in size. FIELD Aspects of present disclosure relates to dendritic-cell targeted lipid nanoparticles (LNP) incorporating mRNA encoding for combinations of specific CD8 and CD4 T-cell epitopes found in mycobacterium tuberculosis. In some embodiments, a LNP comprising one or more ionizable cationic lipid(s) is useful for delivery of mRNA, for dendritic cell targeting or methods of using these LNP compositions as a vaccine for the prevention of tuberculosis or other mycobacterial infections. BACKGROUND Tuberculosis (TB) is one of the leading causes of death worldwide, and it is estimated that a quarter of the global population is infected with the causative microbe, Mycobacterium tuberculosis (Mtb) (WHO Global Tuberculosis Report 2021). A primary method of disease prevention is childhood immunization with bacilli Calmette-Guerin (BCG) vaccine, which is the only approved TB vaccine. BCG has been in existence for over 100 years, and while infant immunization can protect against severe forms of disseminated forms of childhood disease, vaccine protection wanes in adolescence and adulthood and it provides variable to no protection against development of active TB disease. Consequently, there is an urgent need to develop a 1 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 new vaccine that either works in conjunction with or replaces BCG in order to meet the WHO’s End TB Strategy milestones. Lipid nanoparticles (LNP) are used for the delivery of therapeutic nucleic acids to cells. For example, LNP pharmaceutical compositions are employed in vaccines to deliver mRNA therapeutics. LNP formulations typically include an ionizable cationic lipid (ICL). However, it is known in the art that certain ICL compounds are undesirably sensitive to oxidation during storage. Therefore, there is a need for improved ICL compounds with improved stability to oxidative degradation while in storage, while also providing desired transfection activity or potency in cells when incorporated in a LNP with a therapeutic agent such as a nucleic acid. LNP compositions, including stable nucleic acid lipid particle (SNALP) compositions, are useful for delivery of nucleic acid therapies for various infectious diseases. Infectious diseases such as tuberculosis, HIV / AIDS, malaria, and COVID-19 represent significant challenges to human health. Mycobacteria, for example, is a genus of bacteria responsible for tuberculosis (TB). According to the World Health Organization, worldwide, TB is one of the top 10 causes of death and the leading cause of death from a single infectious agent. Despite current best efforts, there have been significant challenges in the development of effective vaccines for the prevention of many infectious diseases. New efforts in the identification of individual or combinations of antigenic peptides has helped improved the efficiency of vaccines. Nonetheless, significant opportunities remain in the engineering of adjuvants to help efficiently deliver and present these antigenic sequences to professional antigen presenting cells, like dendritic cells. mRNA coding for antigenic peptides or proteins combined with ionizable cationic lipid nanoparticles represent a particularly promising strategy in the development of a vaccine. There is a need for safe and effective therapies comprising LNP pharmaceutical compositions for delivery of mRNA for treatment and prevention of various diseases, including vaccine compositions. SUMMARY In some embodiments, immunogenic liposomal nanoparticle (LNP) compositions are provided for stimulating both a CD4+ and CD8+ T-cell response and comprising a single synthetic concatenated mRNA polynucleotide encoding three or more Mycobacterium tuberculosis (Mtb) antigens (a) recognized by both CD4 T-cells and CD8 T-cells, and (b) are not a bacilli Calmette-Guerin (BCG) vaccine antigen proteins; a ionizable cationic lipid; one or more phospholipids (PL) including an anionic phospholipid; cholesterol; and a PEG- conjugated lipid. 2 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the liposomal nanoparticle (LNP) compositions for delivery of nucleic acids are provided herein, including LNP compositions comprising or consisting of: (a) a nucleic acid encoding one or more Mtb antigens, (b) an ionizable cationic lipid, (c) one or more phospholipids including (d) an anionic targeting phospholipid, (e) a conjugated lipid and (f) a sterol. Lipid nanoparticle (LNP) compositions are provided herein, and methods of making and using the same. In some embodiments, the LNP compositions comprise a nucleic acid such as messenger ribonucleic acid (mRNA). In some embodiments, the LNP compositions are vaccines, including LNP formulations comprising mRNA that encodes an immune system epitope, or an antigen recognized by the immune system. In some embodiments, the LNP composition is an immunogenic pharmaceutical composition comprising a nucleic acid sequence for stimulating both a CD4+ and CD8+ T-cell response, the nucleic acid encoding (a) a LAMP-1 signal peptide or a human HLA Class I signal peptide and (b) a lysosome-associated membrane protein 1 (LAMP-1) or a MHC class I trafficking domain (MITD) transmembrane and cytoplasmic domain, each of (a) and (b) operably linked to an open reading frame (ORF) of the nucleic acid sequence encoding one or more antigens that are immunogenic for stimulating the CD4+ T-cell response and the CD8+ T-cell response. In some embodiments, immunogenic liposomal nanoparticle (LNP) compositions for stimulating both a CD4+ and CD8+ T-cell response to one or more Mycobacterium tuberculosis (Mtb) antigens are provided. In some embodiments, the composition can comprise: (a) a concatenated mRNA polynucleotide sequence(s) encoding (i) a signal peptide and (ii) a transmembrane and cytoplasmic domain, each of (i) and (ii) operably linked to open reading frame(s) (ORF) of each mRNA sequence encoding multiple Mtb antigens that are immunogenic for stimulating the CD4+ T-cell response or the CD8+ T-cell response; and (b) a ionizable cationic lipid, one or more phospholipids (PL) including an anionic phospholipid, cholesterol, and a PEG-conjugated lipid, wherein the concatenated mRNA polynucleotide sequence (a) comprises an ORF encoding multiple Mtb antigens each separated by a G / P (gly- pro) spacer, G / S (gly-ser) spacer, a NFL spacer or an AAY spacer mRNA sequence, and (b) the ORF encodes both a CD4 T-cell epitope and a CD8 T-cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by CD4 T-cells and CD8 T-cells. In some embodiments, the mRNA polynucleotide further comprises a 5’ untranslated region (UTR) and 3’ UTR, a polyA tail of about 80 to about 140 nucleotides in length, and (i) 3 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 a 5’ enzymatic or (ii) a 5’ clean cap. In some embodiments, the composition comprises the ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the mRNA. In some embodiments, the mRNA is modified mRNA, wherein the chemically modified mRNA comprises N1- methylpseudouridine. In some embodiments, the polynucleotide encodes a human HLA Class I signal peptide that is a HLA-A signal peptide or a HLA-B (sec) signal peptide comprising the polypeptide of SEQ ID NO:23 or SEQ ID NO:24. In some embodiments, the polynucleotide encodes a LAMP-1 transmembrane and cytoplasmic domain comprising the polypeptide of SEQ ID NO:22 and the MITD transmembrane and cytoplasmic domain comprises the polypeptide of SEQ ID NO:25 or SEQ ID NO:26. In some embodiments, the composition comprises a polynucleotide encoding two or more Mtb antigens selected from the group consisting of CFP10 / Rv3874, Mtb39A / Rv1196, ESAT-6 / Rv3875, EsxW / Rv3620c, TB10.4 / Rv0288, EsxV / Rv3619c, and Ag85B / Rv1886c. In some embodiments, the ORF encodes the Mtb antigens CFP10 / Rv3874, Mtb39A / Rv1196, ESAT-6 / Rv3875, EsxW / Rv3620c, TB10.4 / Rv0288, EsxV / Rv3619c, and Ag85B / Rv1886c. In some embodiments, the polynucleotide encodes CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288 Mycobacterium tuberculosis (Mtb) proteins, each separated by a spacer polynucleotide sequence. In some embodiments, the composition comprises a polynucleotide sequence encoding the Mtb antigen proteins in an order preventing the heterodimer formation of the Esx / A and Esx W / V proteins.In some embodiments, the composition comprises a polynucleotide sequence encoding the following Mtb antigen proteins in relative order from the 5’ to the 3’ direction: EsxB / CFP10, ΔMTB39A, EsxA / ESTAT-6, EsxW, EsxV and ΔAg85b.In some embodiments, the composition comprises a polynucleotide sequence encoding the mRNA polynucleotide encodes the following Mtb antigen proteins in relative order from the 5’ to the 3’ direction:MTB32A, EsxB / CFP10, ΔMTB39A, EsxA / ESTAT-6, EsxW, PE13, EsxV and ΔAg85b. In some embodiments, the composition comprises a polynucleotide sequence encoding the spacer region between the mRNA encoding each Mtb proteins is selected from the group consisting of: a GPGPG spacer polynucleotide sequence, a G / S flexible spacer, a (GGGGS)nspacer where n can be 1 or greater, and a native flexibly linked (NFL) polypeptide spacer. 4 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the composition is a liposomal nanoparticle (LNP) composition that comprises: (a) the ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; (b) the one or more phospholipids selected from distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof; (c) the anionic phospholipid(s) selected from a phosphatidylserine (PS) or a phosphatidylglycerol (PG) or a combination thereof, in a total amount of 2-8 mol% of the total lipid content of the LNP composition; and (d) the PEG-conjugated lipid is selected from PEG(2000)- dimyristoylglycerol (PEG-DMG) or PEG(Mol. weight 2,000)- dimyristoylphosphatidylethanolamine (PEG-DMPE), or a combination thereof, in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition has a ratio of phospholipid (PL) to cholesterol of 0.25 to 1.00. In some embodiments, the composition is an immunogenic pharmaceutical composition comprising a synthetic polynucleotide sequence for stimulating both a CD4+ and CD8+ T-cell response, the synthetic polynucleotide sequence comprises: (a) a 5’ cap structure; (b) a 5’ untranslated region (UTR); (c) an open reading frame (ORF) between the 5’ UTR and the 3’ UTR, the ORF encoding (i) a LAMP-1 signal peptide or a human HLA Class I signal peptide and (ii) a lysosome-associated membrane protein 1 (LAMP-1) or a MHC class I trafficking domain (MITD) transmembrane and cytoplasmic domain, each of (i) and (ii) operably linked to an open reading frame (ORF) of the nucleic acid sequence encoding one or more antigens that are immunogenic for stimulating the CD4+ T-cell response and the CD8+ T-cell response; and (d) a 3’ UTR and a polyA tail of about 80 to about 140 nucleotides in length, and a 5’ Cap structure; wherein the ORF encodes six or more Mycobacterium tuberculosis (Mtb) antigen proteins, each separated by a spacer polynucleotide sequence, wherein the Mtb antigen proteins are encoded by the ORF in the following relative order from the 5’ to the 3’ direction: EsxB / CFP10, ΔMTB39A, EsxA / ESTAT-6, EsxW, EsxV and ΔAg85b, and the ORF sequence further comprises a G / P (gly-pro) spacer, G / S (gly-ser) spacer, a NFL spacer or an AAY spacer sequence between regions encoding each adjacent Mtb antigen protein. In some embodiments, the nucleic acid sequence is mRNA. In some embodiments, the ORF encodes (i) a LAMP-1 signal peptide and a LAMP-1 transmembrane and cytoplasmic domain, or (ii) the nucleic acid encodes a human HLA-A or HLA-B signal peptide and a MITD transmembrane and cytoplasmic domain. In some embodiments, the mRNA is modified mRNA, wherein the 5 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 chemically modified mRNA comprises N1-methylpseudouridine. In some embodiments, the 5’ Cap structure is a 5’ enzymatic Cap or a 5’ clean Cap or a Cap-1 structure. In some embodiments, the composition comprises: (a) an ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; (b) one or more phospholipids selected from distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof; (c) an anionic phospholipid(s) selected from a phosphatidylserine (PS) or a phosphatidylglycerol (PG) or a combination thereof, in a total amount of 2-8 mol% of the total lipid content of the LNP composition; and (d) PEG-conjugated lipid is selected from PEG(2000)-dimyristoylglycerol (PEG-DMG) or PEG(Mol. weight 2,000)- dimyristoylphosphatidylethanolamine (PEG-DMPE), or a combination thereof, in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises a mRNA nucleic acid sequence. In some embodiments, the nucleic acid encodes (i) a LAMP-1 signal peptide and a LAMP-1 transmembrane and cytoplasmic domain, or (ii) the nucleic acid encodes a human HLA-A or HLA-B signal peptide and a MITD transmembrane and cytoplasmic domain. In some embodiments, the nucleic acid sequence encodes the signal peptide 5´to the ORF and encodes the transmembrane and cytoplasmic domain 3´to the ORF, and wherein: (a) the LAMP-1 signal peptide comprises the polypeptide of SEQ ID NO:21 and the HLA-B signal peptide comprises the HLA-B (sec) polypeptide of SEQ ID NO:23 or SEQ ID NO:24; and (b) the LAMP-1 transmembrane and cytoplasmic domain comprises the polypeptide of SEQ ID NO:22 and the MITD transmembrane and cytoplasmic domain comprises the polypeptide of SEQ ID NO:25 or SEQ ID NO:26. In some embodiments, the mRNA nucleic acid further comprises a 5’ untranslated region (UTR) and 3’ UTR, a polyA tail of about 80 to about 140 nucleotides in length, and a 5’ Cap structure. In some embodiments, the mRNA is modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine and the 5’ Cap structure is a 5’ enzymatic Cap or a 5’ clean Cap. In some embodiments, the 5’ Cap structure is a Cap-1 structure. In some embodiments, the LNP composition comprises a polynucleotide encoding the one or more antigens is preceded by a nucleotide sequence encoding ubiquitin with a G76A mutation. In some embodiments, the one or more antigens comprise one or more 6 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Mycobacterium tuberculosis (Mtb) antigens. In some embodiments, the one or more antigens includes at least one Mtb antigen that is not a bacilli Calmette-Guerin (BCG) vaccine antigen protein. In some embodiments, the mRNA polynucleotide encodes three or more Mycobacterium tuberculosis (Mtb) proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288. In some embodiments, the mRNA is a concatenated mRNA polynucleotide sequence comprising an ORF encoding multiple Mtb antigens separated by a spacer comprising a G / P (gly-pro), G / S (gly-ser) or AAY spacer polynucleotide sequence, wherein the multiple Mtb antigens comprise CFP10 / Rv3874, Mtb39A / Rv1196, ESAT-6 / Rv3875, EsxW / Rv3620c, TB10.4 / Rv0288, EsxV / Rv3619c, and Ag85B / Rv1886c. In some embodiments, the spacer is a GPGPG spacer polynucleotide sequence. In some embodiments, the mRNA polynucleotide encodes one or more Mycobacterium tuberculosis (Mtb) proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288. In some embodiments, the LNP composition is a Mycobacterium tuberculosis (Mtb) messenger ribonucleic acid (mRNA) vaccine composition comprising: (a) a concatenated mRNA polynucleotide sequence open reading frame (ORF) encoding (i) a combination of three or more CD8 and CD4 T-cell Mtb epitopes each separated by a G / P (gly-pro), G / S (gly-ser) or AAY spacer polynucleotide sequence, and (ii) a LAMP-1 signal peptide or a signal peptide of human HLA-B (sec) and a LAMP-1 or MITD transmembrane and cytoplasmic domain, each operably linked to the Mtb epitope ORF encoding the Mtb antigens; and (b) a ionizable cationic lipid, one or more phospholipids (PL), cholesterol; and a PEG-conjugated lipid, wherein the composition comprises (i) a ratio of phospholipid (PL) to cholesterol of between 15 mol% PL / 35.5 mol% cholesterol and 25 mol% PL / 25.5 mol% cholesterol; and (ii) the ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the mRNA. In some embodiments, the LNP composition is an immunogenic liposomal nanoparticle (LNP) composition stimulating both a CD4+ and CD8+ T-cell response, the composition comprising: (a) one or more mRNA polynucleotide sequence(s) each encoding (i) a LAMP-1 signal peptide or a human HLA Class I signal peptide and (ii) a lysosome-associated membrane 7 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 protein 1 (LAMP-1) or a MHC class I trafficking domain (MITD) transmembrane and cytoplasmic domain, each of (i) and (ii) operably linked to an open reading frame(s) (ORF) of each mRNA sequence encoding one or more antigens that are immunogenic for stimulating the CD4+ T-cell response or the CD8+ T-cell response; and (b) a ionizable cationic lipid, one or more phospholipids (PL), cholesterol; and a PEG-conjugated lipid, wherein the LNP composition comprises (i) a ratio of phospholipid (PL) to cholesterol of between 15 mol% PL / 35.5 mol% cholesterol and 25 mol% PL / 25.5 mol% cholesterol; and (ii) the ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the mRNA. In some aspects, the LNP comprises nucleic acid containing a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine. In some aspects, the LNP comprises nucleic acid comprising a 5’ untranslated region (UTR) and 3’ UTR, polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. In some aspects, the LNP comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine In some embodiments, a method of eliciting a T cell response in a host is provided, comprising administering to the host a nucleic acid sequence disclosed herein or a nucleic acid having at least 90% sequence identity or complementarity to a sequence disclosed herein, and / or a sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb), or a polynucleotide sequence having at least 90% identity or complementarity to a sequence disclosed herein and / or a polynucleotide sequence of a Mtb antigen recognized by T cells. A lipid nanoparticle (LNP) composition consisting of: a messenger ribonucleic acid (mRNA) encoding one or more Mycobacterium tuberculosis (Mtb) proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288; an ionizable cationic lipid comprising a KC3 ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the mRNA, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; one or more phospholipids selected from the group consisting of distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), and dipalmitoylphosphatidylcholine (DPPC), in a total amount of 10-18 mol% of the total lipid content of the LNP composition; one or more anionic phospholipids selected from the group consisting of dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidylglycerol (DSPG), and dipalmitoyphosphatidylglycerol (DPPG) 8 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 in a total amount of 2-8 mol% of the total lipid content of the LNP composition; PEG(2000)- dimyristoylglycerol (PEG-DMG) in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition; and cholesterol (e.g., 35.5 – 40.5 mol% cholesterol). Aspects of the disclosure relate to a lipid nanoparticle (LNP) composition comprising a KC3 ionizable cationic lipid, cholesterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb). In some aspects, the LNP comprises a nucleic acid sequence (e.g., mRNA) encoding a T cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by T cells. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA encoding a concatenated sequence of T-cell epitopes present in Mtb or a Mtb antigen recognized by T Cells. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA encoding one or more Mtb proteins selected from the group consisting of CFP10 / Rv3874, ESAT- 6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, and Ag85B / Rv1886c. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:220. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA encoding one or more Mtb proteins selected from the group consisting of EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:31, SEQ ID NO:221, and SEQ ID NO:222. In some aspects, the LNP comprises a nucleic acid sequence that comprises the concatenated nucleic acid-encoded sequence includes an N-terminal and C-terminal signal peptide selected from Sec / MITD, Lamp1, HLA-Dra, or tPA. In some aspects, the LNP comprises a nucleic acid sequence that is an mRNA having a sequence selected from SEQ ID NOs: 34, 36, 38, 40, 42, 44, 224 and 226. In some embodiments, the one or more nucleic acid comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises one or more N1-methylpseudouridine. In some aspects, the LNP comprises nucleic acid that is an mRNA encoding an amino acid sequence selected from SEQ ID NOs: 33, 35, 37, 39, 41, 43, 86-105, 207-210, 223 and 225. In some embodiments, the one or more nucleic acids is a mRNA. In some embodiments, the mRNA encodes a concatenated sequence of T-cell epitopes present in Mtb. In some 9 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 embodiments, the concatenated sequence of T-cell epitopes comprise an amino acid sequence set forth in SEQ ID NOs: 1-17, 106-137, 138-203. In some embodiments, the concatenated sequence of T-cell epitopes comprises an amino acid sequence with at least 90% sequence identity (e.g. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) with amino acid sequence set forth in SEQ ID NOs: 1-17, 45-85, 106-137, 138-203. In some embodiments, the concatenated nucleotide sequence comprises two or more sequences encoding for peptides or proteins that can elicit MHC class II-restricted CD4 T cell responses. In some embodiments, the two or more MHC class II epitopes selected from the group: EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), and EsxH / TB10.4 (Rv0288). In some embodiments, the two or more MHC class II epitopes comprises peptides or proteins from EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), and EsxH / TB10.4 (Rv0288) (SEQ ID NOs.1-7). In some embodiments, the concatenated nucleic acid-encoded sequence includes the seven proteins in and order N-terminal to C-terminal selected from: EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), EsxH / TB10.4 (Rv0288), ^Ag85B (Rv1886c), ^Mtb39A (Rv1196), EsxW (Rv3620c), and EsxV (Rv3619), or EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), EsxW (Rv3620c), EsxV (Rv3619), EsxH / TB10.4 (Rv0288), ^Ag85B (Rv1886c), and ^Mtb39A (Rv1196), or EsxB / CFP10 (Rv3874), ^Mtb39A (Rv1196), EsxA / ESAT-6 (Rv3875), EsxW (Rv3620c), EsxH / TB10.4 (Rv0288), EsxV (Rv3619), and ^Ag85B (Rv1886c). (SEQ ID NOs.18, 19, and 20) In some embodiments, the composition comprises a nucleic acid encoding for 5 or more non-overlapping CD4 T cell epitopes in the form of peptides, wherein optionally the peptides are from 12 to 50 amino acids long. In some embodiments, the concatenated nucleic acid-encoded sequence optionally comprises 10 selected MHC-II epitopes comprising: AQIYQAVSAQAAAIH (SEQ ID NO. 9), PSPSMGRDIKVQFQS (SEQ ID NO. 10), GINTIPIAINEAEYV (SEQ ID NO. 11), AAFQGAHARFVAAAA (SEQ ID NO. 12), AGWLAFFRDLVARGL (SEQ ID NO. 13), ASIIRLVGAVLAEQH (SEQ ID NO. 14), MSFVTTQPEALAAAA (SEQ ID NO. 8), MHVSFVMAYPEMLAA (SEQ ID NO.15), AYGSFVRTVSLPVGA (SEQ ID NO.16), and LENDNQLLYNYPGAL (SEQ ID NO.17). In some embodiments, the concatenated nucleic acid-encoded sequence includes GPGPG (SEQ ID NO.228) linker sequences between each of the concatenated epitopes. 10 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the one or more nucleic acid comprises a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. In some embodiments, the one or more nucleic acid comprises a nucleic acid sequence having at least 90% identity, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. In some embodiments, the concatenated nucleic acid-encoded sequence includes an N- terminal and C-terminal signal peptide selected from Sec / MITD, Lamp1, HLA-Drα, or tPA. In some embodiments, the one or more nucleic acid comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine. In some embodiments, the one or more nucleic acid comprises a 5’ untranslated region (UTR) and 3’ UTR, polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. In some embodiments, the one or more nucleic acid is an mRNA having a sequence selected from SEQ ID NOs: 34, 36, 38, 40, 42, 44, 224 and 226. In some embodiments, the one or more nucleic acid is an mRNA and wherein the amino acid sequence encoded by the mRNA is selected from SEQ ID NOs: 33, 35, 37, 39, 41, 43, 86- 105, 207-210, 223 and 225. In some embodiments, the nucleic acid-encoded concatenated sequence comprises two or more MHC class I epitopes selected from SEQ ID NOs: 106-137 and 138-203. In some embodiments, the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes found in mycobacterium tuberculosis, depleted of epitopes found in BCG, and selected from SEQ ID NOs: 86-95. In some embodiments, the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86-105. In some embodiments, the nucleic acid-encoded concatenated sequence includes two to twenty MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86-105. In some embodiments, the nucleic acid-encoded concatenated sequence includes two to fifteen MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86-105. In some embodiments, the nucleic acid-encoded concatenated sequence includes two to ten MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86-105. 11 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the polynucleotide encodes the one or more antigens that do not encode a Bacillus Calmette-Guerin (BCG) vaccine antigen protein. Bacillus Calmette-Guerin (BCG) is the live attenuated vaccine form of Mycobacterium bovis used to prevent tuberculosis and other mycobacterial infections. BCG vaccine antigen proteins include the 85 A complex (Ag85A, Ag85b), Early Secretory Antigenic Target 6 (ESTAT-6) and Culture Filtrate Protein 10 (CFP-10). Aspects of the disclosure relate to a synthetic nucleic acid encoding a concatenated amino acid sequence of T-cell epitopes present in Mycobacterium tuberculosis, the nucleic acid having at least 90% (e.g. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) identity with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1A Immunogenicity of mRNA-LNPs vaccines encoding Mtb antigens containing four unique signal peptides and comparison of KC3OA / DPPS and ALC-0315 LNP formulations. Mtb-specific CD4 T cells were defined as any cell that produced either of these 3 cytokines following peptide stimulation. FIG.1B Immunogenicity of mRNA-LNPs vaccines encoding Mtb antigens containing four unique signal peptides and comparison of KC3OA / DPPS and ALC-0315 LNP formulations. Mtb-specific CD8 T cells were identified as any cell that produced IFN-γ; TNF- α and IL-2 producing CD8 T cells were found within the IFN-γ-producing population. FIG.2A Proportion of total vaccine-induced T cell response to individual or subsets of Mtb antigens. Data correspond to cumulative T cell responses and are normalized to 100%. Profile of CD4 T cell responses using the ALC-0315 comparator. FIG.2B Proportion of total vaccine-induced T cell response to individual or subsets of Mtb antigens. Data correspond to cumulative T cell responses and are normalized to 100%. Profile of CD4 T cell responses using the KC3-OA / DPPS LNP formulation. FIG.2C Proportion of total vaccine-induced T cell response to individual or subsets of Mtb antigens. Data correspond to cumulative T cell responses and are normalized to 100%. Profile of CD8 T cell responses using the ALC-0315 comparator. FIG.2D Proportion of total vaccine-induced T cell response to individual or subsets of Mtb antigens. Data correspond to cumulative T cell responses and are normalized to 100%. Profile of CD8 T cell responses using the KC3-OA / DPPS LNP formulation. 12 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG.3A Cytokine polyfunctionality of vaccine-specific CD4 T cells where CD4 T cell responses were induced by the mRNA incorporating sec / MITD targeting of nascent proteins to the endosomal compartment and signal peptide / transmembrane domain into the LNP formulation. Concatenated CD4 T cell responses across peptide pools were Boolean gated on cells that produced IFN-γ, IL-2 and TNF-α. SP, single producer; DP, double producer; TP, triple producer. FIG.3B Cytokine polyfunctionality of vaccine-specific CD4 T cells where CD4 T cell responses were induced by the mRNA incorporating the LAMP-1 targeting of nascent proteins to the late endosomal / lysosomal compartment into the LNP formulation. Concatenated CD4 T cell responses across peptide pools were Boolean gated on cells that produced IFN-γ, IL-2 and TNF-α. SP, single producer; DP, double producer; TP, triple producer. FIG.3C Cytokine polyfunctionality of vaccine-specific CD4 T cells where CD4 T cell responses were induced by the mRNA using the tPA signal peptide that directs proteins to be secreted into the LNP formulation. Concatenated CD4 T cell responses across peptide pools were Boolean gated on cells that produced IFN-γ, IL-2 and TNF-α. SP, single producer; DP, double producer; TP, triple producer. FIG.4A Total CD4 T cell responses (cell IFN-g) induced by mRNA delivered with the KC3-OA / DPPS or ALC-0315 LNP formulation. Mtb-specific T cell responses were concatenated across peptide pools. FIG.4B Total CD8 T cell responses (cell IFN-g) induced by mRNA delivered with the KC3-OA / DPPS or ALC-0315 LNP formulation. Mtb-specific T cell responses were concatenated across peptide pools. FIG. 5A Comparison of BCG (s.c.) with KC3-OA / DPPS LNP (i.m.) CD4 T cell responses to individual Mtb antigens. Stim 1: EsxH / TB10.4 and Ag85B peptide pools, Stim 2: Mtb39a peptide pool, Stim 3: EsxW and EsxV peptide pools, Stim 4: EsxB / CFP10 and EsxA / ESAT-6 peptide pools, Stim 5: C-terminal set of ten tandem 15mer minimal epitope peptide pool. Mtb-specific CD4 T cells were defined as cells expressing IFN-γ, TNF-α, IL-2, IL-17a or combinations thereof. FIG. 5B Comparison of BCG (s.c.) with KC3-OA / DPPS LNP (i.m.) CD4 T cell responses. Cumulative CD4 T cell response from all peptide stimulations (Sim 1 + Stim 2 + Stim 3 + Stim 4 + Stim 5 – background). Mtb-specific CD4 T cells were defined as cells expressing IFN-γ, TNF-α, IL-2, IL-17a or combinations thereof. 13 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 6A Comparison of BCG (s.c.) with KC3-OA / DPPS LNP (i.m.) CD8 T cell responses to individual Mtb antigens. Stim 1: EsxH / TB10.4 and Ag85B peptide pools, Stim 2: Mtb39a peptide pool, Stim 3: EsxW and EsxV peptide pools, Stim 4: EsxB / CFP10 and EsxA / ESAT-6 peptide pools, Stim 5: C-terminal set of ten tandem 15mer minimal epitope peptide pool. Mtb-specific CD8 T cells expressing IFN-γ, TNF-α, IL-2, IL-17a or combinations thereof. FIG. 6B Comparison of BCG (s.c.) with KC3-OA / DPPS LNP (i.m.) CD8 T cell responses. Cumulative CD8 T cell response from all peptide stimulations (Sim 1 + Stim 2 + Stim 3 + Stim 4 + Stim 5 – background). FIG. 7 Vaccination with three different mRNA constructs encoding putative human MHC class I-restricted Mtb epitopes in a string-on-bead format generates antigen-specific CD8 T cell responses in CB6F1 mice. FIG. 8A Kinetics of vaccine-specific T cell responses. CB6F1 mice were immunized with mRNA encoding for an HLA-II directed fusion protein consisting of 7 Mtb proteins plus 10 minimal epitopes; the antigen was flanked with sec / MITD sequences (SEQ ID NOs.37 and 38), encapsulated in KC3-OA / DPPS LNPs and boosted 4 weeks later. The cumulative CD4 and CD8 T cell responses to all peptide pools are shown. FIG. 8B Kinetics of vaccine-specific CD8 T-cell responses following immunization with mRNA encoding putative human MHC class I Mtb epitopes encapsulated in KC3- OA / DPPS LNPs and boosted 4 weeks later. The cumulative CD8 T cell responses to all peptide pools are shown. FIG. 9A Comparison of CD4 T cell responses between a 1stand 2ndgeneration HLA- II Mtb mRNA vaccine construct encapsulated in KC3-OA / DPPS LNPs showing the cumulative total of the CD4 T-cell response (sum of all individual peptide pools minus the background) following immunization of CB6F1 mice. One group was vaccinated with mRNA formulated with KC3-OA / DPPS LNPs containing an increased amount of 15 mol% DSPC (at the expense of cholesterol) versus the typical 5 mol% DSPC. FIG. 9B Comparison of CD4 T cell responses between a 1stand 2ndgeneration HLA- II Mtb mRNA vaccine construct encapsulated in KC3-OA / DPPS LNPs showing the proportion of total vaccine-induced CD4 T cell responses to individual or subsets of Mtb antigens encoded by the mRNA following immunization of CB6F1 mice. Data correspond to cumulative T cell responses shown in (FIG. 9A) and are normalized to 100%. One group was vaccinated with 14 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 mRNA formulated with KC3-OA / DPPS LNPs containing an increased amount of 15 mol% DSPC (at the expense of cholesterol) versus the typical 5 mol% DSPC. FIG.10A Comparison of CD8 T-cell responses between a 1stand 2ndgeneration HLA- II Mtb mRNA vaccine construct encapsulated in KC3-OA / DPPS LNPs showing the cumulative total of the CD8 T-cell response (sum of all individual peptide pools minus the background) following immunization of CB6F1 mice. One group was vaccinated with mRNA formulated with KC3-OA / DPPS LNPs containing an increased amount of 15 mol% DSPC (at the expense of cholesterol) versus the typical 5 mol% DSPC. FIG.10B Comparison of CD8 T-cell responses between a 1stand 2ndgeneration HLA- II Mtb mRNA vaccine construct encapsulated in KC3-OA / DPPS LNPs showing the proportion of total vaccine-induced CD8 T-cell responses to individual or subsets of Mtb antigens encoded by the mRNA following immunization of CB6F1 mice. Data correspond to cumulative T cell responses shown in (FIG. 10A) and are normalized to 100%. One group was vaccinated with mRNA formulated with KC3-OA / DPPS LNPs containing an increased amount of 15 mol% DSPC (at the expense of cholesterol) versus the typical 5 mol% DSPC. (“AANR” motif (SEQ ID NO: 375)). FIG. 11 is a scheme showing the synthesis of 2-((S)-2,2-di((6Z,12Z)-octadeca-6,12- dien-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylethan-1-amine (AKG-KC2-01) and 3-((S)-2,2- di((6Z,12Z)-octadeca-6,12-dien-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine (AKG-KC3-01) according to some embodiments of the disclosure. FIG. 12 is a scheme showing the synthesis 2-((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3- dioxolan-4-yl)-N,N-dimethylethan-1-amine (AKG-KC2-OA), 2-((S)-2,2-di((Z)-hexadec-9- en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylethan-1-amine (AKG-KC2-PA), 3-((S)-2,2-di((Z)- octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine (AKG-KC3-OA), and 3- ((S)-2,2-di((Z)-hexadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine, (AKG- KC3-PA, O-12418) according to some embodiments of the disclosure. FIG. 13 is a scheme showing the synthesis of 3-((S)-2,2-di((Z)-heptadec-8-en-1-yl)- 1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine, AKG-KC3-C17(C8:1) and (S)-3-(2,2- diheptadecyl-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine, AKG-KC3-C17 according to some embodiments of the disclosure. FIG.14 is a scheme showing the synthesis of a KC3-X1 ionizable lipid. FIG.15 is a scheme showing the synthesis of a KC3-X2 ionizable lipid. 15 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 16A Comparison of splenic CD4 T cell responses in CB6F1 mice after vaccination with a 2ndgeneration HLA-II Mtb mRNA formulated in LNPs containing increasing amounts of phospholipid (PL). DPPS was held constant at 5 mol% and the remaining mol% of PL consisted of DSPC (e.g. 10 mol% PL consists of 5 mol% DPPS and 5 mol% DSPC). DSPC content increased at the expense of cholesterol. FIG.16B Comparison of splenic CD8 T cell responses in CB6F1 mice after vaccination with a 2ndgeneration HLA-II Mtb mRNA formulated in LNPs containing increasing amounts of PL. CD8 T cell responses were quantified in the same mice as in FIG.16A. FIG. 16C Comparison of splenic CD4 T cell responses in CB6F1 mice after vaccination with a 2ndgeneration HLA-II Mtb mRNA formulated in LNPs containing increasing amounts of PL. DPPS was held constant at 5 mol% and the remaining mol% of PL consisted of DSPC. One group was immunized with mRNA produced with unmodified uridine formulated in 25 mol% PL; all other groups received mRNA with all uridines replaced with N1-methylpseudouridine. FIG. 16D Comparison of splenic CD8 T cell responses in CB6F1 mice after vaccination with a 2ndgeneration HLA-II Mtb mRNA formulated in LNPs containing increasing amounts of PL. CD8 T cell responses were quantified in the same mice as in FIG. 16C. FIG. 17A Comparison of splenic CD8 T cell responses in CB6F1 mice after vaccination with a 2ndgeneration HLA-I “Mixed” mRNA formulated in LNPs containing increasing amounts of PL. DPPS was held constant at 5 mol% and the remaining mol% of PL consisted of DSPC. FIG.17B Comparison of splenic CD8 T cell responses in CB6F1 mice after vaccination with a 2ndgeneration HLA-I “Mtb-only” mRNA formulated in LNPs containing increasing amounts of PL. DPPS was held constant at 5 mol% and the remaining mol% of PL consisted of DSPC. FIG. 18 is a bar graph showing the proportion of infected mice after vaccination with BCG, VRN311, VRN312 or VRN757, compared to unvaccinated mice (Example 32). FIG.19A is a bar graph showing the lung CFU measurements from infected mice after vaccination with BCG, VRN311, VRN312 or VRN757, compared to unvaccinated mice (Example 32). 