Hepatitis b virus mRNA vaccines

Abstract

Provided herein are messenger ribonucleic acid vaccines for Hepatitis B virus infection and related methods of treatment.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority of U.S. Provisional Application No. 63 / 637,562, filed on April 23, 2024, and U.S. Provisional Application No. 63 / 770,489, filed on March 12, 2025, the contents of which are incorporated by reference in their entirety herein. 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 April 21, 2025, is named 45817-0192WOl_SL.xml and is 1,183,730 bytes in size. BACKGROUND Chronic HBV infection (CHB) is a significant global health burden, with over 290 million reported cases by WHO, despite effective prophylactic vaccination. Suppressive treatment with standard of care (SOC) nucleoside analogs (NUC) reduces risk of disease progression but is associated with very low functional cure rates. CHB is characterized by persistent latent reservoir with covalently closed circular DNA (cccDNA) and integrated genome in hepatocytes, which are sources of persistent serum HBsAg production - the main driver of immune exhaustion and tolerance. Recent advances in CHB clinical research suggest that combination of HBsAg suppress!on / interference (RNAi) and immune stimulation (IFNa) can break HBV-induced tolerance and achieve sustained serum HBsAg loss (marker of functional cure), although such functional cure rates are still low. As there is currently no effective treatment for CHB, novel immune stimulation approaches are necessary. SUMMARY CHB infection is a significant global burden, despite effective prophylactic vaccination. CHB is characterized by persistent latent viral reservoirs with covalently closed circular DNA (cccDNA) and integrated genomes in hepatocytes, which are sources of persistent serum HBsAg production, a main driver of immune exhaustion and tolerance. While suppressive treatment with SOC nucleoside analogs (NUCs) has reduced the risk of disease progression, it is associated with very low functional cure rates. Combination therapies of HBsAg suppression / interference (RNAi) and immune stimulation (IFNa) have been proposed for breaking HBV-induced tolerance, however, functional cure rates are still low. New immune stimulation approaches for advancing significant improvements, relative to such prior therapies, in the treatment of CHB are disclosed herein. It has been discovered that mRNA technology has the ability to overcome past therapeutic vaccine failures by eliciting robust Thl -skewed immunity against multiple antigen targets. A primary target of HBV vaccines has been the viral Envelope protein, composed of PreSl, PreS2 and Small domains. Multiple HBV Envelope antigens were designed and tested for immunogenicity as mRNA vaccines (i.e., membrane-bound, sub-viral particles (SVP), nanoparticles). As set forth herein, an immuno-focusing B-T cell approach to the PreSl S2 domain of HBV Envelope has been developed and shown to result in robust multifunctional immunity and potent HBV neutralization. These surprising results were achieved in spite of the presence of abundant viral decoys (non-infective serum HBsAg particles), which have been a limitation of prior HBsAg-focused vaccine approaches. Robust polyfunctional CD4+ and CD8+ T cell responses to Core protein (truncated mutant) and Polymerase protein (activity abolished mutant) were demonstrated. In addition, immunity to at least the three selected HBV antigens (PreSlS2, Core and Polymerase) was achieved with a multivalent mRNA formulation delivered in a lipid nanoparticle. The multivalent mRNA vaccine described herein resulted in (1) multifunctional IFN-y producing CD8 T cells with in vivo cytotoxic activity, (2) antibody-mediated ADCC, and (3) authentic virus neutralization in the presence of abundant viral decoys (non-infective serum HBsAg particles). This novel approach achieved viral clearance of infected hepatocytes via lytic and non-lytic mechanisms, suggesting that the cycles of infection-reinfection were blocked and represents a significant advance in the treatment of CHB. This robust immune stimulation of Thl type cells will overcome limitations of previous and current vaccine candidates and the targeting of the reinfection cycle will prove more effective than targeting specific antigens for reduction or elimination. The mRNA formulation described herein can be used as a monotherapy or in combination with additional treatment modalities. In some embodiments, the combination therapy of the mRNA vaccines disclosed herein with inhibitors of viral replication is administered to a subject having CHB. Such replication inhibitors may include current standard of care therapies known in the art, e.g., nucleoside analogs (NUCs) and capsid assembly modulators. In some embodiments, the combination therapy is performed with known agents that reduce HBsAg. Such HBsAg reduction agents may include siRNA / ASOs orNAP / STOP. In some embodiments, combination therapy is performed with immune stimulators. Such immune stimulators may include art recognized TLR 7 / 8 agonists; checkpoint inhibitors (e.g., anti-PD-1, anti-PD-Ll) and / or cytokines (e.g., IFN-g). In some aspects, the present disclosure described herein relates to a composition comprising a lipid nanoparticle and one or more messenger ribonucleic acids (mRNAs), wherein the one or more mRNAs comprise: a first open reading frame (ORF) comprising a nucleic acid sequence encoding a hepatitis B virus (HBV) envelope protein; a second ORF comprising a nucleic acid sequence encoding an HBV core protein; and a third ORF comprising a nucleic acid sequence encoding an HBV polymerase protein. In some embodiments, the HBV envelope protein includes a PreSl domain and a PreS2 domain. In some embodiments, the PreSl domain and a PreS2 domain further include a lumazine synthase domain. In some embodiments, the HBV core protein includes a Core_149 protein. In some embodiments, the HBV polymerase protein includes a Polymerase8mut. In some embodiments, the composition further includes a fourth ORF including a nucleic acid sequence encoding a Small domain of HBV Envelope protein. In some embodiments, the composition includes three different mRNA molecules, wherein the first ORF is present in a first mRNA molecule, the second ORF is present in a second mRNA molecule, and the third ORF is present on a third mRNA molecule. In some embodiments, the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. In some embodiments, the HBV envelope antigen includes the amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. In some embodiments, the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 30-42. In some embodiments, the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 100. In some embodiments, the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence including a nucleic acid sequence of any one of SEQ ID Nos: 3042. In some embodiments, the first ORF further includes a nucleic acid sequence encoding a signal peptide. In some embodiments, the HBV core protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to the amino acid sequence of any one of SEQIDNOs: 2, 26, or 28. In some embodiments, the HBV core protein includes the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28. In some embodiments, the HBV core protein includes SEQ ID NO:2, SEQ ID NO:28, or a protein that differs from SEQ ID NO:2 or SEQ ID NO:28 by 1-10 amino acids. In some embodiments, the HBV core protein is SEQ ID NO:2 or SEQ ID NO:28. In some embodiments, the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 43, 44 or 46. In some embodiments, the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO: 104. In some embodiments, the ORF encoding the HBV core protein includes a nucleic acid sequence including a nucleic acid sequence of any one of SEQ ID Nos:43, 44 or 46 In some embodiments, the HBV polymerase protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1 or 29. In some embodiments, the HBV polymerase protein comprises a protein that differs from SEQ ID NOs: 1 or 29 by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids. In some embodiments, the different amino acids are present in a terminal protein domain, a spacer domain, a reverse transcriptase domain, and / or a RNase H domain of the HBV polymerase protein. In some embodiments, the HBV polymerase protein is SEQ ID NOs: 1 or 29. In some embodiments, the ORF encoding the HBV core protein comprises nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 47 or 48. In some embodiments, the ORF encoding the HBV core protein comprises nucleic acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to SEQ ID NO:109. In some embodiments, the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos:47 or 48. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:24; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:28; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:29. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:24, wherein the first ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 100; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:28, wherein the second ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 104; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:29, wherein the third ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 109. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:28; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:29. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24, wherein the first ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 100; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:28, wherein the second ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 104; and (ii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:29, wherein the third ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 109. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO :29. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24, wherein the first ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 100; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28, wherein the second ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 104; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29, wherein the third ORF is at least 90%, 95%, or 98% identical, or is 100% identical, to the sequence of SEQ ID NO: 109. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24, wherein the first mRNA comprises the sequence set forth in SEQ ID NO:99; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28, wherein the second mRNA comprises the sequence set forth in SEQ ID NO: 103; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29, wherein the third mRNA comprises the sequence set forth in SEQ ID NO:108. In some embodiments, the composition comprises: (i) a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24, wherein the first mRNA comprises the sequence set forth in SEQ ID NO:412; (ii) a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28, wherein the second mRNA comprises the sequence set forth in SEQ ID NO:413; and (iii) a third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29, wherein the third mRNA comprises the sequence set forth in SEQ ID NOAM. In some embodiments, the mRNA composes a chemical modification. In some embodiments, the lipid nanoparticle comprises an ionizable lipid, a neutral lipid, a sterol, and a PEG-modified lipid. In some embodiments, the lipid nanoparticle comprises 40-55 mol% of the ionizable lipid, 30-45 mol% of the sterol, 5-15 mol% of the neutral lipid, and 1-5 mol% of the PEG-modified lipid. In some embodiments, the ionizable lipid is a lipid of Formula (IL*): R2 FVm / VN R1 Wm'xr3 (IL*) or a salt thereof, wherein: R1 is -OH, -NRn-C4-to cycloalkenyl optionally substituted with one or more oxo or -N(Rn RN ); Rn is H or Ci-6 alkyl; RN is H or Ci-6 alkyl; Rn is H or Ci-6 alkyl; o is 1, 2, 3, or 4; n is 4, 5, 6, 7, or 8; m is 4, 5, 6, 7, or 8; M is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R2; M’ is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R3; R2a R2b .1        .1 R2c R2 is                  or-(Ci-6 alkylene)-(C3-8 cycloalkyl)-Ci-6 alkyl; R2a is -H or Ci-io alkyl; R2b is -H or Ci-io alkyl; R2c is Ci-8 alkyl or C2-8 alkenyl; R3js R3a R3b . R3a is H or Ci-io alkyl; R3b is H or Ci-8 alkyl; and R3c is Ci-io alkyl or C2-8 alkenyl. In some embodiments, the ionizable lipid is Compound (1-25) In some embodiments: the ionizable lipid is Compound (1-25) the neutral lipid is l,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); the sterol is cholesterol; and the PEG-modified lipid is PEG2000-DMG. In some aspects, the disclosure relates to a method of treating HBV disease in a human subject in need thereof by administering to the human subject one or more doses of a composition described herein in an effective amount to produce an immune response to an HBV. In some aspects, the disclosure relates to a method, comprising administering a single dose of the composition to the subject or administering a prime dose and at least one booster dose of the vaccine to the subject. In some embodiments, the HBV disease is chronic HBV disease. In some aspects, the disclosure relates to a method of treating chronic HBV disease in a subject in need thereof, the method comprising administering to the subject one or more doses of a trivalent mRNA vaccine encoding a hepatitis B virus (HBV) envelope protein, a HBV core protein, and a HBV polymerase protein. In some embodiments of the methods described herein, the HBV envelope protein comprises a PreSl domain and a PreS2 domain, optionally linked to a lumazine synthase domain, the HBV core protein includes a Core_149 protein and, and the HBV polymerase protein includes a Polymerase8mut. In some embodiments of the methods described herein, the trivalent mRNA vaccine is sufficient to produce sustained undetectable HBsAg and HBV DNA in a treated subject. In some embodiments of the methods described herein, the trivalent mRNA vaccine is sufficient to produce HBsAg seroconversion in a treated subject. In some embodiments of the methods described herein, the trivalent mRNA vaccine is sufficient to produce a functional cure in in a treated subject. In some embodiments of the methods described herein, the trivalent mRNA vaccine comprises a composition including a lipid nanoparticle and one or more mRNAs, wherein the one or more mRNAs comprise at least a first open reading frame (ORF) comprising a nucleic acid sequence encoding the HBV envelope protein, a second ORF comprising a nucleic acid sequence encoding the HBV core protein, and a third ORF comprising a nucleic acid sequence encoding the HBV polymerase protein. In some embodiments of the methods described herein, the trivalent mRNA vaccine comprises at least three different mRNAs, and wherein the first ORF is present in a first mRNA, the second ORF is present in a second mRNA, and the third ORF is present in a third mRNA. In some embodiments of the methods described herein, the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25. In some embodiments of the methods described herein, the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD4+ cell activity against HBV. In some embodiments of the methods described herein, the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD 8+ cell activity against HBV. In some embodiments of the methods described herein, the method further comprises administering PEG-IFN monotherapy and / or Nucleos(t)ide analogues (NUCs) to the subj ect. In some embodiments of the methods described herein, the method further comprises administering siRNA to the subject. In some embodiments of the methods described herein, the method further comprises administering antisense oligonucleotides (ASOs) to the subject. In some embodiments of the methods described herein, the method further comprises administering PEG-IFN monotherapy and / or nucleos(t)ide analogues (NUCs) to the human subject prior to initiation of treatment with the composition. In some embodiments, the PEG-IFN monotherapy and / or the NUCs are administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. In some embodiments of the methods described herein, the method further comprises administering an siRNA that targets HBV to the human subject prior to initiation of treatment with the composition. In some embodiments, the siRNA that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. In some embodiments of the methods described herein, the method further comprises administering an antisense oligonucleotide that targets HBV to the human subject prior to initiation of treatment with the composition. In some embodiments, the antisense oligonucleotide that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition. In some embodiments of the methods described herein, the method further comprises administering to the human subject at least one immunostimulatory antibody or at least one mRNA encoding at least one immunostimulatory antibody. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-OX40 antibody. In some embodiments, the agonist anti-OX40 antibody is tavolimab, MOXR-0916, PF-04518600, GSK3174998, BMS-986178, INCAGN01949, or 9B12. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-CD27 antibody. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-4-lBB (also known as CD137) antibody. In some embodiments, the at least one immunostimulatory antibody is an agonist anti-GITR antibody. In some embodiments, the at least one immunostimulatory antibody is an antagonist of an immune checkpoint molecule. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-PD-lantibody. In some embodiments, the antagonist anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, sintilimab, retifanlimab, AB122, AMP-224, JTX-4014, BGB-108, BCD-100, BAT1306, LZM009, AK105, HLX10, or TSR-042. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-PD-Ll antibody. In some embodiments, the antagonist anti-PD-Ll antibody is atezolizumab, avelumab, durvalumab, tislelizumab, BMS-935559, MEDI4736, FAZ053, KNO35, CS1001, SHR-1316, CBT-502, A167, STI-A101, CK-301, BGB-A333, MSB-2311, HLX20, orLY3300054. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-CTLA-4 antibody. In some embodiments, the antagonist anti-CTLA-4 antibody is ipilimumab, tremelimumab, AGEN1884, or CP-675,206. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-LAG-3 antibody. In some embodiments, the antagonist anti-LAG-3 antibody is relatlimab, LAG525, or INCAGN2385. In some embodiments, the at least one immunostimulatory antibody is an antagonist anti-PD-L2 antibody. In some aspects, the present disclosure described herein relates to a composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a protein including an amino acid sequence that is SEQ ID NOs: 1-7, 16-26, or 28-29. In some aspects, the present disclosure described herein relates to an HBV antigen comprising an amino acid sequence including at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1-7, 16-26, or 28-29. In one embodiment, the mRNA composition comprises a quadrivalent formulation including a fourth antigen, the Small domain of HBV Envelope. The quadrivalent formulation elicited specific antibodies and Thl-skewed T cell responses against all antigens. Inclusion of the Small antigen provides a potential benefit for patients receiving combination therapy (including NUCs and siRNA / ASO), that may result in reduced expression of PreSlS2 antigens by the infected hepatocytes. In contrast the Small antigen is constitutively expressed by integrated HBV DNA in the host cell. BRIEF DESCRIPTION OF THE DRAWINGS FIGs. 1A-1E are graphs depicting the results of studies involving mice administered mRNA encoding HBV envelope antigens (Genotype A), as described in Table 3, to test the immunogenicity of the vaccine. Antigen specific IgG titers from vaccinated mice directed towards PreSl, PreSl / S2, and small HBV envelope antigens are shown in FIGs. 1A, IB, and IC, respectively. Levels of 50% neutralizing titer (NT50) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope antigens are shown in FIG. ID. The percent (%) signal reduction measured by a competition ELISA assay and correlation with antigen specific IgG titers directed towards PreSl or NTso are shown in FIGs. IE. FIGs. 2A-2B are graphs depicting cell-mediated responses of spleen cells obtained from mice immunized with HBV polymerase protein constructs in Table 4. CD4+ T cell responses after stimulation by CD4+ (15-mer) are shown in FIG. 2A. CD8+ T cell responses after stimulation by CD8+ (15-mer) are shown in FIG. 2B. The y-axis shows the percentage (%) of cells that have a marker selected from, CD107a, IFN-y, TNF-a, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). FIGs. 3A-3B are graphs depicting intracellular cytokine staining of splenocytes obtained from mice immunized with polymerase protein constructs in Table 5. CD4+ T cell responses after stimulation by CD4+ (core peptide pool) are shown in FIG. 3A. CD8+ T cell responses after stimulation by CD8+ (core peptide pool) are shown in FIG. 3B. The y-axis shows the percentage (%) of cells that have a marker selected from, CD107a, IFN-y, TNF-a, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). FIGs. 4A-4H are graphs depicting the results of studies involving mice administered multivalent mRNA formulations encoding a combination of HBV envelope (Genotype A), polymerase (Genotype D), and core antigens (Genotype D), as described in Table 6, to test the immunogenicity of the vaccine. Total HBV specific IgG titers directed towards PreSl / S2 are shown in FIG. 4A, with day 22 and day 43 time points in red and blue, respectively. Levels of 50% neutralizing titer (NT50) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope, polymerase, and core antigens are shown in FIG. 4B. CD8+ T cell responses after stimulation by CD8+ preSl / S2 peptide pool, core peptide pool, and polymerase peptide pool are shown in FIGs. 4C, 4D, and 4E, respectively. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD 107a, IFN-y, TNF-a, or IL-2. CD4+ T cell responses after stimulation by CD4+ preSl / S2 peptide pool, core peptide pool, and polymerase peptide pool is shown in FIGs. 4F, 4G, and 4H, respectively. The y-axis shows the percentage (%) of CD4+ T cells that have a marker selected from, IFN-y, TNF-a, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). FIGs. 5A-5O are graphs depicting the results of studies involving mice administered mRNA encoding HBV envelope antigens (Genotype A), as described in Table 7, to test the durability of the vaccine. Total HBV specific IgG titers directed towards PreSl / S2, or small envelope antigen were measured. Levels of 50% neutralizing titer (NTso) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope antigens are shown in FIG. 5A. CD8+ T cell responses after stimulation by CD8+ preSl / S2 peptide pool, large peptide pool, or small peptide pool are shown in FIGs. 5B-5C, 5F-5G, and 5K-5L, respectively. The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-y, TNF-a, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). CD4+ T cell responses after stimulation by CD4+ preSl / S2 peptide pool, large peptide pool, or small peptide pool are shown in FIGs. 5D-5E, 5H-5I, and 5M-5N, respectively. The y-axis shows the percentage (%) of CD4+ T cells that have a marker selected from, IFN-y, TNF-a, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). Plasma cells directed to small and PreSl / S2 or PreSl are shown in FIGs. 50, and 5J, respectively. FIGs. 6A-6C are graphs depicting the results of studies involving mice administered mRNA encoding a combination of HBV envelope (Genotype A) and HBV core (Genotype D) antigen variants, as described in Table 8, to test the immunogenicity of the vaccine. Total HBV specific IgG titers directed towards PreSl, or core antigens were measured. Levels of 50% neutralizing titer (NT50) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope and core antigens are shown in FIG. 6A. CD8+ T cell responses after stimulation by CD8+ preSl / S2 peptide pool, or core peptide pool are shown in FIG. 6B. The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-y, TNF- a, or IL-2. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). CD4+ T cell responses after stimulation by CD4+ preSl / S2 peptide pool, or core peptide pool are shown in FIG. 6C. The y-axis shows the percentage (%) of CD4+ T cells that have a marker selected from, IFN-y, TNF-a, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). FIGs. 7A-7D are graphs depicting the results of studies involving mice administered mRNA encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes, as indicated in Table 9, to test the immunogenicity of alternative HBV genotypes. Levels of 50% neutralizing titer (NT50) depicting vaccine-induced humoral immunity after the vaccination against HBV with HBV envelope, core, and polymerase proteins are shown in FIG. 7A. CD8+ and CD4+ T cell responses after stimulation by preSl / S2 peptide pool, core peptide pool, and polymerase peptide pool are shown in FIGs. 7B, 7C, and 7D, respectively. The y-axis shows the percentage (%) of CD8+ T cells that have a marker selected from, CD107a, IFN-y, TNF-a, or IL-2 or the percentage (%) of CD4+ T cells that have a marker selected from, IFN-y, TNF-a, IL-2, IL-4, IL-5, or IL-13. The x-axis shows which drug product (DP) were administered and at which dose (pg mRNA). FIG 8 is a bar graph depicting the results of a study in mice administered a trivalent mRNA vaccine encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes and measuring CTL-specific killing. Briefly, antigen presenting cells were pulsed with PreSl (HBV Genotype A), Core (HBV Genotype D), Pol (HBV Genotype D) Peptides and IV dosed in vaccinated mice; after 16 hours percent (%) killing was calculated in relation to PBS-treated mice. FIGs. 9A-9D are graphs depicting the results of studies involving mice administered a quadrivalent mRNA vaccine encoding a combination of HBV envelope, core, and polymerase proteins from different HBV Genotypes demonstrating that antigens are immunogenic in quadrivalent combination. FIG. 9A shows that a quadrivalent vaccine induced comparable anti-PreSl / S2 IgG titer and lower anti-Small IgG compared to the respective monovalent vaccine. FIG. 9B shows that a quadrivalent vaccine induced lower live virus neutralization as compared to Small monovalent vaccine, but higher neutralization compared to PreSlS2_LuS vaccine alone. FIG. 9C shows that antibody induced by quadrivalent vaccine displayed enhanced antibodydependent cellular cytotoxicity (ADCC) as compared to PreSlS2 monovalent vaccine. FIGs. 9D shows that a quadrivalent vaccine elicited robust, yet slightly decreased, CD8+ and CD4+ (Th 1-dominated) T cells to all four antigens as compared to monovalent vaccines. FIG. 10 is a graph depicting PreSlS2-binding antibodies in Cynomolgus macaque serum after immunization with the trivalent mRNA vaccine. Serum samples were collected on Days -7, 14, 42, and 70, and IgG binding titers against the HBV PreSlS2 antigen (genotypes A, B, C, and D, as identified in the panel titles) were measured by ELISA. Each dot represents an individual macaque, with the line and error margins representing the geometric mean with 95% confidence intervals. The y-axis represents the antibody titers specific to PreSl S2 of the respective genotype, with the lower limit of detection (LLOD) indicated by the dashed line. FIG. 11 is a graph depicting live HBV (genotype D) neutralization in Cynomolgus macaque serum after immunization with the trivalent mRNA vaccine. Serum samples were collected on Days -7, 14, 42, and 70, and neutralization titer (NT50) of HBV in vitro infectivity was measured. Each dot represents an individual macaque, with the line and error margins represent the geometric mean with 95% confidence intervals. The y-axis represents the NT50 neutralization titer, with LLOD indicated by the dashed line. FIG. 12 contains graphs depicting CD8+ T cell responses (top panel) and CD4+ T cell responses (bottom panel) after immunization with the trivalent mRNA vaccine. Splenocytes were collected on Day 70 and HBV antigen specific CD8+ T cell and CD4+ T cell responses were measured by intracellular cytokine staining. The bar heights and error margins represent the geometric mean with 95% confidence intervals. Y axis indicates the percentage of the CD8+ T cell or CD4+ T cell population expressing the evaluated CD8+ or CD4+ cytokines in combination with CD69+, with the assay LLOD defined by the dashed line. FIG. 13A is a graph depicting serum HBsAg levels over time in mice with differing starting levels ofHBV viremia (1><10A10, 5xlOA9, lxlOA9, or 5xlOA8 of AAV-HBV viral genome administered) following treatment with the trivalent mRNA vaccine (HBV Tx) or PBS. HBV Tx and PBS treatments were administered on Day 0, Day 14, Day 28, and Day 42 (indicated as Vx in the graph). FIG. 13B is a graph depicting serum HBeAg levels over time in mice with differing starting levels ofHBV viremia (lxl0A10, 5xlOA9, lx!0A9, or 5xlOA8 of AAV-HBV viral genome administered) following treatment with the trivalent mRNA vaccine (HBV Tx) or PBS. HBV Tx and PBS treatments were administered on Day 0, Day 14, Day 28, and Day 42 (indicated as Vx in the graph). FIG. 14 is a graph depicting the percentage ofHBV core antigen-positive cells out of total liver cells in HBV Tx-treated mice or PBS-treated mice in each AAV-HBV dose group (1 x 10Al 0, 5x 10A9, 1 x]0A9, or 5x10A8 of AAV-HBV viral genome administered). FIG. 15 is a graph depicting serum HBsAg levels, serum HBeAg levels, and serum HBV DNA levels over time in mice with differing starting levels ofHBV viremia (1 x 10A10 or 5x 10A9 of AAV-HBV viral genome administered) following treatment with the trivalent mRNA vaccine (HBV Tx), the trivalent mRNA vaccine in combination with an agonistic anti-OX40 antibody and an antagonistic anti-PD-Ll antibody (HBV Tx + aOX40 / PD-Ll), or PBS. HBV Tx and PBS treatments were administered on Day 0, Day 14, Day 28, and Day 42 (indicated as Vx in the graph). aOX40 / PD-Ll treatments were administered on Day 49, Day 52, Day 55, Day 58, and Day 61. FIG. 16 is a graph depicting the percentage ofHBV core antigen-positive cells out of total liver cells in HBV Tx-treated mice, HBV Tx + aOX40 / PD-Ll-treated mice, or PBS-treated mice in each AAV-HBV dose group (lxl0A10, 5xlOA9, lxlOA9, or 5x 10A8 of AAV-HBV viral genome administered). DETAILED DESCRIPTION Developing vaccines for chronic Hepatitis B Virus (HBV) has been a significant challenge due to a variety of complex factors. For example, HBV infection produces excess subviral particles (SVPs) that may act as decoys to escape virus neutralization. Also, patients with chronic HBV infections usually have T cells which are exhausted owing to chronic stimulation leading to weak virus-specific T-cell responses and killing, leading to reduced clearance of virus and recovery from hepatitis. In addition to CD4+ and CD8+ T cells with reduced function, HBV-mediated immune exhaustion is associated with dysfunctional HBS envelope antigen (HBsAg)-specific memory B cells responses. Management of chronic hepatitis B disease involves breaking immune tolerance and eliciting durable, protective immunity. An additional challenge to creating a vaccine effective across different populations is that the prevalent HBV Genotype differs by region. In Asia Pacific, Genotypes B and C are most prevalent. In Europe, Genotypes A and D are most prevalent. In Central / South America Genotypes H and / or F are most prevalent. In Africa, Genotype E is most prevalent. In North America, genotype A is most prevalent. Despite greater than 80% global coverage of highly