16 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 19B is a bar graph showing the spleen CFU measurements from infected mice after vaccination with BCG, VRN311, VRN312 or VRN757, compared to unvaccinated mice (Example 32). FIG.20 is a schematic of a mRNA construct comprising a 5’-cap, a 5’-UTR, a cassette comprising a signal peptide, an open reading frame and a terminal domain encoding a synthetic polypeptide, a 3’-UTR and a poly-A region. FIG. 21 is a schematic depicting a 1stgeneration mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. FIG. 22 is a schematic depicting a 2ndgeneration mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. FIG. 23A is a schematic depicting a 3rdgeneration mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. FIG.23B is a schematic depicting a 3rdgeneration (version I) mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. FIG. 23C is a schematic depicting a 3rdgeneration (version II) mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. FIG. 24A is a schematic depicting an mRNA cassette encoding 3 additional Mtb proteins of interest and nonclassical HLA-E-restricted Mtb peptides (Add on 1.0). FIG. 24B is a schematic depicting an mRNA cassette encoding 3 additional Mtb proteins of interest and nonclassical HLA-E-restricted Mtb peptides (Add on 1.1). FIG. 25 is a schematic depicting an mRNA cassette encoding a single chain trimer (SCT) consisting of the Mtb p44 peptide, linker 1, β2m, linker 2, and the HLA-E heavy chain. FIG.26 is a schematic depicting a mRNA cassette encoding 2 additional Mtb proteins of interest. FIG. 27A is an annotated version of SEQ ID NO. 18 (referring to Table 44). The GPGPG spacer (SEQ ID NO.228) is underlined. FIG.27B is an annotated version of SEQ ID NO.19 (refers to Table 45). The GPGPG spacer (SEQ ID NO.228) is underlined. FIG.27C is an annotated version of SEQ ID NO. 20 (refers to Table 46). The GPGPG spacer (SEQ ID NO.228) is underlined. 17 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 28 is an annotated version of SEQ ID NO. 32. Human hemoglobin subunit beta (HBB) untranslated regions (UTRs). NCBI reference nucleotide sequence NM_000518.5. The 5’ UTR is underlined and spans from nucleotides 1-44. The 3’ UTR is underlined and spans from nucleotides 495-628. FIG.29 is an annotated version of SEQ ID NO.33. An Mtb CD4 T cell-focused vaccine construct. Protein sequence consisting of SEQ ID NO. 18 (associated with Table 44) and the LAMP-1 signal sequences (underlined; SEQ ID NOs.21 and 22). FIG. 30 is an annotated version of SEQ ID NO. 34. Codon-optimized forward nucleotide sequence corresponding to the SEQ ID NO. 33 protein sequence. The HBB UTRs are underlined. N1-methylpseudouridine is substituted for all uridines (U) during mRNA synthesis. FIG.31 is an annotated version of SEQ ID NO.35. An Mtb CD4 T cell-focused vaccine construct. Protein sequence consisting of SEQ ID 19 (associated with Table 45) and the LAMP- 1 signal sequences (underlined; SEQ ID NOs. 21 and 22). FIG. 32 is an annotated version of SEQ ID NO. 36. Codon-optimized forward nucleotide sequence corresponding to the SEQ ID NO. 35 protein sequence. The HBB UTRs are underlined. N1-methylpseudouridine is substituted for all uridines (U) during mRNA synthesis. FIG. 33A is an annotated version of SEQ ID NO. 37. An Mtb CD4 T cell-focused vaccine construct. Protein sequence consisting of SEQ ID NO. 20 (associated with Table 46) and the HLA class I sec / MITD signal sequences (underlined; SEQ ID NOs.24 and 25). FIG. 33B is an annotated version of SEQ ID NO. 38. Codon optimized forward nucleotide sequence corresponding to the SEQ ID NO. 37 protein sequence. The HBB UTRs are underlined. N1-methylpseudouridine is substituted for all uridines (U) during mRNA synthesis. FIG. 34A is an annotated version of SEQ ID NO. 39. An Mtb CD4 T cell-focused vaccine construct. Protein sequence consisting of SEQ ID NO. 20 (associated with Table 46) and the LAMP-1 signal sequences (underlined; SEQ ID NOs. 21 and 22). FIG. 34B is an annotated version of SEQ ID NO. 40. Codon optimized forward nucleotide sequence corresponding to the SEQ ID NO. 39 protein sequence. The HBB UTRs are underlined. N1-methylpseudouridine is substituted for all uridines (U) during mRNA synthesis. 18 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 35A is an annotated version of SEQ ID NO. 41. An Mtb CD4 T cell-focused vaccine construct. Protein sequence consisting of SEQ ID NO. 20 (associated with Table 46) and the HLA-DRa SP (underlined; SEQ ID NO.29). FIG. 35B is an annotated version of SEQ ID NO. 42. Codon optimized forward nucleotide sequence corresponding to the SEQ ID NO. 41 protein sequence. The HBB UTRs are underlined. N1-methylpseudouridine is substituted for all uridines (U) during mRNA synthesis. FIG. 36A is an annotated version of SEQ ID NO. 43. An Mtb CD4 T cell-focused vaccine construct. Protein sequence consisting of SEQ ID NO. 20 (associated with Table 46) and the tPA (underlined; SEQ ID NO.30). FIG. 36B is an annotated version of SEQ ID NO. 44. Codon optimized forward nucleotide sequence corresponding to the SEQ ID NO. 43 protein sequence. The HBB UTRs are underlined. N1-methylpseudouridine is substituted for all uridines (U) during mRNA synthesis. FIG.37A is an annotated version of SEQ ID NO.204. Human Polyubiquitin-B (UBB), N terminus with G76A mutation, UniProt P0CG47, aa 1-76. G76A mutation underlined. FIG.37B is an annotated version of SEQ ID NO.205. Human Polyubiquitin-B (UBB), N terminus with G76GR mutation, UniProt P0CG47, aa 1-76. The addition of GR after glycine at residue 76 (G76GR) underlined. FIG. 37C is an annotated version of SEQ ID NO. 207. An example of an “Mtb-only” cassette with the G76A ubiquitin attached to the N-terminus (ubiquitin is underlined). Refer to SEQ ID NO.91 for the polyepitope portion of the cassette. FIG.37D is an annotated version of SEQ ID NO.208. An second example of an “Mtb- only” cassette with the G76A ubiquitin attached to the N-terminus (ubiquitin is underlined). Refer to SEQ ID NO.92 for the polyepitope portion of the cassette. FIG. 37E is an annotated version of SEQ ID NO. 209. An example of a “Mixed” cassette with the G76A ubiquitin attached to the N-terminus (ubiquitin is underlined). Refer to SEQ ID NO.101 for the polyepitope portion of the cassette. FIG. 37F is an annotated version of SEQ ID NO. 210. An example of a “Mixed” cassette with the G76A ubiquitin attached to the N-terminus (ubiquitin is underlined). Refer to SEQ ID NO.102 for the polyepitope portion of the cassette. 19 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 38 is an annotated version of SEQ ID NO. 218. Example of an amino acid sequence for an HLA-I “Mtb-only” antigen with an N-terminal IkBalpha destruction motif peptide (SEQ ID NO.206). The IkBalpha motif is underlined. FIG. 39A is an annotated version of SEQ ID NO. 223. Amino acid sequence of a synthetic antigen for an Mtb vaccine. Contains concatenated polypeptides listed in Table 63, each separated by a GPGPG linker (SEQ ID NO: 228). The antigenic polypeptide is flanked on the N-terminus by the sec signal peptide and the C-terminus by MITD. The N- and C- terminal signal domains are underlined. FIG. 39B is an annotated version of SEQ ID NO. 225. Amino acid sequence of a synthetic antigen for an Mtb vaccine. Contains concatenated polypeptides listed in Table 63, each separated by a GPGPG linker (SEQ ID NO: 228). The antigenic polypeptide is flanked on the N-terminus by the LAMP-1 signal peptide (SEQ ID NO. 21) and TM / CT on the C- terminus (SEQ ID NO.22). The N- and C-terminal domains are underlined. FIG. 40 is an annotated version of SEQ ID NO. 212. Example of an amino acid sequence for an HLA class I “Mixed” antigen flanked on the N-terminus by the sec signal peptide the MITD on the C-terminus. The N- and C-terminal domains are underlined. The antigenic sequence corresponds to SEQ ID NO.101. FIG. 41 is an annotated version of SEQ ID NO. 215. Example of an amino acid sequence for an HLA-I “Mtb-only” antigen flanked on the N-terminus by the sec signal peptide the MITD on the C-terminus. The N- and C-terminal domains are underlined. FIGS.42A-42D. Comparison of T cell responses after prime / boost mRNA vaccination of CB6F1 or B6C3F1 mice with 2ndgeneration and 3rdgeneration mRNA constructs. FIG.42A shows the total vaccine anigen-specific CD4 T cell response. FIG.42B shows the total vaccine anigen-specific CD8 T cell response. FIG. 42C shows the relative distribution of CD4 specificities across the vaccine antigens. FIG. 42D shows the relative distribution of CD8 specificities across the vaccine antigens. FIGS.43A-43D. Comparison of T cell responses after prime / boost mRNA vaccination of CB6F1 or B6C3F1 mice with mRNAs encoding a synthetic Mtb antigen preceded with various HLA class I signal peptides. FIG.43A shows the total vaccine anigen-specific CD4 T cell response. FIG. 43B shows the total vaccine anigen-specific CD8 T cell response. FIG. 43C shows the relative distribution of CD4 specificities across the vaccine antigens in CB6F1 mice (top) and B6C3F1 mice (bottom). FIG. 43D shows the relative distribution of CD8 specificities across the vaccine antigens in CB6F1 mice (top) and B6C3F1 mice (bottom). 20 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIGS. 44A-44E. Immunogenicity of BCG or mRNA vaccines in naïve or chronically infected coMtb mice. FIG.44A shows the total vaccine anigen-specific CD4 T cell response. FIG. 44B shows the total vaccine anigen-specific CD8 T cell response. FIG. 44C shows the magnitude of CD8 T cell responses to TB10.4 and Ag85B antigens. FIG. 44D shows the magnitude of CD8 T cell responses to Mtb32A and Mtb39A antigens. FIG. 44E shows the magnitude of CD4 T cell responses to across Mtb antigens encoded by the mRNA. FIGS. 45A-45C. Vaccine efficacy in coMtb mice challenged with aerosol Mtb. FIG. 45A shows the percent of mice infected with aerosol Mtb. FIG. 45B shows the Mtb CFU counts in the lungs of aerosol-challenged ice. FIG. 45C shows the percent of mice that had bilateral dissemination across lung lobes of a founding aerosol bacteria. FIGS. 46A-46F Dose response after prime / boost vaccination with a 3rdgeneration mRNA-LNP vaccine. FIG.46A shows the total vaccine anigen-specific CD4 T cell response. FIG. 46B shows the total vaccine anigen-specific CD8 T cell response. FIG. 46C shows the magnitude of CD4 T cell responses to the mRNA-encoded antigens. FIG. 46D shows the magnitude of CD8 T cell responses to the mRNA-encoded antigens. Within each mRNA-LNP formulation, statistics show significant increase over background levels. FIG. 46E shows the cytokine polyfunctionality of CD4 T cells across doses for the KC3-OA / DPPS-targeted LNP formulation. FIG. 46F shows the cytokine polyfunctionality of CD4 T cells across doses for the KC3-OA untargeted LNP formulation. FIGS.47A-47B Comparison of T cell responses after prime / boost mRNA vaccination of CB6F1 mice using a panel of biodegradable ionizable cationic lipids. FIG. 47A shows the total magnitude of cytokine-producing (IFNg-, IL-2, or TNF-a) CD4 T cells. FIG.47B shows the total magnitude of cytokine-producing (IFNg-, IL-2, or TNF-a) CD8 T cells. DETAILED DESCRIPTION It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the compositions and methods of the present disclosure. T cells are critical for controlling Mtb infection and preventing active disease. CD4 T cells in particular have a dominant role. Mice depleted of CD4 T cells are highly susceptible to infection and disease, and disruption of T helper 1 (Th1) cytokines such as IFN-γ and TNF-α, and the transcription factor Tbet increases susceptibility (Urdahl (2014) Semin Immunol 26, 578-587; Caruso et al. (1999) J. Immunol 162, 5407-5416). Humans with deficiencies in IFN- 21 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 γ and the Th1 cytokine IL-12 are also more susceptible (source). CD4 T cell depletion in non- human primate models of infection also increases susceptibility to infection, and depletion in latently infected macaques greatly increases the chance reactivation (Urdahl (2014) Semin Immunol 26, 578-587; Flynn et al. (2015) Immunol Rev 264, 60-73). In humans, coinfected people living with HIV and latent TB infection have a 20-30-fold increased lifetime risk of developing active TB disease and experience worse outcomes (Esmail et al. (2018) Annu Rev Immunol 36, 603-638). CD4 T cells are the primary cell type infected by HIV, and while peripheral blood absolute CD4 T cell counts do not necessary correlate with increased risk of TB disease, HIV infection results in decreased Mtb-specific CD4 T cells circulating in the blood, and phenotypic / functional changes in the CD4 T cell compartment correlate with increased risk of developing active disease (Esmail et al. (2018) Annu Rev Immunol 36, 603- 638). CD8 T cells also contribute to controlling Mtb infection. Mtb-specific CD8 T cells recognizing a broad array of proteins are present in the circulation, pulmonary lymph nodes and lungs of latently infected people (Lin and Flynn (2015) Semin Immunopathol 37, 239- 249;Lewinsohn et al. (2013) PLoS One 8, e67016; Commandeur et al. (2011 Clin Vaccine Immunol 18, 676-683; Kamath et al. (2004) J Exp Med 200, 1479-1484 ), are important in controlling bacterial burden (Woodworth et al. (2008) J Immunol 181, 8595-8603; Pinxteren et al. (2000) Eur J Immunol 30, 3689-3698), and contribute to immune protection after BCG immunization (Chen (2009) PLoS Pathog 5, e1000392). Given the importance of both CD4 and CD8 T cells in protection against TB, there has been significant effort to identify T cell antigen specificities in humans. Much more is known about the Mtb-specific CD4 T cell repertoire than for CD8 T cells in latently infected humans. Lindestam Arlehamn, Sette and colleagues conducted unbiased genome-wide approaches using an HLA class II epitope prediction algorithm coupled with high-throughput screening of peptide libraries. Initially using a cohort of healthy latently infected (LTBI) individuals in San Diego, California, they identified a large number of antigen-specificities that, at a population level, were largely focused on antigenic “islands” of proteins (Arlehamn et al. (2013) PLoS Pathog 9, e1003130; Arlehamn et al. (2016) PLoS Pathog 12, e1005760). Importantly, the individual breadth of CD4 T cell responses within these antigenic islands was broad with an average of twenty-four specificities identified per person, but substantial variation existed between individuals (Arlehamn et al. (2013) PLoS Pathog 9, e1003130). Building on these findings, CD4 T cell specificities from a South African LTBI cohort to vaccine candidate antigens and IFN- γ release assay (IGRA) antigens were examined (Arlehamn et al. (2016) 22 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 PLoS Pathog 12, e1005760). From these two studies, pools of epitopes were identified that captured the majority of circulating Mtb-specific IFNg-producing CD4 T cells. A comprehensive list of 300 epitopes was defined (MTB300), a subset of 125 epitopes (MTB125) was recognized by at least one South African individual, and a core of 66 unique immunodominant epitopes (MTB66) recognized by >1 individual was able to capture ~80% of the peripheral CD4 T cell response at a population level. Relative to CD4 T cells, fewer minimal CD8 T cell epitopes have been identified. Using a short list of Mtb proteins known to be immunogenic to CD4 T cells, limited dilution cloning of CD8 T cells from LTBI donors was used to identify class I restricted epitopes (Lewinsohn et al. (2007) PLoS Pathog 3, 1240-1249). This approach yielded a small number of defined epitopes primarily restricted to HLA-B alleles. Tang et al. used a combination of epitope prediction algorithms and experimental filters to identify a larger list of minimal epitopes restricted to the HLA-A2, HLA-A3 and HLA-B7 superfamilies, with the most focus placed on characterizing HLA-A2-restricted epitopes (Tang et al. (2011) J Immunol 186, 1068-1080). While these three HLA class I superfamilies are predicted to capture much of the global population, there will likely be significant population gaps with most HLA alleles falling into nine supertypes (Sidney et al. (2008) BMC Immunol 9:1). More recently, Lewinsohn et al. used overlapping peptide libraries covering 389 Mtb proteins predicted to be immunogenic to characterize CD8 T cell responses in diverse LTBI individuals (Lewinsohn et al. (2017) NPJ Vaccines 2, 8). While minimal HLA class I epitopes were not identified within the libraries, at the protein level secreted proteins were enriched for immunodominant responses, and there was substantial overlap in proteins immunogenic to both CD4 and CD8 T cells. Due to the abundance of characterized CD4 T cell epitopes, the well-studied binding promiscuity of epitopes between different HLA class II alleles (Greenbaum et al. (2011) Immunogenetics 63, 325-335), and the finding that epitopes are focused within antigenic islands, we reasoned that a CD4 T cell-focused mRNA vaccine could be designed from the epitopes in the MTB66, MTB125 and MTB300 pools. However, antigen selection for a CD8 T cell-focused mRNA vaccine is perhaps more challenging. Relative to CD4 T cells, there are fewer defined CD8 T cell epitopes with known HLA I restrictions, and while defined epitopes have been identified for some HLA class I supertypes, these are likely insufficient to provide global vaccine coverage. Thus we used an unbiased approach to identify a set of class I epitopes predicted to provide global coverage. 23 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, an immunogenic liposomal nanoparticle (LNP) composition is provided for stimulating both a CD4+ and CD8+ T-cell response to one or more Mycobacterium tuberculosis (Mtb) antigens, the composition comprising: a mRNA polynucleotide sequence is a single concatenated mRNA polynucleotide sequence open reading frame (ORF) encoding (i) a combination of three or more Mtb antigens containing CD8 and CD4 T-cell epitopes, and (ii) a LAMP-1 signal peptide or a human HLA Class I signal peptide and a LAMP-1 or MITD transmembrane and cytoplasmic domain, each operably linked to the Mtb epitopes ORF encoding the Mtb antigens. In some embodiments, the LNP compositions comprise a nucleic acid such as mRNA or DNA for administration in a pharmaceutical composition such as a vaccine. In some embodiments, the LNP compositions optionally further comprise a conjugated lipid. Other aspects relate to compositions comprising lipidic nanoparticles comprising ionizable cationic lipid, the lipidic nanoparticles containing nucleic acids. In some embodiments, nucleic acids are encapsulated into the lipidic nanoparticles. Lipid Nanoparticle (LNP) compositions comprising mRNA include Stabilized Nucleic Acid Lipid Particles (SNALP) used as a vehicle for the systemic delivery of mRNA or other nucleic acid therapeutics. SNALP compositions include cationic lipids such as MC3 or KC2, comprising a protonatable tertiary amine head group joined to a pair of linear 18 carbon aliphatic chains containing a pair of carbon-carbon double bonds separated by a single methylene group (e.g., linoleic acid). However, while the structure of these hydrocarbon chains, each containing a pair of double bonds separated by a single methylene group, imparts desirable biological properties to the SNALP compositions, this chemical sub-structure also results in the undesired problem of increased sensitivity of the compound to oxidative degradation. What is needed are novel cationic lipids suitable for use in a SNALP composition,but having enhanced resistance to oxidative degradation. Aspects of the present disclosure relates to dendritic-cell targeted lipid nanoparticles (LNP) incorporating mRNA encoding for combinations of specific CD8 and CD4 T-cell epitopes found in mycobacterium tuberculosis. In some embodiments, a LNP comprising one or more ionizable cationic lipid(s) is useful for delivery of mRNA, for dendritic cell targeting or methods of using these LNP compositions as a vaccine for the prevention of tuberculosis or other mycobacterial infections. In some embodiments, a LNP can comprise phosphatidylserine or phosphatidylglycerol as targeting ligands to increase their recognition and activity in dendritic cells. In some embodiments, the mRNA is optimized for presentation of MHC-1 24 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 epitopes and activation of CD8 T-cell, while in other embodiments the mRNA is optimized for presentation of MHC-II epitopes and activation of CD4 T-cells. In some embodiments the LNP vaccine incorporates both MHC-I and MHC-II optimized mRNA sequences. Disclosed herein are compounds, compositions and methods related to the treatment of mycobacterial infections. As used herein, the term “compound”, “drug” and “active agent” are used interchangeably. Some aspects of the disclosure relate to novel ionizable lipids or bioreducible ionizable lipids. These lipids are cationic (i.e. positively charged) at acidic pH, such as encountered intracellularly following endocytosis or phagocytosis by a cell. The same lipids, and compositions containing them, are near neutral in charge when present at pH 7.4. These lipids may also have a single olefin group present in their alkyl or acyl groups. Other aspects relate to compositions comprising lipidic nanoparticles comprising ionizable cationic lipid, the lipidic nanoparticles containing nucleic acids. In some embodiments, nucleic acids are encapsulated into the lipidic nanoparticles. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb). In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding Mycobacterium tuberculosis antigens recognized by T cells. Other aspects of the disclosure relate to lipid nanoparticles or targeted lipid nanoparticles that incorporate mRNA coding for major histocompatibility complex class I (MHC-I) or class II (MHC-II) epitopes. In some embodiments, mRNAs coding for MHC-I and MHC-II epitopes are incorporated into a single LNP vaccine. In some embodiments, the epitopes are enriched for those present in mycobacterium tuberculosis when compared to BCG or nontuberculosis mycobacterium (NTM). In some embodiments, the epitopes in the mRNA cassette are linked with nonimmunogenic linkers. In other embodiments the junctions between epitopes have been optimized to reduce the propensity for forming neoepitopes. Aspects of the disclosure provide for improved compositions of ionizable lipid nanoparticles for the delivery of therapeutic nucleic acids to cells. Anionic phospholipids, including phosphatidylserine and phosphatidylglycerol are included in the lipid nanoparticles to increase the transfection efficiency in dendritic cells. The further incorporation of ionizable lipids in an LNP formulation with gem di-substitution of mono-unsaturated alkyl chains (single 25 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 olefin) on 2-position of 1,3-dioxolane or ketal demonstrated high levels of transfection in human dendritic cells, compared to other ionizable lipids in the same family, and demonstrated good stability to oxidative damage. (I) Definitions For convenience, certain terms employed in the specification, examples, and appended claims are collected here. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. As used herein, the following terms and phrases are intended to have the following meanings: As used herein, the term “about” means acceptable variations within 20%, within 10% and within 5% of the stated value. In certain embodiments, "about" can mean a variation of + / -1%, 2%, 3%, 4%, 5%, 10% or 20%. The term "effective amount" as used herein with respect to a compound or the composition means the amount of active compound (also referred herein as active agent or drug) sufficient to cause a bactericidal or bacteriostatic effect. In some embodiments, the effective amount is a "therapeutically effective amount" meaning the amount of active compound that is sufficient alleviate the symptoms of the bacterial infection being treated. The term "subject" (or, alternatively, "patient") as used herein refers to an animal, preferably a mammal, most preferably a human that receives either prophylactic or therapeutic treatment. The term “administration” or “administering” as used herein includes all means of introducing the compounds or the pharmaceutical compositions to the subject in need thereof, including but not limited to, oral, intravenous, intramuscular, intraperitoneal, subcutaneous, transdermal, inhalation, buccal, ocular, sublingual, vaginal, rectal and the like. Administration of the compound or the composition is suitably parenteral. For example, the compounds or the composition can be preferentially administered intravenously, but can also be administered intraperitoneally or via inhalation like is currently used in the clinic for liposomal amikacin in the treatment of mycobacterium avium (see Shirley et al., Amikacin Liposome Inhalation Suspension: A Review in Mycobacterium avium Complex Lung Disease. Drugs. 2019 Apr; 79(5):555-562) 26 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 The terms “treat,” “treating,” and “treatment,” as used herein, refer to therapeutic or preventative measures such as those described herein. The term “pharmaceutically acceptable salt" refers to a relatively non-toxic, inorganic or organic acid addition salt of a compound of the present disclosure which salt possesses the desired pharmacological activity. The term "alkyl" means saturated carbon chains having from one to twenty carbon atoms which may be linear or branched or combinations thereof, unless the carbon chain is defined otherwise. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, sec- and tert-butyl, pentyl, hexyl, heptyl, octyl, and the like. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted. The term “phosphatidylserine”, with any of it’s acyl chain compositions, refers to the L-isomer of serine in the headgroup unless specified in a particular example. The term “lipid conjugate” refers to a conjugated lipid that inhibits aggregation of lipid particles. Such lipid conjugates include, but are not limited to, polysarcosine (see e.g. WO2021191265A1 which is herein incorporated by reference in its entirety for all purposes), polyamide oligomers (e.g., ATTA-lipid conjugates), PEG-lipid conjugates, such as PEG coupled to dialkyloxypropyls, PEG coupled to diacylglycerols, PEG coupled to cholesterol, PEG coupled to phosphatidylethanolamines, PEG conjugated to ceramides (see, e.g., U.S. Pat. No.5,885,613, the disclosure of which is herein incorporated by reference in its entirety for all purposes), cationic PEG lipids, and mixtures thereof. PEG can be conjugated directly to the lipid or may be linked to the lipid via a linker moiety. Any linker moiety suitable for coupling the PEG to a lipid can be used including, e.g., non-ester containing linker moieties and ester- containing linker moieties. In preferred embodiments, non-ester containing linker moieties are used. The abbreviations for the ionizable cationic lipids may be truncated in the Examples from that used in the Tables. For example, AKG-UO-1 may be referred to as UO1, and AKG- KC2-01 may be referred to as KC2-01. The abbreviation UT used in various studies refers to untreated samples. The term “lipidic nanoparticle”, or “LNP”, refers to particles having a diameter of from about 5 to 500 nm. In some embodiments, the lipid nanoparticle comprises one or more active agents. In some embodiments, the lipid nanoparticle comprises a nucleic acid. In some embodiments, the nucleic acid is condensed in the interior of the nanoparticle with a cationic lipid, polymer, or polyvalent small molecule and an external lipid coat that interacts with the 27 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 biological milieu. Due to the repulsive forces between phosphate groups, nucleic acids are naturally stiff polymers and prefer elongated configurations. In the cell, to cope with volume constraints DNA can pack itself in the appropriate solution conditions with the help of ions and other molecules. Usually, DNA condensation is defined as the collapse of extended DNA chains into compact, orderly particles containing only one or a few molecules. By binding to phosphate groups, cationic lipidic can condense DNA by neutralizing the phosphate charges and allow close packing. The terms “encapsulation” and “entrapped,” as used herein, refer to the incorporation or association of the mRNA, DNA, siRNA or other nucleic acid pharmaceutical agent in or with a lipidic nanoparticle. As used herein, the term “encapsulated” refers to complete encapsulation or partial encapsulation. A siRNA may be capable of selectively knocking down or down regulating expression of a gene of interest. For example, an siRNA could be selected to silence a gene associated with a particular disease, disorder, or condition upon administration to a subject in need thereof of a nanoparticle composition including the siRNA. A siRNA may comprise a sequence that is complementary to an mRNA sequence that encodes a gene or protein of interest. The term “mol%” of a lipid component in the LNP composition refers to the molar percent of the lipid component relative to the sum of molar amounts of all lipid components in the nanoparticle (total lipid). The term “N / P” or “N / P ratio” of a nanoparticle comprising a nucleic acid and a cationic lipid (CL) is the ratio between the total number of cationically charged nitrogen atoms of the cationic lipid and the total number of anionically charged phosphate groups of the nucleic acid in the nanoparticle composition. The term “N / P” or “N / P ratio” of a nanoparticle comprising a nucleic acid and an ionizable cationic lipid (ICL) refers to the ratio between the total number of nitrogen atoms of the cationic lipid ionizable to cationic charge and the total number of anionically charged phosphate groups of the nucleic acid in the nanoparticle composition. The N / P ratio is calculated as the amount of ICL expressed in gram-equivalents of the ionizable nitrogen groups divided by the amount of the nucleic acid expressed in gram-equivalents of the nucleic acid phosphate groups. For calculations of N / P ratios an average equivalent weight of an RNA nucleotide (corresponding to one phosphate group) was assumed to be 330 Da. As used herein, the term “pharmaceutically acceptable carrier, diluent or excipient” includes without limitation any adjuvant, carrier, excipient, glidant, sweetening agent, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, 28 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 suspending agent, stabilizer, isotonic agent, solvent, or emulsifier which has been approved by the United States Food and Drug Administration as being acceptable for use in humans or domestic animals. The term “peptide,” “polypeptide” and “protein” are used interchangeably to denote a sequence polymer of at least two amino acids covalently linked by an amide bond (also referred herein as peptide bond). "Identity," as known in the art, is a relationship between two or more polypeptide or protein sequences, or nucleic acid sequences as determined by comparing the sequences. In the art, "identity" also refers to the degree of sequence relatedness between polypeptides or proteins, as determined by the match between strings of such sequences. "Identity" can be readily calculated by any bioinformational methods known in the art. “Percent (%) identity” is defined as the percentage of residues (amino acid residues or nucleic acid residues) in the candidate amino acid or nucleic acid sequence that are identical with the residues in the amino acid sequence or nucleic acid sequence of a second sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity. The term “substantial identity” or “substantial similarity,” as used herein, when referring to a nucleic acid or fragment thereof, indicates that when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 95% to 99% of the sequence. The term “substantial identity” or “substantial similarity,” as used herein, when referring to a protein or fragment thereof, indicates that when optimally aligned there is an amino acid sequence identity in at least about 95% to 99% of the sequence. As used herein, "cellular immune response”, a "cellular response”, a “cellular response against an antigen” or a similar term are meant to include a cellular response directed to cells characterized by presentation of an antigen with class I or class II MHC. The cellular response relates to cells called T cells or T - lymphocytes which act as either “helper cells” or “killer cells”. The helper T cells (also termed CD4 + T cells play a central role by regulating the immune response and the killer cells (also termed cytotoxic T cells, cytolytic T cells, CD8 + T cells or CTLS ) kill diseased cells such as cancer cells, preventing the production of more diseased cells. In some embodiments, aspects of the present disclosure involves the stimulation of an anti-Mycobacterium tuberculosis CTL response against the mycobacterium expressing one or more expressed antigens and preferably presenting such expressed antigens with class I MHC. 29 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 An “antigen” according to aspects of the disclosure covers any substance that will elicit an immune response. In particular, an “antigen” relates to any substance, preferably a peptide or protein, that reacts specifically with antibodies or T-lymphocytes (T cells). As used herein, the term “antigen” comprises any molecule which comprises at least one epitope. Preferably, an antigen in the context of the present disclosure is a molecule which, optionally after processing, induces an immune reaction, which is preferably specific for the antigen (including cells expressing the antigen). According to aspects of the present disclosure, any suitable antigen may be used, which is a candidate for an immune reaction, wherein the immune reaction is preferably a cellular immune reaction. In the context of the embodiments of the present disclosure, the antigen is presented by a cell, for example by an antigen presenting cell which includes a diseased cell, in particular a cancer cell, in the context of MHC molecules, which results in an immune reaction against the antigen. An antigen can be a product which corresponds to or is derived from a naturally occurring antigen. Such naturally occurring antigens may include tumor antigens. As used herein, an " antigen peptide” refers to a portion or fragment of an antigen which is capable of stimulating an immune response, preferably a cellular response against the antigen or cells characterized by expression of the antigen and preferably by presentation of the antigen such as diseased cells, in particular cancer cells. Preferably, an antigen peptide is capable of stimulating a cellular response against a cell characterized by presentation of an antigen with class I MHC and preferably is capable of stimulating an antigen - responsive cytotoxic T - lymphocyte (CTL). The antigen peptides according to embodiments are MHC class I and / or class II presented peptides or can be processed to produce MHC class I and / or class II presented peptides. In some embodiments, the antigen peptides comprise an amino acid sequence substantially corresponding to the amino acid sequence of a fragment of an antigen. In some embodiments, said fragment of an antigen is an MHC class I and / or class II presented peptide. In some embodiments, an antigen peptide comprises an amino acid sequence substantially corresponding to the amino acid sequence of such fragment and is processed to produce such fragment, i.e., an MHC class I and / or class II presented peptide derived from an antigen. According to some embodiments, if a peptide is to be presented directly, i.e., without processing, in particular without cleavage, the peptide has a length which is suitable for binding to an MHC molecule, in particular a class I MHC molecule. In some embodiments, the peptide has a length of 7-20 amino acids, 7-12 amino acids, 8-11 amino acids, for example 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 amino acids in length. 30 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Various aspects and embodiments are described in further detail in the following subsections. (II) Liposomal Compositions In some embodiments, liposomal nanoparticle (LNP) compositions formulated for delivery of a nucleic acid encoding one or more peptides stimulating both a CD4+ and CD8+ T-cell response to one or more Mycobacterium tuberculosis (Mtb) antigens is provided. The LNP compositions can comprise (A) a nucleic acid, (B) an ionizable cationic lipid, (C) one or more phospholipids, including (D) an anionic phospholipid, (E) a PEG-conjugated lipid and (F) a sterol. (A) Nucleic Acid(s) In some embodiments, the LNP composition is an immunogenic liposomal nanoparticle composition such as a vaccine, for stimulating both a CD4+ and CD8+ T-cell response to one or more Mycobacterium tuberculosis (Mtb) antigens, the composition comprising: a mRNA polynucleotide sequence is a single concatenated mRNA polynucleotide sequence open reading frame (ORF) encoding (i) a combination of three or more Mtb antigens containing CD8 and CD4 T-cell epitopes, and (ii) a LAMP-1 signal peptide or a human HLA Class I signal peptide and a LAMP-1 or MITD transmembrane and cytoplasmic domain, each operably linked to the Mtb epitopes ORF encoding the Mtb antigens. In some embodiments, the LNP compositions comprise a nucleic acid such as mRNA or DNA for administration in a pharmaceutical composition such as a vaccine. In some embodiments, the nucleic acid is an RNA, for example an in vitro transcribed RNA (IVT RNA ) or synthetic RNA. Nucleic acids include according to aspects of the disclosure genomic DNA, cDNA, mRNA, recombinantly produced and chemically synthesized molecules. According to aspects of the disclosure, a nucleic acid may be present as a single - stranded or double - stranded and linear or covalently circularly closed molecule. A nucleic acid can, according to aspects of the disclosure , be isolated. In some embodiments, the nucleic acid (i) was amplified in vitro, for example via polymerase chain reaction (PCR), (ii) was produced recombinantly by cloning, (iii) was purified, for example, by cleavage and separation by gel electrophoresis, or (iv) was synthesized, for example, by chemical synthesis. A nucleic can be employed for introduction into, i.e. transfection of cells , in particular, in the form of RNA which can be prepared by in vitro transcription from a DNA template. The RNA can moreover be modified before application by stabilizing sequences, 31 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 capping, and polyadenylation. In some embodiments, some or all uridine nucleosides in the mRNA are substituted with N1-methyl-pseudouridine. In some embodiments, the mRNA does not include N1-methyl-pseudouridine. According to aspects of the disclosure, the stability and translation efficiency of RNA may be modified as required. For example, RNA may be stabilized and its translation increased by one or more modifications having a stabilizing effect and / or increasing translation efficiency of RNA. In order to increase expression of the RNA used according to aspects of the present disclosure, it may be modified within the coding region, i.e. the sequence encoding the expressed peptide or protein, preferably without altering the sequence of the expressed peptide or protein, so as to increase the GC content to increase mRNA stability and to perform a codon optimization and, thus, enhance translation in cells. In some embodiments, the ionizable lipid encapsulate the nucleic acid in a LNP formulation. In some embodiments, the nucleic acid is a mRNA molecule. In some embodiments, the nucleic acid is entrapped in the lipidic nanoparticle with a compound disclosed herein, including compounds of disclosed herein or combinations thereof, wherein the nucleic acid is either RNA or DNA. In some embodiments, the nucleic acid is mRNA. In some embodiments, the nucleic acid is siRNA. In some embodiments, the nucleic acid is DNA. As used herein, a “nucleic acid” refers to a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). In some embodiments, the nucleic acid is an RNA, for example an in vitro transcribed RNA (IVT RNA) or synthetic RNA. Nucleic acids include according to aspects of the disclosure genomic DNA, cDNA, mRNA, recombinantly produced and chemically synthesized molecules. According to aspects of the disclosure, a nucleic acid may be present as a single - stranded or double - stranded and linear or covalently circularly closed molecule. A nucleic acid can, according to aspects of the disclosure, be isolated. In some embodiments, the nucleic acid (i) was amplified in vitro, for example via polymerase chain reaction (PCR), (ii) was produced recombinantly by cloning, (iii) was purified, for example, by cleavage and separation by gel electrophoresis, or (iv) was synthesized, for example, by chemical synthesis. A nucleic can be employed for introduction into, i.e. transfection of cells, in particular, in the form of RNA which can be prepared by in vitro transcription from a DNA template. The RNA can moreover be modified before application by stabilizing sequences, capping, and polyadenylation. As used herein, the term “RNA” refers to a molecule which comprises ribonucleotide residues and preferably being entirely or substantially composed of ribonucleotide residues. As 32 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 used herein, the term “ribonucleotide” refers to a nucleotide with a hydroxyl group at the 2'- position of a B-D- ribofuranosyl group. As used herein, the term “RNA” comprises double- stranded RNA, single-stranded RNA, isolated RNA such as partially or completely purified RNA, essentially pure RNA, synthetic RNA, and recombinantly generated RNA such as modified RNA which differs from naturally occurring RNA by addition, deletion, substitution and / or alteration of one or more nucleotides. Such alterations can include addition of non- nucleotide material, such as to the end(s) of a RNA or internally, for example at one or more nucleotides of the RNA. Nucleotides in RNA molecules can also comprise non - standard nucleotides, such as non-naturally occurring nucleotides or chemically synthesized nucleotides or deoxynucleotides. These altered RNAs can be referred to as analogs or analogs of naturally occurring RNA. In some embodiments, the RNA is a mRNA. As used herein, the term "mRNA” means "messenger RNA” and refers to a "transcript” which can be generated by using a DNA template and encodes a peptide or polypeptide. Typically, an mRNA comprises a 5'-UTR, a protein coding region, and a 3' -UTR. mRNA only possesses limited half-life in cells and in vitro. In the context of aspects of the present disclosure, mRNA may be generated by in vitro transcription from a DNA template. As used herein, the term “modification” in the context of the RNA used in aspects of the disclosure includes any modification of an RNA which is not naturally present in said RNA. According to some embodiments, the RNA does not have uncapped 5'-triphosphates. Removal of such uncapped 5'- triphosphates can be achieved by treating RNA with a phosphatase. The RNA according to aspects of the disclosure may have modified ribonucleotides in order to increase its stability and / or decrease cytotoxicity. For example, in some embodiment, 5-methylcytidine in the RNA is substituted partially or completely, for cytidine. In some embodiments, 5-methylcytidine in the RNA is substituted completely for cytidine. Alternatively or additionally, in some embodiments, pseudouridine in the RNA used is substituted partially or completely, for uridine. In some embodiments, pseudouridine in the RNA used is substituted completely for uridine. In some embodiments, the RNA can be provided with a 5-cap or 5'- cap analog. The term “5 - cap” refers to a cap structure found on the 5'- end of an mRNA molecule and generally consists of a guanosine nucleotide connected to the mRNA via an unusual 5' to 5 triphosphate linkage. In some embodiments, this guanosine is methylated at the 7-position. The term "conventional 5' - cap” refers to a naturally occurring RNA 5 '-cap, for example to the 7 - methylguanosine cap (m'G). In some embodiments, the 5'-cap includes a 5'-cap analog that 33 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 resembles the RNA cap structure and is modified to possess the ability to stabilize RNA and / or enhance translation of RNA if attached thereto, preferably in vivo and / or in a cell. According to aspects of the disclosure, the stability and translation efficiency of RNA may be modified as required. For example, RNA may be stabilized and its translation increased by one or more modifications having a stabilizing effect and / or increasing translation efficiency of RNA. Such modifications are described, for example, in PCT / EP2006 / 009448 incorporated herein by reference in its entirety. In order to increase expression of the RNA used according to aspects of the present disclosure, it may be modified within the coding region, i.e. the sequence encoding the expressed peptide or protein, preferably without altering the sequence of the expressed peptide or protein, so as to increase the GC content to increase mRNA stability and to perform a codon optimization and, thus, enhance translation in cells. In some embodiments, the active agent is encapsulated into the LNP. In some embodiments, the active agent can be an anionic compounds, for example, but not limited to DNA, RNA, natural and synthetic oligonucleotides (including antisense oligonucleotides, interfering RNA and small interfering RNA), nucleoprotein, peptide, nucleic acid, ribozyme, DNA-containing nucleoprotein, such as an intact or partially deproteinated viral particles (virions), oligomeric and polymeric anionic compounds other than DNA (for example, acid polysaccharides and glycoproteins)). In some embodiments, the active agent can be intermixed with an adjuvant. Lipid nanoparticle (LNP) compositions are provided herein, and methods of making and using the same. In some embodiments, the LNP compositions comprise a nucleic acid such as messenger ribonucleic acid (mRNA). In some embodiments, the LNP compositions are vaccines, including LNP formulations comprising mRNA that encodes an immune system epitope, or an antigen recognized by the immune system. In some aspects, the LNP comprises nucleic acid containing a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine. In other embodiments, the mRNA does not include N1-methyl-pseudouridine. In some aspects, the LNP comprises nucleic acid comprising a 5’ untranslated region (UTR) and 3’ UTR, polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. In some aspects, the LNP comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine. In other embodiments, the mRNA does not include N1-methyl-pseudouridine. 34 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the LNP composition comprises a mRNA oligonucleotide. In some embodiments, the nucleic acid is a DNA oligonucleotide. In some embodiments, the nucleic acid comprises more than one nucleic acid. Provided in some aspect of the disclosure is a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid having at least 90% identity (e.g.90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) with a nucleic acid sequence set forth herein. In some embodiments, the LNP composition a mRNA cassette encoding one or more proteins for stimulating both a CD4+ and CD8+ T-cell response. FIG.20 is a schematic of a mRNA construct comprising a 5’-cap, a 5’-UTR, a cassette comprising a signal peptide, an open reading frame and a terminal domain encoding a synthetic polypeptide, a 3’-UTR and a poly-A region. In some embodiments, the mRNA (100) is a single mRNA comprising a 5’ region (110) and a 3’ region (190) flanking a cassette (150) comprising one or more open reading frames (ORFs). The 5’ region of the mRNA (110) can comprise a 5’ cap and a 5’ UTR region. The 3’ region of the mRNA (190) can comprise a 3’UTR (182) and a polyA sequence (184). The mRNA cassette (150) comprises (from 5’ to 3’) a signal peptide, one or more open reading frame regions encoding one or more proteins optionally separated by mRNA spacer region(s) and a terminal domain comprising a transmembrane and cytoplasmic domain. The mRNA cassette (150) can be configured to encode one or more antigen protein and comprises one or more spacer sequences between mRNA encoding each antigen protein. For example, a first cassette (151) comprises a signal peptide (SP), a ORF encoding a first antigen protein (P.1) and a second antigen protein (P.2) separated by a spacer mRNA sequence (S1). A concatenated mRNA cassette of various lengths (152) can be constructed with a signal peptide (SP), a ORF encoding a first antigen protein (P.1), a spacer sequence (Si) between the first antigen protein (P.1) encoding region and each subsequent antigen protein encoding regions (Pi), and a third or subsequent antigen protein encoding region (Pn+2), where each consecutive antigen encoding region is separated by a spacer mRNA sequence (Sn). Another cassette (153) comprises a signal peptide (SP), a ORF encoding a first antigen protein (P.1), a second antigen protein (P.2), a third antigen protein encoding region (P.3), and a fourth antigen protein encoding region (P.4), wherein each antigen protein encoding region is separated by a spacer mRNA sequence (S1), (S2) and (S3) respectively. The mRNA spacer sequences can comprise a G / P (gly-pro), G / S (gly-ser) or AAY spacer polynucleotide sequence between mRNA polynucleotide ORF regions encoding the Mtb antigens. In some embodiments, the mRNA polynucleotide sequence of the cassette (150) further encodes (a) a LAMP-1 signal 35 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 peptide and a LAMP-1 transmembrane and cytoplasmic domain; or (b) a human HLA Class I signal peptide and a LAMP-1 transmembrane and cytoplasmic domain. In some embodiments, the mRNA polynucleotide sequence encodes the signal peptide 5´to the ORF and encodes the transmembrane and cytoplasmic domain 3´to the ORF, and wherein: (a) the LAMP-1 signal peptide comprises the polypeptide of SEQ ID NO:21 and the human HLA Class I signal peptide is a HLA-A signal peptide or a HLA-B (sec) signal peptide comprising the polypeptide of SEQ ID NO:23 or SEQ ID NO:24; and (b) the LAMP-1 transmembrane and cytoplasmic domain comprises the polypeptide of SEQ ID NO:22 and the MITD transmembrane and cytoplasmic domain comprises the polypeptide of SEQ ID NO:25 or SEQ ID NO:26. In some embodiments, the mRNA polynucleotide sequence further comprises a 5’ untranslated region (UTR) and 3’ UTR, a polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. In some embodiments, the mRNA polynucleotide sequence is a chemically modified mRNA polynucleotide sequence, wherein the chemically modified mRNA polynucleotide sequence comprises N1- methylpseudouridine. In some embodiments, the mRNA polynucleotide sequence encoding the one or more antigens is preceded by a nucleotide sequence encoding ubiquitin with a G76A mutation. In some embodiments, wherein the mRNA encodes one, two, three, four, five, six, seven, or more Mycobacterium tuberculosis (Mtb) antigens. In some embodiments, wherein the mRNA does not encode a bacilli Calmette-Guerin (BCG) vaccine antigen protein. In some embodiments, wherein the mRNA encodes one or more a bacilli Calmette-Guerin (BCG) vaccine antigen protein and one or more antigen proteins that are not a bacilli Calmette-Guerin (BCG) vaccine antigen protein. In some embodiments, wherein the mRNA encodes one or more bacilli Calmette-Guerin (BCG) vaccine antigen proteins. In some embodiments, an immunogenic liposomal nanoparticle (LNP) composition is provided for stimulating both a CD4+ and CD8+ T-cell response to one or more Mycobacterium tuberculosis (Mtb) antigens, the composition comprising: (a) one or more mRNA polynucleotide sequence(s) each encoding (i) a LAMP-1 signal peptide or a human HLA Class I signal peptide and (ii) a lysosome-associated membrane protein 1 (LAMP-1) or a MHC class I trafficking domain (MITD) transmembrane and cytoplasmic domain, each of (i) and (ii) operably linked to open reading frame(s) (ORF) of each mRNA sequence encoding the one or more Mtb antigens that are immunogenic for stimulating the CD4+ T-cell response or the CD8+ T-cell response; and (b) a cationic ionizable lipid, one or more phospholipids (PL), 36 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 cholesterol; and a PEG-conjugated lipid, wherein the LNP composition has a ratio of phospholipid (PL) to cholesterol of greater than 10 mol% PL / 40.5 mol% cholesterol and less than 25 mol% PL / 25.5 mol% cholesterol. In some embodiments, the LNP composition has a ratio of phospholipid (PL) to cholesterol of between 15 mol% PL / 40.5 mol% cholesterol and 20 mol% PL / 30.5 mol% cholesterol. In some embodiments, composition comprises the ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the mRNA. In some embodiments, the LNP composition comprises a mRNA polynucleotide sequence encoding one or more Mycobacterium tuberculosis (Mtb) proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288. In some embodiments, the LNP composition comprises a mRNA is a concatenated mRNA polynucleotide sequence comprising an ORF encoding three or more Mtb antigens separated by a GP (gly-pro) spacer, a GS (gly-ser) spacer or a AAY spacer polynucleotide sequence, wherein the three or more Mtb antigens comprise CFP10 / Rv3874, Mtb39A / Rv1196, ESAT-6 / Rv3875, EsxW / Rv3620c, TB10.4 / Rv0288, EsxV / Rv3619c, and Ag85B / Rv1886c. In some embodiments, the LNP composition comprises a mRNA comprising one or more spacers and at least one spacer is a GPGPG spacer polynucleotide sequence. FIG. 21 is a schematic depicting a 1stgeneration mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. 7 Mtb proteins in either their entirety or a select immunogenic region, were connected with GPGPG linkers. 10 additional 15mer peptides commonly presented on MHC class II and recognized by human CD4 T cells were added to the C-terminal end. An HLA class I or LAMP- 1 signal peptide was added to the N-terminus of the polypeptide and either the HLA class I or LAMP-1 C-terminal domain was added to the C-terminus of the polypeptide. In some embodiments, the mRNA cassette in FIG. 21 is SEQ ID NO. 37 comprising a Mtb-derived antigenic protein sequence (SEQ ID NO.20 and Table 46) and the sec / MITD signal sequences; the associated forward codon optimized nucleotide sequence with HBB UTRs is SEQ ID 38. In some embodiments, the mRNA cassette in FIG.21 is SEQ ID NO.39 comprising the same Mtb-derived antigenic protein sequence (SEQ ID NO.20) but with LAMP-1 signal sequences; the associated forward codon optimized nucleotide sequence with HBB UTRs is SEQ ID NO. 40. 37 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 FIG. 22 is a schematic depicting a 2ndgeneration mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. To test additional Mtb vaccine antigens of interest, several modifications were made to the 1stgeneration mRNA design. First, TB10.4 was removed and replaced with PE13. This was done out of concern that TB10.4 may be a non-protective “decoy” antigen, and PE13 was recently identified as an antigen that may contribute to human “non-progressors” that are resistant to developing active TB disease. Second, the C-terminus of Mtb32A was added at the N-terminus of the protein as it is part of the M72 vaccine antigen currently being tested in a phase 3 clinical trial. Finally, many PPE-family proteins contain an “AANR” motif, and two peptides centered on two distinct AANR-containing sequences were included in order to target T cells to as many PPE-family proteins as possible. In some embodiments, the mRNA cassette of FIG. 22 is the mRNA VRN757 comprising a sec / MITD targeting SP and TD, respectively (SEQ ID NO.224 for the RNA sequence, SEQ ID NO.223 for the associated polypeptide). FIGS.23A-23C are schematics depicting a 3rdgeneration mRNA cassette encoding for a synthetic polypeptide consisting of Mtb proteins concatenated into a single open reading frame. A 3rdgeneration mRNA cassette was designed to specifically test whether flexible gly / ser linkers could be used in place of rigid GPGPG linkers. It is possible that more flexible G / S linkers would allow for increased protein stability and improved antigen presentation on MHC molecules. Three different versions of this 3rdgeneration mRNA were created to test whether different arrangements of EsxA, EsxB, EsxW and EsxV influenced the immunogenicity of the encoded polypeptide. As EsxA and B naturally form heterodimers, and EsxW and V naturally form heterodimers, their ability to form these structures within the synthetic polypeptide could alter antigen processing and presentation. Shown in FIG.23A, the individual Esx proteins were kept intact, but separated by another Mtb protein in order to limit the formation of heterodimers. In FIG.23B, the pairing partners were placed adjacent to each other and separated by G / S linkers, which would allow for a flexible conformation and formation of heterodimers within the longer polypeptide. These heterodimers have functions that could influence immunogenicity. In FIG. 23C, the opposite situation of 33B was created – the Esx proteins were broken into the individual helices (H1 represents the N-terminal helix, H2 represents the C-terminal helix) and spatially separated to prevent any function. The structure of EsxA / ESAT-6 is shown as an example of how the helices were separated. FIGS.24A-24B are schematics depicting an mRNA cassette encoding 3 additional Mtb proteins of interest and nonclassical HLA-E-restricted Mtb peptides. The flexibility of the 38 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 mRNA platform allows for rapid design and synthesis of mRNAs encoding additional vaccine antigens of interest. Here, mRNAs encoding EspA, CysD and the N-terminus of Mtb32a were designed. Shown in FIG. 24A, the first version, called Add-on 1.0, also included HLA-E restricted epitopes with the goal of priming invariant HLA-E-restricted CD8 T cells. We created 3 versions, using different HLA-A signal peptides (SP-3A and SP-2A), we extended the MITD N-terminal from the transmembrane domain to include the membrane-proximal (MP) region. A section of the CD74 invariant chain containing multiple cathepsin S (CTSS) sites was included N-terminal to the MP-MITD to improve release from the lysosomal membrane. FIG. 24B is a schematic depicting an mRNA cassette encoding 3 additional Mtb proteins of interest and nonclassical HLA-E-restricted Mtb peptides (Add on 1.1). FIG. 25 is a schematic depicting an mRNA cassette encoding a single chain trimer (SCT) consisting of the Mtb p44 peptide, linker 1, β2m, linker 2, and the HLA-E heavy chain. As the processing and presentation of HLA-E-restricted peptides may not have been optimal in Add-on 1.0 (FIGs. 24A-24B), we designed a SCT using the human HLA-E heavy chain or the mouse homolog Qa-1. This approach maximized expression and stability of agonist peptides that improved T cell activation. FIG.26 is a schematic depicting a mRNA cassette encoding 2 additional Mtb proteins of interest. Mtb proteins PPE15 and PPE51 were concatenated with a flexible G / S linker in between. In some embodiments, the compounds and compositions described herein promote efficient uptake and transfection of target cells, including tissue macrophages and dendritic cells. The efficient delivery nucleic acids coding for antigen specific for infectious viruses or bacteria, and subsequent presentation of that antigen to elicit the desired immune response to protect against corresponding infections is a result. In some embodiments, the nucleic acid is a synthetic nucleic acid (e.g., engineered codon optimized mRNA) encoding an epitope of mycobacterium tuberculosis. In some embodiments, the epitopes are MHC class II epitopes included in larger open reading frames (ORFs), such as EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), or AsxH / TB10.4 (Rv0288). In some embodiments, the epitopes are shorter non-overlapping MHC II minimal 15-mer epitopes that were identified in individuals with latent tuberculosis infection (LTBI) (U.S. patent No. 10,703,784 which is incorporated herein by reference in its entirety, Arlehamn et al., (2013) PloS Pathog. 9:e1003130, and Arlehamn et al., (2016) PloS Pathog. 12:e1005760). Minimal MHC-II epitopes are defined as the 12-20 residue-long 39 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 peptide containing the 9-residue core that is the primary determinant of binding strength to the class II molecule binding groove. Due to the open-ended class II binding groove, the flanking residues on either side of the core can vary. In some embodiments, these sequences are concatenated and encoded using a single mRNA. In some embodiments, the concatenated sequence is a combination of the larger open reading frames and the minimal 15-mer epitopes. In some embodiments, the combination of sequences included in a single concatenated sequence is selected to remove redundant protein sequences. In some embodiments the selection of minimal epitopes to be included in the single concatenated sequence is selected to provide optimum HLA donor coverage. In some embodiments the concatenated sequences are joined with nonimmunogenic linkers that reduce the potential for MHC Class II neoepitopes. In some embodiments, the sequence of the peptide linker is comprised of GPGPG (SEQ ID NO: 228). In some embodiments, the nucleic acid is encoding MHC Class I epitopes. In some embodiments, the Class I epitopes are found in both tuberculosis mycobacterium and other nontuberculosis mycobacterium, or in the Bacillus Calmette-Guerin (BCG) vaccine. In some embodiments, the epitopes are found in tuberculosis mycobacterium. In some embodiments, the MHC Class I sequences are concatenated and encoded using a single mRNA. In some embodiments, the concatenated MHC Class I sequence is a combination of the larger open reading frames and the minimal 9-10-mer epitopes. In other embodiments, the mRNA cassette codes solely for a concatenated sequence of the minimal epitopes. In some embodiments, the combination of sequences included in a single concatenated sequence is selected to remove redundant protein sequences and in some embodiments the selection of minimal epitopes to be included in the single concatenated sequence is selected to provide optimum HLA donor coverage. In some embodiments, the vaccine candidate includes both an MHC-I and an MHC-II mRNA cassette. In some embodiments, both mRNAs are included in a single targeted LNP preparation. In some embodiments, the MHC-I and MHC-II mRNAs are combined in a 1:1 (wt:wt) ratio (MHC-I / MHC-II). In other embodiments, the mRNAs are included in ratios ranging from about 0.1-to-10 (wt:wt), from about 0.2-to-5 (wt:wt), and from about 0.5-to-2 (wt:wt). In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding a T cell epitope from 40 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Mycobacterium tuberculosis (Mtb). In some embodiments, the nucleic acid sequence encodes a peptide that binds to MHC molecules and is recognized by a T cell receptor (generally 8-11 aa long for MHC class I / CD8 and 12+ for MHC class I / CD4). In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding Mycobacterium tuberculosis antigens recognized by T cells. In some aspects, the nucleic acid sequence encodes a polypeptide that is recognized by T cells. Peptide fragments can be generated from an antigen that are recognized by T cell receptors. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequences encoding a Mtb protein selected from the group consisting of: CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196 and Ag85B / Rv1886c. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:220. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and a nucleic acid sequence comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:220. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequences encodimg a Mtb protein selected from the group consisting of: EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c, and TB10.4 / Rv0288. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:31 SEQ ID NO:221 and SEQ ID NO:222. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid, sterol, one or more 41 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 phospholipids comprising at least one anionic phospholipid, a conjugated lipid and a nucleic acid sequence comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:31 SEQ ID NO:221 and SEQ ID NO:222. In some concatenated sequences, the untranslated regions (3’ and 5’ UTRs) are chosen to maximize mRNA stability and translation efficiency. UTRs may include those from viral proteins, or human proteins such as hemoglobin alpha (HBA) or hemoglobin beta (HBB) chains. In some embodiments, chemically modified nucleic acids are incorporated in concatenated mRNA sequences. In some embodiments, the mRNA comprises a modified nucleoside. In some embodiments, the chemically modified residues incorporated are modifications on uridine. In some embodiments, the chemically modified nucleic acid incorporated is pseudouridine. In some embodiments, the chemically modified nucleic acid incorporated is N1-methylpseudouridine (also referred to as 1-methyl-pseudouridine). In some embodiments, the chemically modified nucleic acid incorporated is thiouridine. In some embodiments, the chemically modified nucleic acid incorporated is 5-methylcytidine. In some embodiments, the chemically modified nucleic acid incorporated is 5-methoxyuridine. In some embodiments, the chemically modified nucleic acid incorporated is 5-methylcytidine. In some embodiments, the chemically modified nucleic acid incorporated is N6-methyladenosine. In some embodiments, the chemically modified nucleic acid incorporated is 2’-O-methyluridine. 2-thiouridine. In some embodiments, the mRNA sequence contains a polyA tail of between about 50-150 nucleotides in length, of between about 80-140 nucleotides in length, of between about 100-140 nucleotides in length. In some embodiments the polyA tail may be interrupted by a short sequence to improve stability. In some embodiments, the one or more nucleic acids is a mRNA. In some embodiments, the mRNA encodes a concatenated sequence of T-cell epitopes present in Mtb. In some embodiments, the concatenated sequence of T-cell epitopes comprise an amino acid sequence set forth in SEQ ID NOs: 1-17, 106-137, 138-203. In some embodiments, the concatenated sequence of T-cell epitopes comprises an amino acid sequence with at least 90% sequence identity (e.g. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) with amino acid sequence set forth in SEQ ID NOs: 1-17, 45-85, 106-137, 138-203. In some embodiments, the concatenated nucleotide sequence comprises two or more sequences encoding for peptides or proteins that can elicit MHC class II-restricted CD4 T cell responses. 42 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the two or more MHC class II epitopes selected from the group: EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), and EsxH / TB10.4 (Rv0288). In some embodiments, the two or more MHC class II epitopes comprises peptides or proteins from EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), and EsxH / TB10.4 (Rv0288) (SEQ ID NOs.1-7). In some embodiments, the concatenated nucleic acid-encoded sequence includes the seven proteins in and order N-terminal to C-terminal selected from: EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), EsxH / TB10.4 (Rv0288), ^Ag85B (Rv1886c), ^Mtb39A (Rv1196), EsxW (Rv3620c), and EsxV (Rv3619), or EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), EsxW (Rv3620c), EsxV (Rv3619), EsxH / TB10.4 (Rv0288), ^Ag85B (Rv1886c), and ^Mtb39A (Rv1196), or EsxB / CFP10 (Rv3874), ^Mtb39A (Rv1196), EsxA / ESAT-6 (Rv3875), EsxW (Rv3620c), EsxH / TB10.4 (Rv0288), EsxV (Rv3619), and ^Ag85B (Rv1886c). (SEQ ID NOs.18, 19, and 20). In some embodiments, the composition comprises a nucleic acid encoding for 5 or more non-overlapping CD4 T cell epitopes in the form of peptides, wherein optionally the peptides are from 12 to 50 amino acids long. In some embodiments, the concatenated nucleic acid-encoded sequence optionally comprises 10 selected MHC-II epitopes comprising: AQIYQAVSAQAAAIH (SEQ ID NO. 9), PSPSMGRDIKVQFQS (SEQ ID NO. 10), GINTIPIAINEAEYV (SEQ ID NO. 11), AAFQGAHARFVAAAA (SEQ ID NO. 12), AGWLAFFRDLVARGL (SEQ ID NO. 13), ASIIRLVGAVLAEQH (SEQ ID NO. 14), MSFVTTQPEALAAAA (SEQ ID NO. 8), MHVSFVMAYPEMLAA (SEQ ID NO.15), AYGSFVRTVSLPVGA (SEQ ID NO.16), and LENDNQLLYNYPGAL (SEQ ID NO.17). In some embodiments, the concatenated nucleic acid-encoded sequence includes GPGPG (SEQ ID NO.228) linker sequences between each of the concatenated epitopes. In some embodiments, the one or more nucleic acid comprises a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. In some embodiments, the one or more nucleic acid comprises a nucleic acid sequence having at least 90% identity, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. 43 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the concatenated nucleic acid-encoded sequence includes an N- terminal and C-terminal signal peptide selected from Sec / MITD, Lamp1, HLA-Drα, or tPA. In some embodiments, the one or more nucleic acid comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine. In some embodiments, the one or more nucleic acid comprises a 5’ untranslated region (UTR) and 3’ UTR, polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. In some embodiments, the one or more nucleic acid is an mRNA having a sequence selected from SEQ ID NOs: 34, 36, 38, 40, 42, 44, 224 and 226. In some embodiments, the one or more nucleic acid is an mRNA and wherein the amino acid sequence encoded by the mRNA is selected from SEQ ID NOs: 33, 35, 37, 39, 41, 43, 86- 105, 207-210, 223 and 225. In some embodiments, the nucleic acid-encoded concatenated sequence comprises two or more MHC class I epitopes selected from SEQ ID NOs: 106-137 and 138-203. In some embodiments, the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes found in Mycobacterium tuberculosis, depleted of epitopes found in BCG, and selected from SEQ ID NOs: 86-95. In some embodiments, the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86-105. In some embodiments, the nucleic acid sequence has at least 90% (e.g. 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%) identity to the nucleic acid sequences of the disclosure. In some embodiments, the polypeptide sequence at least 90% identity (e.g. 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%) to the polypeptide sequences of the disclosure. (B) Ionizable Lipids Ionizable lipids can have different properties or functions with respect to LNPs. Due to the pKa of the amino group, the lipid molecules can become positively charged in acidic conditions. Under these conditions, lipid molecules can electrostatically bind to the phosphate groups of the nucleic acid which allows the formation of LNPs and the entrapment of the nucleic acid. In some embodiments, the pKa can be low enough that it renders the LNP substantially neutral in surface charge in biological fluids, such as blood, which are at 44 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 physiological pH values. High LNP surface charge is associated with toxicity, rapid clearance from the circulation by the fixed and free macrophages, hemolytic toxicities, including immune activation (Filion et al Biochim Biophys Acta.1997 Oct 23;1329(2):345-56). In some embodiments, pKa can be high enough that the ionizable cationic lipid can adopt a positively charged form at acidic endosomal pH values. This way, the cationic lipids can combine with endogenous endosomal anionic lipids to promote membrane lytic nonbilayer structures such as the hexagonal HII phase, resulting in more efficient intracellular delivery. In some embodiments, the pKa ranges between 6.2-7.5. For example, the pKa can be about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7, about 7.1, about 7.2, about 7.3, about 7.4 or about 7.5. Unsaturated tails also contribute to the lipids’ ability to adopt nonbilayer structures. (Jayaraman et al., Angew Chem Int Ed Engl.2012 Aug 20;51(34):8529-33). In an embodiment, the LNP comprises an ionizable cationic lipid. As used herein “ionizable cationic lipid”, “ionizable lipid” and “ICL” are used interchangeably. An ICL is a lipid that comprises an ionizable moiety capable of bearing a charge (e.g., a positive charge e.g., a cationic lipid) under certain conditions (e.g., at a certain pH range, e.g., under physiological conditions). The ionizable moiety may comprise an amine, and preferably a substituted amine. An ionizable lipid may be a cationic lipid or an anionic lipid. In addition to an ionizable moiety, an ionizable lipid may contain an alkyl or alkenyl group, e.g., greater than six carbon atoms in length (e.g., greater than about 8 carbons, 10 carbons, 12 carbons, 14 carbons, 16 carbons, 18 carbons, 20 carbons or more in length). Additional ionizable lipids that may be included in an LNP described herein are disclosed in Jayaraman et al. (Angew. Chem. Int. Ed. 51:8529-8533 (2012)), Semple et al. Nature Biotechnol. 28:172-176 (2010)), and U.S. Patent Nos. 8,710,200 and 8,754,062, each of which is incorporated herein by reference in its entirety. In some embodiments the percentage of oxidative degradation products for the ionizable lipid is less than 50 % of that for a DLin-KC2-DMA or DLin-MC3-DMA control formulation. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable lipid having a chemical structure consisting of a pair of linear polyunsaturated lipid tails covalently bound to a head group, the head group comprising a dialkyl amino group; the head group comprising a heterocyclyl or alkyl portion covalently bound to the dialkyl amino group and optionally further comprising a phosphate group; and each polyunsaturated lipid tail being 45 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 unsaturated except for at least two olefins separated by at least two methylene groups along the length of the lipid tail, and optionally comprising a single acyl group at the end of the lipid tail covalently bound to the head group. In some aspects, each lipid tail in the ionizable lipid is identical, and each lipid tail has a total of two olefins separated only by an unsubstituted ethylene, n-propyl, or n-butyl. In some embodiments, each lipid tail of the ioniziable lipid further comprises an acyl group joined to an oxygen of the headgroup to form an ester, and has a total of 16 or 18 carbon atoms including the acyl group. In some embodiments, a lipidic nanoparticle composition comprises lipids and nucleic acids, the lipidic nanoparticles comprising a compound of Formula I, II, III, IV-B, V-A-1, combinations thereof or pharmaceutically acceptable salts thereof. In some embodiments, the nucleic acid is entrapped in the lipidic nanoparticle with a compound disclosed herein, including compounds of Formula I, II, III, IV-B, V-A-1 or combinations thereof, wherein the nucleic acid is either RNA. In some embodiments, the nucleic acid is entrapped in the lipidic nanoparticle with a compound disclosed herein, including compounds of disclosed herein or combinations thereof, wherein the nucleic acid is either RNA or DNA. In some embodiments, the nucleic acid is mRNA. In some embodiments, the nucleic acid is siRNA. In some embodiments, the nucleic acid is DNA. In some embodiments, v equals 0 and R22is for compounds of Formula (IV-B). In some embodiments, v equals 0 and R22is , and the sum of a and c is 7 or 9 for compounds of Formula (III). In some embodiments, v equals 0 and R22is , and a is 4 and c is 5 for compounds of Formula (III). In some embodiments, v equals 0 and R22is , and a is 1 and c is 8 for compounds of Formula (III). In some embodiments, v equals 0 and R22is , and a is 2 and c is 5 for compounds of Formula (III). 46 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I): wherein , 2, 3 or 4; with hydroxyl; and n is an integer equal to 2, 3 or 4. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein the total length of the R1 hydrocarbon chain is C15- C18. In some embodiments, the total length of the R1hydrocarbon chain is C16 - C18. In some embodiments, the total length of the R1 hydrocarbon chain is C16 or C18. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 and b is 1, 2, 3 or 4. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 and b is 1 or 3. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 and b is 1. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 and b is 3. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 1 and b is 1, 2, 3 or 4. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 1 and b is 1 or 3. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 1 and b is 1. In some embodiments, 47 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 1 and b is 3. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10and R12are the same. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10and R12are each (C1-C4)alkyl optionally substituted with hydroxyl. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10 and R12 are each (C1-C4)alkyl. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10 and R12 are each methyl. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10 and R12 are each ethyl. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10 and R12 are each independently selected from methyl or ethyl. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein R10 and R12 are each independently selected from methyl, ethyl, -(CH2)(CH2)OH, and -(CH2)2(CH2)OH. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 or 1; b is 1, 2, 3 or 4, provided the sum a+b is 1, 2, 3 or 4; R2and R3are each methyl; and n is an integer equal to 2, 3 or 4. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 or 1; b is 1, 2, 3 or 4, provided the sum a+b is 1, 2, 3 or 4; R2 and R3 are each methyl; and n is an integer equal to 2 or 3. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 or 1; b is 1, 2, 3 or 4, provided the sum a+b is 1, 2, 3 or 4; R2and R3are each methyl; and n is an integer equal to 2. n some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I), wherein a is 0 or 1; b is 1, 2, 3 or 4, provided the sum a+b is 1, 2, 3 or 4; R2 and R3 are each methyl; and n is an integer equal to 3. In some embodiments, the LNP compositions comprises a KC3 ionizable cationic lipid. Unless otherwise indicated, the term “KC3 ionizable cationic lipid” as used herein refers to an 48 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 ionizable cationic lipid having the chemical , wherein each R1is the same or different and is a comprising one or more unsaturated alkenyl double chain; R2and R3are each independently methyl; and n is 3. In some aspects, each R1in the KC3 ionizable cationic lipid is the same or different and is a linear C16 or C18 hydrocarbon chain each comprising one or more unsaturated alkenyl double bond within each polyene hydrocarbon chain. In some embodiments, the LNP compositions comprises a KC4 ionizable cationic lipid. Unless otherwise indicated, the term “KC4 ionizable cationic lipid” as used herein refers to an ionizable cationic lipid having the chemical , wherein each R1is the same or different and is a comprising one or more unsaturated alkenyl double bond within each polyene hydrocarbon chain; R2and R3are each independently methyl; and n is 4. In some aspects, each R1 in the KC3 or a KC4 ionizable cationic lipid is the same or , wherein a is 0 or each R1 in the KC3 or a KC4 ionizable cationic lipid is the same or different and is , wherein a is 1 and b is 1 or lipid is the same or , wherein a is 1 and lipid is the 49 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 same or different and is , wherein a is 1 In some or , wherein a is 0 and lipid is the same or , wherein a is 0 and b lipid is the same or , wherein a is 0 and b is 3. cationic lipid is the same or different and is wherein a is 1, 2, 3 or 4; b is 2, 3 or 4; and c is 3, 4, 5, 6, or 7, provided that the sum of a, b and c is 10, 11, 12 or 13. In some aspects, each R1in the KC3 or a KC4 ionizable cationic lipid is the same or different and is wherein a is 1, 2, 3 or 4; b is 4; and c is 3, 4, 5, 6, or 7, provided that the sum of a, b and c is 11 or 13. 50 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some aspects, each R1 in the KC3 or a KC4 ionizable cationic lipid is the same and is a linear C16hydrocarbon chain each comprising one unsaturated alkenyl double bond within each polyene hydrocarbon chain. In some aspects, each R1 in the KC3 or a KC4 ionizable cationic lipid is the same and is a linear C18hydrocarbon chain each comprising one unsaturated alkenyl double bond within each polyene hydrocarbon chain. In some aspects, each R1 in the KC3 or a KC4 ionizable cationic lipid is the same and is a linear C16hydrocarbon chain each comprising two unsaturated alkenyl double bonds within each polyene hydrocarbon chain. In some aspects, each R1in the KC3 or a KC4 ionizable cationic lipid is the same and is a linear C16 hydrocarbon chain each comprising two unsaturated alkenyl double bonds within each polyene hydrocarbon chain, wherein the alkenyl double are separated by two or more saturated alkylene groups. In some aspects, each R1 in the KC3 or a KC4 ionizable cationic lipid is the same and is a linear C18hydrocarbon chain each comprising one unsaturated alkenyl double bond within each polyene hydrocarbon chain. In some aspects, each R1 in the KC3 or a KC4 ionizable cationic lipid is the same or different and is a linear C16or C18hydrocarbon chain each comprising one or two unsaturated alkenyl double bond within each polyene hydrocarbon chain. In some embodiments, the LNP compositions comprises a mixture of a KC3 ionizable cationic lipid and a KC4 ionizable cationic lipid. In some embodiments, the ionizable lipid having the chemical structure: , 2, 3 or 4; R2and R3are each independently methyl; and n is an integer equal to 2 or 3. In some embodiments, n is 3. Some aspects of the disclosure relate to bioreducible ionizable cationic lipids of Formula (I) or (I-A), wherein each R1 is independently linear hydrocarbon alkyl chains each comprising a hydrolysable or bioreducible group, such as an ester group (e.g, -O-CO- or -CO- O-); and R2 and R3 are each independently (C1-C4) alkyl optionally substituted with hydroxyl; 51 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 and n is an integer equal to 2, 3 or 4. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl and n is 3 or 4 and each R1is the same. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3is methyl and each R1is a hydrocarbon chain comprising a single ester group with a total 15-22 atoms, and optionally comprising one or two olefin groups. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl and each R1 is a hydrocarbon chain comprising a single ester group with a total 15-22 atoms, and optionally comprising one olefin group. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2and R3is methyl and each R1is a hydrocarbon chain comprising a single ester group with a total 15-22 atoms, and optionally comprising two olefin groups separated by at least two methylene groups. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2and R3is methyl, n is 3 or 4 and each R1 comprises an ester joining a proximal saturated C7-8 hydrocarbon and a distal C12-15 hydrocarbon optionally comprising one or more olefins and one or more methyl substituents. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl, n is 3 or 4 and each R1comprises an ester joining a proximal saturated C4-10hydrocarbon and a distal C10-20 hydrocarbon optionally comprising one or more olefins and one or more methyl substituents. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2and R3is methyl, n is 3 or 4 and each R1 comprises a proximal C7-10 hydrocarbon and a distal saturated isoprenoid alkane group joined by an ester. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2and R3is methyl, n is 3 or 4 and each R1comprises a proximal C7-10hydrocarbon and a distal saturated phytane group joined by an ester. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl, n is 3 or 4 and each R1 comprises a proximal C7-10 hydrocarbon and a distal unsaturated phytane group comprising one or more olefins joined by 52 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 an ester. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl, n is 3 or 4 and each R1is –(CH2)7-10-A-Y, wherein A is -C(=O)-O- or -O-C(=O)-, and Y is - (CH2-CH2-CH(-CH3)-CH2)3-H or -(CH2-CH2-CH(-CH3)-CH2)3-H or - CH2-CH2 -(CH2-CH2- CH(-CH3)-CH2)2-H. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl, n is 3 or 4 and each R1is –(CH2)7-A-Y, wherein A is -C(=O)-O- or -O-C(=O)-, and Y is -(CH2-CH2-CH(-CH3)-CH2)3-H. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2 and R3 is methyl, n is 3 or 4 and each R1 is –(CH2)8-A-Y, wherein A is -C(=O)-O- or -O- C(=O)-, and Y is -(CH2-CH2-CH(-CH3)-CH2)3-H or -(CH2)2-CH=CH-(CH2)8-H or -(CH2)12-H. In some embodiments, a bioreducible or hydrolysable ionizable cationic lipid comprises a compound of Formula (I) or Formula (I-A) wherein each of R2and R3is methyl, n is 3 or 4 and each R1 is –(CH2)10-A-Y, wherein A is -C(=O)-O- or -O-C(=O)-, and Y is - CH2-CH2 -(CH2- CH2-CH(-CH3)-CH2)2-H. In some embodiments, an ionizable cationic lipid comprises the chemical structure of Formula (II): (II), or a pharmaceutically acceptable Y is, , n is an integer 2, 3 or 4; R22is a hydrocarbon chain with a single olefin and a total length of C15-C18; and each of R10and R12is independently (C1-C4)alkyl optionally substituted with hydroxyl. In some aspects, R22in Formula (II) is a polyene hydrorcarbon chain of Formula A. In some aspects, R10and R12in Formula (II) are each independently selected from methyl, ethyl, propyl, -(CH2)(CH2)OH, and -(CH2)2(CH2)OH. In some aspects, R10 and R12 are each independently methyl in Formula (II). In some aspects, R10and R12are each independently ethyl in Formula (II). In some aspects, at least one of R10 and R12 is n-propyl 53 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 optionally substituted with hydroxyl in Formula (II). In some aspects, R10 is methyl and R12 is selected from methyl, ethyl, -(CH2)(CH2)OH, and -(CH2)2(CH2)OH in Formula (II). In some aspects, R10 is methyl and R12 is selected from -(CH2)(CH2)OH, and -(CH2)2(CH2)OH in Formula (II). In some aspects, R10is methyl and R12is selected from -(CH2)(CH2)OH, and - (CH2)2(CH2)OH in a compound comprising the chemical structure of Formula (II). In some aspects, R10and R12are independently selected from methyl or ethyl, optionally substituted with one or more hydroxyl in Formula (II). In some aspects, one or both of R10 and R12 in Formula (II) are -(CH2)(CH2)OH, or -(CH2)2(CH2)OH in Formula (II). In some aspects, R10is methyl and R12 is methyl or ethyl substituted with hydroxyl in Formula (II). In some aspects, one or both of R10in Formula (II) is methyl and R12is -(CH2)(CH2)OH in Formula (II). In some aspects, one or both of R10 in Formula (II) is methyl and R12 is -(CH2)2(CH2)OH in Formula (II). In some embodiments, an LNP further comprises an ionizable lipid having a structure of Formula (IV-A), or a pharmaceutically acceptable salt thereof wherein each of R10and with or 54 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 4 . embodiments, v equals 1 for compounds of Formula (III). In some embodiments, v equals 1 and q1 equals 1 for compounds of Formula (III). In some embodiments, v equals 1 and q1 equals 2 for compounds of Formula (III). In some embodiments, the sum of a and c is 6, 7, 8 or 9 in R22for compounds of Formula (III). In some embodiments, the sum of a and c is 6 in R22for compounds of Formula (III). In some embodiments, the sum of a and c is 7 in R22for compounds of Formula (III). In some embodiments, the sum of a and c is 9 in R22for compounds of Formula (III). In some embodiments, v equals 0 and the sum of a and c is 6, 7, 8 or 9 in R22for compounds of Formula (III). In some embodiments, v equals 0 and the sum of a and c is 6 in R22for compounds of Formula (IV-B). In some embodiments, v equals 0 and the sum of a and c is 7 in R22for compounds of Formula (III). In some embodiments, v equals 0 and the sum of a and c is 9 in R22for compounds of Formula (III). In some embodiments, R10 and R12 are independently selected from methyl, ethyl, - (CH2)(CH2)OH, and -(CH2)2(CH2)OH for compounds of Formula (III). In some embodiments, R10 and R12 are each methyl and the sum of a and c is 6, 7, 8 or 9 in R22for compounds of Formula (III). In some embodiments, R10and R12are each methyl, v is 0 and the sum of a and c is 6, 7, 8 or 9 in R22for compounds of Formula (III). In some embodiments, the LNP composition comprises an ionizable lipid wherein the ionizable lipid comprises: (a) the dialkyl amino portion of the head group has a chemical structure of Formula (IV- A) wherein 55 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 n is 2, 3 or 4 in Formula (IV-A); and R10and R12in Formula (IV-A) are each independently selected from an alkyl group selected from the group consisting of: methyl, ethyl, and propyl, wherein the alkyl in R10and R12is optionally substituted with one or more hydroxyl; and (b) the ionizable lipid further comprises the chemical comprising the acyl group of each lipid tail covalently of the head group distal to the dialkyl amino portion of Formula (IV-A), indicates attachment to Formula IV-A within the head group, and R22 a portion of each lipid tail covalently bound to the acyl group and having the chemical structure of Formula A: in Formula A indicates attachment of Formula A to R22within each and a is 4, 1, 2, or 3; b is 4, 2, or 3; and c is 4, 3, 5, 6, or 7, provided that the sum of a, b and c is in Formula A is 12, 10, 11, or 13. In some embodiments, the ionizable lipid is a compound of Formula (IV-A), wherein R10and R12in Formula (IV-A) are each independently methyl, ethyl, -(CH2)(CH2)OH, or – (CH2)2(CH2)OH. In some embodiments, the ionizable lipid is a compound of Formula (IV- A), wherein b is 4 and R10and R12in Formula (IV-A) are each methyl. In some embodiments, the present disclosure provides compositions comprising ionizable cationic lipids. Aspects of the disclosure include compositions comprising 3-rac-2,2- di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine (AKG-KC3-OA 56 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 racemate) or chiral purified forms of the AKG-KC3-OA racemate such as KC3-OA(S) and KC3-OA(R), and methods of making and purifying the same. Aspects of the disclosure include compositions comprising 4-rac-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N- dimethylbutan-1-amine (AKG-KC4-OA), and methods of making the same. In some embodiments, a composition comprises an ionizable cationic lipid selected from one or more of the following: (a) a racemic mixture of 3-rac-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4- yl)-N,N-dimethylpropan-1-amine (KC3-OA racemate), or KC3-OA enantiomer; and (b) 4-rac- 2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylbutan-1-amine (AKG-KC4- OA racemate). In some embodiments, a composition comprises a mixture of (R) and (S) enantiomers of KC3-OA ionizable cationic lipid, or a mixture of (R) and (S) enantiomers of KC4-OA ionizable cationic lipid. In some embodiments, a composition comprises a mixture of (R) and (S) enantiomers of KC3-OA ionizable cationic lipid, or a mixture of (R) and (S) enantiomers of KC4-OA ionizable cationic lipid, and the mixture is racemic. In some embodiments, the compounds have the structure of the compounds listed in the tables below. Table 1A show examples of cationic lipids. 57 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Table 1A. Exemplary cationic lipids 58 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Table 3A. Exemplary dialkyl and branched ionizable cationic lipids In some embodiments, a LNP composition comprises an ionizable cationic lipid selected from the group consisting of: 59 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 the ionizable cationic lipid is KC3-C15 (C8:1). In some embodiments, the ionizable cationic lipid is KC3-C16 (C8:1). In some embodiments, the ionizable cationic lipid is KC3-C17 (C8:1). In some embodiments, the ionizable cationic lipid is KC3-C18 (C8:1). In some embodiments, the ionizable cationic lipid is KC3-15. In some embodiments, the ionizable cationic lipid is KC3-16. In some embodiments, the ionizable cationic lipid is KC3-17. In some embodiments, the ionizable cationic lipid is KC3-18. 60 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the ionizable lipid can be a branched ionizable lipid selected from ALC-0315 and SM-102: In some embodiments, combinations of ionizable cationic lipids (ICLs) are provided. Cationic lipids are engineered with improved stability to oxidative degradation while in storage, while retaining high transfection activity or potency in cells. Aspects of the disclosure are based in part on the discovery that LNP compositions comprising mRNA and certain ionizable cationic lipids (ICL) enhanced expression of the mRNA in human dendritic cells. Aspects of the disclosure are based in part on the discovery that selection of certain ionizable cationic lipids can enhance the transfection of human dendritic cells. For example, the KC3 cationic ionic lipids were more active in transfecting human dendritic cells in LNP compositions than either the KC2 or diacyl ionizable lipids (UO series). Among the LNP compositions comprising KC3 ionizable cationic lipids, those LNP compositions with ionizable cationic lipids having monounsaturated alkyl chains were unexpectedly both more active and more stable to oxidative degradation than those containing those with the dilinoleyl alkyl chains. In some embodiments, ionizable cationic lipid compositions useful in the preparation of liposomal nanoparticle (LNP) compositions are provided. In some embodiments, liposomal compositions are provided comprising an ionizable cationic lipid having (a) a pair of linear C1661 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 or C18 hydrocarbon chains each comprising a single unsaturated alkenyl double bond within each polyene hydrocarbon chain, covalently bound to a head group comprising a dialkyl amino alkyl group. In some embodiments, the head group of the ionizable cationic lipid has a dialkyl amino group having a pKa of about 6.3 -7.5. In some embodiments, the head group of the ionizable cationic lipid comprises a heterocyclyl or alkyl portion covalently bound to the dialkyl amino group. In some embodiments, the head group of the ionizable cationic lipid optionally further comprises a phosphate group. In some embodiments, each lipid tail of the ionizable cationic lipid compound is identical, and each lipid tail has a total of one olefin with a total length of 15, 16, 17 or 18 carbons. (C) Phospholipids In an embodiment, the LNP comprises one or more phospholipids. A phospholipid is a lipid that comprises a phosphate group and at least one alkyl, alkenyl, or heteroalkyl chain. A phospholipid may be naturally occurring or non-naturally occurring (e.g., a synthetic phospholipid). A phospholipid may comprise an amine, amide, ester, carboxyl, choline, hydroxyl, acetal, ether, carbohydrate, sterol, or a glycerol. In some embodiments, a phospholipid may comprise a phosphocholine, phosphosphingolipid, or a plasmalogen. Exemplary phospholipids include 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2- dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3- phosphoethanolamine (DOPE), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-distearoyl-sn-glycero-3- phosphoethanolamine (DSPE), 1-myristoyl-2-oleoyl-sn-glycero-3-phosphocholine (MOPC), 1,2-diarachidonoyl-sn-glycero-3-phosphocholine (DAPC), 1-palmitoyl-2-linoleoyl-sn- glycero-3-phosphatidylcholine (PLPC), 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), 1-stearoyl-2-myristoyl-sn-glycero-3-phosphocholine (SMPC), 1-palmitoyl-2- myristoyl-sn-glycero-3-phosphocholine (PMPC), bis(monoacylglycerol)phosphate (BMP), L- α-phosphatidylcholine, 1,2-Diheptadecanoyl-sn-glycero-3-phosphorylcholine (DHDPC), and 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (SAPC). Additional phospholipids that may be included in an LNP described herein are disclosed in Li, J. et al. (Asian J. Pharm. Sci.10:81-98 (2015)), which is incorporated herein by reference in its entirety. In some embodiments, the phospholipid is 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). In some embodiments, the phospholipid is 1,2-dioleoyl-sn-glycero-3- phosphocholine(DOPC). In some embodiments, the phospholipid is 1,2-dipalmitoyl-sn- 62 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 glycero-3-phosphocholine(DPPC). In some embodiments, the phospholipid is 1,2-dioleoyl- sn-glycero-3-phosphoethanolamine (DOPE). In some embodiments, ionizable cationic lipid compositions are provided. In some embodiments, a lipid nanoparticle (LNP) composition comprises an ionizable cationic lipid having the chemical structure of Formula (I) wherein a and b of the two R1 hydrocarbon chains are the same or different, or one of the two R1hydrocarbon chains is a saturated C12-C18alkyl. In some embodiments, the LNP comprises at least two types of lipids. In an embodiment, the LNP comprises two of an ionizable lipid, a phospholipid, a sterol, and an alkylene glycol-containing lipid. In some embodiments, the LNP comprises at least three types of lipids. In an embodiment, the LNP comprises three of an ionizable lipid, a phospholipid, a sterol, and an alkylene glycol-containing lipid. In some embodiments, the LNP comprises at least four types of lipids. In an embodiment, the LNP comprises each of an ionizable lipid, a phospholipid, a sterol, and an alkylene glycol-containing lipid. In some embodiments, a LNP composition comprises an ionizable cationic lipid comprises a pair of identical, lipid hydrocarbon tails at R1 in Formula (I) or Formula (I-A), each having a total of 15, 16, 17 or 18 carbons and comprising a single olefin group, or a pair of olefin groups. In some embodiments, a and b of the two R1 hydrocarbon chains are the same. In some embodiments, a and b of the two R1 hydrocarbon chains are different. In some embodiments, one of the two R1hydrocarbon chains in Formula (I) or Formula (I-A) is a saturated C12-C18 alkyl. In some embodiments, a and b of the two R1 hydrocarbon chains in Formula (I) or Formula (I-A) are the same. In some embodiments, a and b of the two R1hydrocarbon chains in Formula (I) or Formula (I-A) are different. (D) Anionic phospholipid In some embodiments, compositions further comprising ligands, such as antibody conjugates, directed against cell surface receptors to target lipid nanoparticles in a highly specific manner to dendritic cells are provided. In some embodiments, the composition further comprises a targeting ligand, wherein the targeting ligand is oriented to the outside of the nanoparticle. In some embodiments, the targeting ligand is an antibody. In some embodiments, LNPs that have been modified with a targeting ligand such as phosphatidylserine are administered into a subject at a dose of about 1 µg to about 500 µg mRNA. In other embodiments, the targeting ligand is phosphatidylglycerol. In some embodiments the targeted LNPs are administered at a reduced dose of about 1 µg to about 100 ug mRNA. According to some embodiments, a higher proportion of LNPs can be taken up DC 63 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 cells, allowing for increased production of antigenic peptide compared to non-targeted LNP and a more efficient vaccination against the pathogen. For example, assessing the CD8+ reactivity to the in vivo produced antigen could be accomplished by measuring INFγ plasma levels by species specific IFN-gamma Quantikine ELISA Kits from R&D Systems. Some aspects of the disclosure relate to LNP comprising a ligand (also referred herein as targeting ligand) having a binding specificity for a cell surface antigen, wherein the binding of the ligand to the antigen induces the internalization of the ligand. Some embodiments relate to compositions comprising LNP comprising a ligand as described herein. LNP targeting can also accomplished by adding lipids to the formulation. Anionic phospholipids, separate from phosphatidyl-L-serine, were also considered as targeting lipids for LNPs. These include phosphatidylglycerol (PG), phosphatidic acid (PA), N-glutaryl-phosphatidylethanolamine (N-Glu-PE), N-succinyl-phosphatidylethanolamine (N- Suc-PE), and cardiolipin. In some embodiments, a LNP comprises anionic phospholipids, separate from phosphatidyl-L-serine, useful as targeting lipids for LNPs. In some embodiments, a LNP comprises anionic phospholipids selected from the group consisting of: phosphatidylglycerol (PG), phosphatidic acid (PA), N-glutaryl-phosphatidylethanolamine (N- Glu-PE), N-succinyl-phosphatidylethanolamine (N-Suc-PE), and cardiolipin. Distearoylphosphatidylglycerol (DSPG), dipalmitoyphosphatidylglycerol (DPPG), N- succinyl-distearoylphosphatidylethanolamine (N-Suc-DSPE), N-glutaryl- distearoylphosphatidylethanolamine (N-glu-DSPE), distearoylphosphatidic acid (DSPA), and cardiolipin are also provided as anionic phospholipids. For example, phosphatidylserine is known to redistribute to the external surface of the plasma membrane during apoptosis and is a molecular cue for phagocytotic cell attraction (Fadok et al. Curr Biol. 2003 Aug 19;13(16):R655-7). Phosphatidylserine (PS) and phosphatidylglycerol (PG) are recognized by dendritic cells and can induce uptake and activation of dendritic cells LNP targeting can also accomplished by adding certain anionic phospholipids to the formulation (Table 2A). For example, phosphatidylserine is known to redistribute to the external surface of the plasma membrane during apoptosis and is a molecular cue for phagocytotic cell attraction (Fadok et al. Curr Biol. 2003 Aug 19;13(16):R655-7). Phosphatidylserine (PS) and phosphatidylglycerol (PG) are recognized by dendritic cells and can induce uptake and activation of dendritic cells (Caronni et al., Nat Comm. 2021 April 14; 12: 2237-2253; Ischihashi et al., PLOS One 2013). Although anionic phospholipids have been used previously in the context of liposomes, their inclusion in lipidic nanoparticles that include 64 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 condensed nucleic acids is unexpected since anionic headgroups may compete for binding sites of the ionizable cationic lipids with the phosphate backbone of mRNA, may inhibit intracellular escape by altering the surface charge, or may result in aggregation of LNPs during formation or storage. In some embodiments, the LNP composition further comprises an anionic lipid selected from the group consisting of: DSPS (L-isomer), DPPS (L-isomer), DMPS (L-isomer), DOPS (L-isomer), and DSPS (D-isomer). In some embodiments, a composition comprises an anionic phospholipid targeting moiety from the table below. 65 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Table 2A. Anionic Phospholipid Targeting Moieties In some embodiments, a composition comprises an anionic phospholipid targeting moiety from the table below. 66 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Table 2B. Phosphatidylserine Targeting Moieties phosphatidylserine (PS), phoshatidylglycerol (PG), N-glutaryl-phosphatidylethanolamine (N- glu-PE), or N-succinyl-phosphatidylethanolamine (N-Suc-PE). In some embodiments, the anionic phospholipid used is phosphatidylserine. In another embodiment, the phosphatidylserine contains the L-isomer of serine. In another embodiment, the acyl chains for the phosphatidylserine are fully saturated, such as the case for dimyristoylphosphatidyl-L- serine (DMPS), dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS). In a preferred embodiment, the PS used is the L-isomer of either DPPS or DSPS. The phosphatidylserine may also contain an asymmetric acyl chain composition, for example where one acyl chain is stearic acid and another is palmitic acid. In some embodiments, the anionic phospholipid is selected from a group other than phosphatidylserine. In some embodiments, these non-PS anionic phospholipids include phosphatidylglycerol (PG), phosphatidic acid (PA), N-glutaryl-phosphatidylethanolamine (N- 67 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Glu-PE), N-succinyl-phosphatidylethanolamine (N-Suc-PE), and cardiolipin. In some embodiments, these anionic phospholipids include saturated acyl chains of 16 or 18 carbons such as distearoylphosphatidylglycerol (DSPG), dipalmitoyphosphatidylglycerol (DPPG), N- succinyl-distearoylphosphatidylethanolamine (N-Suc-DSPE), N-glutaryl- distearoylphosphatidylethanol-amine (N-Glu-DSPE), distearoylphosphatidic acid (DSPA), and cardiolipin. In some embodiments, a composition comprises an anionic phospholipid targeting moiety from the table below. Table 2C. Nonphosphatidylserine anionic phospholipids 68 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 are as the case for dimyristoylphosphatidylglycerol (DMPG), dipalmitoylphosphatidylglycerol (DPPG), or distearoylphosphatidylglycerol (DSPG). In a preferred embodiment, the PG used is either DPPG or DSPG. The phosphatidylglycerol may also contain an asymmetric acyl chain composition, for example where one acyl chain is stearic acid and another is palmitic acid. In some embodiments, PS or PG are added to the LNP lipid formulation at a concentration between about 0.1 mol% to about 20 mol%, about 0.1 mol% to about 10 mol%, about 0.1 mol% to about 5 mol%, about 0.5 mol% to about 20 mol%, about 0.5 mol% to about 10 mol%, about 0.5 mol% to about 5 mol%, about 1 mol% to about 20 mol%, about 1 mol% to about 10 mol%, or about 1 mol% to about 5 mol%, of the total lipid content of the LNP. In some embodiments, the PS is added to the LNP lipid formulation at a concentration between about 1 mol% to about 20 mol%, about 2.5 mol% to about 10 mol%, about 3 mol% to about 9 mol%, or about 4 mol% to about 8 mol%, of the total lipid content of the LNP. In some embodiments, the PS or PG lipid is included in the LNP composition comprising ionizable cationic lipids known in the art, including DODAP, AKG-OA-DM2, O- 11769, DLin-MC3-DMA, DLin-KC2-DMA, DLin-KC3-DMA, ALC-0315, and SM-102. In another embodiment the PS lipid is included in the LNP composition comprising ICLs of Formula I, II, III, IV-B, V-A-1, combinations thereof or pharmaceutically salts thereof. In another embodiment the PS lipid is included in the LNP composition using N / P ratios between 3 and 8, between 4 and 7, or between 5 and 6. In some embodiments, LNP compositions comprise a targeting ligand directed against cell surface receptors to target lipid nanoparticles in a highly specific manner, including to 69 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 dendritic cells. In some embodiments, the LNP composition comprises a phosphatidyl-L- serine compound as a targeting ligand, such as dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS). In some embodiments, the LNP composition comprises a phosphatidyl-L-serine compound as a targeting ligand and an anionic phospholipid. In some embodiments, the LNP composition comprises a phosphatidylglycerol- containing compound as a targeting ligand such as distearoylphosphatidylglycerol (DSPG) or dipalmitoyphosphatidylglycerol (DPPG), for enhancing expression in human dendritic cells. In some embodiments, LNP compositions comprise both a phosphatidyl-L-serine compound as a targeting ligand, and distearoylphosphatidylcholine (DSPC) as the second phospholipid. In some embodiments, LNP compositions comprise both a phosphatidyl-L-serine compound as a targeting ligand, and distearoylphosphatidylcholine (DSPC) as the second phospholipid without dipalmitoylphosphatidylcholine (DPPC). Salt forms of Anionic Phospholipids In some embodiments, certain salts of the phosphatidylserine targeting lipids are provided. For example, in some embodiments, the phosphatidylserine targeting lipids can be provided as an ammonium salt of DPPS having improved biophysical properties and higher solubility in the presence of ethanol, a preferred solvent for preparation of LNPs. The sodium salts of DSPS or DSPS were insoluble in ethanol and required both the presence of methanol and heating to allow for their formation, as did the ammonium salt of DSPS. It is contemplated that the other ammonium salts of phosphatidylserine will give rise to the same advantages in solubility and biophysical properties. The salt form of the targeting lipid can influence it’s solubility in alcohol containing solvents used in the preparation of lipid nanoparticles. In some embodiments, ionizable cationic lipid compositions are provided. In some embodiments, a lipid nanoparticle (LNP) composition comprises a nucleic acid; an ionizable lipid disclosed herein; a sterol; one or more phospholipids comprising a phosphatidylserine (PS) lipid; and optionally further comprising a conjugated lipid. In some embodiments, a lipid nanoparticle (LNP) composition comprises a mRNA nucleic acid; an ionizable lipid disclosed herein; cholesterol;.one or more phospholipids selected from the group consisting of: DSPC, DPPC and DOPC; and a PS lipid selected from the group consisting of: DPPS, DSPS and DOPS; and optionally further comprising a conjugated lipid comprising PEG. In some embodiments, a LNP composition can comprise an anionic phospholipid. In some embodiments, a LNP composition is prepared using a sodium or ammonium salt of an 70 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 anionic phospholipid. In some embodiments, the anionic phospholipid salt is a compound of Formula (V-A-1), having the chemical structure: X+is an ammonium (NH4+) or sodium (Na+) cation; and a is 14, 15 or 16. In some embodiments, X is an ammonium cation selected from the group consisting of: ammonium (NH4+), an alkylammonium, a dialkylammonium, and a trialkylammonium salt. In some embodiments, X is X is an ammonium cation selected from the group consisting of: ammonium, dimethylamine, diethylamine, triethylamine, trimethylamine, 2- (dimethyamino)ethanol, diethanolamine, 2-(diethyamino)ethanol, ethanolamine, ethylenediamine, N-methyl-glucamine, imidazole, histidine, lysine, arginine, 4-(2- hydroxyethyl)-morpholine, piperazine, 1-(2-hydroxyethyl)-pyrrolidine, triethanolamine, and tromethamine (tris(hydroxymethyl)aminomethane). In some embodiments, the anionic phospholipid of Formula (V-A-1) is a sodium salt of distearoylphosphatidyl-L-serine (DSPS L-isomer). In some embodiments, the anionic phospholipid of Formula (V-A-1) is an ammonium salt of distearoylphosphatidyl-L-serine (DSPS L-isomer). In some embodiments, the anionic phospholipid of Formula (V-A-1) is a sodium salt of DPPS (L-isomer). In some embodiments, the anionic phospholipid of Formula (V-A-1) is an ammonium salt of DPPS (L-isomer). Some embodiments relate to the use of the salt form composition in the preparation of a liposomal nanoparticle (LNP) composition. In some embodiments, the use is in combination with one or more of the following LNP components during the preparation of the LNP composition: a mRNA nucleic acid; an ionizable cationic lipid (ICL); cholesterol; a (L-Serine) PS lipid; one or more phospholipids; and a conjugated lipid. In some embodiments, the use comprises the step of combining the ammonium or salt form of a compound of Formula (V-A-1) with one or more of the following 71 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 LNP components during the preparation of the LNP composition: a mRNA nucleic acid; an ionizable cationic lipid (ICL); cholesterol; a (L-Serine) PS lipid; one or more phospholipids; and a conjugated lipid. In some embodiments, the anionic phospholipid salt is selected from the salts listed below. Table 2D. Ammonium and sodium salt forms of dipalmitoyl- or distearoyl- phosphatidylserine. In some embodiments, the anionic phospholipid salt is DSPS (L-isomer) sodium salt. In some embodiments, the anionic phospholipid salt is DSPS (L-isomer) ammonium salt. In some embodiments, the anionic phospholipid salt is DPPS (L-isomer) sodium salt. In some embodiments, the anionic phospholipid salt is DPPS (L-isomer) ammonium salt. In some embodiments the targeting lipid is a sodium or ammonium salt of dipalmitoylphosphatidyl-L- 72 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 serine (DPPS) or distearoylphosphatidyl-L-serine (DSPS). In some embodiments the targeting lipid is a sodium or ammonium salt of dipalmitoylphosphatidyl-L-serine (DPPS) or distearoylphosphatidyl-L-serine (DSPS). In some embodiments, a LNP composition can comprise an anionic phospholipid selected from the group consisting of: In some embodiments, the salt form of phosphatidylserine is highly soluble in ethanol. In some embodiments it is soluble at greater than 0.5 mg / ml, greater than 1 mg / mL, greater 73 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 than 5 mg / mL, greater than 10 mg / mL, or greater than 20 mg / mL. In some embodiments, the salt is an ammonium salt. In some embodiments, the salt is ammonium itself, an alkylammonium, a dialkylammonium, or a trialkylammonium salt. In some embodiments, the amine is chosen from ammonia, dimethylamine, diethylamine, triethylamine, trimethylamine, 2-(dimethyamino)ethanol, diethanolamine, 2-(diethyamino)ethanol, ethanolamine, ethylenediamine, N-methyl-glucamine, imidazole, histidine, lysine, arginine, 4-(2- hydroxyethyl)-morpholine, piperazine, 1-(2-hydroxyethyl)-pyrrolidine, triethanolamine, and tromethamine (tris(hydroxymethyl)aminomethane), In some embodiments, this targeting lipid is an ammonium salt of DPPS. To obtain phosphatidylserine in the form of ammonium or substituted ammonium salt, any method known in the art may be used. In some embodiments, a sodium salt of phosphatidylserine (PS) is dissolved in a monophase system of chloroform, methanol, and water, containing a chloride salt of ammonium or substituted ammonium (a Bligh-Dyer monophase), and the system is brought to the two-phase state by adding extra methanol and / or water containing the ammonium or substituted ammonium chloride. The chloroform-rich phase, containing the PS, is separated, and the process is repeated. Finally, the chloroform-rich phase is washed with water to remove excess chloride, and the ammonium (substituted ammonium) salt of PS is obtained by evaporation of the chloroform-rich phase. Optionally, the obtained ammonium or substituted ammonium salt of PS is vacuum dried or dissolved in cyclohexane and lyophilized. In another embodiment, the PS as a sodium or potassium salt is dissolved in a water-immiscible organic solvent, such as chloroform or a chloroform-methanol mixture, and washed with diluted aqueous solution of an acid, such as HCl, to obtain a free acid form of the PS, which is then neutralized with ammonium hydroxide or substituted amine in free base form. In yet another embodiment, the organic solution of PS as a sodium or potassium salt is treated with a cation-exchange resin in the ammonium of substituted ammonium form. In yet another embodiment, the PS is prepared in the form of a calcium or magnesium salt and treated with ammonium or substituted ammonium salt of a chelator, such as EDTA, or with ammonium or substituted ammonium phosphate, in the presence of an organic solvent, causing displacement of calcium or magnesium ion in the form of a chelate or a yet less soluble phosphate, which is separated, e.g., by filtration, while ammonium or substituted ammonium salt of PS is left in the organic (e.g., ethanol) solution. 