effective prophylactic vaccination in infants, the World Health Organization estimates over 290 million people are living with chronic HBV. Although current therapeutic HBV therapies (including vaccines) have been found to be relatively safe for chronic HBV patients, they have not been shown to achieve sustained rates of cure in this population. The majority of acute infections by the highly transmissible HBV are cleared spontaneously. Progression to chronic HBV (CHB) is age dependent. Untreated chronic HBV can progress to cirrhosis, liver failure, and / or hepatocellular carcinoma. Both PEG-IFN monotherapy and Nucleos(t)ide analogues (NUCs) are recommended as first-line therapies in treatment-naive chronic HBV patients. Despite these standard of care treatments, the global burden of CHB disease is immense and even incremental improvements in functional cure rate will be of high clinical value. The vaccine compositions and methods of the present disclosure overcome one or more of the foregoing challenges. In one aspect, they increase CD4+ cell activity against HBV, as compared to limited CD4+ immune response in CHB that occurs because of immune exhaustion and / or tolerance. In another aspect, they increase CD8+ cell activity against HBV, as compared to limited CD8+ immune response in CHB that occurs because of immune exhaustion and / or tolerance. In another aspect, they increase B cell activity against HBV, as compared to limited B immune response in CHB that occurs because of immune exhaustion and / or tolerance. In another aspect, vaccine compositions and methods of the present disclosure are useful for treating a patient chronically infected with HBV, who has had an HBV infection that lasts more than six months (chronic infection, CHB), by inducing a functional cure of CHB. A “functional cure” of CHB in a subject is associated with reaching certain clinical markers. In some embodiments, a functional cure in a subject is defined as near undetectable HBV DNA in serum of the subject and near undetectable levels of hepatitis B surface antigen (HBsAg), with or without achieving anti-HBs seroconversion, elimination of detectable HBV RNA, and / or HBcrAg, using standard clinical measurements. Near undetectable HBsAg, in some embodiments refers to <100 lU / mL HBsAg in serum. Nearly undetectable HBV DNA, in some embodiments refers to <20 lU / mL HBV DNA in serum. In some embodiments the functional cure is determined after a defined time period of treatment. In some embodiments a functional cure is determined at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, or at least 11 months following treatment with the vaccine compositions of the disclosure. In some embodiments a functional cure is determined 3-6 months, 4-6 months, 5-6 months, 6-12 months, 7-12 months, 8-12 months, 9-12 months, 10-12 months, or 11-12 months following treatment with the vaccine compositions of the disclosure. In some embodiments a functional cure is determined 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months, or 1, 2, 3, 4, or 5 years following treatment with the vaccine compositions of the disclosure. In one embodiment, functional cure of CHB is measured in the absence of NUC treatment. In an embodiment, the instant vaccine improves the rate of functional cure as compared to NUC treatment (with or without IFNg) thereby allowing patients to forgo lifelong treatment with NUC. In some embodiments before achieving functional cure, the vaccine compositions and methods of the disclosure result in a favorable HBsAg response (FHR). A FHR is defined as HBsAg seroclearance or HBsAg <100 lU / mL at a time period following initiation of treatment. In another aspect, the vaccine compositions and methods of the present disclosure treat a patient chronically infected with HBV by generating functional T cell and B cell immunity in the patient. In another aspect the vaccine compositions and methods establish functional immunity in a patient chronically infected with HBV. In another aspect the vaccine compositions and methods achieves any one or all of the foregoing advantages across multiple genotypes. Hepatitis B Virus Proteins The Hepatitis B Virus (HBV), a member of the Hepadnaviridae family, includes a relaxed, circular, partially double stranded DNA genome that uses an RNA intermediate, pregenomic RNA (pgRNA), and reverse transcriptase for its genome replication. HBV produces 3 different types of virus-related particles as follows i) spherical, double shelled particles, 42-47 nm in diameter, ii) spherical particles, 17-22 nm in diameter, and iii) filaments 20 nm in diameter and of variable length. The 42-47 nm double shelled particles, called Dane particles, are the infectious particles. HBV DNA codes for Envelope (HBsAg), Core (HbcAg), and E (HbeAg), X protein HBx) and Polymerase (Pol). HBV enters hepatocytes by low-affinity binding to heparan sulfate proteoglycans and subsequent high-affinity interaction with sodium taurocholate co-transporting polypeptide (NTCP) receptors. Once internalized, circular viral DNA (rcDNA) is processed by cellular enzymes to stable minichromosomes of covalently closed circular DNA (cccDNA). Linear dsDNA is produced as a result of infection and integrated into the genome. Pregenomic RNA (pgRNA) is reverse transcribed by HBV Pol inside nascent nucleocapsids and the resultant gapped circular dsDNA is encapsidated into new infectious viral particles. The vaccine compositions of the disclosure are mRNA vaccines encoding HBV antigens. As an aspect of the present disclosure is it has been discovered that mRNA vaccines encoding HBV antigens, such as three or four different antigens are useful and effective for treating a patient chronically infected with HBV, and in some embodiments producing a functional cure. In some embodiments the mRNA vaccines encode an HBV envelope antigen, an HBV polymerase antigen and a core antigen. HBV Viral polymerase (Pol) In some embodiments, an HBV protein encoded by an mRNA of the present disclosure comprises an HBV polymerase protein. In some embodiments the HBV polymerase protein comprises a Pol-8mut (D). As described herein, the term, “HBV polymerase protein” refers to a wild-type HBV Viral polymerase (Pol) or a variant thereof. In some embodiments, an HBV polymerase protein “variant thereof’ is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% identical to SEQ ID NO: 1. In some embodiments, the HBV polymerase protein is an HBV genotype A, B, C, D, E, F, G, or H. The HBV polymerase is encoded by Gene P and has four domains with three enzymatic activities. Pol is the central enzyme in genome replication. The four domains are: (1) a terminal protein (TP) domain with protein-priming function; (2) a non-conserved spacer domain with no enzymatic activity; (3) a reverse transcriptase (RT) domain with RNA-dependent DNA polymerase (RT) and DNA-dependent DNA polymerase activity; and (4) a RNase H domain with ribonuclease H activity. In some embodiments, the polymerase protein comprises a wild-type polymerase protein, or a variant thereof. In some embodiments, the wild-type polymerase protein is from HBV genotype D. In some embodiments, the wild-type polymerase protein is encoded by the amino acid sequence of: MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSI PWTHKVGNFTGLYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTV 23 NEKRRLQL1MPARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTL WKAGILYKRETTHS ASFC GSP YSWEQELQHGAESFHQQ S SGIL SRPP VGS S LQSKHSKSRLGLQSQQGHLARRQQGRSWSIRAGIHPTARRPFGVEPSGSG HNTNLASKSASCLYQSPLRKAAYPAVSTFEKHSSSGHAVELHNLPPNSAR SQGERPVFPCWWLQFRNSKPCSDYCLSHIVNLLEDWGPCAEHGEHHIRIP RTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGNYRVSWPKFAVPNL Q SLTNLL S SNL S WLSLD VS A AF YHLPLHP A AMPHL L VGS SGL SRYVARLS SNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFR KIPMGVGL SPFLL AQF T S AIC S VVRRAFPHCL AF S YMDD VVLGAK S VQHL ESLFTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQK IKECFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQ AFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLVMGHQ RMRGTFLAPLPIHTAELLAACFARSRSGANILGTDNSVVLSRKYTSFPWLL GC AANWILRGT SF V Y VP S ALNP ADDP SRGRLGL SRPLLRLPFRPTTGRTSL YADSPSVPSHLPDRVHFASPLHVAWRPP (SEQ ID NO: 1) In some embodiments, the polymerase protein comprises a polymerase protein variant that comprises one or more mutations relative to a naturally occurring HBV polymerase protein. The terms “naturally occurring” and “wild type” are used interchangeably herein to refer to a protein sequence that is comprised of the same type of amino acids found in a protein that is present in nature. A naturally occurring HBV polymerase protein is an HBV polymerase protein that comprises an amino acid sequence that is the same as an amino acid sequence of an HBV polymerase protein that occurs in nature, i.e., which is a naturally occurring isolate. A naturally occurring protein is not genetically (or otherwise) modified to substitute, remove, or add any amino acids relative to the protein found in nature. However, a naturally occurring or wild type protein may be produced by recombinant technology or other synthetic techniques. In some embodiments, the polymerase protein comprises at least one mutation(s) relative to the wild-type polymerase protein encoded by SEQ ID NO: 1. In some embodiments, the polymerase protein comprises at least one mutation(s) and not more than 10 mutations relative to the wild-type polymerase protein encoded by SEQ ID NO: 1. In some embodiments, the polymerase protein comprises 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more mutation(s) relative to the wild-type polymerase protein encoded by SEQ ID NO: 1. In some embodiments, the polymerase protein comprises a Pol-8mut (D), which comprises at least 1, 2, 3, 4, 5, 6, 7 or 8 amino acid mutation(s) at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 63. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a valine (V) at amino acid position 63. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A) at amino acid position 63. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 312. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 312. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 312. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 312. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 323. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 323. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 323. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 323. In some embodiments, the Polymerase protein comprises, relative to the ammo acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 327. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 327. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 327. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 327. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 341. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, a cysteine (C) at amino acid position 341. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 341. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 341. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 703. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, an arginine (R) at amino acid position 703. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 703. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 703. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 777. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, an aspartic acid (D) at amino acid position 777. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 777. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 777. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an amino acid mutation at amino acid position 781. In some embodiments, the Polymerase protein does not comprise, relative to the amino acid sequence of SEQ ID NO: 1, an arginine (R) at amino acid position 781. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an aliphatic amino acid (i.e., alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V)) at amino acid position 781. In some embodiments, the Polymerase protein comprises, relative to the amino acid sequence of SEQ ID NO: 1, an alanine (A), glycine (G), isoleucine (I), leucine (L), proline (P) or valine (V) at amino acid position 781. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 are present in the TP domain, Spacer domain and / or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and / or Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and / or RNAseH domain. In some embodiments, the at least one mutation at ammo acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain and / or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain, Spacer domain and RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain and RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain and RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain, Spacer domain or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain or Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain or RNAseH domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the TP domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the Spacer domain. In some embodiments, the at least one mutation at amino acid positions 63, 312, 323, 327, 341, 703, 777, and 781, relative to SEQ ID NO: 1 is present in the RNAseH domain. In some embodiments, the at least one, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 mutations are present in the polymerase protein. In some embodiments the mutations are selected from Y63A, C312A, C323A, C327A, C341A, R703A, D777A, and R781A. In some embodiments the polymerase protein comprises any combination of one or more of such mutations, such as those depicted in Table 12. In Table 12 an “X” is used to denote the presence of an amino acid mutation at the 5 indicated amino acid position. Table 12: HBV polymerase protein mutant described herein. No. SEQ ID NO: Amino acid position 1-1 111 Y63A 1-2 112 Y63A-C312A 1-3 113 Y63A-C312A-C323A 1-4 114 Y63 A-C312 A-C323A-C327A 1-5 115 Y63A-C312A-C323A-C327A-C341A 1-6 116 Y63A-C312A-C323A-C327A-C341A-R703A 1-7 117 Y63A-C312A-C323A-C327A-C341A-R703A-D777A 1-8 29 Y63A-C312A-C323A-C327A-C341A-R703A-D777A-R781A No. SEQ ID NO: Amino acid position 1-9 118 Y63A- C323A 1-10 119 Y63A- C323A- C327A 1-11 120 Y63A-C323A-C327A-C341A 1-12 121 Y63A-C323A-C327A-C341A-R703A 1-13 122 Y63A-C323A-C327A-C341A-R703A-D777A 1-14 123 Y63A-C323A-C327A-C341A-R703A-D777A-R781A 1-15 124 Y63A-C327A 1-16 125 Y63A-C327A-C341A 1-17 126 Y63A-C327A-C341A-R703A 1-18 127 Y63A-C327A-C341A-R703A-D777A 1-19 128 Y63A-C327A-C341A-R703A-D777A-R781A 1-20 129 Y63A-C312A-C327A-C341A-R703A-D777A-R781A 1-21 130 Y63A-C341A 1-22 131 Y63A-C341A-R703A 1-23 132 Y63A-C341A-R703A-D777A 1-24 133 Y63A-C341A-R703A-D777A-R781A 1-25 134 Y63A-C312A-C341A-R703A-D777A-R781A 1-26 135 Y63A-C312A-C323A-C341A-R703A-D777A-R781A 1-27 136 Y63A-R703A 1-28 137 Y63A-R703A-D777A 1-29 138 Y63A-R703A-D777A-R781A 1-30 139 Y63A-C312A-R703A-D777A-R781A 1-31 140 Y63A-C312A-C323A-R703A-D777A-R781A T-32 141 Y63 A-C312 A-C323 A-C327A-R703 A-D777A-R781A 1-33 142 Y63A-D777A 1-34 143 Y63A-D777A-R781A 1-35 144 Y63A-C312A-D777A-R781A 1-36 145 Y63A-C312A-C323A-D777A-R781A 1-37 146 Y63A-C312A-C323A-C327A-D777A-R781A No. SEQ ID NO: Amino acid position 1-38 147 Y63A-C312A-C323A-C327A-C341A-D777A-R781A 1-39 148 Y63A-R781A 1-40 149 Y63A-C312A-R781A 1-41 150 Y63A-C312A-C323A-R781A 1-42 151 Y63A-C312A-C323A-C327A-R781A 1-43 152 Y63A-C312A-C323A-C327A-C341A-R781A 1-44 153 Y63A-C312A-C323A-C327A-C341A-R703A-R781A II-1 154 C312A II-2 155 C312A-C323A II-3 156 C312A-C323A-C327A II-4 157 C312A-C323A-C327A-C341A II-5 158 C312A-C323A-C327A-C341A-R703A II-6 159 C312A-C323A-C327A-C341A-R703A-D777A II-7 160 C312A-C323A-C327A-C341A-R703A-D777A-R781A II-8 161 C312A-C327A II-9 162 C312A-C327A-C341A 11-10 163 C312A-C327A-C341A-R703A