74 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the salt form of phosphatidylglycerol or phosphatidylserine is highly soluble in ethanol. In some embodiments, the salt form of phosphatidylserine is highly soluble in ethanol. In some embodiments it is soluble at greater than 0.5 mg / ml, greater than 1 mg / mL, greater than 5 mg / mL, greater than 10 mg / mL, or greater than 20 mg / mL. In some embodiments the salt form of phosphatidylglycerol or phosphatidylserine is soluble is at least 0.3 mM, at least 0.4 mM, at least 0.5 mM, at least 0.6 mM, or at least 0.8 mM, as determined by a shake flask method in 200 proof ethanol, at the temperature of 22ºC of less. In some embodiments, the salt is an ammonium salt. In some embodiments, the phosphatidylserine is added to the LNP lipids in the form of ammonium or a substituted ammonium salt. Substituted ammonium salt can be mono-, di-. tri-, or tetraalkylammonium having alkyl groups with one to six, one to four, one to three, one, two, or three carbon atoms each. One or more alkyl groups can be n-alkyl, or branched alkyl groups (such as, for example, isopropyl groups), or form a ring (such as for example, cyclohexyl group). An alkyl group and the nitrogen ammonium atom may form a heterocyclic ring. The substituted ammonium salt may be also formed by an alkylenediamine. Tris(hydroxymethyl)aminomethane and triethanolamine can also be used as the amine bases to form PS salts. In some embodiments, the amine is chosen from ammonia, dimethylamine, diethylamine, triethylamine, trimethylamine, 2-(dimethyamino)ethanol, diethanolamine, 2-(diethyamino)ethanol, ethanolamine, ethylenediamine, N-methyl- glucamine, imidazole, histidine, lysine, arginine, 4-(2-hydroxyethyl)-morpholine, piperazine, 1-(2-hydroxyethyl)-pyrrolidine, triethanolamine, and tromethamine (tris(hydroxymethyl)aminomethane), In some embodiments, this targeting lipid is an ammonium salt of DPPS. (E) PEG-conjugated lipid Release of nucleic acids from LNP formulations, among other characteristics such as liposomal clearance and circulation half-life, can be modified by the presence of polyethylene glycol and / or sterols (e.g. cholesterol) or other potential additives in the LNP, as well as the overall chemical structure, including pKa of any ionizable cationic lipid included as part of the formulation. In some embodiments, the LNP comprises an alkylene glycol-containing lipid. An alkylene glycol-containing lipid is a lipid that comprises at least one alkylene glycol moiety, for example, a methylene glycol or an ethylene glycol moiety. In some embodiments, the alkylene glycol-containing lipid comprises a polyethylene glycol (PEG). An alkylene glycol- containing lipid may be a PEG-containing lipid. Polymer-conjugated lipids may include 75 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 poly(ethylene glycol)-conjugated (pegylated)phospholipids (PEG-lipids) such as PEG(Mol. weight 2,000) methoxy-poly(ethylene glycol)-1,2-distearoyl-sn-glycerol (PEG-DSG), PEG(Mol. weight 2,000) methoxy-poly(ethylene glycol)-1,2-palmitoyl-sn-glycerol (PEG- DPG), PEG(Mol. weight 2,000) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (PEG-DSPE) or N-palmitoyl-sphingosine-1- {succinyl[methoxy(polyethylene glycol)2000]} (PEG-ceramide). The molecular weight of the PEG portion in the PEG-lipid component can also vary from 500-10,000 g / mol, from 1,500- 6000 g / mol, but is preferably about 2,000 MW. Other polymers used for conjugation to lipid anchors may include poly(2-methyl-2-oxazoline) (PMOZ), poly(2-ethyl-2-oxazoline) (PEOZ), poly-N-vinylpyrrolidone (PVP), polyglycerol, poly(hydroxyethyl L-asparagine) (PHEA), and poly(hydroxyethyl L-glutamine) (PHEG). A PEG-containing lipid may further comprise an amine, amide, ester, carboxyl, phosphate, choline, hydroxyl, acetal, ether, heterocycle, or carbohydrate. PEG-containing lipids may comprise at least one alkyl or alkenyl group, e.g., greater than six carbon atoms in length (e.g., greater than about 8 carbons, 10 carbons, 12 carbons, 14 carbons, 16 carbons, 18 carbons, 20 carbons or more in length), e.g., in addition to a PEG moiety. In an embodiment, a PEG-containing lipid comprises a PEG moiety comprising at least 20 PEG monomers, e.g., at least 30 PEG monomers, 40 PEG monomers, 45 PEG monomers, 50 PEG monomers, 100 PEG monomers, 200 PEG monomers, 300 PEG monomers, 500 PEG monomers, 1000 PEG monomers, or 2000 PEG monomers. Exemplary PEG-containing lipids include PEG-DMG (e.g., DMG-PEG2k), PEG-c-DMG, PEG-DSG, PEG-DPG, PEG-DSPE, PEG-DMPE, PEG- DPPE, PEG-DOPE, and PEG-DLPE. In some embodiments, the PEG-lipids include PEG- DMG (e.g., DMG-PEG2k), PEG-c-DMG, PEG-DSG, and PEG-DPG. Additional PEG-lipids that may be included in an LNP described herein are disclosed in Fahy, E. et al. (J. Lipid. Res. 46:839-862 (2005) which is incorporated herein by reference in its entirety. In some embodiments, the PEG-lipid is PEG-DMG (e.g., DMG-PEG2k). In some embodiments, the PEG-lipid is α-(3’-{[1,2-di(myristyloxy)propanoxy] carbonylamino}propyl)-ω-methoxy, polyoxyethylene (PEG-c-DMG). In some embodiments, the PEG-lipid is PEG-DSG. In some embodiments, the PEG-lipid is PEG-DPG. An LNP may comprise an alkylene glycol-containing lipid at a concentration greater than about 0.1mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an alkylene glycol-containing lipid at a concentration of greater than about 0.5mol%, about 1mol%, about 1.5mol%, about 2mol%, about 3mol%, about 4mol%, about 5mol%, about 76 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 6mol%, about 8mol%, about 10mol%, about 12mol%, about 15mol%, about 20mol%, about 50mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an alkylene glycol-containing lipid at a concentration of greater than about 1mol%, about 4mol%, or about 6mol%. In an embodiment, the LNP comprises an alkylene glycol-containing lipid at a concentration between about 0.1mol% to about 50mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an alkylene glycol-containing lipid at a concentration between about 0.5mol% to about 40mol%, about 1mol% to about 35mol%, about 1.5mol% to about 30mol%, about 2mol% to about 25mol%, about 2.5mol% to about 20%, about 3mol% to about 15mol%, about 3.5mol% to about 10mol%, or about 4mol% to 9mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an alkylene glycol-containing lipid at a concentration between about 3.5mol% to about 10mol%. In an embodiment, the LNP comprises an alkylene glycol-containing lipid at a concentration between about 4mol% to 9mol%. (F) Sterol In some embodiments, an LNP comprises a sterol. In some embodiments, the sterol is cholesterol. In some embodiments, the sterol is dehydroergosterol. In some embodiments, the sterol is ergosterol. In some embodiments, the sterol is campesterol. In some embodiments, the sterol is β-sitosterol. In some embodiments, the sterol is stigmasterol. In some embodiments, the sterol is a corticosteroid. (e.g., corticosterone, hydrocortisone, cortisone, or aldosterone). An LNP may comprise a sterol at a concentration greater than about 0.1mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a sterol at a concentration greater than about 0.5mol%, about 1mol%, about 5mol%, about 10mol%, about 15mol%, about 20mol%, about 25mol%, about 35mol%, about 40mol%, about 45mol%, about 50mol%, about 55mol%, about 60mol%, about 65mol%, or about 70mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a sterol at a concentration greater than about 10mol%, about 15mol%, about 20mol%, or about 25mol%. In an embodiment, the LNP comprises a sterol at a concentration between about 1mol% to about 95mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a sterol at a concentration between about 5mol% to about 90mol%, about 10mol% to about 85mol%, about 20mol% to about 80mol%, about 20mol% to about 60mol%, about 20mol% to about 50mol%, or about 20mol% to 40mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a sterol at a concentration between about 20mol% to about 77 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 50mol%. In an embodiment, the LNP comprises a sterol at a concentration between about 30mol% to about 60mol%. (III) Preparing Lipid Nanoparticle (LNP) Compositions The method of making an LNP can comprise mixing a first solution with a second solution. Mixing can be achieved using standard liquid mixing techniques, such as propellor mixing, vortexing solutions or preferably through microfluidic mixing or high efficiency T- mixing. In some embodiments, the first solution comprises a lipid or a plurality of lipids and a nucleic acid, where all components are solubilized, in water / solvent system. The solvent may be any water miscible solvent (e.g., ethanol, methanol, isopropanol, acetonitrile, dimethylformamide, dimethylsulfoxide, dioxane or tetrahydrofuran). In some embodiments, the first solution comprises a small percentage of water or pH buffered water. The first solution may comprise up to at least 60% by volume of water, e.g., up to at least about 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50%, 55% or 60% by volume of water. In an embodiment, the first solution comprises between about 0.05% and 60% by volume of water, e.g., between about 0.05% and 50%, about 0.05% and 40%, or about 5% and 20% by volume of water. In some embodiments, the first solution comprises a single type of lipid, for example, an ionizable lipid, a phospholipid, a sterol, or a PEG-containing lipid. In some embodiments, the first solution comprises a plurality of lipids. In some embodiments, the plurality comprises an ionizable lipid, a phospholipid, a sterol, or a PEG-containing lipid. In some embodiments, the plurality of lipids comprise cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC),1,2-dimyristoyl-rac-glycero-3-methylpolyoxyethylene2000 (DMG-PEG2k) or α-(3’- {[1,2-di(myristyloxy)propanoxy] carbonylamino}propyl)-ω-methoxy, polyoxyethylene (PEG2000- C-DMG), and an ionizable lipid. The plurality of lipids may exist in any ratio. In an embodiment, the plurality of lipids comprises an ionizable lipid or sterol, a phospholipid, a sterol, a PEG-containing lipid of the above lipids or a combination thereof in a particular ratio (e.g., a ratio described herein). In some embodiments, the second solution is water. In some embodiments, the second solution is an aqueous buffer with a pH between 3-6 (e.g., a pH of about 3, about 4, about 5, or about 6). The second solution may comprise a load component, e.g., a nucleic acid (e.g., mRNA). The second solution may comprise a small percentage of water-miscible organic solvent. The second solution may comprise up to at least 60% by volume of at least one water miscible organic solvent, e.g., up to at least about 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 78 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 6%, 7%, 8%, 9%,10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55% , 60% or any percent therebetween by volume of at least one organic solvent (e.g., a water miscible organic solvent). In an embodiment, the second solution comprises between about 0.05% and 60% by volume of organic solvent, e.g., between about 0.05% and 50%, about 0.05% and 40%, or about 5% and 20% by volume of organic solvent (e.g., a water miscible organic solvent). The aqueous buffer solution can be an aqueous solution of citrate buffer. In some embodiments, the aqueous buffer solution is a citrate buffer solution with a pH between 4-6 (e.g., a pH of about 4, about 5, or about 6). In an embodiment, the aqueous buffer solution is a citrate buffer solution with a pH of about 6. In some embodiments, the solution comprising a mixture of the first and second solutions comprising the LNP suspension can be diluted. In some embodiments, the pH of the solution comprising a mixture of the first and second solutions comprising the LNP suspension can be adjusted. Dilution or adjustment of the pH of the LNP suspension can be achieved with the addition of water, acid, base or aqueous buffer. In some embodiments, no dilution or adjustment of the pH of the LNP suspension is carried out. In some embodiments, both dilution and adjustment of the pH of the LNP suspension is carried out. In some embodiments, excess reagents, solvents, unencapsulated nucleic acid maybe removed from the LNP suspension by tangential flow filtration (TFF) (e.g., diafiltration). The organic solvent (e.g., ethanol) and buffer may also be removed from the LNP suspension with TFF. In some embodiments, the LNP suspension is subjected to dialysis and not TFF. In some embodiments, the LNP suspension is subjected to TFF and not dialysis. In some embodiments, the LNP suspension is subjected to both dialysis and TFF. In one aspect, the present disclosure features a method comprising treating a sample of LNPs comprising nucleic acid, with a fluid comprising a detergent (e.g., Triton X-100, or anionic detergents (such as, but not limited to, sodium dodecyl sulfate (SDS), or non-ionic detergent, such as but not limited to β-octylglucoside, or Zwittergent 3-14) for a period of time suitable to degrade the lipid layer and thereby release the encapsulated and / or entrapped nucleic acid(s). In an embodiment, the method further comprises analyzing the sample for the presence, absence, and / or amount of the released nucleic acid(s). In some embodiments, the composition further comprises a pharmaceutical excipient. In some embodiments, the lipidic nanoparticles are in an aqueous medium. In some embodiments, the lipidic nanoparticles are in an aqueous medium. In some embodiments, the nucleic acid is entrapped in the lipidic nanoparticle with an 79 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 ionizable cationic lipid compound provided herein or combinations thereof, wherein the nucleic acid is either RNA or DNA. In some embodiments, the nucleic acid is mRNA. In some embodiments, the nucleic acid is siRNA. In some embodiments, the nucleic acid is DNA. In some embodiments, the ionizable lipid encapsulate the nucleic acid. In some embodiments, the ionizable lipid encapsulate the nucleic acid in a LNP formulation. In some embodiments, the nucleic acid is a mRNA molecule. In some embodiments, the lipidic nanoparticle comprises a membrane comprising phosphatidylcholine and a sterol. In some embodiments, the sterol is cholesterol. In some embodiments, the lipidic nanoparticle comprises a membrane comprising phosphatidylcholine, ionizable cationic lipid (ICL). In some embodiments, the ICL have a structure of Formula I, II, III, IV-B, V-A-1, and cholesterol, wherein the membrane separates the inside of the lipidic nanoparticles from the aqueous medium. In some embodiment, the ICL have a structure as shown in Table 1. In some embodiments, the phosphatidylcholine is distearoylphosphatidylcholine (DSPC) or hydrogenated soy phosphatidylcholine (HSPC). In some embodiments, the ionizable cationic lipid to cholesterol molar ratios is from about 65:35 to 40:60. In some embodiments, the ICL to cholesterol molar ratio is from about 60:40 to about 45:55. In some embodiments, the phosphatidylcholine to cholesterol molar ratio is from about 1:5 to about 1:2. In some embodiments, the membrane further comprises a polymer-conjugated lipid. In some embodiments, the lipidic nanoparticle comprises ICL, DSPC, cholesterol and polymer-conjugated lipid in a about 49.5:10.3:39.6:2.5 molar ratio. In some embodiments, the polymer-conjugated lipid is PEG(2000)-dimyristoylglycerol (PEG-DMG) or PEG(Mol. weight 2,000)-dimyristoylphosphatidylethanolamine (PEG- DMPE). (IV) Pharmaceutical Compositions In some embodiments, the composition is a liquid pharmaceutical formulation for parenteral administration. In some embodiments, the composition is a liquid pharmaceutical formulation for subcutaneous, intramuscular, or intradermal administration. In some embodiments, the composition is in the form of a lyophilized powder, that is subsequently reconstituted with aqueous medium prior to administration. In a LNP vaccine product, the active agent is generally contained in the interior of the LNP. In some embodiments, the active agent comprises a nucleic acid. Typically, water soluble 80 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 nucleic acids are condensed with cationic lipids or polycationic polymers in the interior of the particle and the surface of the particle is enriched in neutral lipids or PEG-lipid derivatives. Additional ionizable cationic lipid may also be at the surface and respond to acidification in the environment by becoming positively charged, facilitating endosomal escape. In some embodiments, the LNP composition is formulated as a Mycobacterium tuberculosis (Mtb) vaccine composition comprising a ionizable cationic lipid, one or more phospholipids, a sterol and a PEG-conjugated lipid, and wherein the vaccine composition comprises: (a) a nucleic acid sequence encoding both a CD4 T-cell epitope and a CD8 T-cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by CD4 T-cells and a CD8 T-cells; (b) an ionizable cationic lipid comprising an ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; (c) one or more phospholipids selected from distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof; (d) one or more anionic phospholipids selected from a phosphatidylserine (PS) or a phosphatidylglycerol (PG) or a combination thereof, in a total amount of 2-8 mol% of the total lipid content of the LNP composition; and (e)a PEG-conjugated lipid selected from PEG(2000)-dimyristoylglycerol (PEG-DMG) or PEG(Mol. weight 2,000)- dimyristoylphosphatidylethanolamine (PEG-DMPE), or a combination thereof, in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition. A lipid nanoparticle (LNP) composition can comprise: a messenger ribonucleic acid (mRNA) encoding one or more Mycobacterium tuberculosis (Mtb) proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288; an ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the mRNA, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; one or more phospholipids selected from the group consisting of distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), and dipalmitoylphosphatidylcholine (DPPC), in a total amount of 10-18 mol% of the total lipid content of the LNP composition; one or more anionic phospholipids selected from the group consisting of dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidylglycerol (DSPG), and dipalmitoyphosphatidylglycerol (DPPG) in a total amount of 2-8 mol% of the total lipid content 81 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 of the LNP composition; PEG(2000)-dimyristoylglycerol (PEG-DMG) in a total amount of 1- 3.5 mol% of the total lipid content of the LNP composition; and cholesterol (e.g., 35.5 – 40.5 mol% cholesterol). In some aspects, the LNP comprises a nucleic acid sequence (e.g., mRNA) encoding a T cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by T cells. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA encoding a concatenated sequence of T-cell epitopes present in Mtb or a Mtb antigen recognized by T Cells. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA encoding one or more Mtb proteins selected from the group consisting of CFP10 / Rv3874, ESAT- 6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, and Ag85B / Rv1886c. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:220. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA encoding one or more Mtb proteins selected from the group consisting of EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288. In some aspects, the LNP comprises a nucleic acid sequence that is mRNA comprising one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:31, SEQ ID NO:221, and SEQ ID NO:222. In some aspects, the LNP comprises a nucleic acid sequence that comprises the concatenated nucleic acid-encoded sequence includes an N-terminal and C-terminal signal peptide selected from Sec / MITD, Lamp1, HLA-Dra, or tPA. In some aspects, the LNP comprises a nucleic acid sequence that is an mRNA having a sequence selected from SEQ ID NOs: 34, 36, 38, 40, 42, 44, 224 and 226. In some aspects, the LNP comprises nucleic acid that is an mRNA encoding an amino acid sequence selected from SEQ ID NOs: 33, 35, 37, 39, 41, 43, 86-105, 207-210, 223 and 225. Aspects of the disclosure relate to a lipid nanoparticle (LNP) composition comprising a KC3 ionizable cationic lipid, cholesterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb). Aspects of the present disclosure feature a lipid nanoparticle comprising mRNA and lipids. Exemplary lipids include ionizable cationic lipids (ICLs), phospholipids, sterol lipids, alkylene glycol lipids (e.g., polyethylene glycol lipids), sphingolipids, glycerolipids, glycerophospholipids, prenol lipids, saccharolipids, fatty acids, and polyketides. In some 82 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 embodiments, the LNP comprises a single type of lipid. In some embodiments, the LNP comprises a plurality (e.g. two or more) of lipids. An LNP may comprise one or more of an ionizable cationic lipid, a phospholipid, a sterol, or an alkylene glycol lipid (e.g., a polyethylene glycol lipid). In some embodiments, the lipidic nanoparticle comprises a membrane comprising phosphatidylcholine and a sterol. In some embodiments, the sterol is cholesterol. In some embodiments, the lipidic nanoparticle comprises a membrane comprising phosphatidylcholine, ionizable cationic lipid (ICL). In some embodiments, the ICL have a structure of Formula I, and cholesterol, wherein the membrane separates the inside of the lipidic nanoparticles from the aqueous medium. In some embodiment, the ICL have a structure as shown in Table 1A. In some embodiments, the phosphatidylcholine is distearoylphosphatidylcholine (DSPC) or hydrogenated soy phosphatidylcholine (HSPC). In some embodiments, the ionizable cationic lipid to cholesterol molar ratios is from about 65:35 to 40:60. In some embodiments, the ICL to cholesterol molar ratio is from about 60:40 to about 45:55. In some embodiments, the phosphatidylcholine to cholesterol molar ratio is from about 1:5 to about 1:2. In some embodiments, the membrane further comprises a polymer-conjugated lipid. In some embodiments, the lipidic nanoparticle comprises ICL, DSPC, cholesterol and polymer-conjugated lipid in a about 49.5:10.3:39.6:2.5 molar ratio. In some embodiments, the polymer-conjugated lipid is PEG(2000)-dimyristoylglycerol (PEG-DMG) or PEG(Mol. weight 2,000)-dimyristoylphosphatidylethanolamine (PEG- DMPE). The compositions of this disclosure may be administered by various routes, for example, to effect systemic delivery via intravenous, parenteral, intraperitoneal, or topical routes. The compositions may be administered intravenously, subcutaneously, or intraperitoneally to a subject. In some embodiments, the disclosure provides methods for in vivo delivery of nucleic acids to a subject. In some embodiments, the composition is a liquid pharmaceutical formulation for parenteral administration. In some embodiments, the composition is a liquid pharmaceutical formulation for subcutaneous, intramuscular, or intradermal administration. In some embodiments, the composition is in the form of a lyophilized powder, that is subsequently reconstituted with aqueous medium prior to administration. 83 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the disclosure provides certain LNP compositions. In some aspects, the LNP compositions comprise: a nucleic acid; an ionizable cationic lipid at a N / P ratio of 3 to 8 relative to the nucleic acid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; a sterol in a total amount of 0.5-50 mol% of the total lipid content of the LNP composition; one or more phospholipids in a total amount of phospholipids of 5-50 mol% of the total lipid content of the LNP composition; and a conjugated lipid in a total amount of 0.5-2.5 mol% of the total lipid content of the LNP composition. In some aspects, the LNP composition is further characterized in that: the nucleic acid is mRNA; the ionizable cationic lipid is present in the LNP composition at a N / P ratio of 4 to 7 relative to the nucleic acid; the sterol is cholesterol; and the conjugated lipid is a PEG-containing conjugated lipid. In some aspects, the one or more phospholipids in the LNP comprise at least two phospholipids having mismatched acyl chain lengths. In some aspects, the one or more phospholipids in the LNP comprise a phosphatidylserine (PS) lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. In some aspects, the phosphatidylserine (PS) lipid in the LNP consists of, consists essentially of or comprises dipalmitoylphosphatidyl-L-serine ((L-serine)DPPS). In some aspects, the one or more phospholipids in the LNP comprise a phospholipid selected from the group consisting of: distearoylphosphatidylcholine (DSPC) and hydrogenated soy phosphatidylcholine (HSPC). In some aspects, the one or more phospholipids in the LNP consist of distearoylphosphatidylcholine (DSPC) and dipalmitoylphosphatidyl-L-serine ((L- serine)DPPS). In some aspects, the PEG-containing conjugated lipid in the LNP is PEG(2000)- dimyristoylglycerol (PEG-DMG). In some aspects, the LNP composition has 5-50 mol% total phospholipid, including compositions with 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 mol% total phospholipid. In some embodiments, the LNP composition is further characterized by: the sterol in a total amount of 0.5-45.5 mol% of the total lipid content of the LNP composition; and the one or more phospholipids in a total amount of phospholipids of 5-50 mol% of the total lipid content of the LNP composition. In some embodiments, the sterol in the LNP composition is cholesterol. In some embodiments, the ionizable cationic lipid is KC3-OA (Racemic). In some embodiments, the ionizable cationic lipid is KC3-OA(S). In some embodiments, the ionizable cationic lipid is KC3-OA(R). In some embodiments, the ionizable cationic lipid is KC4-OA (Racemic). In some embodiments, the ionizable cationic lipid is KC4-OA(S). In some embodiments, the ionizable cationic lipid is KC3-OA(R). In some embodiments, the ionizable cationic lipid is a 84 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 mixture of KC3-OA and KC4-OA. In some embodiments, the LNP composition comprises a total of 48-54 mol% of the ionizable cationic lipid. In some embodiments, the one or more phospholipids comprise a phosphatidylserine (PS) lipid. In some embodiments, the PS lipid in the LNP composition is DPPS. In some embodiments, the PS lipid in the LNP composition is present in a total of 5 mol%. In some embodiments, the LNP composition comprises a DSPC phospholipid. In some embodiments, the LNP composition comprises 7.5-20 mol% of a DSPC phospholipid. In some embodiments, the sterol in the LNP composition is cholesterol. In some embodiments, the LNP composition comprises 25-40 mol% cholesterol. In some embodiments, the sterol in the LNP composition is beta sitosterol. In some embodiments, the LNP composition comprises 33-35.5 mol% beta sitosterol. In some embodiments, the PEG-containing conjugated lipid in the LNP composition is PEG-DMG. In some embodiments, the LNP composition comprises 1.5-4.0 mol% PEG- containing conjugated lipid in the LNP composition is PEG-DMG. In some embodiments, the PEG-containing conjugated lipid in the LNP composition is PEG-DLG. In some embodiments, the LNP composition comprises 1.0-4.0 mol% PEG-containing conjugated lipid in the LNP composition is PEG-DLG. In some embodiments, a lipid nanoparticle (LNP) vaccine composition comprises: a nucleic acid; a KC3 ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the nucleic acid in a total amount of 46-54 mol% of the total lipid content of the LNP composition; one or more phospholipids in a total amount of phospholipids of 5-20 mol% of the total lipid content of the LNP composition; a conjugated lipid in a total amount of 1.0-3.5 mol% of the total lipid content of the LNP composition; and cholesterol. In some embodiments, the one or more phospholipids in the LNP comprises an anionic phospholipid in a total of 2-8 mol% of the total lipid content of the LNP composition. In some aspects, the anionic phospholipid is a phosphatidylserine (PS). In some embodiments, the anionic phospholipid is an anionic phospholipid selected from the group consisting of: distearoylphosphatidylglycerol (DSPG) and dipalmitoyphosphatidylglycerol (DPPG). In some embodiments, the anionic phospholipid is an anionic phospholipid selected from the group consisting of: dipalmitoylphosphatidyl-L- serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS). An LNP may comprise an ionizable lipid at a concentration greater than about 0.1 mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an ionizable lipid at a concentration of greater than about 1 mol%, about 2mol%, about 4mol%, 85 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 about 8mol%, about 20mol%, about 40mol%, about 50mol%, about 60mol%, about 80mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an ionizable lipid at a concentration of greater than about 20mol%, about 40mol%, or about 50mol%. In an embodiment, the LNP comprises an ionizable lipid at a concentration between about 1mol% to about 95mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an ionizable lipid at a concentration between about 2mol% to about 90mol%, about 4mol% to about 80mol%, about 10mol% to about 70mol%, about 20mol% to about 60mol%, about 40mol% to about 55mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises an ionizable lipid at a concentration between about 20mol% to about 60mol%. In an embodiment, the LNP comprises an ionizable lipid at a concentration between about 40 mol% to about 55 mol%. The LNP (e.g., as described herein) may comprise one or more of the following components: (i) Ionizable cationic lipid (ICL) containing a C16 alkyl or C16 alkenyl group or C18 alkyl or C18 alkenyl group at a concentration between about 1mol% to about 95mol% (or any value therebetween, e.g. about 20mol% to about 80mol%); (ii) A phospholipid at a concentration between 0.1mol% to about 20 mol% (or any value there between, e.g. between about 2.5 mol% to about 10 mol%) where the phospholipid also contains C16 or C18 alkyl or alkenyl groups; (iii) cholesterol at a concentration between about 1mol% to about 95mol% (or any value therebetween, e.g. about 20mol% to about 80mol%); (iv) a phosphatidylserine (PS) or phosphatidylglycerol (PG) added to the LNP lipid formulation at a concentration between about 0.5 mol% to about 20 mol%, about 2.5 mol% to about 10 mol%, about 4 mol% to about 8 mol%, or any value therebetween of the total lipid content of the LNP, and (v) a polyethyleneglycol (PEG)-2000-containing lipid (e.g., DPG-PEG2000, DPPE-PEG2000, DMPE-PEG2000, DMG-PEG2000) at a concentration between about 0.1mol% to about 5 mol% (or any value therebetween, e.g. between about 1 mol% to about 2.5 mol%). In an embodiment, the LNP comprises two of (i)-(v). In an embodiment, the LNP comprises three of (i)-(v). In an embodiment, the LNP comprises four of (i)-(v). In an embodiment, the LNP comprises each of (i)-(v). In some embodiments, the LNP comprises (i) and (ii). In some embodiments, the LNP comprises (i) and (iii). In some embodiments, the LNP comprises (i) and (v). In some embodiments, the LNP comprises (ii) and (iii). In some embodiments, the LNP comprises (ii) and (v). In some embodiments, the LNP comprises (iii) and (iv). In some embodiments, the LNP comprises (iii) and (v). In some embodiments, the LNP comprises (i), (ii), and (iii). In some embodiments, the LNP comprises (i), (ii), and (v). In some 86 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 embodiments, the LNP comprises (ii), (iii), and (v). In some embodiments, the LNP comprises (ii), (iii), (iv) and (v). In an embodiment, the LNP consists or consists essentially of four of (i)- (v). In an embodiment, the LNP consists or consists essentially of each of (i)-(v). In some embodiments, the LNP consists or consists essentially of (i) and (ii). In some embodiments, the LNP consists or consists essentially of (i) and (iii). In some embodiments, the LNP consists or consists essentially of (i) and (v). In some embodiments, the LNP consists or consists essentially of (ii) and (iii). In some embodiments, the LNP comprises (ii) and (v). In some embodiments, the LNP consists or consists essentially of (iii) and (iv). In some embodiments, the LNP consists or consists essentially of (iii) and (v). In some embodiments, the LNP consists or consists essentially of (i), (ii), and (iii). In some embodiments, the LNP consists or consists essentially of (i), (ii), and (v). In some embodiments, the LNP comprises (ii), (iii), and (v). In some embodiments, the LNP consists or consists essentially of (ii), (iii), (iv) and (v). An LNP may comprise a phospholipid at a concentration greater than about 0.1mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a phospholipid at a concentration of greater than about 0.5mol%, about 1mol%, about 1.5mol%, about 2mol%, about 3mol%, about 4mol%, about 5mol%, about 6mol%, about 8mol%, about 10mol%, about 12mol%, about 15mol%, about 20mol%, about 50mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a phospholipid at a concentration of greater than about 1mol%, about 5mol%, or about 10mol%. In an embodiment, the LNP comprises a phospholipid at a concentration between about 0.1mol% to about 50mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a phospholipid at a concentration between about 0.5mol% to about 40mol%, about 1mol% to about 30mol%, about 5mol% to about 25mol%, about 10mol% to about 20mol%, about 10mol% to about 15mol%, or about 15mol% to about 20mol%, e.g., of the total lipid content of the LNP. In an embodiment, the LNP comprises a phospholipid at a concentration between about 5mol% to about 25mol%. In an embodiment, the LNP comprises a phospholipid at a concentration between about 10mol% to 20mol%. In an embodiment, the LNP comprises a sterol or ionizable sterol molecule. A sterol is a lipid that comprises a polycyclic structure and an optionally a hydroxyl or ether substituent, and may be naturally occurring or non-naturally occurring (e.g., a synthetic sterol). Sterols may comprise no double bonds, a single double bond, or multiple double bonds. Sterols may further comprise an alkyl, alkenyl, halo, ester, ketone, hydroxyl, amine, polyether, carbohydrate, or cyclic moiety. An exemplary listing of sterols includes cholesterol, 87 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 dehydroergosterol, ergosterol, campesterol, β-sitosterol, stigmasterol, lanosterol, dihydrolanosterol, desmosterol, brassicasterol, lathosterol, zymosterol, 7-dehydrodesmosterol, avenasterol, campestanol, lupeol, and cycloartenol. In some embodiments, the sterol comprises cholesterol, dehydroergosterol, ergosterol, campesterol, β-sitosterol, or stigmasterol. Additional sterols that may be included in an LNP described herein are disclosed in Fahy, E. et al. (J. Lipid. Res.46:839-862 (2005). The LNP (e.g., as described herein) may comprise one or more of the following components: (i) an ionizable cationic lipid at a concentration between about 1mol% to about 95mol% (e.g. about 20mol% to about 80mol%); (ii) a phospholipid at a concentration between 0.1mol% to about 50mol% (e.g. between about 2.5mol% to about 20mol%); (iii) a sterol at a concentration between about 1mol% to about 95mol% (e.g. about 20mol% to about 80mol%); and (iv) a PEG-containing lipid at a concentration between about 0.1mol% to about 50mol% (e.g. between about 2.5mol% to about 20mol%). In an embodiment, the LNP comprises one of (i)-(iv). In an embodiment, the LNP comprises two of (i)-(iv). In an embodiment, the LNP comprises three of (i)-(iv). In an embodiment, the LNP comprises each of (i)-(iv). In some embodiments, the LNP comprises (i) and (ii). In some embodiments, the LNP comprises (i) and (iii). In some embodiments, the LNP comprises (i) and (iv). In some embodiments, the LNP comprises (ii) and (iii). In some embodiments, the LNP comprises (ii) and (iv). In some embodiments, the LNP comprises (iii) and (iv). In some embodiments, the LNP comprises (i), (ii), and (iii). In some embodiments, the LNP comprises (i), (ii), and (iv). In some embodiments, the LNP comprises (ii), (iii), and (iv). The LNP (e.g., as described herein) may comprise one or more of the following components: (i) Ionizable cationic lipid (ICL) at a concentration between about 1mol% to about 95mol% (e.g. about 20mol% to about 80mol%); (ii) DSPC at a concentration between 0.1mol% to about 50mol% (e.g. between about 2.5mol% to about 20mol%); (iii) cholesterol at a concentration between about 1mol% to about 95mol% (e.g. about 20mol% to about 80mol%); and (iv) DMG-PEG2k at a concentration between about 0.1mol% to about 50mol% (e.g. between about 2.5mol% to about 20mol%). In an embodiment, the LNP comprises two of (i)- (iv). In an embodiment, the LNP comprises three of (i)-(iv). In an embodiment, the LNP comprises each of (i)-(iv). In some embodiments, the LNP comprises (i) and (ii). In some embodiments, the LNP comprises (i) and (iii). In some embodiments, the LNP comprises (i) and (iv). In some embodiments, the LNP comprises (ii) and (iii). In some embodiments, the LNP comprises (ii) and (iv). In some embodiments, the LNP comprises (iii) and (iv). In some 88 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 embodiments, the LNP comprises (iii) and (iv). In some embodiments, the LNP comprises (i), (ii), and (iii). In some embodiments, the LNP comprises (i), (ii), and (iv). In some embodiments, the LNP comprises (ii), (iii), and (iv). In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 45 mol% of the KC3 ionizable cationic lipid, 42.7 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 50 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L- Serine) DPPS lipid, and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 46.5 mol% of the KC3 ionizable cationic lipid, 42 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 15 mol% total phospholipid and 35.5 mol% cholesterol. In some embodiments, the LNP composition comprises 10 mol% total phospholipid and 40.5 mol% cholesterol. In some embodiments, the LNP composition comprises 40.5 mol% cholesterol, 5% anionic lipid (DPPS) and 5% PC (DSPC or DPPC) and a total of 10 mol% phospholipid concentration. In some embodiments, the LNP composition 89 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 comprises 48 mol% cationic ionizable lipid, 5 mol% PC (DPPC), 5 mol% anionic lipid (DPPS), 40.5 mol% cholesterol, 1.5 mol% conjugated lipid (PEG-DMG). In some embodiments, the liposomal nanoparticle (LNP) composition further comprises a cationic ionizable lipid, one or more phospholipids, a sterol and a PEG-conjugated lipid, wherein the sterol is cholesterol, and the LNP composition comprises a ratio of phospholipid (PL) to cholesterol of between 10 mol% PL / 40.5 mol% cholesterol and 30 mol% PL / 20.5 mol% cholesterol. In some embodiments, the sterol is cholesterol, and the LNP composition comprises a ratio of phospholipid (PL) to cholesterol of between 15 mol% PL / 25.5 mol% cholesterol and 30 mol% PL / 20.5 mol% cholesterol. In some embodiments, the polynucleotide is mRNA comprising the ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the mRNA. In some embodiments, the LNP composition comprises: (a) a nucleic acid sequence encoding a CD4 T-cell epitope and a CD8 T-cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by CD4 T-cells and a CD8 T-cells; (b) an ionizable cationic lipid comprising an ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; (c) one or more phospholipids selected from distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof, in a total amount of 10-25 mol% of the total lipid content of the LNP composition; (d) one or more anionic phospholipids selected from a phosphatidylserine (PS) or a phosphatidylglycerol (PG) or a combination thereof, in a total amount of 2-8 mol% of the total lipid content of the LNP composition; and (e) a PEG-conjugated lipid selected from PEG(2000)-dimyristoylglycerol (PEG-DMG) or PEG(Mol. weight 2,000)-dimyristoylphosphatidylethanolamine (PEG- DMPE), or a combination thereof, in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises: (a) a nucleic acid; (b) an ionizable cationic lipid comprising a KC3 ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; (c) one or more phospholipids in a total amount of 5-20 mol% of the total lipid content of the LNP composition; (d) one or more anionic phospholipids in a total amount of 2-8 mol% of the total lipid content of the LNP composition; (e) a conjugated lipid in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition; and (f) a sterol such cholesterol (e.g., in an amount providing the 90 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 remainder of the LNP composition). In some aspects, the one or more anionic phospholipids is a phosphatidylserine (PS) or phosphatidylglycerol (PG). In some aspects, the one or more anionic phospholipids is selected from the group consisting of: dipalmitoylphosphatidyl-L- serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidylglycerol (DSPG), and dipalmitoyphosphatidylglycerol (DPPG). In some aspects, the one or more phospholipids comprises distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof. In some aspects, the conjugated lipid is PEG(2000)-dimyristoylglycerol (PEG-DMG). In some aspects, the sterol is cholesterol. In some aspects, the ionizable cationic lipid comprises 3-((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1- amine (KC3-OA). In some aspects, the ionizable cationic lipid further comprises a KC4 ionizable cationic lipid, such as 4-rac-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N- dimethylbutan-1-amine (AKG-KC4-OA). In some aspects, the LNP composition consists of: 48 mol% KC3-OA; 5 mol% DPPS or DSPG; 5-10 mol% DSPC or HSPC; 1.5 mol% PEG- DMG; and cholesterol. In some aspects, the LNP composition consists of: 48 mol% KC3-OA; 5 mol% DPPS or DSPG; 5 mol% DSPC or HSPC; 1.5 mol% PEG-DMG; and 40.5 mol% cholesterol. In some aspects, the LNP composition consists of: 48 mol% KC3-OA; 5 mol% DPPS or DSPG; 10 mol% DSPC or HSPC; 1.5 mol% PEG-DMG; and 35.5 mol% cholesterol. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 45 mol% of the KC3 ionizable cationic lipid, 42.7 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 50 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid 91 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 46.5 mol% of the KC3 ionizable cationic lipid, 42 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises 15 mol% total phospholipid and 35.5 mol% cholesterol. In some embodiments, the LNP composition comprises 10 mol% total phospholipid and 40.5 mol% cholesterol. In some embodiments, the LNP composition comprises 40.5 mol% cholesterol, 5% anionic lipid (DPPS) and 5% PC (DSPC or DPPC) and a total of 10 mol% phospholipid concentration. In some embodiments, the LNP composition comprises 48 mol% cationic ionizable lipid, 5 mol% PC (DPPC), 5 mol% anionic lipid (DPPS), 40.5 mol% cholesterol, 1.5 mol% conjugated lipid (PEG-DMG). In some embodiments, the cationic lipid is KC3-OA, KC3-PA, KC3-01, KC3-C17 (8:1), or KC3-C15 (C8:1). In some embodiments, the LNP comprises the conjugated lipid in a total amount of less than 2 mol% of the total lipid content of the LNP composition. In some embodiments, the ionizable cationic lipid in a total amount of 45-55 mol% of the total lipid content of the LNP composition; cholesterol is in a total amount of 35-45 mol% of the total lipid content of the LNP composition; the total amount of the one more phospholipid is 7-15 mol% of the total lipid content of the LNP composition; the one or more phospholipids consist of DSPC and the PS lipid is one or more lipids selected from the group consisting of the L-serine configuration of DPPS and DSPS; and the total amount of the PS lipid is about 5 mol% of the total lipid content of the LNP composition. In some embodiments, the conjugated lipid is PEG-DMG; and the PS lipid is selected from the group consisting of: DSPS (L-isomer) and DPPS. In some embodiments, the ionizable cationic lipid is KC3-OA. In some embodiments, the LNP composition has a N / P ratio of 4 to 7. In some embodiments, the LNP composition has a N / P ratio of 5 to 6. 92 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Provided in some aspect of the disclosure is a nucleic acid lipid nanoparticle (LNP) composition comprising: a mRNA having at least 90% identity (e.g. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44, ionizable cationic lipid KC3-PA, and a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the PS lipid is (L-Serine) DSPS, (L-Serine) DPPS, or a mixture thereof, and the LNP composition further comprises cholesterol and a second phospholipid selected from the group consisting of: DSPC, DOPC, DPPC, HSPC, and SM. Provided in some aspect of the disclosure isa nucleic acid lipid nanoparticle (LNP) composition comprising: a mRNA having at least 90% identity (e.g. 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more) with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44; a KC3 ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 23.5 - 43.5 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC or HSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and a PEG-containing conjugated lipid in a total amount of 0.5 mol% to 2.5 mol% of the total lipid content of the LNP composition. In some embodiments, lipid nanoparticle (LNP) compositions comprising an ionizable cationic lipid compositions are provided. In some embodiments, lipid nanoparticle (LNP) compositions comprising an ionizable cationic lipid are provided. In some embodiments, the LNP composition comprises a mRNA nucleic acid. In some embodiments, a lipid nanoparticle (LNP) composition further comprises the PS lipid in a total amount of 2.5-10 mol% of the total lipid in the composition of the LNP. In some embodiments, a lipid nanoparticle (LNP) composition further comprises a PS lipid selected from the group consisting of: DSPS (L- isomer) and DPPS. In some embodiments, a lipid nanoparticle (LNP) composition comprises a conjugated lipid in a total amount of 0.5-2.0 mol% of the total lipid content of the LNP composition. In some embodiments, a lipid nanoparticle (LNP) composition comprises the conjugated lipid in a total amount of less than 2 mol% of the total lipid content of the LNP composition, and the conjugated lipid is PEG-DMG. In some embodiments, a lipid nanoparticle (LNP) composition comprises a nucleic acid; an ionizable lipid disclosed herein; a sterol; one or more phospholipids comprising a phosphatidylserine (PS) lipid; and optionally further comprising a conjugated lipid. In some 93 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 embodiments, a lipid nanoparticle (LNP) composition comprises a mRNA nucleic acid; an ionizable lipid disclosed herein; cholesterol; one or more phospholipids selected from the group consisting of: SM, DSPC, HSPC, DPPC and DOPC; and a PS lipid selected from the group consisting of: DPPS and DSPS; and optionally further comprising a conjugated lipid comprising PEG. In some embodiments, a nucleic acid lipid nanoparticle (LNP) composition comprises: a nucleic acid; an ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; a sterol in a total amount of 25-45 mol% of the total lipid content of the LNP composition; and one or more phospholipids in a total amount of phospholipids of 5-25 mol% of the total lipid content of the LNP composition, and comprising a phosphatidylserine (PS) in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; and optionally further comprising a conjugated lipid in a total amount of 0.5 – 2.5 mol% of the total lipid content of the LNP composition. In an embodiment, the LNP comprises a ratio of ionizable lipid to phospholipid of about 50:1 to about 1:1 (e.g., 40:1, 32:3, 6:1, 7:1, 5:1, 24:5, 26:5, 10:3, 15:2, 16:7, 18:1, 3:1, 3:2, or 1:1). In an embodiment, the LNP comprises a ratio of ionizable lipid to phospholipid of about 15:2. In an embodiment, the LNP comprises a ratio of ionizable lipid to phospholipid of about 5:1. In an embodiment, the LNP comprises a ratio of ionizable lipid to a sterol of about 10:1 to about 1:10 (e.g., 9:1, 8:1, 8:7, 7:1, 7:5, 7:3, 6:1, 6:5, 5:1, 5:3, 4:1, 4:3, 3:1, 2:1, 1:1, 1:2, 1:3, 3:4, 1:4, 3:5, 1:5, 4:5, 1:6, 5:6, 7:6, 7:8, or 8:9). In an embodiment, the LNP comprises a ratio of ionizable lipid to an alkylene-containing lipid of about 1:10 to about 10:1 (e.g., 1:9, 1:8, 7:8, 7:1, 7:5, 7:3, 6:1, 6:5, 5:1, 5:3, 4:1, 4:3, 3:1, 2:1, 1:1, 1:2, 1:3, 3:4, 1:4, 3:5, 1:5, 4:5, 1:6, 5:6, 7:6, 7:8, or 8:9). In an embodiment, the LNP comprises a ratio of phospholipid to an alkylene- containing lipid of about 10:1 to about 1:10 (e.g., 9:1, 8:1, 8:7, 7:1, 7:5, 7:3, 6:1, 6:5, 5:1, 5:3, 4:1, 4:3, 3:1, 2:1, 1:1, 1:2, 1:3, 3:4, 1:4, 3:5, 1:5, 4:5, 1:6, 5:6, 7:6, 7:8, or 8:9). In an embodiment, the LNP comprises a ratio of a sterol to an alkylene-containing lipid of about 50:1 to about 1:1 (e.g., 40:1, 32:3, 6:1, 7:1, 5:1, 24:1, 22:1, 20:1, 22:5, 24:5, 26:5, 10:3, 15:2, 16:7, 18:1, 3:1, 3:2, or 1:1). In an embodiment, a LNP (e.g., described herein) comprises two of an ionizable lipid, a phospholipid, a sterol, and an alkylene glycol-containing lipid (e.g., PEG-containing lipid). In another embodiment, a LNP (e.g., described herein) comprises three of an ionizable lipid, a phospholipid, a sterol, and an alkylene glycol-containing lipid (e.g., PEG-containing lipid). In 94 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 an embodiment LNP (e.g., described herein) comprises each of an ionizable lipid, a phospholipid, a sterol, and an alkylene glycol-containing lipid (e.g., PEG-containing lipid). In some embodiments, an LNP described herein has a diameter between 5 and 500 nm, e.g., between 10 and 400 nm, 20 and 350 nm, 25 and 325 nm, 30 and 300 nm, 50 and 250 nm, 60 and 200 nm, 75 and 190 nm, 80 and 180 nm, 100 and 200 nm, 200 and 300 nm, and 150 and 250 nm. The diameter of an LNP may be determined by any method known in the art, for example, dynamic light scattering, transmission electron microscopy (TEM) or scanning electron microscopy (SEM). In some embodiments, an LNP has a diameter between 50 and 100 nm, between 70 and 100 nm, and between 80 and 100 nm. In an embodiment, an LNP has a diameter of about 90 nm. In some embodiments, an LNP described herein has a diameter greater than about 30 nm. In some embodiments, an LNP has a diameter greater than about 35 nm, about 40 nm, about 45 nm, about 50 nm, about 60 nm, about 70 nm, about 80 nm, about 90 nm, about 100 nm, about 120 nm, about 140 nm, about 160 nm, about 180 nm, about 200 nm, about 225 nm, about 250 nm, about 275 nm or about 300 nm. In an embodiment, an LNP has a diameter greater than about 70 nm. In an embodiment, an LNP has a diameter greater than about 90 nm. In an embodiment, an LNP has a diameter greater than about 180 nm. In some embodiments, a plurality of LNPs described herein has an average diameter ranging from about 40 nm to about 180 nm. In some embodiments, a plurality of LNPs described herein has an average diameter from about 50 nm to about 150 nm. In some embodiments, a plurality of LNPs described herein has an average diameter from about 50 nm to about 120 nm. In some embodiments, a plurality of LNPs described herein has an average diameter from about 60 nm to about 120 nm. In some embodiments, a plurality of LNPs has an average diameter of about 40 nm, about 45 nm, about 50 nm, about 60 nm, about 70 nm, about 80 nm, about 90 nm, about 100 nm, about 120 nm, about 140 nm, about 160 nm, about 180 nm. In some embodiments, a nanoparticle or plurality of nanoparticles described herein has an average neutral to negative surface charge of less than -100 mv, for example, less than -90 mv, -80 mv, -70 mv, -60 mv, -50 mv, -40 mv, -30 mv, and -20 mv. In some embodiments, a nanoparticle or plurality of nanoparticles has a neutral to negative surface charge of between - 100 mv and 100 mv, between -75 mv to 0, or between -50 mv and -10 mv. In some embodiments, at least 5% (e.g., at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99%) of the nanoparticles of a plurality of nanoparticles have an 95 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 average neutral to negative surface charge of less than -100 mv. In some embodiments, a nanoparticle or plurality of nanoparticles has an average surface charge of between -20 mv to +20, between -10 mv and +10 mv, or between -5 mv and +5 mv at pH 7.4. LNPs that are neutral in charge have improved pharmacokinetics and biological performance compared to cationic LNPs. In some embodiments, the LNP composition comprises: (a) a nucleic acid; (b) an ionizable cationic lipid comprising a KC3 ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; (c) one or more phospholipids in a total amount of 5-20 mol% of the total lipid content of the LNP composition; (d) one or more anionic phospholipids in a total amount of 2-8 mol% of the total lipid content of the LNP composition; (e) a conjugated lipid in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition; and (f) a sterol such cholesterol (e.g., in an amount providing the remainder of the LNP composition). In some aspects, the one or more anionic phospholipids is a phosphatidylserine (PS) or phosphatidylglycerol (PG). In some aspects, the one or more anionic phospholipids is selected from the group consisting of: dipalmitoylphosphatidyl-L- serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidylglycerol (DSPG), and dipalmitoyphosphatidylglycerol (DPPG). In some aspects, the one or more phospholipids comprises distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof. In some aspects, the conjugated lipid is PEG(2000)-dimyristoylglycerol (PEG-DMG). In some aspects, the sterol is cholesterol. In some aspects, the ionizable cationic lipid comprises 3-((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1- amine (KC3-OA). In some aspects, the ionizable cationic lipid further comprises a KC4 ionizable cationic lipid, such as 4-rac-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N- dimethylbutan-1-amine (AKG-KC4-OA). In some aspects, the LNP composition consists of: 48 mol% KC3-OA; 5 mol% DPPS or DSPG; 5-10 mol% DSPC or HSPC; 1.5 mol% PEG- DMG; and cholesterol. In some aspects, the LNP composition consists of: 48 mol% KC3-OA; 5 mol% DPPS or DSPG; 5 mol% DSPC or HSPC; 1.5 mol% PEG-DMG; and 40.5 mol% cholesterol. In some aspects, the LNP composition consists of: 48 mol% KC3-OA; 5 mol% DPPS or DSPG; 10 mol% DSPC or HSPC; 1.5 mol% PEG-DMG; and 35.5 mol% cholesterol. In some embodiments, the LNP is a nucleic acid lipid nanoparticle vaccine composition comprising: a mRNA nucleic acid with a N / P ratio of 4 to 7; an ionizable cationic lipid in a 96 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25-40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and PEG-DMG in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises the ionizable cationic lipid in a total amount of 46-65 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition comprises the PS in a total amount of about 5 mol% of the total lipid in the composition. In some embodiments, the LNP composition comprises the conjugated lipid in a total amount of about 1.5 mol% of the total lipid content of the LNP composition. In some embodiments, the conjugated lipid is PEG-DMG; and the PS lipid is selected from the group consisting of: DSPS (L-isomer) and DPPS. In some embodiments, the ionizable cationic lipid is one or more compounds selected from the group consisting of: KC3-OA, KC3-PA, KC3-C17 (C8:1), and KC3-C15 (C8:1). In some embodiments, the ionizable cationic lipid is KC3-PA. In some embodiments, the ionizable cationic lipid is KC3-OA. In some embodiments, the ionizable cationic lipid is KC3-C17 (C8:1). Some embodiments relate to the use of a (L-Serine) PS lipid in combination with an ionizable cationic lipid described herein in the LNP for targeting of the LNP to dendritic cells. In some embodiments, the LNP comprises mRNA. In some embodiments, the LNP further comprises cholesterol. In some embodiments, the total amount of (L-Serine) PS lipid in the LNP is 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP further comprises one or more additional phospholipids including DSPC. In some embodiments, the LNP further comprises a conjugated lipid. In some embodiments, the LNP comprises: a mRNA nucleic acid with a N / P ratio of 3 to 8; a KC3-PA or KC3-C17 (C8:1) ionizable cationic lipid (ICL), in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25- 40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and a 97 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 conjugated lipid in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. In some embodiments, the ICL is KC3-PA. In some embodiments, the ICL is KC3-C17 (C8:1). In some embodiments, the composition comprises an anionic phospholipid selected from the group consisting of: DSPG and DPPG, in a total amount of 2.5-7.5% of the total lipid content of the LNP composition. In some embodiments, the composition comprises DSPG anionic phospholipid in a total amount of 2.5-7.5% of the total lipid content of the LNP composition. In some embodiments, the composition comprises DPPG anionic phospholipid in a total amount of 2.5-7.5% of the total lipid content of the LNP composition. In some embodiments, the LNP further comprises one or more additional phospholipids including DSPC. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid; a KC3 ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 23.5 - 43.5 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC or HSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and a PEG- containing conjugated lipid in a total amount of 0.5 mol% to 2.5 mol% of the total lipid content of the LNP composition. In some embodiments, the nucleic acid is mRNA. In some embodiments, the N / P ratio is 3 to 8. In some embodiments, the KC3 ionizable cationic lipid is selected from the group consisting of: KC3-OA, KC3-PA, KC3-C17 (8:1), and KC3-C15 (C8:1). In some embodiments, the KC3 ionizable cationic lipid is KC3-OA. In some embodiments, the KC3 ionizable cationic lipid is KC3-PA. In some embodiments, the KC3 ionizable cationic lipid is KC3-C17(C8:1). In some embodiments, the KC3 ionizable cationic lipid is KC3-C15(C8:1). In some embodiments, the conjugated lipid is PEG-DMG or PEG-DSG. In some embodiments, the composition comprises the PEG-containing conjugated lipid in a total amount of 0.5 –2.0 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the KC3 ionizable cationic lipid in a total amount of 48 mol% of the total lipid content of the LNP composition. 98 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the composition comprises DSPC and DSPS in a total amount of 10 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 5 % DSPC or HSPC in a total amount of 5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises PEG-DMG in a total of 1.5 mol % of the total lipid content of the LNP composition. In some embodiments, the composition comprises cholesterol in a total amount of 40.5 mol % cholesterol of the total lipid content of the LNP composition. In some embodiments, the composition comprises the DSPC phospholipid in a total amount of 10 mol% of the total lipid content of the LNP composition. In some embodiments, the PEG-containing conjugated lipid is PEG2000-DMG. In some embodiments, the composition comprises the cholesterol in a total amount of 23.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the cholesterol in a total amount of 33.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the cholesterol in a total amount of 38.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the cholesterol in a total amount of 40.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the cholesterol in a total amount of 42.7 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the cholesterol in a total amount of 43.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the cholesterol in a total amount of 33.5-43.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the KC3 ionizable cationic lipid in a total amount of 45-55 mol% of the total lipid content of the LNP composition. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a mRNA nucleic acid; a KC3 ionizable cationic lipid selected from the group consisting of: KC3-OA, KC3-PA, KC3-C17 (8:1), and KC3-C15 (C8:1), in a total amount of 45-55 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 33.5-43.5 mol% of the total lipid content of the LNP composition; a (L-Serine) DPPS lipid in a total amount of 5 mol% of the total lipid content of the LNP composition; DSPC or HSPC phospholipid in a total amount of 5 mol% of the total lipid content of the LNP composition; and a PEG-DMG conjugated lipid in a total amount of 1.5 mol% of the total lipid content of the LNP composition. 99 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Aspects of the disclosure relate to a lipid nanoparticle (LNP) composition comprising a KC3 ionizable cationic lipid, a (L-Serine) PS lipid, cholesterol, one or more phospholipids comprising at least one anionic phospholipid, and a conjugated lipid, wherein the LNP is obtained by a process comprising the step of dissolving a sodium or ammonium salt of the anionic phospholipid. In some embodiments, the composition comprises a nucleic acid. In some embodiments, the nucleic acid is mRNA. In some embodiments, the composition is a vaccine. In some embodiments, the composition is an injectable vaccine composition. In some embodiments, the total amount of phospholipids in the composition is 5-25 mol% of the total lipid content of the LNP composition, and the total amount of the phosphatidylserine (PS) is 2.5-10 mol% of the total lipid content of the LNP composition; and the total amount of the conjugated lipid in the composition is a total amount of 0.5 – 2.5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 46-54 mol% of the KC3 ionizable cationic lipid, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 45 mol% of the KC3 ionizable cationic lipid, 42.7 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 50 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% phospholipid concentration; wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% 100 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 phospholipid concentration; wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration; wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises 46.5 mol% of the KC3 ionizable cationic lipid, 42 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. In some embodiments, the composition further comprises a total of 5 mol% DSPC or HSPC of the total lipid content of the LNP composition. In some embodiments, the composition further comprises a total of 1.5 mol% PEG-DMG of the total lipid content of the LNP composition. In some embodiments, the composition comprises a total of 10 mol% of DSPC / DPPC phospholipid of the total lipid content of the LNP composition. Aspects of the disclosure relate to a phosphatidylserine salt selected from the group consisting of DSPS sodium, DPPS sodium, DSPS ammonium and DPPS ammonium. Aspects of the disclosure relate to the use of a DSPS-Na salt or a DPPS-NH4+salt in the preparation of a LNP comprising a (L-Serine) PS lipid, a sterol, a conjugated lipid, a phospholipid for targeting the LNP to dendritic cells. Aspects of the disclosure relate to a solution comprising ethanol and DSPS or DPPS, the solution obtained by a process comprising the step of dissolving a phosphatidylserine salt in ethanol, wherein the phosphatidylserine salt is selected from the group consisting of DSPS sodium, DPPS sodium, DSPS ammonium and DPPS ammonium. (V) Use of Liposomal Nanoparticle (LNP) Compositions Administration of a vaccine for inducing a second immune response may provide MHC class II - presented epitopes that are capable of eliciting a CD4+ helper T cell response against cells expressing antigens from which the MHC presented epitopes are derived. Alternatively or additionally, administration of a vaccine for inducing a second immune response may provide MHC class I - presented epitopes that are capable of eliciting a CD8+ T cell response against cells expressing antigens from which the MHC presented epitopes are derived. Furthermore, administration of a vaccine for inducing a second immune response may provide one or more neo - epitopes (including known neo epitopes) as well as one or more 101 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 epitopes not containing cancer specific somatic mutations but being expressed by cancer cells and preferably inducing an immune response against cancer cells, preferably a cancer specific immune response. In some embodiments, administration of a vaccine for inducing a second immune response provides neo - epitopes that are MHC class Il - presented epitopes and / or are capable of eliciting a CD4+ helper T cell response against cells expressing antigens from which the MHC presented epitopes are derived as well as epitopes not containing cancer - specific somatic mutations that are MHC class I - presented epitopes and / or are capable of eliciting a CD8+ T cell response against cells expressing antigens from which the MHC presented epitopes are derived. In some embodiments, the epitopes do not contain cancer - specific somatic mutations. In some aspects, a method of delivering a nucleic acid to a cell is provided, the method comprising: contacting the cell with a composition comprising an LNP comprising a ligand (also referred herein as targeting ligand) having a binding specificity for a cell surface antigen, wherein the binding of the ligand to the antigen induces the internalization of the ligand. In some embodiments, the targeting ligand can be, but is not limited to, an internalizing antibody, or a fragment thereof, a small molecule conjugates or gylcoconjugates. In some embodiments, the binding of the targeting ligand to a specific cell surface antigen induces the internalization of the LNP with the targeting ligand attached by a cell expressing at least 100,000 or at least 1,000,000 molecules of the antigen when contacted and incubated with the cell under internalizing conditions. Other aspects of the disclosure relate to the use of these ionizable lipids or lipidic nanoparticles compositions comprising ionizable lipids in vaccines for the prevention of infectious diseases. In some embodiments, the compositions described herein can be used to prevent infections related to tuberculosis. In some embodiments, the vaccine is used for the prevention mycobacterium infections. Some embodiments relate to an injectable pharmaceutical vaccine composition comprising a composition of the present disclosure. In some embodiments, the vaccine can be used for the prevention of tuberculosis, nontuberculous mycobacteria (NTM), nontuberculosis lung disease, leprosy, mycobacterium avium- intracellulare, mycobacterium kansasii, mycobacterium marinum, mycobacterium ulcerans, mycobacterium chelonae, mycobacterium fortuitum, or mycobacterium abscessus. In some embodiments, the bacterial infection is Mycobacterium tuberculosis infection. In some embodiments, the bacterial infection is a form of nontuberculosis mycobacterium. 102 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Disclosed herein are methods for preventing mycobacteria infection, such as Mycobacterium tuberculosis. Additional mycobacteria include, but are not limited to, Mycobacterium avium complex, Mycobacterium leprae, Mycobacterium gordonae, Mycobacterium abscessus, Mycobacterium abscessus, Mycobacterium mucogenicum, and Mycobacterium. Other aspects of the disclosure relate to a method of preventing a bacterial or viral infection, the method comprising administering to a subject in need thereof an effective amount of the composition provided herein to elicit an immune response. Some embodiments provide methods of vaccinating a subject in need thereof, the method comprising administering the composition comprising a nucleic acid encoding an antigenic protein. Aspects of the disclosure relate to a method of preventing a bacterial or viral infection, the method comprising administering to a subject in need thereof an effective amount of the composition provided herein to elicit an immune response. Aspects of the disclosure provide methods of vaccinating a subject comprising administering to the subject a single dosage of the compositions described herein comprising a nucleic acid (e.g. mRNA) encoding a polypeptide in an effective amount to vaccinate the subject. In some embodiments, the nucleic acid is formulated within a cationic lipidic nanoparticle. In some embodiments, the lipidic nanoparticle composition is administered as a single injection. In some embodiments, the bacterial infection is Mycobacterium tuberculosis infection. In some embodiments, the lipidic nanoparticle is administered parenterally. “Parenteral” as used herein in the context of administration means modes of administration other than enteral and topical administration, usually by injection, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal, epidural and intrasternal injection and infusion. The phrases “parenteral administration” and “administered parenterally” as used herein refer to modes of administration other than enteral (i.e., via the digestive tract) and topical administration, usually by injection or infusion, and includes, without limitation, intravenous, intramuscular, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, inhalation, subcapsular, subarachnoid, respiratory mucosal, intraspinal, epidural and intrasternal injection 103 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 and infusion. Intravenous injection and infusion are often (but not exclusively) used for liposomal drug administration. Dosage regimens can be adjusted to provide the optimum desired response (e.g., a therapeutic response). For example, one or more doses may be administered over time or the dose may be proportionally reduced or increased as indicated by the exigencies of the therapeutic situation. In some embodiments, the dose comprises between 0.01 to 5 mg / kg of nucleic acid. In some embodiments, the dose comprises between 0.01 to 5 mg / kg of mRNA. In some embodiments, the dose comprises between 0.01 to 3 mg / kg of nucleic acid. In some embodiments, the dose comprises between 0.01 to 3 mg / kg of mRNA. In some embodiments, the dose comprises between 0.01 to 1 mg / kg of nucleic acid. In some embodiments, the dose comprises between 0.01 to 1 mg / kg of mRNA. In some embodiments, the dose comprises between 0.01 to 0.5 mg / kg of nucleic acid. In some embodiments, the dose comprises between 0.01 to 0.5 mg / kg of mRNA. In some embodiments, the dose comprises between 0.01 to 1 mg / kg of mRNA. In some embodiments, the dose comprises between 0.01 to 0.1 mg / kg of nucleic acid. In some embodiments, the dose comprises between 0.01 to 0.05 mg / kg of mRNA. In some embodiments, the dose comprises between 0.01 to 0.1 mg / kg of nucleic acid. In some embodiments, the dose comprises between 0.01 to 0.05 mg / kg of mRNA. The dosage of the compounds and / or of their pharmaceutically acceptable salts or the LNPs comprising the compounds and / or of their pharmaceutically acceptable salts may vary within wide limits and should naturally be adjusted, in each particular case, to the individual conditions and to the pathogenic agent to be controlled. In general, administration to a patient is by intradermal injection is possible. However, injection may also be carried out intranodally into a lymph node (Maloy et al. (2001), Proc Natl Acad Sci USA 98:3299-3033). The resulting cells present the complex of interest and are recognized by autologous cytotoxic T lymphocytes which then propagate. In some embodiments, the composition is administered by inhalation. In some embodiments, the composition is formulated as nasal spray, and / or aerosol. Actual dosage levels of the active agents in the pharmaceutical compositions disclosed herein may be varied so as to obtain an amount of the active agent which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. 