II-11 164 C312A-C327A-C341A-R703A-D777A 11-12 165 C312A-C327A-C341A-R703A-D777A-R781A 11-13 166 C312A-C341A 11-14 167 C312A-C341A-R703A 11-15 168 C312A-C341A-R703A-D777A 11-16 169 C312 A-C341A-R703 A-D777A-R781A 11-17 170 C312A-R703A 11-18 171 C312A-R703A-D777A 11-19 172 C312A-R703A-D777A-R781A 11-20 173 C312A-D777A 11-21 174 C312A-D777A-R781A 11-22 175 C312A-R781A No. SEQ ID NO: Amino acid position III-l 176 C323A III-2 177 C323A-C327A III-3 178 C323A-C327A-C341A III-4 179 C323A-C327A-C341A-R703A III-5 180 C323A-C327A-C341A-R703A-D777A III-6 181 C323A-C327A-C341A-R703A-D777A-R781A III-7 182 C323A-C341A III-8 183 C323A-C341A-R703A III-9 184 C323A-C341A-R703A-D777A III-10 185 C323A-C341A-R703A-D777A-R781A III-11 186 Y63A-C323A-C341A-R703A-D777A-R781A III-12 187 C323A-R703A III-13 188 C323A-R703A-D777A III-14 189 C323A-R703A-D777A-R781A III-15 190 Y63A-C323A-R703A-D777A-R781A III-16 191 C323A-D777A III-17 192 C323A-D777A-R781A III-18 193 Y63A-C323A-D777A-R781A III-19 194 C323A-R781A III-20 195 Y63A-C323A-R781A IV-1 196 C327A TV-2 197 Y63A-C312A-C327A IV-3 198 C327A-C341A-R781A IV-4 199 C327A-C341A-R703A IV-5 200 C327A-C341A-R703A-D777A IV-6 201 C327A-C341A-R703A-D777A-R781A IV-7 202 C327A-R703A IV-8 203 C327A-R703A-D777A 1V-9 204 C327A-R703A-D777A-R781A No. SEQ ID NO: Amino acid position IV-10 205 Y63A-C327A-R703A-D777A-R781A IV-11 206 Y63A-C312A-C327A-R703A-D777A-R781A IV-12 207 C327A-D777A IV-13 208 C327A-D777A-R781A IV-14 209 Y63A-C327A-D777A-R781A IV-15 210 Y63A-C312A-C327A-D777A-R781A IV-16 211 C327A-R781A IV-17 212 Y63A-C327A-R781A IV-18 213 Y63A-C312A-C327A-R781A V-l 214 C341A V-2 215 Y63A-C312A-C341A V-3 216 Y63A-C312A-C323A-C341A V-4 217 C312A-C323A-C341A V-5 218 C327A-C341A V-6 219 C341A-R703A V-7 220 C341A-R703A-D777A V-8 221 C341A-R703A-D777A-R781A V-9 222 C341A-D777A V-10 223 C341A-D777A-R781A V-ll 224 Y63A-C341A-D777A-R781A V-l 2 225 Y63 A-C312 A-C341A-D777A-R781A V-13 226 Y63A-C312A-C323A-C341A-D777A-R781A V-14 227 C341A-R781A V-l 5 228 Y63A-C341A-R781A V-16 229 Y63A-C312A-C341A-R781A V-17 230 Y63A-C312A-C323A-C341A-R781A VI-1 231 R703A VI-2 232 Y63A-C312A-R703A VI-3 233 Y63 A-C312 A-C323 A-R703A No. SEQ ID NO: Amino acid position VI-4 234 Y63A-C312A-C323A-C327A-R703A VI-5 235 C312A-C323A-R703A VI-6 236 C312A-C323 A-C327A-R703 A VI-7 237 C323A-C327A-R703A VI-8 238 R703A-D777A VI-9 239 R703A-D777A-R781A VI-10 240 R703A-R781A VI-11 241 Y63A-R703A-R781A VI-12 242 Y63A-C312A-R703A-R781A VI-13 243 Y63A-C312A-C323A-R703A-R781A VI-14 244 Y63A-C312A-C323A-C327A-R703A-R781A VII-1 245 D777A VII-2 246 Y63A-C312A-D777A VII-3 247 Y63 A-C312A-C323 A-D777A VIM 248 Y63 A-C312 A-C323 A-C327A-D777A VII-5 249 Y63A-C312A-C323A-C327A-C341A-D777A VII-6 250 C312A-C323A-D777A VII-7 251 C312 A-C323 A-C327A-D777A VII-8 252 C312A-C323A-C327A-C341A-D777A VIT-9 253 C323A-C327A-D777A VII-10 254 C323A-C327A-C341A-D777A VII-11 255 C327A-C341A-D777A VII-12 256 D777A-R781A VIII-1 257 R781A VIII-2 258 C312A-C323A-R781A VIII-3 259 C312A-C323A-C327A-R781A V1I1-4 260 C312A-C323A-C327A-C341A-R781A VII-5 261 C312A-C323A-C327A-C341A-R703A-R781A VIII-6 262 C323A-C327A-R781A No. SEQ ID NO: Amino acid position VIII-7 263 C323A-C327A-C341A-R781A VIII-8 264 C323A-C327A-C341A-R703A-R781A VIII-9 265 C327A-C341A-R703A-R781A VIII-10 266 C341A-R703A-R781A IX-1 1 IX-2 267 C327A-R703A-R781A IX-3 268 C327A-C341A-D777A-R781A IX-4 269 C323A-R703A-R781A IX-5 270 C323A-C341A-R781A IX-6 271 C323A-C341A-D777A IX-7 272 C323A-C341A-D777A-R781A IX-8 273 C323A-C341A-R703A-R781A IX-9 274 C323A-C327A-D777A-R781A IX-10 275 C323A-C327A-R703A-R781A IX-11 276 C323A-C327A-R703A-D777A IX-12 277 C323A-C327A-R703A-D777A-R781A IX-13 278 C323A-C327A-C341A-D777A-R781A IX-14 279 C312A-R703A-R781A IX-15 280 C312A-C341A-R781A IX-16 281 C312A-C341A-D777A IX-17 282 C312A-C341A-D777A-R781A IX-18 283 C312A-C341A-R703A-R781A IX-19 284 C312A-C327A-R781A IX-20 285 C312A-C327A-D777A IX-21 286 C312A-C327A-D777A-R781A IX-22 287 C312A-C327A-R703A IX-23 288 C312A-C327A-R703A-R781A IX-24 289 C312A-C327A-R703 A-D777A IX-25 290 C312A-C327A-R703A-D777A-R781A No. SEQ ID NO: Amino acid position IX-26 291 C312A-C327A-C341A-R781A IX-27 292 C312A-C327A-C341A-D777A IX-28 293 C312 A-C327A-C341A-D777A-R781A IX-29 294 C312A-C327A-C341A-R703A-R781A IX-30 295 C312A-C323A-D777A-R781A IX-31 296 C312A-C323A-R703A-R781A IX-32 297 C312A-C323 A-R703 A-D777A IX-33 298 C312A-C323A-R703A-D777A-R781A IX-34 299 C312A-C323A-C341A-R781A IX-35 300 C312A-C323A-C341A-D777A IX-36 301 C312A-C323A-C341A-D777A-R781A IX-37 302 C312A-C323A-C341A-R703A IX-38 303 C312A-C323A-C341A-R703A-R781A IX-39 304 C312A-C323A-C341A-R703A-D777A IX-40 305 C312A-C323A-C341A-R703A-D777A-R781A IX-41 306 C312A-C323A-C327A-D777A-R781A IX-42 307 C312A-C323A-C327A-R703A-R781A IX-43 308 C312A-C323 A-C327A-R703A-D777A IX-44 309 C312A-C323A-C327A-R703A-D777A-R781A IX-45 310 C312A-C323A-C327A-C341A-D777A-R781A IX-46 311 Y63A-C341A-D777A IX-47 312 Y63A-C341A-R703A-R781A IX-48 313 Y63A-C327A-D777A 1X-49 314 Y63A-C327A-R703A IX-50 315 Y63A-C327A-R703A-R781A IX-51 316 Y63A-C327A-R703A-D777A IX-52 317 Y63A-C327A-R341A-R781A IX-53 318 Y63A-C327A-R341A-D777A IX-54 319 Y63A-C327A-R341A-D777A-R781A No. SEQ ID NO: Amino acid position IX-55 320 Y63A-C327A-R341A-R703A-R781A IX-56 321 Y63A-C323A-D777A IX-57 322 Y63A-C323A-R703A IX-58 323 Y63A-C323A-R703A-R781A IX-59 324 Y63A-C323A-R703A-D777A IX-60 325 Y63A-C323A-C341A IX-61 326 Y63A-C323A-C341A-R781A IX-62 327 Y63A-C323A-C341A-D777A IX-63 328 Y63A-C323A-C341A-D777A-R781A IX-64 329 Y63A-C323A-C341A-R703A IX-65 330 Y63A-C323A-C341A-R703A-R781A IX-66 331 Y63A-C323A-C341A-R703A-D777A IX-67 332 Y63A-C323A-C327A-R781A IX-68 333 Y63A-C323A-C327A-D777A IX-69 334 Y63A-C323A-C327A-D777A-R781A IX-70 335 Y63A-C323A-C327A-R703A IX-71 336 Y63A-C323A-C327A-R703A-R781A IX-72 337 Y63A-C323A-C327A-R703A-D777A IX-73 338 Y63A-C323A-C327A-R703A-D777A-R781A IX-74 339 Y63A-C323A-C327A-C341A-R781A IX-75 340 Y63A-C323A-C327A-C341A-D777A IX-76 341 Y63A-C323A-C327A-C341A-D777A-R781A 1X-77 342 Y63A-C323A-C327A-C341A-R703A-R781A IX-78 343 Y63 A-C312 A-R703A-D777A IX-79 344 Y63A-C312A-C341A-D777A IX-80 345 Y63 A-C312A-C341A-R703A IX-81 346 Y63A-C312A-C341A-R703A-R781A IX-82 347 Y63A-C312A-C341A-R703A-D777A IX-83 348 Y63 A-C312 A-C327A-D777A No. SEQ ID NO: Amino acid position IX-84 349 Y63 A-C312A-C327A-R703A IX-85 350 Y63A-C312A-C327A-R703A-R781A IX-86 351 Y63 A-C312A-C327A-R703A-D777A IX-87 352 Y63A-C312A-C327A-C341A IX-88 353 Y63A-C312A-C327A-C341A-R781A IX-89 354 Y63A-C312A-C327A-C341A-D777A IX-90 355 Y63A-C312A-C327A-C341A-D777A-R781A IX-91 356 Y63A-C312A-C327A-C341A-R703A IX-92 357 Y63A-C312A-C327A-C341A-R703A-R781A IX-93 358 Y63A-C312A-C327A-C341A-R703A-D777A IX-94 359 Y63 A-C312A-C323 A-R703 A-D777A IX-95 360 Y63A-C312A-C323A-C341A-D777A IX-96 361 Y63A-C312A-C323A-C341A-R703A IX-97 362 Y63A-C312A-C323A-C341A-R703A-R781A IX-98 363 Y63 A-C312 A-C323 A-C341A-R703 A-D777A IX-99 364 Y63A-C312A-C323A-C327A-R703A-D777A HBVCore antigen As described herein, the term, “HBV core protein” refers to a wild-type HBV core protein (HBc and HBe antigens) or a variant thereof. In some embodiments, an HBV core 5 protein “variant thereof’ is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% identical to SEQ ID NO: 2. In some embodiments, the HBV core protein is an HBV genotype A, B, C, D, E, F, G, or H. The HBV core proteins are encoded by Gene C. The core genes encode the structural protein of the nucleocapsids as well as the ‘e’ antigen (HBeAg). The HBc antigen is an icosahedral nucleocapsid and the 10 HBe antigen has immunoregulatory roles. The core protein is a 183 amino acid residue protein that self-assembles to form the viral capsid. In an infected cell core modulates almost every step of the viral lifecycle. Core participates in regulation of reverse transcription and signals completion of reverse transcription to support virus secretion. Core carries both nuclear localization signals and HBV envelope antigen (HBsAg) 15 binding sites. The assembly domain of the HBV core protein is amino acid residues 1149. In some embodiments, an HBV protein encoded by an mRNA of the present disclosure comprises an HBV core protein (alone or in multimeric form as disclosed herein). In some embodiments, the core protein comprises a wild-type core protein, or a variant thereof. In some embodiments, the wild-type core protein is from HBV genotype D. In some embodiments, the wild-type core protein is encoded by the amino acid sequence of MDIDP YKEFGAT VELL SFLP SDFFP S VRDLLDTAS AL YREALESPEHC SPH HTALRQAILCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQ LLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRR RGRSPRRRRTPSPRRRRSQSPRRRRSQSRESQC (SEQ ID NO: 2) In some embodiments, the core protein comprises a C-terminal truncation relative to a wild-type core protein amino acid sequence. In some embodiments, the core protein comprises a C-terminal truncation relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acids 1149 relative to a wild-type core protein (e.g., SEQ ID NO: 2). In some embodiments, the core protein comprises a C-terminal truncation of about 35 (e.g., 20, 25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45) amino acids relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the core protein comprises a C-terminal truncation of about 20, 25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 45 amino acids relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the core protein comprises a C-terminal truncation of about 35 amino acids relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acid positions about 1-149(1-200, 1-150, 1-149, 1-140, 1-123, 1-100, 1-50, 10-200, 10150, 10-149, 10-140, 10-123, 10-100, 10-50, 25-200, 25-150, 25-149, 25-140, 25-123, 25-250, 25-50) relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acid positions about 1-200, 1-150, 1-149, 1-140, 1-123, 1-100, 1-50, 10-200, 10-150, 10-149, 10-140, 10-123, 10-100, 10-50, 25-200, 25-150, 25-149, 25-140, 25-123, 25-250, 25-50 relative to the amino acid sequence of SEQ ID NO: 2. In some embodiments, the C-terminal truncated core protein comprises amino acid positions about 1-149 relative to the amino acid sequence of SEQ ID NO: 2. HBVEnvelope antigen As described herein, the term, “HBV envelope antigen” refers to the HBV envelope antigen or variants thereof. In some embodiments, an “HBV envelope antigen variant thereof’ is at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, at least 99% identical to any one of SEQ ID NOs: 3-7, or 49. In some embodiments, the HBV envelope antigen is an HBV genotype A, B, C, D, E, F, G, or H. The HBV envelope antigens are encoded by Gene S. The Gene S region encodes three different envelope glycoproteins, small (SHBs), middle (MELBs), and large (LHBs). The small, middle, and large envelope antigen share a common C-terminal. The N-terminal portion of the large envelope antigen is the PreSl domain. The N-terminal portion of the middle envelope antigen is the PreS2 domain. The large envelope antigen is approximately 400 amino acids in length. The middle envelope antigen is approximately 281 amino acids in length. The small envelope antigen is approximately 226 amino acids in length. The large, middle, and small envelope antigen protein share a common C terminus. In some embodiments the mRNA encodes the HBV envelope antigen or variants thereof (alone or in multimeric form as disclosed herein). In each of the descriptions of fusion proteins presented herein the proteins are listed in N-terminal to C-terminal orientation. The N-terminal of the large envelope antigen is the PreSl domain. The PreSl domain extends from amino acid position 1 to 119 of the large envelope antigen. The PreSl domain contains functional sites, B-cell epitopes, and T-cell epitopes. The N-terminal of the middle envelope antigen is the PreS2 domain. The PreS2 domain extends from amino acid 120 to 174 of the large envelope antigen. The PreS2 domain contains functional sites, B-cell epitopes, and T-cell epitopes. In some embodiments, an HBV protein encoded by an mRNA of the present disclosure comprises an HBV envelope antigen. In some embodiments, the envelope antigen comprises a small envelope antigen or a variant thereof. In some embodiments, the envelope antigen comprises a PreSl / S2 or variants thereof. In some embodiments, the envelope antigen comprises a small envelope antigen variant that comprises one or more mutations relative to a naturally occurring HBV small envelope antigen. In some embodiments, the PreSl / S2 antigen comprises a PreSl / S2 variant that comprises one or more mutations relative to a naturally occurring HBV PreSl / S2 protein. In some embodiments, the envelope antigen comprises a wild-type envelope antigen, or a variant thereof. In some embodiments, the wild-type envelope antigen is from HBV genotype A. In some embodiments, the wild-type envelope antigen is a wild-type HBV small envelope antigen encoded by the amino acid sequence of: MENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQ NSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGML PVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSW AFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGP SLYSIVSPFIPLLPIFFCLWVYI (SEQ ID NO: 3) In some embodiments, the wild-type envelope antigen is a wild-type HBV middle envelope antigen encoded by the amino acid sequence of: MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTG DPVTNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSP VCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLD YQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCI PIPSSWAFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMM WYWGPSLYSIVSPFIPLLPIFFCLWVYI (SEQ ID NO: 4) In some embodiments, the wild-type envelope antigen is a wild-type HBV large envelope antigen encoded by the amino acid sequence of: MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIK DHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNR Q SGRQPTPISPPLRD SHPQ AMQ WNST AFHQ ALQDPRVRGL YFPAGGS S SG TVNPAPNIASHISSISARTGDPVTNMENITSGFLGPLLVLQAGFFLLTRILTI PQSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLR RFIIFEFLLLLCLIFLLVLEDYQGMEPVCPLIPGSTTTSTGPCKTCTTPAQGNS MFP SCCC TKPTDGNCTCIPIP S SW AF AKYLWEWAS VRFS WL SLL VPF VQW FVGLSPTVWLSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLWVYI (SEQ ID NO: 5) In some embodiments, the PreSl domain of a wild-type envelope antigen is a PreSl domain of wild-type HBV envelope antigen encoded by the amino acid sequence of: GGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKD HWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQ SGRQPTPISPPLRDSHPQA (SEQ ID NO: 6) In some embodiments, the PreS2 domain of a wild-type envelope antigen is a PreS2 domain of wild-type HBV envelope antigen encoded by the amino acid sequence of: MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTG DPVTN (SEQ ID NO: 49) In some embodiments, the PreSl / S2 domain of a wild-type envelope antigen is a PreSl / S2 domain of wild-type HBV envelope antigen encoded by the amino acid sequence of: GGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKD HWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQ SGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGT VNPAPNIASHISSISARTGDPVTN (SEQ ID NO: 7) In some embodiments, the envelope antigen comprises one or more (i.e., at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10) mutation(s) relative to the wild-type envelope antigen encoded by SEQ ID NO: 3. In some embodiments, the envelope antigen comprises between one and 10 mutation(s) relative to the wild-type envelope antigen encoded by SEQ ID NO: 3. In some embodiments, the envelope antigen comprises 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more mutation(s) relative to the wild-type envelope antigen encoded by SEQ ID NO: 3. In some embodiments, the HBV envelope antigen comprises a signal peptide. In some embodiments, the signal peptide is a cytomegalovirus ULI30 Protein signal peptide. In some embodiments, a first open reading frame (ORF) including a nucleic acid sequence encoding the HBV envelope antigen further comprises a nucleic acid sequence encoding a signal peptide. In some embodiments, the first ORF comprises a PreSl / S2 and a signal peptide. In some embodiments, the first ORF comprises a small envelope antigen and a cytomegalovirus ULI30 Protein signal peptide. In some embodiments, the first ORF comprises a PreSl / S2 and a cytomegalovirus UL130 Protein signal peptide. In some embodiments, the first open reading frame (ORF) including a nucleic acid sequence encoding the HBV envelope antigen further comprises a nucleic acid sequence encoding a linker. In some embodiments, the first ORF comprises a small envelope antigen and a linker. In some embodiments, the first ORF comprises a PreS2 and a linker. In some embodiments, the first ORF comprises a PreSl / S2 and a linker. In some embodiments, the HBV Envelope antigen is soluble. In some embodiments, the HBV Envelope antigen comprises a small Envelope antigen and is soluble. In some embodiments, the HBV Envelope antigen comprises a PreSl / S2 and is soluble. In some embodiments, the first ORF comprises and HBV Envelope antigen and a lumazine synthase domain. In some embodiments, the first ORF comprises a small Envelope antigen and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreSl / S2 and a lumazine synthase domain. In some embodiments, the lumazine synthase domain comprises the amino acid sequence of: MQIYEGKLTAEGLRFGIVASRANHALVDRL VEGAID AIVRHGGREEDITL VRVCGSWEIPVAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKGLA DLSLELRKPITFGVITADTLEQAIEAAGTCHGNKGWEAALCAIEMANLFKS LR(SEQIDNO: 13) In some embodiments, the first ORF comprises a PreSl / S2, a signal peptide, a linker, and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreSl / S2, a cytomegalovirus UL130 Protein signal peptide, a linker, and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreSl / S2, the 5   cytomegalovirus ULI30 Protein signal peptide (SEQ ID NO: 9), a linker, and a lumazine synthase domain. In some embodiments, the first ORF comprises a PreSl / S2, the cytomegalovirus ULI30 Protein signal peptide (SEQ ID NO: 9), a linker, and the lumazine synthase domain of SEQ ID NO: 13. In some embodiments, the first ORF comprises a PreSl / S2, a signal peptide, a 10 linker sequence of GSGSA (SEQ ID NO: 15), and a lumazine synthase domain of SEQ ID NO: 13. In some embodiments, the first ORF comprises a PreSl / S2, a cytomegalovirus ULI30 Protein signal peptide, a linker sequence of GSGSA (SEQ ID NO: 15), and a lumazine synthase domain of SEQ ID NO: 13. In some embodiments, the first ORF comprises a PreSl / S2, the cytomegalovirus UL130 Protein signal peptide (SEQ 15 ID NO: 9), a linker sequence of GSGSA (SEQ ID NO: 15), and a lumazine synthase domain of SEQ ID NO: 13. Table 1A. Vaccine Sequences and Naturally Occurring Protein Sequences Name Sequence SEQ ID NO: Large S Ag wt SEQ ID NO: 69 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 30. and 3' UTR SEQ ID NO: 65. 69 Chemical Modification 1 -methylpseudo uridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGGGCGGCUGGAGCAGCAAGCCUAGAAAGGGCAUGGGCACCAACC UGAGCGUGCCUAACCCUCUGGGCUUCUUCCCUGACCACCAGCUGGAC CCUGCCUUCGGCGCCAACAGCAACAACCCUGACUGGGACUUCAACCC UAUCAAGGACCACUGGCCUGCCGCCAACCAGGUGGGCGUGGGCGCCU UCGGCCCUGGCCUGACCCCUCCUCACGGCGGCAUCCUGGGCUGGAGC CCUCAGGCCCAGGGCAUCCUGACCACCGUGAGCACCAUCCCUCCUCC UGCCAGCACCAACAGACAGAGCGGCAGACAGCCUACCCCUAUCAGCC CUCCUCUGAGAGACAGCCACCCUCAGGCCAUGCAGUGGAACAGCACC GCCUUCCACCAGGCCCUGCAGGACCCUAGAGUGAGAGGCCUGUACUU CCCUGCCGGCGGCAGCAGCAGCGGCACCGUGAACCCUGCCCCUAACA UCGCCAGCCACAUCAGCAGCAUCAGCGCCAGAACCGGCGACCCUGUG 30 Name Sequence SEQ ID NO: ACCAACAUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGU GCUGCAGGCCGGCUUCUUCCUGUUGACGAGAAUCCUGACCAUCCCAC AGAGCUUAGACUCCUGGUGGACCAGCCUGAACUUCUUAGGAGGCAG CCCCGUGUGCCUGGGCCAGAACAGCCAGAGCCCCACCAGCAACCACA GCCCGACCUCUUGCCCACCCAUCUGCCCCGGCUACCGGUGGAUGUGC CUGAGAAGAUUCAUCAUCUUCCUCUUCAUCCUGCUGCUGUGCCUUA UUUUCCUACUCGUUUUGCUGGACUACCAGGGAAUGUUGCCAGUGUG UCCCCUGAUCCCCGGCAGCACCACAACUUCCACCGGCCCCUGCAAGA CCUGCACCACACCAGCCCAGGGCAACAGCAUGUUCCCCUCUUGCUGU UGCACCAAGCCCACCGACGGCAACUGCACCUGCAUCCCCAUCCCCUC CAGCUGGGCCUUCGCCAAGUACCUGUGGGAGUGGGCCAGCGUGAGA UUCAGCUGGCUGUCACUCCUUGUGCCCUUCGUACAGUGGUUCGUGG GCCUCUCACCGACAGUGUGGCUCAGUGCCAUCUGGAUGAUGUGGUA CUGGGGCCCCAGCCUGUACAGCAUCGUGAGCCCCUUCAUCCCACUGC UGCCAAUCUUCUUCUGCCUGUGGGUGUACAUC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIK DHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNR QSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSG TVNPAPNIASHISSISARTGDPVTNMENITSGFLGPLLVLQAGFFLLTRILTIP QSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRR FIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNS MFPSCCCTKPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLSLLVPFVQW FVGLSPTVWLSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLWVYI 5 Large S Ag 2Ala SEQ ID NO: 70 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 31, and 3' UTR SEQ ID NO: 65. 70 Chemical Modification 1 -methylpseudo uridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGGGCGGCUGGAGCAGCAAGCCUAGAAAGGGCAUGGGCACCAACC UGAGCGUGCCUAACCCUCUGGGCUUCUUCCCUGACCACCAGCUGGAC CCUGCCUUCGGCGCCAACAGCAACAACCCUGACUGGGACUUCAACCC UAUCAAGGACCACUGGCCUGCCGCCAACCAGGUGGGCGUGGGCGCCU UCGGCCCUGGCCUGACCCCUCCUCACGGCGGCAUCCUGGGCUGGAGC CCUCAGGCCCAGGGCAUCCUGACCACCGUGAGCACCAUCCCUCCUCC UGCCAGCACCAACAGACAGAGCGGCAGACAGCCUACCCCUAUCAGCC CUCCUCUGAGAGACAGCCACCCUCAGGCCAUGCAGUGGAACAGCACC GCCUUCCACCAGGCCCUGCAGGACCCUAGAGUGAGAGGCCUGUACUU CCCUGCCGGCGGCAGCAGCAGCGGCACCGUGAACCCUGCCCCUAACA UCGCCAGCCACAUCAGCAGCAUCAGCGCCAGAACCGGCGACCCUGUG ACCAACAUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGU GCUGGCCGCCGGCUUCUUCCUGUUGACGGCCAUCCUGACCAUCCCAC AGAGCUUAGACUCCUGGUGGACCAGCCUGAACUUCUUAGGAGGCAG CCCCGUGUGCCUGGGCCAGAACAGCCAGAGCCCCACCAGCAACCACA 31 Name Sequence SEQ ID NO: GCCCGACCUCUUGCCCACCCAUCUGCCCCGGCUACCGGUGGAUGUGC CUGAGAAGAUUCAUCAUCUUCCUCUUCAUCCUGCUGCUGUGCCUUA UUUUCCUACUCGUUUUGCUGGACUACCAGGGAAUGUUGCCAGUGUG UCCCCUGAUCCCCGGCAGCACCACAACUUCCACCGGCCCCUGCAAGA CCUGCACCACACCAGCCCAGGGCAACAGCAUGUUCCCCUCUUGCUGU UGCACCAAGCCCACCGACGGCAACUGCACCUGCAUCCCCAUCCCCUC CAGCUGGGCCUUCGCCAAGUACCUGUGGGAGUGGGCCAGCGUGAGA UUCAGCUGGCUGUCACUCCUUGUGCCCUUCGUACAGUGGUUCGUGG GCCUCUCACCGACAGUGUGGCUCAGUGCCAUCUGGAUGAUGUGGUA CUGGGGCCCCAGCCUGUACAGCAUCGUGAGCCCCUUCAUCCCACUGC UGCCAAUCUUCUUCUGCCUGUGGGUGUACAUC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MGGWSSKPRKGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIK DHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNR QSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFPAGGSSSG TVNPAPNIASHISSISARTGDPVTNMENITSGFLGPLLVLaAGFFLLTalLTIP QSLDSWWTSLNFLGGSPVCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRR FIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNS MFPSCCCTKPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLSLLVPFVQW FVGLSPTVWLSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLWVYI 16 NATM Large S Ag 2Ala SEQ ID NO: 71 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 32, and 3' UTR SEQ ID NO: 65. 71 Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGAACCCCAACCAGAAGAUCAUCACCAUCGGCAGCGUGAGCCUGAC CAUCAGCACCAUCUGCUUCUUCAUGCAGAUCGCCAUCCUGAUCACCA CCGUGACCCUGCACUUCAAGCAGGGCGGCUGGAGCAGCAAGCCUAGA AAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGCUUCUU CCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAACAACC CUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCGCCAAC CAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCUCACGG CGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGACCACCG UGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCGGCAGA CAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCUCAGGC CAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGACCCUA GAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCGGCACC GUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUCAGCGC CAGAACCGGCGACCCUGUGACCAACAUGGAGAACAUCACCAGCGGCU UCCUGGGCCCUCUGCUGGUGCUGGCCGCCGGCUUCUUCCUGCUGACC GCCAUCCUGACCAUUCCACAGAGCCUGGACAGCUGGUGGACCAGCCU GAACUUCCUGGGCGGCAGCCCCGUGUGCCUGGGCCAGAACAGCCAGA GCCCCACCAGCAACCACAGCCCGACGUCCUGCCCUCCCAUCUGCCCC GGCUACCGGUGGAUGUGCCUGAGAAGAUUCAUCAUCUUCCUGUUCA 32 Name Sequence SEQ ID NO: UACUGCUCUUGUGCCUGAUCUUCUUACUUGUGCUGCUGGACUACCA GGGCAUGCUGCCCGUGUGUCCUCUGAUCCCCGGCAGCACCACCACCA GCACCGGCCCCUGCAAGACCUGCACCACCCCUGCCCAGGGCAACAGC AUGUUCCCCAGCUGCUGCUGCACCAAGCCCACCGACGGCAACUGCAC CUGCAUCCCCAUCCCCAGCAGCUGGGCCUUCGCCAAGUACCUGUGGG AGUGGGCCAGCGUGAGAUUCAGCUGGCUGAGCCUGCUGGUGCCCUU CGUGCAGUGGUUCGUGGGCCUGAGCCCCACCGUGUGGCUGAGCGCCA UCUGGAUGAUGUGGUACUGGGGCCCCAGCCUGUACAGCAUCGUGAG CCCCUUCAUCCCUCUGCUGCCCAUCUUCUUCUGCCUGUGGGUGUACA UC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MNPNQKIITIGSVSLTISTICFFMQIAILITTVTLHFKQGGWSSKPRKGMGTN LSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFG PGLTPPHGGILGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHP QAMQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISART GDPVTNMENITSGFLGPLLVLaAGFFLLTalLTIPQSLDSWWTSLNFLGGSP VCLGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLD YQGMLPVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCI PIPSSWAFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMM WYWGPSLYSIVSPFIPLLPIFFCLWVYI 17 UL130sigP Large S Ag 2Ala SEQ ID NO: 72 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 33, and 3' UTR SEQ ID NO: 65. 72 Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACAUGGAGAACAUCACCAG CGGCUUCCUGGGCCCUCUGCUGGUGCUGGCCGCCGGCUUCUUCCUGC UGACCGCCAUCCUGACCAUUCCACAGAGCCUGGACAGCUGGUGGACC AGCCUGAACUUCCUGGGCGGCAGCCCCGUGUGCCUGGGCCAGAACAG CCAGAGCCCCACCAGCAACCACAGCCCGACGUCCUGCCCUCCCAUCU GCCCCGGCUACCGGUGGAUGUGCCUGAGAAGAUUCAUCAUCUUCCU GUUCAUACUGCUCUUGUGCCUGAUCUUCUUACUUGUGCUGCUGGAC 33 Name Sequence SEQ ID NO: UACCAGGGCAUGCUGCCCGUGUGUCCUCUGAUCCCCGGCAGCACCAC CACCAGCACCGGCCCCUGCAAGACCUGCACCACCCCUGCCCAGGGCA ACAGCAUGUUCCCCAGCUGCUGCUGCACCAAGCCCACCGACGGCAAC UGCACCUGCAUCCCCAUCCCCAGCAGCUGGGCCUUCGCCAAGUACCU GUGGGAGUGGGCCAGCGUGAGAUUCAGCUGGCUGAGCCUGCUGGUG CCCUUCGUGCAGUGGUUCGUGGGCCUGAGCCCCACCGUGUGGCUGAG CGCCAUCUGGAUGAUGUGGUACUGGGGCCCCAGCCUGUACAGCAUC GUGAGCCCCUUCAUCCCUCUGCUGCCCAUCUUCUUCUGCCUGUGGGU GUACAUC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNME NITSGFLGPLLVLaAGFFLLTalLTIPQSLDSWWTSLNFLGGSPVCLGQNSQS PTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCP LIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWAFAK YLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYSI VSPFIPLLPIFFCLWVYI 18 UL130sigP PreSlS2 ferritin - A SEQ ID NO: 73 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 34, and 3' UTR SEQ ID NO: 65. 73 Chemical Modification 1 -methylpseudouridine Cap 7 mG( 5 ’ )ppp(5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACGGCGGCAGCGGCGGCAU GCUGAGCAAGGACAUCAUCAAGCUGCUGAACGAGCAGGUGAACAAG GAGAUGAACAGCAGCAACCUGUACAUGAGCAUGAGCAGCUGGUGCU ACACCCACAGCCUGGACGGCGCCGGCCUGUUCCUGUUCGACCACGCC GCCGAGGAGUACGAGCACGCCAAGAAGCUGAUCGUGUUCCUGAACG AGAACAACGUGCCUGUGCAGCUGACCAGCAUCAGCGCCCCUGAGCAC AAGUUCGAGGGCCUGACCCAGAUCUUCCAGAAGGCCUACGAGCACG AGCAGCACAUCAGCGAGAGCAUCAACAACAUCGUGGACCACGCCAUC 34 Name Sequence SEQ ID NO: AAGGGCAAGGACCACGCCACCUUCAACUUCCUGCAGUGGUACGUGA GCGAGCAGCACGAGGAGGAGGUGCUGUUCAAGGACAUCCUGGACAA GAUCGAGCUGAUCGGCAACGAGAACCACGGCCUGUACCUGGCCGACC AGUACGUGAAGGGCAUCGCCAAGAGCAGAAAGAGC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNggsg gMLSKDIIKLLNEQVNKEMNSSNLYMSMSSWCYTHSLDGAGLFLFDHAA EEYEHAKKLIVFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISES INNIVDHAIKGKDHATFNFLQWYVSEQHEEEVLFKDILDKIELIGNENHGL YLADQYVKGIAKSRKS 19 UL130sigP PreSlS2 ferritin - B SEQ ID NO: 88 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 89, mRNA ORF SEQ ID NO: 90, and 3' UTR SEQ ID NO: 65. 88 Chemical Modification 1-methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUGCGCCG UGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGCCUAGAAAGGG CAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGCUUCUUCCCUGACCAC CAGCUGGACCCUGCCUUCGGCGCCAACAGCAACAACCCUGACUGGGACUUCA ACCCUAUCAAGGACCACUGGCCUGCCGCCAACCAGGUGGGCGUGGGCGCCUU CGGCCCUGGCCUGACCCCUCCUCACGGCGGCAUCCUGGGCUGGAGCCCUCAG GCCCAGGGCAUCCUGACCACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCA ACAGACAGAGCGGCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAG CCACCCUCAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAG GACCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCGGCA CCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUCAGCGCCAG AACCGGCGACCCUGUGACCAACGGCGGCAGCGGCGGCAUGCUGAGCAAGGAC AUCAUCAAGCUGCUGAACGAGCAGGUGAACAAGGAGAUGAACAGCAGCAAC CUGUACAUGAGCAUGAGCAGCUGGUGCUACACCCACAGCCUGGACGGCGCCG GCCUGUUCCUGUUCGACCACGCCGCCGAGGAGUACGAGCACGCCAAGAAGCU GAUCGUGUUCCUGAACGAGAACAACGUGCCUGUGCAGCUGACCAGCAUCAGC GCCCCUGAGCACAAGUUCGAGGGCCUGACCCAGAUCUUCCAGAAGGCCUACG AGCACGAGCAGCACAUCAGCGAGAGCAUCAACAACAUCGUGGACCACGCCAU CAAGGGCAAGGACCACGCCACCUUCAACUUCCUGCAGUGGUACGUGAGCGAG CAGCACGAGGAGGAGGUGCUGUUCAAGGACAUCCUGGACAAGAUCGAGCUG AUCGGCAACGAGAACCACGGCCUGUACCUGGCCGACCAGUACGUGAAGGGCA UCGCCAAGAGCAGAAAGAGC 90 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFFPDHQL DPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGIL TTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFP 19 Name Sequence SEQ ID NO: AGGSSSGTVNPAPNIASHISSISARTGDPVTNGGSGGMLSKDIIKLLNEQVNKEMNS SNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAKKLIVFLNENNVPVQLTSISAP EHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKGKDHATFNFLQWYVSEQHEEEVL FKDILDKIELIGNENHGLYLADQYVKGIAKSRKS Middle S Ag wt SEQ ID NO: 74 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 35, and 3' UTR SEQ ID NO: 65. 74 Chemical Modification 1 -methylpseudo uridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGACCCUAG AGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCGGCACCG UGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUCAGCGCC AGAACCGGCGACCCUGUGACCAACAUGGAGAACAUCACCAGCGGCUU CCUGGGCCCACUACUGGUGCUGCAGGCCGGCUUCUUCCUGUUGACGA GAAUCCUGACCAUCCCACAGAGCUUAGACUCCUGGUGGACCAGCCUG AACUUCUUAGGAGGCAGCCCCGUGUGCCUGGGCCAGAACAGCCAGA GCCCCACCAGCAACCACAGCCCGACCUCUUGCCCACCCAUCUGCCCC GGCUACCGGUGGAUGUGCCUGAGAAGAUUCAUCAUCUUCCUCUUCA UCCUGCUGCUGUGCCUUAUUUUCCUACUCGUUUUGCUGGACUACCA GGGAAUGUUGCCAGUGUGUCCCCUGAUCCCCGGCAGCACCACAACUU CCACCGGCCCCUGCAAGACCUGCACCACACCAGCCCAGGGCAACAGC AUGUUCCCCUCUUGCUGUUGCACCAAGCCCACCGACGGCAACUGCAC CUGCAUCCCCAUCCCCUCCAGCUGGGCCUUCGCCAAGUACCUGUGGG AGUGGGCCAGCGUGAGAUUCAGCUGGCUGUCACUCCUUGUGCCCUU CGUACAGUGGUUCGUGGGCCUCUCACCGACAGUGUGGCUCAGUGCC AUCUGGAUGAUGUGGUACUGGGGCCCCAGCCUGUACAGCAUCGUGA GCCCCUUCAUCCCACUGCUGCCAAUCUUCUUCUGCCUGUGGGUGUAC AUC 35 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MQWNSTAFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGD PVTNMENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVC LGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQ GMLPVCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIP SSWAFAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWY WGPSLYSIVSPFTPLLPTFFCLWVYI 4 Small S Ag wt-A SEQ ID NO: 75 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 36. and 3' UTR SEQ ID NO: 65. 75 Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 Name Sequence SEQ ID NO: mRNAORF AUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGUGCUGCA GGCCGGCUUCUUCCUGUUGACGAGAAUCCUGACCAUCCCACAGAGCU UAGACUCCUGGUGGACCAGCCUGAACUUCUUAGGAGGCAGCCCCGU GUGCCUGGGCCAGAACAGCCAGAGCCCCACCAGCAACCACAGCCCGA CCUCUUGCCCACCCAUCUGCCCCGGCUACCGGUGGAUGUGCCUGAGA AGAUUCAUCAUCUUCCUCUUCAUCCUGCUGCUGUGCCUUAUUUUCCU ACUCGUUUUGCUGGACUACCAGGGAAUGUUGCCAGUGUGUCCCCUG AUCCCCGGCAGCACCACAACUUCCACCGGCCCCUGCAAGACCUGCAC CACACCAGCCCAGGGCAACAGCAUGUUCCCCUCUUGCUGUUGCACCA AGCCCACCGACGGCAACUGCACCUGCAUCCCCAUCCCCUCCAGCUGG GCCUUCGCCAAGUACCUGUGGGAGUGGGCCAGCGUGAGAUUCAGCU GGCUGUCACUCCUUGUGCCCUUCGUACAGUGGUUCGUGGGCCUCUCA CCGACAGUGUGGCUCAGUGCCAUCUGGAUGAUGUGGUACUGGGGCC CCAGCCUGUACAGCAUCGUGAGCCCCUUCAUCCCACUGCUGCCAAUC UUCUUCUGCCUGUGGGUGUACAUC 36 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQN SQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLP VCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWA FAKYLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGPS LYSIVSPFIPLLPIFFCLWVYI 3 Small S Ag wt-B SEQ ID NO: 92 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 89, mRNA ORF SEQ ID NO: 36, and 3' UTR SEQ ID NO: 65. 