104 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the composition is administered subcutaneously, intramuscularly, or intradermally. In some embodiments, the lipidic nanoparticle is administered parenterally. In some embodiments, the lipidic nanoparticle composition is administered as part of a single injection. In some embodiments the lipid nanoparticle is administered in multiple injections spaced in time to optimize the T-cell response to them. In some embodiments the lipid nanoparticle is administered intramuscularly (IM). In some embodiments, the LNP compositions target dendritic cells. Dendritic cells (DCs) are specialized antigen-presenting cells that play a central role in initiating and regulating adaptive immunity. Owing to their potent antigen (Ag) presentation capacity and ability to generate distinct T-cell responses, efficient and specific delivery of Ags to DCs is the cornerstone for generating Ag-specific effector and memory cells against tumors or pathogens. Dendritic cells can be generated from human blood monocytes by adding granulocyte- macrophage colony-stimulating factor (GM-CSF), IL-4, and IFN-gamma to differentiate monocyte-derived DC in vitro. Cells in culture exhibit both dendritic and veiled morphologies, the former being adherent, and the latter suspended. Phenotypically, they are CD1a- / dim, CD11a+, CD11b++, CD11c+, CD14dim / -, CD16a- / dim, CD18+, CD32dim / -, CD33+, CD40+, CD45R0+, CD50+, CD54+, CD64- / dim, CD68+, CD71+, CD80dim, CD86+ / ++, MHC class I++ / , HLA-DR++ / , HLA-DP+, and HLA-DQ (Geiseler et al. Dev Immunol.1998;6(1-2):25- 39). Alternatively, human primary blood dendritic cell lines have been developed and are commercially available from Creative Biolabs. The main types of professional antigen - presenting cells are dendritic cells, which have the broadest range of antigen presentation, and are probably the most important antigen - presenting cells, macrophages, B - cells, and certain activated epithelial cells. Dendritic cells (DCs) are leukocyte populations that present antigens captured in peripheral tissues to T cells via both MHC class II and I antigen presentation pathways. It is well known that dendritic cells are potent inducers of immune responses and the activation of these cells is a critical step for the induction of antitumoral immunity. Dendritic cells are conveniently categorized as “immature” and “mature” cells, which can be used as a simple way to discriminate between two well characterized phenotypes. However, this nomenclature should not be construed to exclude all possible intermediate stages of differentiation. Immature dendritic cells are characterized as antigen presenting cells with a high capacity for antigen uptake and processing, which correlates with 105 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 the high expression of Fcγ receptor and mannose receptor. The mature phenotype is typically characterized by a lower expression of these markers, but a high expression of cell surface molecules responsible for T cell activation such as class I and class II MHC, adhesion molecules (e.g. CD54 and CD11) and costimulatory molecules (e.g., CD40 , CD80 , CD86 and 4 - 1 BB). Dendritic cell maturation is referred to as the status of dendritic cell activation at which such antigen - presenting dendritic cells lead to T cell priming, while presentation by immature dendritic cells results in tolerance. Dendritic cell maturation is chiefly caused by biomolecules with microbial features detected by innate receptors (bacterial DNA, viral RNA, endotoxin, etc), pro-inflammatory cytokines (TNF, IL - 1, IFNs), ligation of CD40 on the dendritic cell surface by CD4OL, and substances released from cells undergoing stressful cell death. The dendritic cells can be derived by culturing bone marrow cells in vitro with cytokines, such as granulocyte - macrophage colony - stimulating factor (GM CSF) and tumor necrosis factor alpha. Non - professional antigen-presenting cells do not constitutively express the MHC class II proteins required for interaction with naive T cells; these are expressed only upon stimulation of the non - professional antigen-presenting cells by certain cytokines such as IFNγ. "Antigen presenting cells” can be loaded with MHC class I presented peptides by transducing the cells with nucleic acid, preferably mRNA, encoding a peptide or polypeptide comprising the peptide to be presented, e.g. a nucleic acid encoding the antigen. In some embodiments, a pharmaceutical composition comprising a gene delivery vehicle that targets a dendritic or other antigen presenting cell is administered to a patient, resulting in transfection that occurs in vivo. In some embodiments, a method of eliciting a T cell response in a host is provided, comprising administering to the host a nucleic acid sequence disclosed herein or a nucleic acid having at least 90% sequence identity or complementarity to a sequence disclosed herein, and / or a sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb), or a polynucleotide sequence having at least 90% identity or complementarity to a sequence disclosed herein and / or a polynucleotide sequence of a Mtb antigen recognized by T cells. In some embodiments, the LNP compositions target CD8+ T-cells. CD8+ T cells can produce IL2, IFN-γ, and TNF, cytokines that are known to have critical functions during mycobacterium tuberculosis infection. Importantly, CD8+ T cells have cytolytic functions to kill mycobacterium tuberculosis -infected cells via granule-mediated function (via perforin, granzymes, and granulysin) or Fas-Fas ligand interaction to induce apoptosis. In humans, CD8+ T cell can produce granulysin, which can kill mycobacterium tuberculosis directly. 106 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Therefore, it is anticipated that antigen generating mRNA LNPs delivered to DC will stimulate a CD8+ T cell response to fight against mycobacterium tuberculosis infection. CD8+ T cells are able to recognize M. tuberculosis specific antigens (as peptides) presented by classical and non-classical MHC molecules. Classically restricted CD8+ T cells have been identified that recognize antigens presented by antigen presenting cells in the context of classical MHC Ia (HLA-A, -B, -C) molecules. Non-classically restricted CD8+ T cells include those CD8+ T cells that are capable of recognizing Mg antigen in the context of HLA- E molecules (non-MHC 1a), glycolipids associated with group 1 CD1 molecules and MHC I- related molecules (MR1) such as mucosal associated invariant T cells (MAIT). Finally, γδ T cells represent a separate population of CD8 (and CD4) T cells that have both innate and adaptive functions in response to mycobacterium tuberculosis infection. CD8+ T cells have been shown to play direct functions in response to mycobacterium tuberculosis infection but they also play important roles in orchestrating many different functions in the overall host immune response (e.g., interaction to provide optimal CD4 T cell function) In some embodiments, LNPs are added to cultured human dendritic cells at an appropriate concentration, (e.g. 1-5 µg / mL mRNA). After some time to allow for cellular uptake and antigen expression, human T cells (HemaCare) can be added, and the cell culture media is sampled at various times for INF-γ by Elisa (R&D Systems, DIF50C). Alternatively, the cells can be analyzed by flow cytometry for CD8+ marker or intracellular INFγ production (PE anti-human IFN- γ antibody, Biolegend). In some embodiments, LNPs are administered into a subject at a dose of about 0.01 to about 5 mg / kg mRNA by any route of administration known in the art and / or outlined above. According to some embodiments, a proportion of LNPs are taken up DC cells, while most will accumulate in the liver and spleen. The DC cells can express the antigenic peptide, process it for MHC I presentation and travel to the lymph node for presentation to naïve T cells inducing an education of memory T-cells towards the antigen. In some embodiments, the comprises a nucleic acid; the ionizable lipid described herein, a sterol; one or more phospholipids comprising a phosphatidylserine (PS) lipid; and optionally a conjugated lipid. In some embodiments, the nucleic acid is mRNA. In some embodiments, the sterol is cholesterol. In some embodiments, the one or more phospholipids consist of: one or more phospholipids selected from the group consisting of: SM, DSPC, HSPC, DPPC and DOPC; and a PS lipid selected from the group consisting of: DPPS, and DSPS. In some embodiments, the one or more phospholipids consist of: DSPC; and one or more PS lipids 107 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 selected from the group consisting of (L-Serine) DPPS and (L-Serine) DSPS. In some embodiments, the composition comprises the PS lipid in a total amount of 2.5-10 mol% of the total lipid in the composition. In some embodiments, the conjugated lipid comprises PEG. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid; an ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; a sterol in a total amount of 25-45 mol% of the total lipid content of the LNP composition; and one or more phospholipids in a total amount of phospholipids of 5-25 mol% of the total lipid content of the LNP composition, and comprising a phosphatidylserine (PS) in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; and optionally a conjugated lipid in a total amount of 0.5 – 2.5 mol% of the total lipid content of the LNP composition. In some embodiments, the nucleic acid is mRNA. In some embodiments, the sterol is cholesterol. In some embodiments, the one or more phospholipids consist of: DSPC and a L-serine PS. In some embodiments, the composition comprises the PS in a total amount of 2.5-7.5 mol% of the total lipid in the composition. In some embodiments, the conjugated lipid comprises PEG. In some embodiments, conjugated lipid is PEG-DMG. In some embodiments, the LNP comprises the conjugated lipid in a total amount of 0.5-2.0 mol% of the total lipid content of the LNP composition. In some embodiments, the conjugated lipid in a total amount of less than 2 mol% of the total lipid content of the LNP composition. In some embodiments, the nucleic acid is a mRNA, the ionizable cationic lipid in a total amount of 45-55 mol% of the total lipid content of the LNP composition; a sterol is cholesterol in a total amount of 35-45 mol% of the total lipid content of the LNP composition; the total amount of phospholipid of 7-15 mol% of the total lipid content of the LNP composition; the one or more phospholipids consist of DSPC and the PS lipid is one or more lipids selected from the group consisting of the L-serine configuration of DPPS and DSPS; and the total amount of the PS lipid is about 5 mol% of the total lipid content of the LNP composition. In some embodiments, the composition comprises the PS lipid in a total amount selected from 1.25 mol%, 2.5 mol%, 5 mol%, 7.5 mol%, and 10 mol% of the total lipid content of the LNP composition. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid, wherein the nucleic acid is mRNA; an ionizable cationic lipid, the ionizable cationic lipid in a total amount of 45-55 mol% of the total lipid content of the LNP 108 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 composition; a sterol, wherein the sterol is cholesterol in a total amount of 35-45 mol% of the total lipid content of the LNP composition; one or more phospholipids, wherein the one or more phospholipids in a total amount of phospholipids of 10 mol% of the total lipid content of the LNP composition, and comprising a phosphatidylserine (PS) in a total amount of 3-9 mol% of the total lipid content of the LNP composition; and a conjugated lipid, the conjugated lipid in a total amount of 0.5 – 2.0 mol% of the total lipid content of the LNP composition. In some embodiments, the one or more phospholipid is selected from the group consisting of: DSPS (L-isomer), DPPS (L-isomer), DMPS (L-isomer), DOPS (L-isomer), and DSPS (D- isomer). In some embodiments, the conjugated lipid is PEG-DMG; and the PS lipid is selected from the group consisting of: DSPS (L-isomer) and DPPS. In some embodiments, the ionizable cationic lipid is one or more compounds selected from the group consisting of: KC3-OA, KC3-PA, KC3-C17 (8:1), and KC3-C15 (C8:1). In some embodiments, the ionizable cationic lipid is KC3-PA. In some embodiments, the ionizable cationic lipid is KC3-OA. In some embodiments, the ionizable cationic lipid is KC3-C17 (C8:1). In some embodiments, the LNP comprises a nucleic acid; an ionizable cationic lipid in a total amount of 50 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 38.5 mol% of the total lipid content of the LNP composition; one or more phospholipids in a total amount of 7-15 mol% of the total lipid content of the LNP composition, and comprising a phosphatidylserine (PS) lipid in a total amount of 3-9 mol% of the total lipid content of the LNP composition; and a PEG-containing lipid in a total amount of 0.5 –2.0 mol% of the total lipid content of the LNP composition. In some embodiments, the phospholipids consist of one or more phospholipids selected from the group consisting of: DSPC, DOPC, DPPC, HSPC, and SM. In some embodiments, the PS lipid is one or more L-serine lipids selected from the group consisting of DPPS and DSPS. In some embodiments, the one or more phospholipids comprise at least two (L-Serine) PS lipids having mismatched acyl chain lengths. In some embodiments, the phospholipids are DSPC and DPPS. In some embodiments, the DSPC and DPPS are each present in the LNP at a total amount of 5 mol% each, based on the total lipid content of the LNP composition. 109 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid, ionizable cationic lipid KC3-PA or KC3-OA, and a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the nucleic acid is mRNA, the PS lipid is (L-Serine) DSPS, (L- Serine) DPPS, or a mixture thereof, and the LNP composition further comprises cholesterol and a second phospholipid selected from the group consisting of: DSPC, DPPC, HSPC, and SM. In some embodiments, the LNP composition further comprises 0.5-2.0 mol% PEG-DMG or PEG-DSG, based on the total lipid content in the LNP composition. In some embodiments, the ionizable cationic lipid is KC3-PA. In some embodiments, the ionizable cationic lipid KC3-OA. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid, a KC3-C17 (C8:1) ionizable cationic lipid; and a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP composition has a N / P ratio 4 to 7. In some embodiments, the composition has a N / P ratio of 5 to 6. In some embodiments, the composition has a N / P ratio of 5.3. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid, ionizable cationic lipid KC3-PA, and a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the nucleic acid is mRNA, the PS lipid is (L-Serine) DSPS, (L- Serine) DPPS, or a mixture thereof, and the LNP composition further comprises cholesterol and a second phospholipid selected from the group consisting of: DSPC, DOPC, DPPC, HSPC, and SM. In some embodiments, the LNP composition further comprises 0.5-2.0 mol% PEG-DMG or PEG-DSG, based on the total lipid content in the LNP composition. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) composition comprising: a nucleic acid, an ionizable cationic lipid selected from KC3-C17 (C8:1); and a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the N / P ratio is 4 to 7. In some embodiments, the N / P ratio is 5 to 6. In some embodiments, the N / P ratio is 3. In some embodiments, the N / P ratio is 7. In some embodiments, the nucleic acid is an mRNA encoding SARS-CoV-2 spike protein. 110 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) vaccine composition comprising: a mRNA nucleic acid with a N / P ratio of 4 to 7; an KC3-PA ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25-40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and PEG-DMG in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) vaccine composition comprising: a mRNA nucleic acid with a N / P ratio of 3 to 8; a KC3-C17 (C8:1) ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25-40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and PEG-DMG in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) vaccine composition comprising: a mRNA nucleic acid with a N / P ratio of 4 to 7; a KC3-C15 (C8:1) ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25-40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and PEG-DMG in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. Aspects of the disclosure relate to a nucleic acid lipid nanoparticle (LNP) vaccine composition comprising: a mRNA nucleic acid with a N / P ratio of 3 to 8; a KC3-C18 ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25-40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and PEG-DMG in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. 111 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the nucleic acid is a mRNA encoding a concatenated sequence of T-cell epitopes. In some embodiments, the mRNA encodes a concatenated sequence of MHC- II epitopes. In some embodiments, the mRNA encodes a concatenated sequence of MHC-I epitopes. Aspects of the disclosure relate to the use of a (L-Serine) PS lipid in combination with an ionizable cationic lipid described herein in the LNP for targeting of the LNP to dendritic cells. In some embodiments, the LNP comprises mRNA. In some embodiments, the LNP further comprises cholesterol. In some embodiments, the total amount of (L-Serine) PS lipid in the LNP is 2.5-10 mol% of the total lipid content of the LNP composition. In some embodiments, the LNP further comprises one or more additional phospholipids including DSPC. In some embodiments, the LNP further comprises a conjugated lipid. In some embodiments, the LNP comprises: a mRNA nucleic acid with a N / P ratio of 3 to 8; a KC3-PA or KC3-C17 (C8:1) ionizable cationic lipid (ICL), in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 25-40 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and a conjugated lipid in a total amount of 0-2.5 mol% of the total lipid content of the LNP composition. In some embodiments, the ICL is KC3- PA. In some embodiments, the ICL is KC3-C17 (C8:1). In some embodiments, the composition comprises an anionic lipid selected from the group consisting of: phosphatidylglycerol (PG), phosphatidic acid (PA), N-glutaryl- phosphatidylethanolamine (N-Glu-PE), N-succinyl-phosphatidylethanolamine (N-Suc-PE), and cardiolipin. Distearoylphosphatidylglycerol (DSPG), dipalmitoyphosphatidylglycerol (DPPG), N-succinyl-distearoylphosphatidylethanolamine (N-Suc-DSPE), N-glutaryl- distearoylphosphatidylethanolamine (N-glu-DSPE), distearoylphosphatidic acid (DSPA), and cardiolipin. In some embodiments, the composition comprises an anionic targeting phospholipid other than phosphatidyl-L-serine. In some embodiments, the composition comprises an anionic phospholipid selected from the group consisting of: DSPG and DPPG. In some embodiments, the composition comprises an anionic phospholipid selected from the group consisting of: N-Glu-DSPE and N-Suc-DSPE. In some embodiments, the composition comprises a DSPA anionic phospholipid. 112 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 In some embodiments, the composition comprises a Cardiolipin anionic phospholipid. (VI) Additional Embodiments The following additional embodiments are provided for illustrative purposes. Embodiment 1: A lipid nanoparticle (LNP) composition comprising a KC3 ionizable cationic lipid, cholesterol, one or more phospholipids comprising at least one anionic phospholipid, a conjugated lipid and one or more nucleic acid sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb). Embodiment 2: The composition of embodiment 1, wherein the composition comprises: 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration; wherein each mol% refers to the mol% of the total lipid content of the LNP composition. Embodiment 3: The composition of embodiment 1 or embodiment 2, wherein the one or more nucleic acids is a mRNA. Embodiment 4: The composition of embodiment 3, wherein the mRNA encodes a concatenated sequence of T-cell epitopes present in Mtb. Embodiment 5: The composition of embodiment 4, wherein the concatenated sequence of T-cell epitopes comprise an amino acid sequence set forth in SEQ ID NOs: 1-17, 106-137, 138-203. Embodiment 6: The composition of embodiment 4, wherein the concatenated sequence of T-cell epitopes comprises an amino acid sequence with at least 90% sequence identity with amino acid sequence set forth in SEQ ID NOs: 1-17, 45-85, 106-137, 138-203. Embodiment 7: The composition of embodiment 5 or embodiment 6, wherein the concatenated nucleotide sequence comprises two or more sequences encoding for peptides or proteins that can elicit MHC class II-restricted CD4 T cell responses. Embodiment 8: The composition of embodiment 7, wherein the two or more MHC class II epitopes selected from the group: EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), and EsxH / TB10.4 (Rv0288). 113 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Embodiment 9: The composition of embodiment 7, wherein the two or more MHC class II epitopes comprises peptides or proteins from EsxV (Rv3619), EsxW (Rv3620c), EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), ^Mtb39A (Rv1196), Ag85B (Rv1886c), and EsxH / TB10.4 (Rv0288) (SEQ ID NOs.1-7). Embodiment 10: The composition of embodiment 5 or embodiment 6 wherein the concatenated nucleic acid-encoded sequence includes the seven proteins in and order N- terminal to C-terminal selected from: EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), EsxH / TB10.4 (Rv0288), ^Ag85B (Rv1886c), ^Mtb39A (Rv1196), EsxW (Rv3620c), and EsxV (Rv3619), or EsxB / CFP10 (Rv3874), EsxA / ESAT-6 (Rv3875), EsxW (Rv3620c), EsxV (Rv3619), EsxH / TB10.4 (Rv0288), ^Ag85B (Rv1886c), and ^Mtb39A (Rv1196), or EsxB / CFP10 (Rv3874), ^Mtb39A (Rv1196), EsxA / ESAT-6 (Rv3875), EsxW (Rv3620c), EsxH / TB10.4 (Rv0288), EsxV (Rv3619), and ^Ag85B (Rv1886c). (SEQ ID NOs.18, 19, and 20) Embodiment 11: The composition of any one of embodiments 7-10, the composition comprising a nucleic acid encoding for 5 or more non-overlapping CD4 T cell epitopes in the form of peptides, wherein optionally the peptides are from 12 to 50 amino acids long. Embodiment 12: The composition of embodiment 5 or embodiment 6, wherein the concatenated nucleic acid-encoded sequence optionally comprises 10 selected MHC-II epitopes comprising: AQIYQAVSAQAAAIH (SEQ ID NO.9), PSPSMGRDIKVQFQS (SEQ ID NO.10), GINTIPIAINEAEYV (SEQ ID NO.11), AAFQGAHARFVAAAA (SEQ ID NO. 12), AGWLAFFRDLVARGL (SEQ ID NO. 13), ASIIRLVGAVLAEQH (SEQ ID NO. 14), MSFVTTQPEALAAAA (SEQ ID NO. 8), MHVSFVMAYPEMLAA (SEQ ID NO. 15), AYGSFVRTVSLPVGA (SEQ ID NO.16), and LENDNQLLYNYPGAL (SEQ ID NO.17). Embodiment 13: The composition of embodiment 7, wherein the concatenated nucleic acid-encoded sequence includes GPGPG (SEQ ID NO: 228) linker sequences between each of the concatenated epitopes. Embodiment 14: The composition of any one of embodiments 3-13, wherein the one or more nucleic acid comprises a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. 114 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Embodiment 15: The composition of any one of embodiments 3-13, wherein the one or more nucleic acid comprises a nucleic acid sequence having at least 90% identity, at least 95%, or at least 99% with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. Embodiment 16: The composition of any one of embodiments 3-13, wherein the concatenated nucleic acid-encoded sequence includes an N-terminal and C-terminal signal peptide selected from Sec / MITD, Lamp1, HLA-Drα, or tPA. Embodiment 17: The composition of any one of embodiments 3-16, wherein the one or more nucleic acid comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1-methylpseudouridine. Embodiment 18: The composition of any one of embodiments 3-16, wherein the one or more nucleic acid comprises a 5’ untranslated region (UTR) and 3’ UTR, polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. Embodiment 19: The composition of any one of embodiments 3-16, wherein the one or more nucleic acid is an mRNA having a sequence selected from SEQ ID NOs: 34, 36, 38, 40, 42, and 44. Embodiment 20: The composition of any one of embodiments 3-16, wherein the one or more nucleic acid is an mRNA and wherein the amino acid sequence encoded by the mRNA is selected from SEQ ID NOs: 33, 35, 37, 39, 41, 43, 86-105, and 207-210. Embodiment 21: The composition of embodiment 5 or embodiment 6, wherein the nucleic acid-encoded concatenated sequence comprises two or more MHC class I epitopes selected from SEQ ID NOs: 106-137 and 138-203. Embodiment 22: The composition of embodiment 5 or embodiment 6, wherein the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes found in mycobacterium tuberculosis, depleted of epitopes found in BCG, and selected from SEQ ID NOs: 86-95. Embodiment 23: The composition of embodiment 5 or embodiment 6, wherein the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86- 105. Embodiment 24: The composition of any one of embodiments 1-23, wherein the cationic lipid is KC3-OA, KC3-PA, KC3-01, KC3-C17 (8:1), or KC3-C15 (C8:1). 115 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 Embodiment 25: The composition of any one of embodiments 1-24, wherein the LNP comprises the conjugated lipid in a total amount of less than 2 mol% of the total lipid content of the LNP composition. Embodiment 26: The composition of any one of embodiments 1-24, wherein the ionizable cationic lipid in a total amount of 45-55 mol% of the total lipid content of the LNP composition; wherein cholesterol is in a total amount of 35-45 mol% of the total lipid content of the LNP composition; wherein the total amount of the one more phospholipid is 7-15 mol% of the total lipid content of the LNP composition; wherein the one or more phospholipids consist of DSPC and the PS lipid is one or more lipids selected from the group consisting of the L-serine configuration of DPPS and DSPS; and the total amount of the PS lipid is about 5 mol% of the total lipid content of the LNP composition. Embodiment 27: The composition of any one of embodiments 1-24, wherein the conjugated lipid is PEG-DMG; and wherein the PS lipid is selected from the group consisting of: DSPS (L-isomer) and DPPS. Embodiment 28: The composition of any one of embodiments 1-27, wherein the ionizable cationic lipid is KC3-OA. Embodiment 29: The composition of any one of embodiments 1-28, wherein the LNP composition has a N / P ratio of 4 to 7. Embodiment 30: The composition of any one of embodiments 1-28, wherein the LNP composition has a N / P ratio of 5 to 6. Embodiment 31: A nucleic acid lipid nanoparticle (LNP) composition comprising: a mRNA having at least 90% identity with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44, ionizable cationic lipid KC3-PA, and a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition. Embodiment 32: The composition of embodiment 31, wherein the PS lipid is (L-Serine) DSPS, (L-Serine) DPPS, or a mixture thereof, and the LNP composition further comprises cholesterol and a second phospholipid selected from the group consisting of: DSPC, DOPC, DPPC, HSPC, and SM. Embodiment 33: A nucleic acid lipid nanoparticle (LNP) composition comprising: 116 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 a mRNA having at least 90% identity with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44; a KC3 ionizable cationic lipid in a total amount of 40-65 mol% of the total lipid content of the LNP composition; cholesterol in a total amount of 23.5 - 43.5 mol% of the total lipid content of the LNP composition; a (L-Serine) PS lipid in a total amount of 2.5-10 mol% of the total lipid content of the LNP composition; DSPC or HSPC phospholipid in a total amount of 5-25 mol% of the total lipid content of the LNP composition; and a PEG-containing conjugated lipid in a total amount of 0.5 mol% to 2.5 mol% of the total lipid content of the LNP composition. Embodiment 34: The composition of embodiment 1 comprising an ionizable lipid having the chemical structure: , 2, 3 or 4; R2and R3are each independently methyl; and n is an integer equal to 2 or 3. Embodiment 35: The composition of embodiment 34, wherein n is 3. Embodiment 36: The composition of any of the preceding embodiments, wherein the composition is a vaccine. Embodiment 37: A pharmaceutical composition comprising the lipid nanoparticle of any one of the precenting embodiments, and a pharmaceutically acceptable carrier. Embodiment 38: A nucleic acid encoding a concatenated amino acid sequence of T-cell epitopes present in mycobacterium tuberculosis, the nucleic acid having at least 90% identity with a nucleic acid sequence set forth in SEQ ID NOs: 34, 36, 38, 40, 42, and 44. Additional Embodiments include the numbered embodiments listed below: 117 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 1. A lipid nanoparticle (LNP) composition consisting of: a. a messenger ribonucleic acid (mRNA) encoding one or more Mycobacterium tuberculosis (Mtb) proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, Ag85B / Rv1886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288; b. an ionizable cationic lipid comprising a ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the mRNA, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; c. one or more phospholipids selected from the group consisting of distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), and dipalmitoylphosphatidylcholine (DPPC), in a total amount of 10- 18 mol% of the total lipid content of the LNP composition; d. one or more anionic phospholipids selected from the group consisting of dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidylglycerol (DSPG), and dipalmitoyphosphatidylglycerol (DPPG) in a total amount of 2-8 mol% of the total lipid content of the LNP composition; e. PEG(2000)-dimyristoylglycerol (PEG-DMG) in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition; and f. cholesterol. 2. A lipid nanoparticle (LNP) composition comprising: a. a nucleic acid comprising a nucleic acid sequence encoding a T cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by T cells; b. an ionizable cationic lipid comprising a KC3 ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; c. one or more phospholipids in a total amount of 5-20 mol% of the total lipid content of the LNP composition; 118 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 d. one or more anionic phospholipids in a total amount of 2-8 mol% of the total lipid content of the LNP composition; e. a conjugated lipid in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition; and f. a sterol. 3. The composition of embodiment 2, wherein the one or more anionic phospholipids is a phosphatidylserine (PS) or phosphatidylglycerol (PG). 4. The composition of embodiment 3, wherein the one or more anionic phospholipids is selected from the group consisting of: dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidylglycerol (DSPG), and dipalmitoyphosphatidylglycerol (DPPG). 5. The composition of embodiment 2, wherein the one or more phospholipids comprises distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof. 6. The composition of embodiment 5, wherein the conjugated lipid is PEG(2000)- dimyristoylglycerol (PEG-DMG). 7. The composition of embodiment 6, wherein the sterol is cholesterol. 8. The composition of embodiment 7, wherein the ionizable cationic lipid comprises 3- ((S)-2,2-di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylpropan-1-amine (KC3-OA). 9. The composition of embodiment 8, wherein the ionizable cationic lipid further comprises a KC4 ionizable cationic lipid. 10. The composition of embodiment 9, wherein the ionizable cationic lipid is 4-rac-2,2- di((Z)-octadec-9-en-1-yl)-1,3-dioxolan-4-yl)-N,N-dimethylbutan-1-amine (AKG- KC4-OA). 11. The composition of embodiment 7, wherein the composition consists of: a. 48 mol% KC3-OA; b. 5 mol% DPPS or DSPG; c. 5-10 mol% DSPC or HSPC; d. 1.5 mol% PEG-DMG; and e. 35.5-40.5 mol% cholesterol. 119 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 12. The composition of any one of embodiments 2-11, wherein the nucleic acid sequence is mRNA encoding a concatenated sequence of T-cell epitopes present in Mtb or a Mtb antigen recognized by T Cells. 13. The composition of embodiment 12, wherein the mRNA encodes one or more Mtb proteins selected from the group consisting of CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / Rv0125, Mtb39A / Rv1196, and Ag85B / Rv1886c. 14. The composition of embodiment 12, wherein the mRNA comprises one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:6, SEQ ID NO:7, and SEQ ID NO:220. 15. The composition of embodiment 12, wherein the mRNA encodes one or more Mtb proteins selected from the group consisting of EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rv1195, PPE30 / Rv1802, PPE40 / Rv2356c and TB10.4 / Rv0288. 16. The composition of embodiment 12, wherein the mRNA comprises one or more nucleic acid sequences selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 31, SEQ ID NO: 221, and SEQ ID NO: 222. 17. The composition of any one of embodiments 2-11, wherein the nucleic acid sequence encodes a concatenated sequence, wherein the concatenated nucleic acid-encoded sequence includes an N-terminal and C-terminal signal peptide selected from Sec / MITD, Lamp1, HLA-Drα, or tPA. 18. The composition of any one of embodiments 2-11, wherein the nucleic acid comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1- methylpseudouridine. 19. The composition of any one of embodiments 2-11, wherein nucleic acid comprises a 5’ untranslated region (UTR) and 3’ UTR, polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap. 20. The composition of any one of embodiments 2-11, wherein the nucleic acid is an mRNA having a sequence selected from SEQ ID NOs: 34, 36, 38, 40, 42, 44, 224 and 226. 21. The composition of embodiment 20, wherein the nucleic acid comprises a chemically modified mRNA, wherein the chemically modified mRNA comprises N1- methylpseudouridine. 120 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 22. The composition of any one of embodiments 2-11, wherein the nucleic acid is an mRNA encoding an amino acid sequence selected from SEQ ID NOs: 33, 35, 37, 39, 41, 43, 86-105, 207-210, 223 and 225. 23. The composition of any one of embodiments 2-11, wherein the nucleic acid sequence encodes a concatenated sequence, wherein the nucleic acid-encoded concatenated sequence comprises two or more MHC class I epitopes selected from SEQ ID NOs: 106-137 and 138-203. 24. The composition of any one of embodiments 2-11, wherein the nucleic acid sequence encodes a concatenated sequence, wherein the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes found in mycobacterium tuberculosis, depleted of epitopes found in BCG, and selected from SEQ ID NOs: 86- 95. 25. The composition of any one of embodiments 2-11, wherein the nucleic acid sequence encodes a concatenated sequence, wherein the nucleic acid-encoded concatenated sequence includes two or more MHC class I epitopes that are ordered to minimize junctional neoepitope generation, and selected from SEQ ID NOs: 86-105 26. The composition of any one of embodiments 2-7, wherein the ionizable cationic lipid is KC3-OA, KC3-PA, KC3-01, KC3-C17 (8:1), or KC3-C15 (C8:1). 27. A lipid nanoparticle (LNP) composition comprising: a. a nucleic acid comprising a nucleic acid sequence encoding a polypeptide that is a T cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by T cells and having at least 90% sequence identity to a nucleic acid sequence disclosed herein; b. an ionizable cationic lipid comprising a KC3 ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the nucleic acid, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; c. one or more phospholipids in a total amount of 5-20 mol% of the total lipid content of the LNP composition; d. one or more anionic phospholipids in a total amount of 2-8 mol% of the total lipid content of the LNP composition; e. a conjugated lipid in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition; and 121 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 f. a sterol. 28. The composition of embodiment 27, wherein the nucleic acid is a messenger ribonucleic acid (mRNA) comprising a polynucleotide sequence encoding a polypeptide that is a T cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by T cells, wherein the mRNA polynucleotide sequence has at least 90% identity to a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 220, or has at least 90% identity to a polynucleotide sequence selected from the group consisting of: SEQ ID NO: 1, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 31, SEQ ID NO: 221, and SEQ ID NO: 222. 29. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises cholesterol in a total amount of 35.5-42.7 mol% of total lipid in the LNP composition. 30. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 31. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 32. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 45 mol% of the KC3 ionizable cationic lipid, 42.7 mol% cholesterol, and 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 33. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 50 mol% of the KC3 ionizable cationic lipid, 38.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 34. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, and a total of 10 mol% phospholipid 122 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 35. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 48 mol% of the KC3 ionizable cationic lipid, 40.5 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, 5 mol% DSPC or DPPC; and a total of 10 mol% phospholipid concentration, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 36. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 46.5 mol% of the KC3 ionizable cationic lipid, 42 mol% cholesterol, 5 mol% (L-Serine) DPPS lipid, wherein each mol% refers to the mol% of the total lipid content of the LNP composition. 37. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 15 mol% total phospholipid and 35.5 mol% cholesterol. 38. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 10 mol% total phospholipid and 40.5 mol% cholesterol. 39. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 40.5 mol% cholesterol, 5% anionic lipid (DPPS) and 5% PC (DSPC or DPPC) and a total of 10 mol% phospholipid concentration. 40. The composition of embodiment 1 or any one of embodiments 7-10, wherein the composition comprises 48 mol% cationic ionizable lipid, 5 mol% PC (DPPC), 5 mol% anionic lipid (DPPS), 40.5 mol% cholesterol, 1.5 mol% conjugated lipid (PEG-DMG). 41. The composition of any one of embodiments 1-40, wherein the composition is a vaccine. 42. A pharmaceutical composition comprising the LNP composition of any one of embodiments 1-40, and a pharmaceutically acceptable carrier. 43. A method comprising administering to a subject in need thereof the composition of embodiment 41 or embodiment 42 in an amount effective to induce in the subject an immune response against mycobacterium tuberculosis infection. Additional embodiments include the numerical embodiments listed below: 1. A lipid nanoparticle (LNP) composition consisting of: a. a messenger ribonucleic acid (mRNA) encoding one or more Mycobacterium tuberculosis (Mtb) proteins; 123 ACTIVE 712238933v1 Attorney Docket No.191016-011101 / PCT Electronically Filed: June 20, 2025 b. an ionizable cationic lipid comprising a ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the mRNA, the ionizable cationic lipid present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; c. one or more phospholipids selected from the group consisting of distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), and dipalmitoylphosphatidylcholine (DPPC), in a total amount of 10- 18 mol% of the total lipid content of the LNP composition; d. one or more anionic phospholipids selected from the group consisting of dipalmitoylphosphatidyl-L-serine (DPPS), or distearoylphosphatidyl-L-serine (DSPS), distearoylphosphatidyl...