92 Chemical Modification 1-methylpseudouridine Cap 7 mG(5 ’ )ppp(5 ’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNAORF AUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGUGCUGCAGGCCG GCUUCUUCCUGUUGACGAGAAUCCUGACCAUCCCACAGAGCUUAGACUCCUG GUGGACCAGCCUGAACUUCUUAGGAGGCAGCCCCGUGUGCCUGGGCCAGAAC AGCCAGAGCCCCACCAGCAACCACAGCCCGACCUCUUGCCCACCCAUCUGCCC CGGCUACCGGUGGAUGUGCCUGAGAAGAUUCAUCAUCUUCCUCUUCAUCCUG CUGCUGUGCCUUAUUUUCCUACUCGUUUUGCUGGACUACCAGGGAAUGUUG CCAGUGUGUCCCCUGAUCCCCGGCAGCACCACAACUUCCACCGGCCCCUGCA AGACCUGCACCACACCAGCCCAGGGCAACAGCAUGUUCCCCUCUUGCUGUUG CACCAAGCCCACCGACGGCAACUGCACCUGCAUCCCCAUCCCCUCCAGCUGG GCCUUCGCCAAGUACCUGUGGGAGUGGGCCAGCGUGAGAUUCAGCUGGCUG UCACUCCUUGUGCCCUUCGUACAGUGGUUCGUGGGCCUCUCACCGACAGUGU GGCUCAGUGCCAUCUGGAUGAUGUGGUACUGGGGCCCCAGCCUGUACAGCAU CGUGAGCCCCUUCAUCCCACUGCUGCCAAUCUUCUUCUGCCUGUGGGUGUAC AUC 36 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQNSQSPTS NHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTST 3 Name Sequence SEQ ID NO: GPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLS LLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLWVYI Small S Ag wt - C SEQIDNO: 93 consists of from 5' end to 3' end: 5' UTRSEQIDNO: 94, mRNA ORF SEQ ID NO: 95, and 3' UTR SEQ ID NO: 96. 93 Chemical Modification 1-methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5' UTR AGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 94 mRNA ORF AUGGAGAACAUCACCAGCGGCUUCCUGGGCCCACUACUGGUUCUGCAGGCCG GCUUCUUCCUGUUGACGAGAAUCCUGACCAUCCCACAGAGCUUAGACUCCUG GUGGACCAGCCUGAACUUCUUAGGAGGCAGCCCCGUGUGCCUGGGCCAGAAC AGCCAGAGCCCCACCAGCAACCACAGCCCGACCUCUUGCCCACCCAUCUGCCC CGGCUACCGGUGGAUGUGCCUGAGAAGAUUCAUCAUCUUCCUCUUCAUCCUG CUGCUGUGCCUUAUCUUCCUACUCGUAUUGCUGGACUACCAGGGAAUGUUGC CAGUGUGUCCCCUGAUCCCCGGCAGCACCACAACUUCCACCGGCCCCUGCAA GACCUGCACCACACCAGCCCAGGGCAAUAGCAUGUUCCCCUCUUGCUGUUGC ACCAAGCCCACCGACGGCAACUGCACCUGCAUCCCCAUCCCCUCCAGCUGGG CCUUCGCCAAGUACCUGUGGGAGUGGGCCAGCGUGAGAUUCAGCUGGCUGUC ACUCCUUGUGCCCUUCGUACAGUGGUUCGUGGGCCUCUCACCGACAGUGUGG CUCAGUGCCAUCUGGAUGAUGUGGUACUGGGGUCCCAGCCUGUACAGCAUCG UGAGCCCCUUCAUCCCACUGCUGCCAAUCUUCUUCUGCCUGUGGGUGUACAU C 95 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCAUUGUGGGGGUGGUCUUUGAAUAAAGUC UGAGUGGGCGGC 96 PolyA 100 nucleotides 411 Corresponding Protein MENITSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGSPVCLGQNSQSPTS NHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIPGSTTTST GPCKTCTTPAQGNSMFPSCCCTKPTDGNCTCIPIPSSWAFAKYLWEWASVRFSWLS LLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLWVYI 3 UL130sigP Large S Ag_2Ala noGlvcan SEQ ID NO: 76 consists of from 5’ end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 37, and 3' UTR SEQ ID NO: 65. 76 Chemical Modification 1 -methylpseudo uridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGGCCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGCAGAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACAUGGAGCAGAUCACCAG 37 Name Sequence SEQ ID NO: CGGCUUCCUGGGCCCUCUGCUGGUGCUGGCCGCCGGCUUCUUCCUGC UGACCGCCAUCCUGACCAUUCCACAGAGCCUGGACAGCUGGUGGACC AGCCUGAACUUCCUGGGCGGCAGCCCCGUGUGCCUGGGCCAGAACAG CCAGAGCCCCACCAGCAACCACAGCCCGACGUCCUGCCCUCCCAUCU GCCCCGGCUACCGGUGGAUGUGCCUGAGAAGAUUCAUCAUCUUCCU GUUCAUACUGCUCUUGUGCCUGAUCUUCUUACUUGUGCUGCUGGAC UACCAGGGCAUGCUGCCCGUGUGUCCUCUGAUCCCCGGCAGCACCAC CACCAGCACCGGCCCCUGCAAGACCUGCACCACCCCUGCCCAGGGCA ACAGCAUGUUCCCCAGCUGCUGCUGCACCAAGCCCACCGACGGCGGC UGCACCUGCAUCCCCAUCCCCAGCAGCUGGGCCUUCGCCAAGUACCU GUGGGAGUGGGCCAGCGUGAGAUUCAGCUGGCUGAGCCUGCUGGUG CCCUUCGUGCAGUGGUUCGUGGGCCUGAGCCCCACCGUGUGGCUGAG CGCCAUCUGGAUGAUGUGGUACUGGGGCCCCAGCCUGUACAGCAUC GUGAGCCCCUUCAUCCCUCUGCUGCCCAUCUUCUUCUGCCUGUGGGU GUACAUC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLaVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWqSTA FHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNMEql TSGFLGPLLVLaAGFFLLTalLTIPQSLDSWWTSLNFLGGSPVCLGQNSQSPT SNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLIP GSTTTSTGPCKTCTTPAQGNSMFPSCCCTKPTDGgCTCIPIPSSWAFAKYL WEWASVRFSWLSLLVPFVQWFVGLSPTVWLSAIWMMWYWGPSLYSIVS PFIPLLPIFFCLWVYI 20 UL130sigP PreSl ferritin SEQ ID NO: 77 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 38, and 3' UTR SEQ ID NO: 65. 77 Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp( 5 ’) N1 mpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCGGCGGCAGCGGCGGCAUGCUGAGCAAGGACAUCAUCAAGC UGCUGAACGAGCAGGUGAACAAGGAGAUGAACAGCAGCAACCUGUA CAUGAGCAUGAGCAGCUGGUGCUACACCCACAGCCUGGACGGCGCCG GCCUGUUCCUGUUCGACCACGCCGCCGAGGAGUACGAGCACGCCAAG AAGCUGAUCGUGUUCCUGAACGAGAACAACGUGCCUGUGCAGCUGA 38 Name Sequence SEQ ID NO: CCAGCAUCAGCGCCCCUGAGCACAAGUUCGAGGGCCUGACCCAGAUC UUCCAGAAGGCCUACGAGCACGAGCAGCACAUCAGCGAGAGCAUCA ACAACAUCGUGGACCACGCCAUCAAGGGCAAGGACCACGCCACCUUC AACUUCCUGCAGUGGUACGUGAGCGAGCAGCACGAGGAGGAGGUGC UGUUCAAGGACAUCCUGGACAAGAUCGAGCUGAUCGGCAACGAGAA CCACGGCCUGUACCUGGCCGACCAGUACGUGAAGGGCAUCGCCAAGA GCAGAAAGAGC 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAggsggMLS KDIIKLLNEQVNKEMNSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYE HAKKLIVFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIV DHAIKGKDHATFNFLQWYVSEQHEEEVLFKDILDKIELIGNENHGLYLAD QYVKGIAKSRKS 21 UL130sigP Pre S1S2 HATM SEQ ID NO: 78 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 39. and 3' UTR SEQ ID NO: 65. 78 Chemical Modification 1 -methylpseudo uridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACAGCGGCGGCGGCAGCAU CCUGGCCAUCUACAGCACCGUGGCCAGCAGCCUGGUGCUGCUGGUGA GCCUGGGCGCCAUCAGCUUC 39 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNsggg sILAIYSTVASSLVLLVSLGAISF 22 Name Sequence SEQ ID NO: UL130sigP Pre SI HATM SEQ ID NO: 79 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 40, and 3' UTR SEQ ID NO: 65. 79 Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAGCGGCGGCGGCAGCAUCCUGGCCAUCUACAGCACCGUGGC CAGCAGCCUGGUGCUGCUGGUGAGCCUGGGCGCCAUCAGCUUC 40 3'UTR UAAAGCU CCCCGGGGGCCU CGGUGGCCUAGCU UCU U GCCCCU UGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAsgggsILAIY STVASSLVLLVSLGAISF 23 UL130sigP Pre S1S2 LuS SEQ ID NO: 80 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 41, and 3' UTR SEQ ID NO: 65. 80 Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp(5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACGGCAGCGGCAGCGCCAU GCAGAUCUACGAGGGCAAGCUGACCGCCGAGGGCCUGCGGUUCGGC AUCGUGGCCAGCCGGGCCAACCACGCCCUGGUGGACCGGCUGGUGGA 41 Name Sequence SEQ ID NO: GGGCGCCAUCGACGCCAUAGUCCGGCACGGCGGCAGAGAGGAGGAC AUCACCCUGGUGCGGGUGUGCGGCAGCUGGGAGAUACCUGUGGCCG CCGGCGAACUGGCACGGAAGGAGGAUAUCGACGCCGUGAUCGCCAU UGGAGUGCUGUGCAGGGGCGCGACCCCCAGCUUCGACUACAUCGCCA GCGAGGUGAGCAAGGGCCUGGCCGACCUGAGCCUGGAGCUGCGGAA GCCCAUCACCUUCGGCGUGAUCACCGCCGACACCCUGGAGCAGGCCA UCGAGGCCGCCGGCACUUGCCACGGCAACAAGGGCUGGGAGGCCGCC CUGUGUGCCAUCGAGAUGGCCAACCUGUUCAAGAGCCUGCGG 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNGS GSAMQIYEGKLTAEGLRFGIVASRANH AL VDRL VEGAID AI VRHGGREED ITLVRVCGSWEIPVAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKG LADLSLELRKPITFGVITADTLEQAIEAAGTCHGNKGWEAALCAIEMANLF KSLR 24 PreSlS2-LuS (A) 1 SEQ ID NO:395 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:375, mRNA ORF SEQ ID NO:41, and 3' UTR SEQ ID NO:58. Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCC GGCGCCGCCACC 375 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACGGCAGCGGCAGCGCCAU GCAGAUCUACGAGGGCAAGCUGACCGCCGAGGGCCUGCGGUUCGGC AUCGUGGCCAGCCGGGCCAACCACGCCCUGGUGGACCGGCUGGUGGA GGGCGCCAUCGACGCCAUAGUCCGGCACGGCGGCAGAGAGGAGGAC AUCACCCUGGUGCGGGUGUGCGGCAGCUGGGAGAUACCUGUGGCCG CCGGCGAACUGGCACGGAAGGAGGAUAUCGACGCCGUGAUCGCCAU UGGAGUGCUGUGCAGGGGCGCGACCCCCAGCUUCGACUACAUCGCCA GCGAGGUGAGCAAGGGCCUGGCCGACCUGAGCCUGGAGCUGCGGAA GCCCAUCACCUUCGGCGUGAUCACCGCCGACACCCUGGAGCAGGCCA 41 Name Sequence SEQ ID NO: UCGAGGCCGCCGGCACUUGCCACGGCAACAAGGGCUGGGAGGCCGCC CUGUGUGCCAUCGAGAUGGCCAACCUGUUCAAGAGCCUGCGG 3'UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGG CCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC 58 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNGS GSAMQIYEGKLTAEGLRFGIVASRANH AL VDRL VEGAID AIVRHGGREED ITLVRVCGSWEIPVAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKG LADLSLELRKPITFGVITADTLEQAIEAAGTCHGNKGWEAALCAIEMANLF KSLR 24 Corel49(D) 1 SEQ ID NO:396 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:375, mRNA ORF SEQ ID NO:46, and 3' UTR SEQ ID NO: 58. Chemical Modification 1 -methylpseudouridine Cap 7mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GAGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCC GGCGCCGCCACC 375 mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACCGUGGAGCUGCU GAGCUUCCUGCCCAGCGACUUCUUCCCCAGCGUGAGAGAUCUGCUGG ACACCGCCAGCGCCCUGUACAGAGAGGCCCUGGAGAGCCCCGAGCAC UGCUCGCCUCACCACACCGCCCUGAGACAGGCCAUCCUGUGCUGGGG CGAGCUGAUGACCCUGGCCACCUGGGUGGGCGUGAACCUGGAGGAC CCCGCCAGCAGGGAUCUGGUGGUGAGCUACGUGAACACCAACAUGG GCCUGAAGUUCAGACAGCUGCUGUGGUUCCACAUCAGCUGCCUGACC UUCGGCAGAGAGACAGUGAUCGAGUACCUGGUGAGCUUCGGCGUGU GGAUCAGAACACCACCCGCCUACAGACCACCCAACGCCCCAAUCCUG AGCACCCUGCCCGAGACUACCGUGGUG 46 3'UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGG CCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC 58 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYK.EFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHH TALRQA1LCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQL LWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTW 28 Pol 8mut (D) 1 SEQ ID NO:397 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:375, mRNA ORF SEQ ID NO:48, and 3' UTR SEQ ID NO: 58. Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp(5 ’ )NlmpNp 5'UTR GAGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCC GGCGCCGCCACC 375 mRNA ORF AUGCCCCUGAGCUACCAGCACUUCCGGCGGCUGCUGCUGCUGGACGA CGAGGCCGGACCCCUGGAGGAGGAGCUCCCACGGCUCGCCGACGAGG ACCUGAACCGGCGGGUGGCCGAAGACCUGAACCUGGGCAACCUGAAC 48 Name Sequence SEQID NO: GUGAGCAUCCCCUGGACCCACAAGGUGGGCAACUUCACCGGCCUGGC CAGCAGCACCGUGCCCGUGUUCAACCCUCACUGGAAGACACCCAGCU UCCCCAACAUCCACCUGCACCAGGACAUCAUCAAGAAGUGCGAGCAG UUCGUGGGCCCACUGACAGUGAACGAGAAGCGGCGGCUGCAGCUGA UCAUGCCCGCCCGGUUCUACCCCAAGGUGACCAAGUACCUGCCCCUG GACAAGGGCAUCAAGCCCUACUACCCCGAGCACCUGGUGAACCACUA CUUCCAGACCCGGCACUACCUGCACACCCUGUGGAAGGCCGGCAUCC UGUACAAGCGGGAGACCACCCACAGCGCCAGCUUCUGCGGCAGCCCC UACAGCUGGGAGCAGGAGCUGCAGCACGGCGCCGAGAGCUUCCACCA GCAGAGCAGCGGCAUCCUGAGCCGGCCUCCAGUGGGCAGCAGCCUGC AGAGCAAGCACAGCAAGAGCCGGCUGGGCCUGCAGAGCCAGCAGGG CCACUUGGCAAGGAGGCAGCAGGGCCGGAGCUGGAGCAUCAGAGCC GGCAUCCACCCCACGGCAAGGAGACCUUUUGGCGUGGAGCCUAGCGG CAGCGGCCACAACACCAACCUGGCCAGCAAGAGCGCCAGCUGCCUGU ACCAGAGCCCUCUGCGGAAGGCCGCCUACCCCGCAGUGAGCACCUUC GAGAAGCACAGUAGCAGCGGCCACGCAGUGGAGCUGCACAACCUGCC ACCCAACUCUGCCCGGAGUCAAGGCGAGCGCCCCGUGUUCCCAGCCU GGUGGCUGCAGUUCCGGAACAGCAAGCCCGCCAGCGACUACGCCCUG AGCCACAUCGUGAACCUGUUAGAGGACUGGGGUCCUGCAGCCGAGC ACGGCGAGCACCACAUCCGGAUUCCACGCACACCUGCUCGGGUGACU GGCGGCGUGUUCCUGGUGGACAAGAAUCCCCACAACACCGCCGAGUC ACGGCUGGUGGUGGACUUCAGCCAGUUCAGCCGGGGCAACUACCGG GUGAGCUGGCCCAAGUUCGCCGUGCCCAACCUGCAGAGCCUGACCAA CCUGCUGAGCAGCAACCUGAGCUGGCUGAGCCUGGACGUGAGCGCCG CCUUCUACCAUCUUCCCCUGCAUCCCGCAGCCAUGCCCCACCUGCUG GUGGGCAGCAGCGGCCUGAGCAGGUACGUGGCCCGCCUGAGCAGCA ACAGCCGGAUCUUCAACCACCAGCGGGGCACCAUGCAGAACCUGCAC GACUACUGCAGCCGGAACCUGUACGUGAGCCUGCUGCUGCUGUACCA GACCUUCGGCCGGAAGCUGCACCUGUACAGCCACCCCAUCAUCCUGG GCUUCCGGAAGAUCCCCAUGGGCGUGGGUCUGAGCCCCUUCCUGCUG GCCCAGUUCACCAGCGCCAUCUGCAGCGUUGUGCGGCGGGCAUUCCC ACACUGCCUGGCCUUCAGCUACAUGGACGACGUGGUGCUGGGCGCCA AGAGCGUGCAGCACCUGGAGAGCCUGUUCACCGCCGUGACCAACUUC CUGCUGAGCCUGGGCAUCCACCUGAACCCCAACAAGACCAAGCGGUG GGGCUACAGCCUGAACUUCAUGGGCUACGUGAUCGGCUGCUACGGC AGCCUGCCCCAGGACCACAUCAUCCAGAAGAUCAAGGAGUGCUUCCG GAAGCUGCCCGUGAACCGGCCCAUCGACUGGAAGGUGUGCCAGCGG AUCGUGGGCCUGCUGGGCUUCGCCGCACCCUUCACCCAGUGCGGCUA CCCCGCCCUGAAGCCCCUGUACGCCUGCAUCCAGAGCCGGCAGGCCU UCACCUUCAGCCCCACCUACAAGGCCUUCCUGUGCAAGCAGUACCUG AACCUGUAUCCAGUGGCACGGCAGAGGAGCGGUCUGUGCCAGGUGU UCGCCGACGCCACUCCCACCGGCUGGGGACUGGUGAUGGGCCACCAG GCCAUGCGGGGCACCUUCCUGGCCCCUCUGCCCAUCCACACAGCCGA ACUGCUGGCCGCCUGCUUUGCCCGCAGCAGAAGCGGAGCCAACAUCC UGGGCACCGACAAUAGCGUGGUGCUGAGCCGGAAGUACACCAGCUU CCCCUGGCUCCUCGGGUGUGCCGCGAACUGGAUCCUGCGGGGCACCA GCUUCGUGUACGUGCCCAGCGCCCUGAAUCCCGCCGCCGAUCCAAGC GCUGGCCGUCUCGGACUGUCACGGCCCCUGCUGAGACUGCCCUUCCG CCCUACCACAGGCCGGACCAGCCUGUACGCCGACAGCCCAAGCGUGC CCAGCCACCUCCCCGAUCGGGUGCACUUCGCCAGCCCACUUCACGUU GCCUGGCGGCCACCU Name Sequence SEQ ID NO: 3'UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGG CCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC 58 PolyA 411 Corresponding Protein MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSI PWTHKVGNFTGLASSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTV NEKRRLQLIMPARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTL WKAGILYKRETTHSASFCGSPYSWEQELQHGAESFHQQSSGILSRPPVGSS LQSKHSKSRLGLQSQQGHLARRQQGRSWSIRAGIHPTARRPFGVEPSGSG HNTNLASKSASCLYQSPLRKAAYPAVSTFEKHSSSGHAVELHNLPPNSAR SQGERPVFPAWWLQFRNSKPASDYALSHIVNLLEDWGPAAEHGEHHIRIP RTPARVTGGVFLVDKNPHNTAESRLWDFSQFSRGNYRVSWPKFAVPNL QSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYVARLS SNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFR KIPMGVGLSPFLLAQFTSAICSWRRAFPHCLAFSYMDDWLGAKSVQHL ESLFTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQK IKECFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQ AFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLVMGHQA MRGTFLAPLPIHTAELLAACFARSRSGANILGTDNSVVLSRKYTSFPWLLG CAANWILRGTSFVYVPSALNPAADPSAGRLGLSRPLLRLPFRPTTGRTSLY ADSPSVPSHLPDRVHFASPLHVAWRPP 29 UL130sigP Pre SI LuS-A SEQ ID NO: 81 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 42, and 3' UTR SEQ ID NO: 65. 81 Chemical Modification 1 -methylpseudo uridine Cap 7mG(5 ’)ppp(5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCGGCAGCGGCAGCGCCAUGCAGAUCUACGAGGGCAAGCUGAC CGCCGAGGGCCUGCGGUUCGGCAUCGUGGCCAGCCGGGCCAACCACG CCCUGGUGGACCGGCUGGUGGAGGGCGCCAUCGACGCCAUAGUCCGG CACGGCGGCAGAGAGGAGGACAUCACCCUGGUGCGGGUGUGCGGCA GCUGGGAGAUACCUGUGGCCGCCGGCGAACUGGCACGGAAGGAGGA UAUCGACGCCGUGAUCGCCAUUGGAGUGCUGUGCAGGGGCGCGACC CCCAGCUUCGACUACAUCGCCAGCGAGGUGAGCAAGGGCCUGGCCGA CCUGAGCCUGGAGCUGCGGAAGCCCAUCACCUUCGGCGUGAUCACCG CCGACACCCUGGAGCAGGCCAUCGAGGCCGCCGGCACUUGCCACGGC AACAAGGGCUGGGAGGCCGCCCUGUGUGCCAUCGAGAUGGCCAACC UGUUCAAGAGCCUGCGG 42 Name Sequence SEQ ID NO: 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAgsgsaMQIY EGKLTAEGLRFGIVASRANH AL VDRL VEGAID AIVRHGGREEDITLVRVC GSWEIPVAAGELARKEDIDAVIAIGVLCRGATPSFDYIASEVSKGLADLSLE LRKPITFGVITADTLEQAIEAAGTCHGNKGWEAALCAIEMANLFKSLR 25 UL130sigP PreSlS2-LuS (A) 2 SEQ ID NO: 97 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 89, mRNA ORF SEQ ID NO: 98, and 3' UTR SEQ ID NO: 65. 97 Chemical Modification 1-methylpseudouridine Cap 7 mG(5 ’ )ppp(5 ’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCUGAGACUGCUGCUCAGACACCACUUCCAUUGCCUGCUGCUGUGCGCCG UGUGGGCCACACCUUGCUUAGCCGGCGGUUGGAGCAGCAAGCCUAGAAAGG GCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGCUUCUUCCCUGACCA CCAGCUGGACCCUGCUUUCGGCGCCAACAGCAACAACCCUGACUGGGACUUC AACCCUAUCAAGGACCACUGGCCUGCCGCCAACCAGGUGGGCGUGGGCGCCU UCGGCCCUGGCCUGACCCCUCCUCACGGCGGCAUCCUGGGCUGGUCACCUCA GGCCCAGGGCAUCCUUACCACCGUGAGCACCAUCCCUCCUCCUCtCCAGCACC AACAGACAGAGCGGCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACA GCCACCCUCAGGCUAUGCAGUGGAACAGCACCGCCUUCCACCAAGCCCUGCA GGACCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGGAGCUCAAGCGGC ACCGUGAACCCUGCCCCUAACAUCGCAAGCCACAUCAGCAGCAUCAGCGCCA GAACCGGCGACCCUGUGACCAACGGCAGCGGCAGCGCCAUGCAGAUCUACGA GGGCAAGCUGACCGCCGAGGGCCUGCGGUUCGGCAUCGUGGCCAGCCGGGCC AACCACGCCCUGGUGGACCGGCUGGUGGAGGGCGCCAUAGACGCCAUAGUCC GGCACGGAGGCAGAGAGGAGGACAUCACCCUGGUGCGGGUGUGCGGCAGCU GGGAGAUACCUGUGGCCGCCGGCGAACUGGCACGGAAGGAGGAUAUCGACG CCGUGAUCGCCAUUGGAGUGCUGUGCAGGGGCGCGACCCCUAGCUUCGACUA CAUCCtCCAGCGAGGUCtAGCAAGGGCCUGGCCGACCUGAGCCUGGAGCUCtCGG AAGCCCAUCACCUUCGGCGUGAUCACCGCCGACACCCUGGAGCAGGCCAUUG AGGCCGCUGGCACUUGCCACGGCAACAAGGGCUGGGAGGCCGCCCUGUGUGC CAUCGAGAUGGCCAACCUGUUCAAGAGCCUGCGG 98 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFFPDHQL DPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGIL TTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGLYFP AGGSSSGTVNPAPNIASinSSISARTGDPVTNGSGSAMQIYEGKLTAEGLRFGIVASR ANHALVDRLVEGAIDAIVRHGGREEDITLVRVCGSWEIPVAAGELARKEDIDAVIAI GVLCRGATPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIEAAGTCHGNK GWEAALCAIEMANLFKSLR 24 PreSlS2-LuS (A) 3 SEQ ID NO: 99 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 94, mRNA ORF SEQ ID NO: 100, and 3' UTR SEQ ID NO: 101. 99 Name Sequence SEQ ID NO: Chemical Modification 1-methylpseudouridine Cap m7G(5')ppp(5')G-2'-O-methyl 5' UTR AGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 94 mRNA ORF AUGCUGCGGCUGUUACUGCGGCACCACUUCCAUUGCCUGCUGCUGUGCGCCG UGUGGGCCACCCCUUGCCUGGCAGGCGGUUGGAGCUCUAAGCCGCGGAAGGG CAUGGGCACCAACUUAAGCGUGCCCAACCCACUGGGCUUCUUCCCCGACCAU CAGCUGGAUCCCGCCUUCGGGGCCAACUCAAACAACCCCGACUGGGACUUCA ACCCCAUCAAGGACCAUUGGCCCGCCGCCAACCAGGUGGGCGUGGGAGCCUU UGGACCCGGCUUGACCCCACCCCACGGCGGCAUCCUGGGCUGGAGCCCGCAA GCCCAGGGGAUUCUGACCACUGUGAGCACCAUCCCACCUCCCGCGUCCACCA AUCGGCAAAGUGGGCGGCAGCCCACUCCUAUCUCUCCGCCCUUGCGGGACUC CCAUCCUCAGGCUAUGCAGUGGAACAGCACCGCCUUUCACCAAGCCCUGCAG GACCCAAGGGUGCGGGGCCUGUACUUCCCCGCCGGAGGUAGCAGCUCUGGCA CCGUGAACCCUGCCCCAAACAUCGCCAGCCAUAUAUCCAGCAUCUCGGCCCG GACUGGUGACCCCGUGACAAACGGCAGCGGAAGCGCCAUGCAGAUCUACGAG GGCAAGCUCACAGCCGAAGGCCUGCGGUUCGGCAUUGUGGCCUCACGGGCCA ACCACGCCCUGGUGGACCGGCUGGUAGAAGGCGCCAUUGACGCCAUCGUGCG GCACGGAGGACGGGAGGAGGACAUCACACUGGUGCGGGUGUGCGGCAGCUG GGAGAUCCCUGUGGCCGCUGGCGAACUUGCCCGGAAAGAGGAUAUCGACGCC GUGAUUGCCAUCGGCGUGCUUUGCCGGGGCGCUACCCCUAGCUUCGACUACA UUGCAAGCGAGGUGAGUAAGGGCCUGGCCGACCUGUCUCUGGAGCUGCGGA AGCCCAUUACCUUCGGCGUGAUCACCGCCGACACCCUGGAGCAGGCUAUCGA GGCUGCUGGCACCUGCCACGGCAACAAGGGUUGGGAGGCGGCACUGUGUGCC AUAGAGAUGGCCAACCUGUUCAAGAGCCUGCGG 100 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCAUUUUGGCGUGGUCUUUGAAUAAAGUCU GAGUGGGCGGC 101 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFFPDHQL DPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGILGWSPQAQGIL TT VS TIPPPA S TNRQSGRQPTPISPPLRDSHPQAMQWNSTAFHQALQDPRVRGL YFP AGGSSSGTVNPAPNIASHISSISARTGDPVTNGSGSAMQIYEGKLTAEGLRFGIVASR ANELALVDRLVEGAIDAIVRHGGREEDITLVRVCGSWEIPVAAGELARKEDIDAVIAI GVLCRGATPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIEAAGTCHGNK GWEAALCAIEMANLFKSLR 24 UL130sigP PreSlS2-LuS (B) 2 SEQ ID NO:398 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:376. and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7 mG( 5 ’ )ppp( 5 ’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCUGAGACUGUUGCUGCGGCACCACUUCCAUUGCCUGCUGCUGUGUGCCG UGUGGGCCACACCUUGCCUGGCCGGUGGGUGGAGCAGCAAACCCCGGAAGGG CAUGGGAACCAAUCUGAGCGUGCCCAAUCCCCUGGGCUUCUUCCCCGACCAU CAGCUUGACCCCGCCUUCAAGGCCAACAGCGAGAACCCAGACUGGGAUCUGA AUCCCCACAAGGACAACUGGCCGGACGCCAACAAGGUUGGCGUGGGCGCAUU CGGCCCCGGGUUCACCCCACCUCACGGCGGCCUGCUGGGCUGGAGCCCUCAG GCCCAAGGCCUGCUAACUACUGUGCCGGCUGCACCUCCACCCGCCAGCACUA ACCGGCAGAGCGGCCGACAGCCGACCCCUCUGUCCCCUCCGCUGCGGGACAC CCACCCACAGGCUAUGCAGUGGAACAGCACCACCUUCCAUCAGACACUGCAA GACCCUCGUGUGCGGGCCUUGUACUUCCCCGCAGGCGGUAGCAGCAGCGGUA CCGUGUCUCCCGCACAGAACACCGUGAGCGCUAUCUCUUCUAUCCUGAGCAA 376 Name Sequence SEQ ID NO: GACCGGCGACCCAGUGCCCAACGGCAGCGGAAGCGCCAUGCAGAUCUACGAG GGCAAGCUGACCGCCGAAGGCUUACGGUUCGGCAUCGUGGCCAGCCGGGCUA ACCACGCCCUGGUGGACCGGCUGGUAGAGGGCGCCAUCGACGCCAUCGUACG GCACGGUGGCCGGGAGGAGGACAUCACUCUGGUGAGGGUGUGCGGCAGCUG GGAGAUUCCCGUUGCCGCAGGAGAACUGGCCCGGAAAGAGGACAUUGACGCC GUGAUCGCCAUAGGCGUGCUUUGCCGGGGCGCUACACCAAGCUUCGACUACA UCGCCUCCGAGGUGAGCAAAGGUCUGGCCGACCUGUCCCUUGAGCUGCGCAA GCCGAUCACCUUCGGAGUUAUCACCGCCGAUACCCUGGAGCAGGCCAUCGAG GCUGCCGGCACCUGCCACGGCAAUAAAGGCUGGGAGGCCGCCCUGUGCGCAA UCGAGAUGGCCAACCUGUUUAAGAGCCUGCGG 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFFPDHQL DPAFKANSENPDWDLNPHKDNWPDANKVGVGAFGPGFTPPHGGLLGWSPQAQG LLTTVPAAPPPASTNRQSGRQPTPLSPPLRDTHPQAMQWNSTTFHQTLQDPRVRAL YFPAGGSSSGTVSPAQNTVSAISSILSKTGDPVPNGSGSAMQIYEGKLTAEGLRFGIV ASRANHALVDRLVEGAIDAIVRHGGREEDITLVRVCGSWEIPVAAGELARKEDIDA VIAIGVLCRGATPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIEAAGTCH GNKGWEAALCAIEMANLFKSLR 386 UL130sigP PreSlS2-LuS (C) 2 SEQ ID NO:399 consists of from 5' end to 3’ end: 5’ UTR SEQ ID NO: 89. mRNA ORF SEQ ID NO:377, and 3’ UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7mG( 5 ’ )ppp(5 ’ )NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCUGCGGCUGCUACUGCGGCACCACUUCCACUGUCUGCUCUUGUGCGCCG UGUGGGCCACACCUUGUCUCGCCGGCGGGUGGAGCAGCAAGCCCCGGCAGGG CAUGGGCACCAACCUGAGCGUCCCCAACCCACUGGGCUUCUUCCCCGGCCAC CAGCUGGACCCUGCCUUCGGGGCCAAUAGCAAUAACCCCGACUGGGACUUCA ACCCCAACAAGGACCAGUGGCCCGCUGCACACCAGGUGGGCGUUGGCAGCUU CGGCCCCGGCUUCACCCCUCCUCACGGCAACCUGCUGGGCUGGAGCCCGCAA GCCCAGGGCAUCCUGACCACCGUGCCCGCCGCUCCACCACCAGCAAGCACAA AUCGGCAGAGCGGUCGGCAACCCACCCCGAUCUCACCGCCUCUCAGGGACAG CCACCCACAGGCUAUGCAGUGGAACAGCAGCACUUUCCACCAAGCCUUGCUG GAUCCACGGGUGCGGGGCCUGUAUUUCCCCGCGGGCGGAAGCUCUAGCGGCA CCGUGAACCCAGUUCCCACCACCGCCAGCCCCAUUAGCAGCAUCUUCAGCCG GACCGGUGACCCAGCACCCAACGGCAGUGGCAGCGCCAUGCAGAUCUACGAG GGCAAGCUGACCGCCGAGGGCCUGCGGUUCGGCAUCGUGGCCAGCCGGGCCA ACCACGCCCUGGUGGACCGGCUGGUGGAGGGCGCCAUCGACGCCAUUGUGCG UCACGGCGGACGGGAGGAAGACAUCACACUGGUGCGCGUGUGCGGCAGCUG GGAGAUCCCUGUGGCGGCAGGGGAACUCGCCCGGAAGGAGGACAUUGACGCC GUGAUCGCCAUCGGCGUGCUGUGUAGAGGCGCUACCCCGAGCUUCGAUUACA UCGCCAGCGAGGUGAGCAAGGGCCUCGCCGACCUGAGCCUGGAACUCCGGAA GCCCAUCACCUUCGGCGUGAUCACCGCCGACACUCUGGAGCAGGCCAUCGAG GCAGCCGGCACCUGUCACGGAAACAAGGGCUGGGAGGCCGCCCUUUGCGCUA UCGAGAUGGCCAACCUGUUCAAGAGCCUGCGG 377 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRQGMGTNLSVPNPLGFFPGHQL DPAFGANSNNPDWDFNPNKDQWPAAIIQVGVGSFGPGFTPPIIGNLLGWSPQAQGI 387 Name Sequence SEQ ID NO: LTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSSTFHQALLDPRVRGLYF PAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNGSGSAMQIYEGKLTAEGLRFGIVAS RANHALVDRLVEGAIDAIVRHGGREEDITLVRVCGSWEIPVAAGELARKEDIDAVI AIGVLCRGATPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIEAAGTCHGN KGWEAAECATEMANEFKSER UL130sigP PreSlS2-LuS (D) 2 SEQ ID N0:400 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:378, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7 mG (5 ’ )ppp(5 ’ )NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGiniGCGGCUCCUUCUCCGGCACCACUUCCACUGUCUGCUGCUGUGCGCCG UGUGGGCCACCCCUUGCCUGGCUGGCGGCAUGGGCCAGAACCUGUCAACCAG CAACCCACUGGGCUUCUUCCCCGACCAUCAGCUGGAUCCUGCCUUCAGAGCC AACACCGCCAACCCCGACUGGGACUUUAACCCUAACAAGGACACCUGGCCCG ACGCCAACAAGGUAGGGGCUGGUGCCUUUGGCCUUGGCUUCACACCACCCCA CGGAGGACUGCUGGGGUGGAGCCCACAGGCCCAGGGCAUCCUGCAGACCCUG CCCGCCAAUCCACCUCCGGCUAGCACAAACCGGCAGAGCGGUCGGCAACCGA CCCCACUGAGCCCGCCUCUCCGGAACACCCACCCUCAGGCCAUGCAGUGGAA CAGCACCACCUUCCACCAGACCUUGCAGGACCCAAGGGUGCGGGGCCUGUAC UUCCCCGCUGGCGGAAGUAGCUCUGGCACCGUUAACCCCGUUCCCACGACCG UGAGCCACAUCUCAAGCAUCUUCAGCAGAAUCGGUGACCCGGCCCUGAACGG CUCUGGUUCAGCCAUGCAAAUCUACGAAGGCAAGCUGACCGCCGAGGGCCUG CGGUUCGGAAUCGUGGCCAGCCGGGCCAACCACGCCCUGGUGGACCGGCUGG UGGAGGGCGCCAUCGACGCCAUCGUCCGCCACGGUGGUCGGGAGGAGGACAU CACCCUGGUGCGGGUGUGCGGCAGCUGGGAGAUUCCCGUGGCCGCAGGCGAA CUGGCCCGGAAAGAGGACAUUGACGCCGUGAUCGCCAUCGGCGUGUUGUGCA GAGGCGCUACCCCUAGCUUCGACUACAUCGCCAGCGAGGUGAGCAAGGGCCU GGCCGACCUGAGCCUGGAACUGCGGAAACCCAUCACCUUCGGAGUGAUAACU GCCGACACCCUGGAGCAGGCCAUCGAAGCAGCUGGCACCUGCCACGGCAACA AGGGCUGGGAGGCCGCCCUUUGCGCAAUCGAGAUGGCCAACCUAUUCAAGAG CUUGCGG 378 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 Poly A 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGMGQNLSTSNPLGFFPDHQLDPAFRANTA NPDWDFNPNKDTWPDANKVGAGAFGLGFTPPHGGLLGWSPQAQGILQTLPANPPP ASTNRQSGRQPTPLSPPLRNTHPQAMQWNSTTFHQTLQDPRVRGLYFPAGGSSSGT VNPVPTTVSHISSIFSRIGDPALNGSGSAMQIYEGKLTAEGLRFGIVASRANHALVD REVEGAIDA1VRHGGREED1TEVRVCGSWE1PVAAGEEARKED1DAVIAIGVLCRGA TPSFDYIASEVSKGLADLSLELRKPITFGVITADTLEQAIEAAGTCHGNKGWEAALC AIEMANLFKSLR 388 Core-wt SEQ ID NO: 82 consists of from 5’ end to 3' end: 5' UTR SEQ ID NO: 55. mRNA ORF SEQ ID NO: 43. and 3' UTR SEQ ID NO: 65. 82 Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 Name Sequence SEQ ID NO: mRNAORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACCGUGGAGCUGCU GAGCUUCCUGCCCAGCGACUUCUUCCCCAGCGUGAGAGAUCUGCUGG ACACCGCCAGCGCCCUGUACAGAGAGGCCCUGGAGAGCCCCGAGCAC UGCUCGCCUCACCACACCGCCCUGAGACAGGCCAUCCUGUGCUGGGG CGAGCUGAUGACCCUGGCCACCUGGGUGGGCGUGAACCUGGAGGAC CCCGCCAGCAGGGAUCUGGUGGUGAGCUACGUGAACACCAACAUGG GCCUGAAGUUCAGACAGCUGCUGUGGUUCCACAUCAGCUGCCUGACC UUCGGCAGAGAGACAGUGAUCGAGUACCUGGUGAGCUUCGGCGUGU GGAUCAGAACACCACCCGCCUACAGACCACCCAACGCCCCAAUCCUG AGCACCCUGCCCGAGACUACCGUGGUGAGAAGAAGAGGCAGAAGCC CCAGAAGAAGAAGAACCCCGAGCCCACGGCGCAGGCGCAGCCAGAGU CCUAGACGGAGAAGAAGUCAGAGCCGUGAGAGCCAGUGC 43 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYK.EFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHH TALRQAILCWGELMTLATWVGVNLEDPASRDLWSYVNTNMGLKFRQL LWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRR GRSPRRRRTPSPRRRRSQSPRRRRSQSRESQC 2 Core-P5W SEQ ID NO: 83 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 44, and 3' UTR SEQ ID NO: 65. 83 Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNAORF AUGGACAUCGACUGGUACAAGGAGUUCGGCGCCACCGUGGAGCUGC UGAGCUUCCUGCCCAGCGACUUCUUCCCCAGCGUGAGAGAUCUGCUG GACACCGCCAGCGCCCUGUACAGAGAGGCCCUGGAGAGCCCCGAGCA CUGCUCGCCUCACCACACCGCCCUGAGACAGGCCAUCCUGUGCUGGG GCGAGCUGAUGACCCUGGCCACCUGGGUGGGCGUGAACCUGGAGGA CCCCGCCAGCAGGGAUCUGGUGGUGAGCUACGUGAACACCAACAUG GGCCUGAAGUUCAGACAGCUGCUGUGGUUCCACAUCAGCUGCCUGA CCUUCGGCAGAGAGACAGUGAUCGAGUACCUGGUGAGCUUCGGCGU GUGGAUCAGAACACCACCCGCCUACAGACCACCCAACGCCCCAAUCC UGAGCACCCUGCCCGAGACUACCGUGGUGAGAAGAAGAGGCAGAAG CCCCAGAAGAAGAAGAACCCCGAGCCCACGGCGCAGGCGCAGCCAGA GUCCUAGACGGAGAAGAAGUCAGAGCCGUGAGAGCCAGUGC 44 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MDIDWYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPH HTALRQAILCWGELMTLATWVGVNLEDPASRDLWSYVNTNMGLKFRQ LLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRR GRSPRRRRTPSPRRRRSQSPRRRRSQSRESQC 26 UL130sigP PreSlS2 D core-wt Name Sequence SEQ ID NO: SEQ ID NO: 369 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 54, mRNA ORF SEQ ID NO: 370. and 3' UTR SEQ ID NO: 58. 369 Chemical Modification 1 -methylpseudouridine Cap 7mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCCG GCGCCGCCACC 54 mRNA ORF AUGCUGAGACUGCUGUUAAGACACCACUUCCACUGCCUGCUUCUGU GCGCGGUCUGGGCCACACCUUGCCUGGCCGGCGGGUGGAGCAGCAAG CCUAGAAAGGGCAUGGGCACCAACCUGGCCGUGCCUAACCCUCUGGG CUUCUUCCCUGACCAUCAACUGGACCCUGCCUUCGGAGCCAACAGCA ACAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCC GCCAACCAGGUGGGAGUCGGCGCCUUCGGCCCUGGCCUGACCCCACC UCACGGCGGCAUCCUGGGCUGGAGCCCUCAAGCCCAGGGCAUCCUUA CCACCGUGAGCACCAUCCCACCUCCUGCCAGCACCAACAGACAGAGC GGCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGGGACAGCCACCC UCAGGCCAUGCAGUGGCAGAGCACCGCCUUCCACCAGGCCCUGCAGG ACCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGC GGCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUUAGCAGCAU CAGCGCCAGAACCGGCGACCCUGUGACCAACGGCGGCGGAUCUGGCG GAGGCUCUGGAGGCGGCAUGGACAUCGACCCCUACAAGGAGUUCGG CGCCACCGUGGAGCUGCUGAGCUUCCUGCCCAGCGACUUCUUUCCCA GCGUGAGAGAUCUGCUGGACACCGCCAGCGCCCUGUACAGAGAGGCC CUGGAGAGCCCCGAGCACUGCUCGCCUCACCACACCGCCCUGAGACA GGCCAUCCUGUGCUGGGGCGAGCUGAUGACCCUGGCCACCUGGGUG GGCGUGAACCUGGAGGACCCCGCCAGCAGGGAUCUGGUGGUCAGCU ACGUGAACACCAACAUGGGCCUGAAGUUCAGACAGCUGCUGUGGUU CCACAUCAGCUGCCUGACCUUCGGCAGAGAGACAGUGAUCGAGUACC UGGUGAGCUUCGGCGUGUGGAUCAGAACACCUCCCGCCUACAGACCA CCCAACGCCCCAAU CCU GAGCACCCUGCCAGAGACU ACCGU GGU GAG ACGAAGAGGCAGAAGCCCCAGAAGACGCAGAACCCCGAGCCCACGGC GCAGGCGCAGCCAGAGUCCUAGACGGAGAAGAAGUCAGAGCCGUGA GAGCCAGUGC 370 3'UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGG CCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC 58 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLAVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWQST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNGG GSGGGSGGGMDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREAL ESPEHCSPHHTALRQAILCWGELMTLATWVGVNLEDPASRDLWSYVNT NMGLKFRQLLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTL PETTWRRRGRSPRRRRTPSPRRRRSQSPRRRRSQSRESQC 371 UL130sigP PreSlS2 HBcAg(l-149) SEQ ID NO: 84 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 45, and 3' UTR SEQ ID NO: 65. 84 Chemical Modification 1 -methylpseudouridine Name Sequence SEQ ID NO: Cap 7mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCUGAGACUGCUGCUGAGACACCACUUCCACUGCCUGCUGCUGUG CGCCGUGUGGGCCACACCCUGCCUGGCCGGCGGCUGGAGCAGCAAGC CUAGAAAGGGCAUGGGCACCAACCUGAGCGUGCCUAACCCUCUGGGC UUCUUCCCUGACCACCAGCUGGACCCUGCCUUCGGCGCCAACAGCAA CAACCCUGACUGGGACUUCAACCCUAUCAAGGACCACUGGCCUGCCG CCAACCAGGUGGGCGUGGGCGCCUUCGGCCCUGGCCUGACCCCUCCU CACGGCGGCAUCCUGGGCUGGAGCCCUCAGGCCCAGGGCAUCCUGAC CACCGUGAGCACCAUCCCUCCUCCUGCCAGCACCAACAGACAGAGCG GCAGACAGCCUACCCCUAUCAGCCCUCCUCUGAGAGACAGCCACCCU CAGGCCAUGCAGUGGAACAGCACCGCCUUCCACCAGGCCCUGCAGGA CCCUAGAGUGAGAGGCCUGUACUUCCCUGCCGGCGGCAGCAGCAGCG GCACCGUGAACCCUGCCCCUAACAUCGCCAGCCACAUCAGCAGCAUC AGCGCCAGAACCGGCGACCCUGUGACCAACGGCGGCGGAUCUGGAGG CGGCUCUGGCGGAGGCAUGGACAUCGACCCCUACAAGGAGUUCGGC GCCACCGUGGAGCUGCUGAGCUUCCUGCCCAGCGACUUCUUCCCCAG CGUGAGAGAUCUGCUGGACACCGCCAGCGCCCUGUACAGAGAGGCCC UGGAGAGCCCCGAGCACUGCUCGCCUCACCACACCGCCCUGAGACAG GCCAUCCUGUGCUGGGGCGAGCUGAUGACCCUGGCCACCUGGGUGG GCGUGAACCUGGAGGACCCCGCCAGCAGGGAUCUGGUGGUGAGCUA CGUGAACACCAACAUGGGCCUGAAGUUCAGACAGCUGCUGUGGUUC CAC AU CAGCU GCCU GACCU U CGGCAGAGAGACAGU GAUCGAGU ACC UGGUGAGCUUCGGCGUGUGGAUCAGAACACCACCCGCCUACAGACCA CCCAACGCCCCAAUCCUGAGCACCCUGCCCGAGACUACCGUGGUG 45 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MLRLLLRHHFHCLLLCAVWATPCLAGGWSSKPRKGMGTNLSVPNPLGFF PDHQLDPAFGANSNNPDWDFNPIKDHWPAANQVGVGAFGPGLTPPHGGI LGWSPQAQGILTTVSTIPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNST AFHQALQDPRVRGLYFPAGGSSSGTVNPAPNIASHISSISARTGDPVTNGG GSGGGSGGGMDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREAL ESPEHCSPHHTALRQAILCWGELMTLATWVGVNLEDPASRDLWSYVNT NMGLKFRQLLWFHISCLTFGRETVIEYLVSFGVWIRTPPAYRPPNAPILSTL PETTVV 27 Corel-19 (A) 2 SEQ ID NO:85 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:379, and 3' UTR SEQ ID NO:65. 85 Chemical Modification 1 -methylpseudouridine Cap 7mG( 5 ’ )ppp(5 ’ )NlmpNp 5'UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU CUCGCAACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACCGUGGAGCUGCU GAGCUUCCUGCCCAGCGACUUCUUCCCCAGCGUGCGGGAUCUGCUGG ACACUGCCAGCGCCCUGUACCGGGAGGCCCUGGAGAGCCCCGAGCAC UGCAGCCCACACCACACCGCCCUGCGGCAGGCCAUCCUGUGCUGGGG 379 Name Sequence SEQ ID NO: CGAGCUGAUGACCCUGGCCACCUGGGUGGGCAACAACCUGGAGGACC CUGCCAGCCGGGACCUGGUGGUGAACUACGUGAACACCAACAUGGG CCUGAAGAUCCGGCAGCUGCUGUGGUUCCACAUCAGCUGCCUGACCU UCGGCCGGGAGACGGUGCUGGAGUACCUGGUGAGCUUCGGCGUGUG GAUCCGGACACCGCCUGCCUACCGGCCUCCAAACGCCCCAAUCCUGA GCACCCUGCCCGAGACAACCGUGGUG 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHH TALRQAILCWGELMTLATWVGNNLEDPASRDLWNYVNTNMGLKIRQL LWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTW 389 Corel-19 (B) 2 SEQ ID NO: 102 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:380, and 3' UTR SEQ ID NO: 65. 102 Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCAGCGUGGAGCUGCUGAGCU UCCUGCCCAGCGACUUCUUCCCCAGCAUCCGGGACCUGCUGGACACAGCCAG CGCCCUGUACCGGGAGGCCCUGGAGAGCCCCGAGCACUGCAGCCCACACCAC ACCGCCCUGCGGCAGGCCAUCCUGUGCUGGGGCGAGCUGAUGAACCUGGCCA CCUGGGUGGGCAGCAACCUGGAGGACCCUGCCAGCCGGGAGCUGGUGGUUAG CUACGUGAACGUGAACAUGGGCCUGAAGAUCCGGCAGCUGCUGUGGUUCCAC AUCAGCUGCCUGACCUUCGGCCGGGAGACAGUGCUGGAGUACCUGGUGAGCU UCGGCGUGUGGAUCCGGACACCGCCAGCCUACCGGCCACCUAACGCCCCAAU CCUGAGCACCCUGCCCGAGACGACCGUGGUG 380 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEIICSPiniTALRQA ILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRE TVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVV 390 Corel49 (C) 2 SEQ ID NO:401 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 89, mRNA ORF SEQ ID NO:381, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7 mG( 5 ’ )ppp( 5 ’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGGACAUCGACCCAUACAAGGAGUUCGGCGCCAGCGUGGAGCUGCUGAGCU UCCUGCCCAGCGACUUCUUCCCCAGCAUCCGGGACCUGCUGGACACCGCCAG CGCCCUGUACCGGGAGGCCCUGGAGAGCCCCGAGCACUGCAGCCCUCACCAC ACCGCCCUGCGGCAGGCCAUCCUGUGUUGGGGCGAGCUGAUGAACCUGGCCA CCUGGGUGGGCAGCAACCUGGAGGACCCAGCCAGCCGGGAGCUGGUGGUCAG CUACGUGAACGUGAACAUGGGCCUGAAGAUCCGGCAGCUGCUGUGGUUCCAC AUCAGCUGCCUGACCUUCGGCCGGGAGACUGUGCUGGAGUACCUGGUGAGCU UCGGCGUGUGGAUCCGGACCCCUACCGCCUACCGGCCACCUAACGCCCCAAU CCUGAGCACCCUGCCCGAGACUACCGUGGUG 381 Name Sequence SEQ ID NO: 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQA ILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRE TVLEYLVSFGVWIRTPTAYRPPNAPILSTLPETTVV 391 Corel49 (D) 2 SEQ ID NO:402 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 89, mRNA ORF SEQ ID NO:46, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7 mG( 5 ’ )ppp( 5 ’INlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACCGUGGAGCUGCUGAGCU UCCUGCCCAGCGACUUCUUCCCCAGCGUGAGAGAUCUGCUGGACACCGCCAG CGCCCUGUACAGAGAGGCCCUGGAGAGCCCCGAGCACUGCUCGCCUCACCAC ACCGCCCUGAGACAGGCCAUCCUGUGCUGGGGCGAGCUGAUGACCCUGGCCA CCUGGGUGGGCGUGAACCUGGAGGACCCCGCCAGCAGGGAUCUGGUGGUGA GCUACGUGAACACCAACAUGGGCCUGAAGUUCAGACAGCUGCUGUGGUUCCA CAUCAGCUGCCUGACCUUCGGCAGAGAGACAGUGAUCGAGUACCUGGUGAGC UUCGGCGUGUGGAUCAGAACACCACCCGCCUACAGACCACCCAACGCCCCAA UCCUGAGCACCCUGCCCGAGACUACCGUGGUG 46 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEIICSPiniTALRQ AILCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFG RETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVV 28 Corel49 (D)_3 SEQ ID NO: 103 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 94, mRNA ORF SEQ ID NO: 104, and 3' UTR SEQ ID NO: 105. 