Claims

AMENDED CLAIMS received by the International Bureau on 18 DEC 2025 (18.12.2025)1. An immunogenic liposomal nanoparticle (LNP) composition stimulating both a CD4+ and CD8+ T-cell response, the LNP composition comprising a single synthetic concatenated mRNA polynucleotide encapsulated into lipidic nanoparticles, wherein the mRNA polynucleotide encodes three or more Mycobacterium tuberculosis (Mtb) antigens comprising Esx / A and Esx W / V proteins in an order preventing heterodimer formation of the Esx / A and Esx W / V proteins, wherein the Mtb antigens (a) are recognized by both CD4 T-cells and CD8 T-cells and (b) are not Ag85A or Ag85b proteins, Early Secretory Antigenic Target 6 (ESAT-6) or Culture Filtrate Protein 10 (CFP-10); and wherein the lipidic nanoparticles comprise an ionizable cationic lipid; one or more phospholipids (PL) including an anionic phospholipid; cholesterol; and a PEG-conjugated lipid.

2. An immunogenic liposomal nanoparticle (LNP) composition stimulating both a CD4+ and CD8+ T-cell response to one or more Mycobacterium tuberculosis (Mtb) antigens, the composition comprising: a. a concatenated mRNA polynucleotide sequence(s) encoding (i) a signal peptide and (ii) a transmembrane and cytoplasmic domain, each of (i) and (ii) operably linked to open reading frame(s) (ORF) of each mRNA sequence encoding multiple Mtb antigens that are immunogenic for stimulating the CD4+ T-cell response or the CD8+ T-cell response; and b. the mRNA polynucleotide encapsulated into lipidic nanoparticles comprising an ionizable cationic lipid; one or more phospholipids (PL) including an anionic phospholipid; cholesterol; and a PEG-conjugated lipid, wherein the concatenated mRNA polynucleotide sequence comprises an ORF encoding multiple Mtb antigens each separated by a G / P (gly-pro) spacer, G / S (gly-ser) spacer, a NFL spacer or an AAY spacer mRNA sequence, wherein the ORF encodes both a CD4 T- cell epitope and a CD 8 T-cell epitope from Mycobacterium tuberculosis (Mtb), or a Mtb antigen recognized by both CD4 T-cells and CD8 T-cells, and wherein the concatenated mRNA polynucleotide sequence encodes Esx / A and Esx W / V Mtb antigens in an order preventing heterodimer formation of the Esx / A and Esx W / V proteins.2593. The composition of claim 2, wherein (a) the mRNA polynucleotide sequence further comprises a 5’ untranslated region (UTR) and 3’ UTR, a polyA tail of about 80 to about 140 nucleotides in length, and (i) a 5’ enzymatic or (ii) a 5’ clean cap; and (b) the composition comprises the ionizable cationic lipid at a N / P ratio of 3 to 7 relative to the mRNA.

4. The composition of claim 3, wherein the mRNA is a chemically modified mRNA, wherein the chemically modified mRNA comprises N1 -methylpseudouridine.

5. The composition of claim 4, wherein the Mtb antigens are selected from the group consisting of CFP10 / Rv3874, Mtb39A / Rvl l96, ESAT-6 / Rv3875, EsxW / Rv3620c, TB10.4 / Rv0288, EsxV / Rv3619c, and Ag85B / Rvl886c.

6. The composition of claim 5, wherein the ORF encodes the Mtb antigens CFP10 / Rv3874, Mtb39A / Rvl 196, ESAT-6 / Rv3875, EsxW / Rv3620c, TB10.4 / Rv0288, EsxV / Rv3619c, and Ag85B / Rvl886c.

7. The composition of any one of claims 1-6, wherein the composition comprises: a. the ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the mRNA, wherein the ionizable cationic lipid is present in the LNP composition in a total amount of 46-54 mol% of a total lipid content of the LNP composition; b. the one or more phospholipids selected from distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof; c. the anionic phospholipid selected from a phosphatidylserine (PS) or a phosphatidylglycerol (PG) or a combination thereof, in a total amount of 2-8 mol% of the total lipid content of the LNP composition; and d. the PEG-conjugated lipid selected from PEG(2000)-dimyristoylglycerol (PEG- DMG) or PEG(Mol. weight 2,000)-dimyristoylphosphatidylethanolamine (PEG- DMPE), or a combination thereof, in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition.

8. The composition of claim 7, wherein the LNP composition has a ratio of phospholipid (PL) to cholesterol of 0.25 to 1.00.

9. The composition of claim 7, wherein the one or more antigens do not encode a bacilli Calmette-Guerin (BCG) vaccine antigen protein.

10. The composition of claim 7, wherein the concatenated mRNA polynucleotide sequence encodes a signal peptide, wherein the signal peptide is human HLA Class I signal peptide [[is a]] HLA- A signal peptide or a HLA-B (sec) signal peptide comprising the polypeptide of SEQ ID NO: 23 or SEQ ID NO: 24.

11. The composition of claim 10, wherein the mRNA polynucleotide encodes a lysosome- associated membrane protein 1 (LAMP-1) transmembrane and cytoplasmic domain comprising the polypeptide of SEQ ID NO:22 and MITD transmembrane and cytoplasmic domain comprising the polypeptide of SEQ ID NO:25 or SEQ ID NO:26.

12. The composition of claim 11, wherein the mRNA polynucleotide encodes CFP10 / Rv3874, ESAT-6 / Rv3875, Mtb32A / RvO125, Mtb39A / Rvl 196, Ag85B / Rvl886c, EsxW / Rv3620c, EsxV / Rv3619c, PE13 / Rvl l95, PPE30 / Rvl802, PPE40 / Rv2356c and TB10.4 / Rv0288 Mycobacterium tuberculosis (Mtb) proteins, each separated by a spacer polynucleotide sequence13. The composition of claim 12, wherein the polynucleotide sequence encoding the spacer region between the mRNA encoding each Mtb proteins is selected from the group consisting of: a GPGPG spacer polynucleotide sequence, a G / S flexible spacer, a (GGGGS)n spacer where n can be 1 or greater, and a native flexibly linked (NFL) polypeptide spacer.

14. The composition of claim 13, wherein the mRNA polynucleotide encodes the Esx / A and Esx W / V proteins in the relative order from the 5’ to the 3’ direction: EsxA, EsxW, and EsxV.

15. The composition of claim 14, wherein the mRNA polynucleotide encodes the following Mtb antigen proteins in relative order from a 5’ to a 3’ direction: EsxB / CFPIO, AMTB39A, EsxA / ESAT-6, EsxW, EsxV and AAg85b.

16. The composition of claim 15, wherein the mRNA polynucleotide encodes the following Mtb antigen proteins in relative order from a 5’ to a 3’ direction: MTB32A, EsxB / CFPIO, AMTB39A, EsxA / ESAT-6, EsxW, PE13, EsxV and AAg85b.

17. An immunogenic pharmaceutical composition comprising a synthetic polynucleotide sequence for stimulating both a CD4+ and CD8+ T-cell response, the synthetic polynucleotide sequence comprising:a. a 5’ cap structure; b. a 5’ untranslated region (UTR); c. an open reading frame (ORF) between the 5 ’ UTR and a 3 ’ UTR, the ORF encoding (a) a lysosome-associated membrane protein 1 (LAMP-1) signal peptide or a human HLA Class I signal peptide and (b) a LAMP-1 or a MHC class I trafficking domain (MITD) transmembrane and cytoplasmic domain, each of (a) and (b) operably linked to an open reading frame (ORF) of the polynucleotide sequence encoding one or more antigens that are immunogenic for stimulating the CD4+ T-cell response and the CD8+ T-cell response; and d. a 3’ UTR and a polyA tail of about 80 to about 140 nucleotides in length, wherein the ORF encodes six or more Mycobacterium tuberculosis (Mtb) antigen proteins, each separated by a spacer polynucleotide sequence, wherein the Mtb antigen proteins are encoded by the ORF in the following relative order from a 5’ to a 3’ direction: EsxB / CFPIO, AMTB39A, EsxA / ESAT -6, EsxW, EsxV and AAg85b, and wherein the ORF sequence further comprises a G / P (gly-pro) spacer, G / S (gly-ser) spacer, a NFL spacer or an AAY spacer sequence between regions encoding each adjacent Mtb antigen protein; and wherein the polynucleotide sequence encodes the Mtb antigen proteins in an order preventing the heterodimer formation of the Esx / A and Esx W / V proteins.

18. The composition of claim 17, wherein the nucleic acid sequence is mRNA.

19. The composition of claim 18, wherein a. the ORF encodes (i) a LAMP-1 signal peptide and a LAMP-1 transmembrane and cytoplasmic domain, or (ii) the nucleic acid encodes a human HLA-A or HLA-B signal peptide and a MITD transmembrane and cytoplasmic domain; b. the mRNA is a chemically modified mRNA, wherein the chemically modified mRNA comprises N1 -methylpseudouridine; and c. the 5’ Cap structure is a 5’ enzymatic Cap or a 5’ clean Cap or a Cap-1 structure;20. The composition of claim 19, wherein the composition is a liposomal nanoparticle (LNP) composition comprising:a. an ionizable cationic lipid at a N / P ratio of 4 to 6 relative to the nucleic acid, wherein the ionizable cationic lipid present in the LNP composition in a total amount of 46- 54 mol% of a total lipid content of the LNP composition; b. one or more phospholipids selected from distearoylphosphatidylcholine (DSPC), hydrogenated soy phosphatidylcholine (HSPC), dipalmitoylphosphatidylcholine (DPPC) or a combination thereof; c. one or more anionic phospholipids selected from a phosphatidylserine (PS) or a phosphatidylglycerol (PG) or a combination thereof, in a total amount of 2-8 mol% of the total lipid content of the LNP composition; and d. a PEG-conjugated lipid is selected from PEG(2000)-dimyristoylglycerol (PEG- DMG) or PEG(Mol. weight 2,000)-dimyristoylphosphatidylethanolamine (PEG- DMPE), or a combination thereof, in a total amount of 1-3.5 mol% of the total lipid content of the LNP composition.

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