103 Chemical Modification 1-methylpseudouridine Cap m7G(5')ppp(5')G-2'-O-methyl 5' UTR AGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 94 mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACAGUGGAGCUGCUGAGCU UCCUGCCCAGCGACUUCUUCCCCAGCGUGCGGGAUCUGCUGGACACUGCCAG CGCCCUGUAUCGGGAGGCCCUAGAGAGCCCCGAGCACUGCAGCCCUCACCAC ACCGCUCUCCGGCAGGCCAUCCUGUGCUGGGGCGAGCUGAUGACCCUGGCAA CGUGGGUGGGCGUGAACCUGGAGGACCCCGCCUCAAGAGAUCUGGUCGUGA GCUACGUGAACACCAACAUGGGCCUGAAGUUCCGGCAGCUGCUGUGGUUCCA CAUCAGCUGCCUGACCUUCGGCCGGGAGACUGUGAUCGAGUACCUGGUGAGC UUCGGCGUGUGGAUCCGGACACCACCAGCCUACCGGCCUCCAAACGCCCCGA UCCUGAGCACCCUGCCCGAGACUACCGUGGUG 104 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCAUUUUGGCCCAGUGGUCUUUGAAUAAAG UCUGAGUGGGCGGC 105 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHHTALRQ AILCWGELMTLATWVGVNLEDPASRDLVVSYVNTNMGLKFRQLLWFHISCLTFG RETVIEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVV 28 Name Sequence SEQ ID NO: Corel49-Y132A SEQ ID NO: 372 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 54, mRNA ORF SEQ ID NO: 373, and 3' UTR SEQ ID NO: 58. 372 Chemical Modification 1 -methylpseudo uridine Cap 7 mG( 5 ’ )ppp(5 ’ )NlmpNp 5'UTR GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCCG GCGCCGCCACC 54 mRNA ORF AUGGACAUCGACCCCUACAAGGAGUUCGGCGCCACCGUGGAGCUGCU GAGCUUCCUGCCCAGCGACUUCUUCCCCAGCGUGAGAGAUCUGCUGG ACACCGCCAGCGCCCUGUACAGAGAGGCCCUGGAGAGCCCCGAGCAC UGCUCGCCUCACCACACCGCCCUGAGACAGGCCAUCCUGUGCUGGGG CGAGCUGAUGACCCUGGCCACCUGGGUGGGCGUGAACCUGGAGGAC CCCGCCAGCAGGGAUCUGGUGGUGAGCUACGUGAACACCAACAUGG GCCUGAAGUUCAGACAGCUGCUGUGGUUCCACAUCAGCUGCCUGACC UUCGGCAGAGAGACAGUGAUCGAGUACCUGGUGAGCUUCGGCGUGU GGAUCAGAACACCACCCGCCGCCAGACCACCCAACGCCCCAAUCCUG AGCACCCUGCCCGAGACUACCGUGGUG 373 3'UTR UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGG CCUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC 58 PolyA 100 nucleotides 411 Corresponding Protein MDIDPYKEFGATVELLSFLPSDFFPSVRDLLDTASALYREALESPEHCSPHH TALRQAILCWGELMTLATWVGVNLEDPASRDLWSYVNTNMGLKFRQL LWFHISCLTFGRETVIEYLVSFGVWIRTPPAARPPNAPILSTLPETTW 374 Pol wt SEQ ID NO: 86 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 47, and 3' UTR SEQ ID NO: 65. 86 Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCCCCUGAGCUACCAGCACUUCCGGCGGCUGCUGCUGCUGGACGA CGAGGCCGGACCCCUGGAGGAGGAGCUCCCACGGCUCGCCGACGAGG ACCUGAACCGGCGGGUGGCCGAAGACCUGAACCUGGGCAACCUGAAC GUGAGCAUCCCCUGGACCCACAAGGUGGGCAACUUCACCGGCCUGUA CAGCAGCACCGUGCCCGUGUUCAACCCUCACUGGAAGACACCCAGCU UCCCCAACAUCCACCUGCACCAGGACAUCAUCAAGAAGUGCGAGCAG UUCGUGGGCCCACUGACAGUGAACGAGAAGCGGCGGCUGCAGCUGA UCAUGCCCGCCCGGUUCUACCCCAAGGUGACCAAGUACCUGCCCCUG GACAAGGGCAUCAAGCCCUACUACCCCGAGCACCUGGUGAACCACUA CUUCCAGACCCGGCACUACCUGCACACCCUGUGGAAGGCCGGCAUCC UGUACAAGCGGGAGACCACCCACAGCGCCAGCUUCUGCGGCAGCCCC UACAGCUGGGAGCAGGAGCUGCAGCACGGCGCCGAGAGCUUCCACCA GCAGAGCAGCGGCAUCCUGAGCCGGCCUCCAGUGGGCAGCAGCCUGC AGAGCAAGCACAGCAAGAGCCGGCUGGGCCUGCAGAGCCAGCAGGG CCACUUGGCAAGGAGGCAGCAGGGCCGGAGCUGGAGCAUCAGAGCC GGCAUCCACCCCACGGCAAGGAGACCUUUUGGCGUGGAGCCUAGCGG CAGCGGCCACAACACCAACCUGGCCAGCAAGAGCGCCAGCUGCCUGU 47 Name Sequence SEQID NO: ACCAGAGCCCUCUGCGGAAGGCCGCCUACCCCGCAGUGAGCACCUUC GAGAAGCACAGUAGCAGCGGCCACGCAGUGGAGCUGCACAACCUGCC ACCCAACUCUGCCCGGAGUCAAGGCGAGCGCCCCGUGUUCCCAUGCU GGUGGCUGCAGUUCCGGAACAGCAAGCCCUGCAGCGACUACUGCCUG AGCCACAUCGUGAACCUGUUAGAGGACUGGGGUCCUUGCGCCGAGC ACGGCGAGCACCACAUCCGGAUUCCACGCACACCUGCUCGGGUGACU GGCGGCGUGUUCCUGGUGGACAAGAAUCCCCACAACACCGCCGAGUC ACGGCUGGUGGUGGACUUCAGCCAGUUCAGCCGGGGCAACUACCGG GUGAGCUGGCCCAAGUUCGCCGUGCCCAACCUGCAGAGCCUGACCAA CCUGCUGAGCAGCAACCUGAGCUGGCUGAGCCUGGACGUGAGCGCCG CCUUCUACCAUCUUCCCCUGCAUCCCGCAGCCAUGCCCCACCUGCUG GUGGGCAGCAGCGGCCUGAGCAGGUACGUGGCCCGCCUGAGCAGCA ACAGCCGGAUCUUCAACCACCAGCGGGGCACCAUGCAGAACCUGCAC GACUACUGCAGCCGGAACCUGUACGUGAGCCUGCUGCUGCUGUACCA GACCUUCGGCCGGAAGCUGCACCUGUACAGCCACCCCAUCAUCCUGG GCUUCCGGAAGAUCCCCAUGGGCGUGGGUCUGAGCCCCUUCCUGCUG GCCCAGUUCACCAGCGCCAUCUGCAGCGUUGUGCGGCGGGCAUUCCC ACACUGCCUGGCCUUCAGCUACAUGGACGACGUGGUGCUGGGCGCCA AGAGCGUGCAGCACCUGGAGAGCCUGUUCACCGCCGUGACCAACUUC CUGCUGAGCCUGGGCAUCCACCUGAACCCCAACAAGACCAAGCGGUG GGGCUACAGCCUGAACUUCAUGGGCUACGUGAUCGGCUGCUACGGC AGCCUGCCCCAGGACCACAUCAUCCAGAAGAUCAAGGAGUGCUUCCG GAAGCUGCCCGUGAACCGGCCCAUCGACUGGAAGGUGUGCCAGCGG AUCGUGGGCCUGCUGGGCUUCGCCGCACCCUUCACCCAGUGCGGCUA CCCCGCCCUGAAGCCCCUGUACGCCUGCAUCCAGAGCCGGCAGGCCU UCACCUUCAGCCCCACCUACAAGGCCUUCCUGUGCAAGCAGUACCUG AACCUGUAUCCAGUGGCACGGCAGAGGAGCGGUCUGUGCCAGGUGU UCGCCGACGCCACUCCCACCGGCUGGGGACUGGUGAUGGGCCACCAG AGAAUGCGGGGCACCUUCCUGGCCCCUCUGCCCAUCCACACAGCCGA ACUGCUGGCCGCCUGCUUUGCCCGCAGCAGAAGCGGAGCCAACAUCC UGGGCACCGACAAUAGCGUGGUGCUGAGCCGGAAGUACACCAGCUU CCCCUGGCUCCUCGGGUGUGCCGCGAACUGGAUCCUGCGGGGCACCA GCUUCGUGUACGUGCCCAGCGCCCUGAAUCCCGCCGACGAUCCAAGC AGAGGCCGUCUCGGACUGUCACGGCCCCUGCUGAGACUGCCCUUCCG CCCUACCACAGGCCGGACCAGCCUGUACGCCGACAGCCCAAGCGUGC CCAGCCACCUCCCCGAUCGGGUGCACUUCGCCAGCCCACUUCACGUU GCCUGGCGGCCACCU 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSI PWTHKVGNFTGLYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTV NEKRRLQLIMPARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTL WKAGILYKRETTHSASFCGSPYSWEQELQHGAESFHQQSSGILSRPPVGSS LQSKHSKSRLGLQSQQGHLARRQQGRSWSIRAGIHPTARRPFGVEPSGSG HNTNLASKSASCLYQSPLRKAAYPAVSTFEKHSSSGHAVELHNLPPNSAR SQGERPVFPCWWLQFRNSKPCSDYCLSHIVNLLEDWGPCAEHGEHHIRIP RTPARVTGGVFLVDKNPHNTAESRLWDFSQFSRGNYRVSWPKFAVPNL QSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYVARLS SNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFR 1 Name Sequence SEQ ID NO: KIPMGVGLSPFLLAQFTSAICSWRRAFPHCLAFSYMDDWLGAKSVQHL ESLFTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQK IKECFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQ AFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLVMGHQR MRGTFLAPLPIHTAELLAACFARSRSGANILGTDNSVVLSRKYTSFPWLLG CAANWILRGTSFVYVPSALNPADDPSRGRLGLSRPLLRLPFRPTTGRTSLY ADSPSVPSHLPDRVHFASPLHVAWRPP Pol 8mut -D SEQ ID NO: 87 consists of from 5' end to 3’ end: 5’ UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 48, and 3' UTR SEQ ID NO: 65. 87 Chemical Modification 1 -methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCCCCUGAGCUACCAGCACUUCCGGCGGCUGCUGCUGCUGGACGA CGAGGCCGGACCCCUGGAGGAGGAGCUCCCACGGCUCGCCGACGAGG ACCUGAACCGGCGGGUGGCCGAAGACCUGAACCUGGGCAACCUGAAC GUGAGCAUCCCCUGGACCCACAAGGUGGGCAACUUCACCGGCCUGGC CAGCAGCACCGUGCCCGUGUUCAACCCUCACUGGAAGACACCCAGCU UCCCCAACAUCCACCUGCACCAGGACAUCAUCAAGAAGUGCGAGCAG UUCGUGGGCCCACUGACAGUGAACGAGAAGCGGCGGCUGCAGCUGA UCAUGCCCGCCCGGUUCUACCCCAAGGUGACCAAGUACCUGCCCCUG GACAAGGGCAUCAAGCCCUACUACCCCGAGCACCUGGUGAACCACUA CUUCCAGACCCGGCACUACCUGCACACCCUGUGGAAGGCCGGCAUCC UGUACAAGCGGGAGACCACCCACAGCGCCAGCUUCUGCGGCAGCCCC UACAGCUGGGAGCAGGAGCUGCAGCACGGCGCCGAGAGCUUCCACCA GCAGAGCAGCGGCAUCCUGAGCCGGCCUCCAGUGGGCAGCAGCCUGC AGAGCAAGCACAGCAAGAGCCGGCUGGGCCUGCAGAGCCAGCAGGG CCACUUGGCAAGGAGGCAGCAGGGCCGGAGCUGGAGCAUCAGAGCC GGCAUCCACCCCACGGCAAGGAGACCUUUUGGCGUGGAGCCUAGCGG CAGCGGCCACAACACCAACCUGGCCAGCAAGAGCGCCAGCUGCCUGU ACCAGAGCCCUCUGCGGAAGGCCGCCUACCCCGCAGUGAGCACCUUC GAGAAGCACAGUAGCAGCGGCCACGCAGUGGAGCUGCACAACCUGCC ACCCAACUCUGCCCGGAGUCAAGGCGAGCGCCCCGUGUUCCCAGCCU GGUGGCUGCAGUUCCGGAACAGCAAGCCCGCCAGCGACUACGCCCUG AGCCACAUCGUGAACCUGUUAGAGGACUGGGGUCCUGCAGCCGAGC ACGGCGAGCACCACAUCCGGAUUCCACGCACACCUGCUCGGGUGACU GGCGGCGUGUUCCUGGUGGACAAGAAUCCCCACAACACCGCCGAGUC ACGGCUGGUGGUGGACUUCAGCCAGUUCAGCCGGGGCAACUACCGG GUGAGCUGGCCCAAGUUCGCCGUGCCCAACCUGCAGAGCCUGACCAA CCUGCUGAGCAGCAACCUGAGCUGGCUGAGCCUGGACGUGAGCGCCG CCUUCUACCAUCUUCCCCUGCAUCCCGCAGCCAUGCCCCACCUGCUG GUGGGCAGCAGCGGCCUGAGCAGGUACGUGGCCCGCCUGAGCAGCA ACAGCCGGAUCUUCAACCACCAGCGGGGCACCAUGCAGAACCUGCAC GACUACUGCAGCCGGAACCUGUACGUGAGCCUGCUGCUGCUGUACCA GACCUUCGGCCGGAAGCUGCACCUGUACAGCCACCCCAUCAUCCUGG GCUUCCGGAAGAUCCCCAUGGGCGUGGGUCUGAGCCCCUUCCUGCUG GCCCAGUUCACCAGCGCCAUCUGCAGCGUUGUGCGGCGGGCAUUCCC ACACUGCCUGGCCUUCAGCUACAUGGACGACGUGGUGCUGGGCGCCA 48 Name Sequence SEQ ID NO: AGAGCGUGCAGCACCUGGAGAGCCUGUUCACCGCCGUGACCAACUUC CUGCUGAGCCUGGGCAUCCACCUGAACCCCAACAAGACCAAGCGGUG GGGCUACAGCCUGAACUUCAUGGGCUACGUGAUCGGCUGCUACGGC AGCCUGCCCCAGGACCACAUCAUCCAGAAGAUCAAGGAGUGCUUCCG GAAGCUGCCCGUGAACCGGCCCAUCGACUGGAAGGUGUGCCAGCGG AUCGUGGGCCUGCUGGGCUUCGCCGCACCCUUCACCCAGUGCGGCUA CCCCGCCCUGAAGCCCCUGUACGCCUGCAUCCAGAGCCGGCAGGCCU UCACCUUCAGCCCCACCUACAAGGCCUUCCUGUGCAAGCAGUACCUG AACCUGUAUCCAGUGGCACGGCAGAGGAGCGGUCUGUGCCAGGUGU UCGCCGACGCCACUCCCACCGGCUGGGGACUGGUGAUGGGCCACCAG GCCAUGCGGGGCACCUUCCUGGCCCCUCUGCCCAUCCACACAGCCGA ACUGCUGGCCGCCUGCUUUGCCCGCAGCAGAAGCGGAGCCAACAUCC UGGGCACCGACAAUAGCGUGGUGCUGAGCCGGAAGUACACCAGCUU CCCCUGGCUCCUCGGGUGUGCCGCGAACUGGAUCCUGCGGGGCACCA GCUUCGUGUACGUGCCCAGCGCCCUGAAUCCCGCCGCCGAUCCAAGC GCUGGCCGUCUCGGACUGUCACGGCCCCUGCUGAGACUGCCCUUCCG CCCUACCACAGGCCGGACCAGCCUGUACGCCGACAGCCCAAGCGUGC CCAGCCACCUCCCCGAUCGGGUGCACUUCGCCAGCCCACUUCACGUU GCCUGGCGGCCACCU 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSI PWTHKVGNFTGLaSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTV NEKRRLQLIMPARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTL WKAGILYKRETTHSASFCGSPYSWEQELQHGAESFHQQSSGILSRPPVGSS LQSKHSKSRLGLQSQQGHLARRQQGRSWSIRAGIHPTARRPFGVEPSGSG HNTNLASKSASCLYQSPLRKAAYPAVSTFEKHSSSGHAVELHNLPPNSAR SQGERPVFPaWWLQFRNSKPaSDYaLSHIVNLLEDWGPaAEHGEHHIRIPRT PARVTGGVFLVDKNPHNTAESRLWDFSQFSRGNYRVSWPKFAVPNLQS LTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYVARLSSN SRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFRKIP MGVGLSPFLLAQFTSAICSWRRAFPHCLAFSYMDDWLGAKSVQHLESL FTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQKIKE CFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQAFT FSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLVMGHQaMR GTFLAPLPIHTAELLAACFARSRSGANILGTDNSVVLSRKYTSFPWLLGCA ANWILRGTSFVYVPSALNPAaDPSaGRLGLSRPLLRLPFRPTTGRTSLYADS PSVPSHLPDRVHFASPLHVAWRPP 29 Pol dYMDD SEQ ID NO: 366 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 55, mRNA ORF SEQ ID NO: 367, and 3' UTR SEQ ID NO: 65. 366 Chemical Modification 1 -methylpseudo uridine Cap 7mG( 5 ’ )ppp( 5 ’ )NlmpNp 5'UTR GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUU UCUCGCAACUAGCAAGCUUUUUGUUCUCGCC 55 mRNA ORF AUGCCCCUGAGCUACCAGCACUUCCGGCGGCUGCUGCUGCUGGACGA CGAGGCCGGACCCCUGGAGGAGGAGCUCCCACGGCUCGCCGACGAGG 367 Name Sequence SEQID NO: ACCUGAACCGGCGGGUGGCCGAAGACCUGAACCUGGGCAACCUGAAC GUGAGCAUCCCCUGGACCCACAAGGUGGGCAACUUCACCGGCCUGUA CAGCAGCACCGUGCCCGUGUUCAACCCUCACUGGAAGACACCCAGCU UCCCCAACAUCCACCUGCACCAGGACAUCAUCAAGAAGUGCGAGCAG UUCGUGGGCCCACUGACAGUGAACGAGAAGCGGCGGCUGCAGCUGA UCAUGCCCGCCCGGUUCUACCCCAAGGUGACCAAGUACCUGCCCCUG GACAAGGGCAUCAAGCCCUACUACCCCGAGCACCUGGUGAACCACUA CUUCCAGACCCGGCACUACCUGCACACCCUGUGGAAGGCCGGCAUCC UGUACAAGCGGGAGACCACCCACAGCGCCAGCUUCUGCGGCAGCCCC UACAGCUGGGAGCAGGAGCUGCAGCACGGCGCCGAGAGCUUCCACCA GCAGAGCAGCGGCAUCCUGAGCCGGCCUCCAGUGGGCAGCAGCCUGC AGAGCAAGCACAGCAAGAGCCGGCUGGGCCUGCAGAGCCAGCAGGG CCACUUGGCAAGGAGGCAGCAGGGCCGGAGCUGGAGCAUCAGAGCC GGCAUCCACCCCACGGCAAGGAGACCUUUUGGCGUGGAGCCUAGCGG CAGCGGCCACAACACCAACCUGGCCAGCAAGAGCGCCAGCUGCCUGU ACCAGAGCCCUCUGCGGAAGGCCGCCUACCCCGCAGUGAGCACCUUC GAGAAGCACAGUAGCAGCGGCCACGCAGUGGAGCUGCACAACCUGCC ACCCAACUCU GCCCGGAGU CAAGGCGAGCGCCCCGU GU UCCCAU GCU GGUGGCUGCAGUUCCGGAACAGCAAGCCCUGCAGCGACUACUGCCUG AGCCACAUCGUGAACCUGUUAGAGGACUGGGGUCCUUGCGCCGAGC ACGGCGAGCACCACAUCCGGAUUCCACGCACACCUGCUCGGGUGACU GGCGGCGUGUUCCUGGUGGACAAGAAUCCCCACAACACCGCCGAGUC ACGGCUGGUGGUGGACUUCAGCCAGUUCAGCCGGGGCAACUACCGG GUGAGCUGGCCCAAGUUCGCCGUGCCCAACCUGCAGAGCCUGACCAA CCUGCUGAGCAGCAACCUGAGCUGGCUGAGCCUGGACGUGAGCGCCG CCUUCUACCAUCUUCCCCUGCAUCCCGCAGCCAUGCCCCACCUGCUG GUGGGCAGCAGCGGCCUGAGCAGGUACGUGGCCCGCCUGAGCAGCA ACAGCCGGAUCUUCAACCACCAGCGGGGCACCAUGCAGAACCUGCAC GACUACUGCAGCCGGAACCUGUACGUGAGCCUGCUGCUGCUGUACCA GACCUUCGGCCGGAAGCUGCACCUGUACAGCCACCCCAUCAUCCUGG GCUUCCGGAAGAUCCCCAUGGGCGUGGGUCUGAGCCCCUUCCUGCUG GCCCAGUUCACCAGCGCCAUCUGCAGCGUUGUGCGGCGGGCAUUCCC ACACUGCCUGGCCUUCAGCGUGGUGCUGGGCGCCAAGAGCGUGCAGC ACCUGGAGAGCCUGUUCACCGCCGUGACCAACUUCCUGCUGAGCCUG GGCAUCCACCUGAACCCCAACAAGACCAAGCGGUGGGGCUACAGCCU GAACUUCAUGGGCUACGUGAUCGGCUGCUACGGCAGCCUGCCCCAGG ACCACAUCAUCCAGAAGAUCAAGGAGUGCUUCCGGAAGCUGCCCGU GAACCGGCCCAUCGACUGGAAGGUGUGCCAGCGGAUCGUGGGCCUG CUGGGCUUCGCCGCACCCUUCACCCAGUGCGGCUACCCCGCCCUGAA GCCCCUGUACGCCUGCAUCCAGAGCCGGCAGGCCUUCACCUUCAGCC CCACCUACAAGGCCUUCCUGUGCAAGCAGUACCUGAACCUGUAUCCA GUGGCACGGCAGAGGAGCGGUCUGUGCCAGGUGUUCGCCGACGCCA CUCCCACCGGCUGGGGACUGGUGAUGGGCCACCAGAGAAUGCGGGG CACCUUCCUGGCCCCUCUGCCCAUCCACACAGCCGAACUGCUGGCCG CCUGCUUUGCCCGCAGCAGAAGCGGAGCCAACAUCCUGGGCACCGAC AAUAGCGUGGUGCUGAGCCGGAAGUACACCAGCUUCCCCUGGCUCCU CGGGUGUGCCGCGAACUGGAUCCUGCGGGGCACCAGCUUCGUGUAC GUGCCCAGCGCCCUGAAUCCCGCCGACGAUCCAAGCAGAGGCCGUCU CGGACUGUCACGGCCCCUGCUGAGACUGCCCUUCCGCCCUACCACAG GCCGGACCAGCCUGUACGCCGACAGCCCAAGCGUGCCCAGCCACCUC Name Sequence SEQ ID NO: CCCGAUCGGGUGCACUUCGCCAGCCCACUUCACGUUGCCUGGCGGCC ACCU 3'UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSI PWTHKVGNFTGLYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTV NEKRRLQLIMPARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTL WKAGILYKRETTHSASFCGSPYSWEQELQHGAESFHQQSSGILSRPPVGSS LQSKHSKSRLGLQSQQGHLARRQQGRSWSIRAGIHPTARRPFGVEPSGSG HNTNLASKSASCLYQSPLRKAAYPAVSTFEKHSSSGHAVELHNLPPNSAR SQGERPVFPCWWLQFRNSKPCSDYCLSHIVNLLEDWGPCAEHGEHHIRIP RTPARVTGGVFLVDKNPHNTAESRLWDFSQFSRGNYRVSWPKFAVPNL QSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYVARLS SNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFR KIPMGVGLSPFLLAQFTSAICSWRRAFPHCLAFSWLGAKSVQHLESLFT AVTNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQKIKECF RKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQAFTFS PTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLVMGHQRMRGT FLAPLPIHTAELLAACFARSRSGANILGTDNSVVLSRKYTSFPWLLGCAAN WILRGTSFVYVPSALNPADDPSRGRLGLSRPLLRLPFRPTTGRTSLYADSPS VPSHLPDRVHFASPLHVAWRPP 368 Pol 8mut (A) 2 SEQ ID NO:403 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:382, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU CUCGCAACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCCGCUGAGCUACCAGCACUUUCGUAAACUGCUUCUGCUUGACG ACGGCACUGAGGCCGGCCCUCUGGAGGAGGAGCUGCCCAGACUGGCC GACGCCGACCUGAAUCGGCGGGUGGCCGAGGACCUGAACCUGGGCA ACCUGAACGUGAGCAUCCCUUGGACCCACAAGGUGGGCAACUUCACC GGCCUGGCGAGCUCCACCGUGCCCAUCUUCAACCCAGAGUGGCAAAC CCCGAGCUUUCCCAAGAUCCACCUGCAGGAGGACAUCAUCAACCGGU GCCAGCAGUUCGUGGGACCCCUGACCGUGAACGAGAAGCGACGGCU GAAGCUGAUCAUGCCCGCCCGGUUCUACCCCACCCACACCAAGUACC UGCCCCUGGACAAGGGCAUCAAGCCCUACUACCCCGACCAGGUGGUG AACCACUAUUUCCAGACCCGGCACUACCUGCAUACCCUGUGGAAGGC AGGCAUCCUGUACAAGCGGGAGACGACCCGGAGCGCUAGCUUCUGC GGCUCCCCUUACAGCUGGGAGCAGGAGCUACAGCACGGCCGUCUGGU AAUCAAGACCAGCCAGAGACACGGCGACGAGAGCUUCUGUAGCCAG CCCUCGGGGAUCCUGAGCAGAAGUAGCGUGGGCCCGUGCAUCCGGA GCCAGCUGAAGCAGAGCCGGCUUGGUUUACAACCGCACCAGGGCCCA CUGGCCUCCAGCCAACCCGGAAGGAGCGGCAGCAUUCGGGCGCGGGC ACAUCCUUCGACCCGGCGGUACUUCGGCGUGGAGCCCAGUGGGUCCG GCCAUAUCGACCACAGCGUGAACAACAGCAGUAGCUGCCUGCACCAG AGCGCCGUUAGGAAAGCCGCCUACAGCCAUCUGAGCACCAGCAAGCG GCAGAGCUCCUCUGGCCACGCCGUGGAGUUCCAUUGCUUACCACCGU 382 Name Sequence SEQID NO: CGAGCGCCGGAAGCCAGAGCCAGGGCAGCGUGUUCAGCGCCUGGUG GCUGCAGUUCCGAAACUCUAAGCCUGCCAGCGAGUACGCCCUGAGCC ACCUCGUGAACCUCCGGGAGGACUGGGGCCCUGCCGACGAGCACGGC GAGCAUCACAUCCGGAUCCCGCGAACCCCAGCCAGGGUGACCGGCGG CGUGUUUCUGGUGGACAAGAACCCUCACAACACCGCCGAAUCCCGGC UGGUGGUGGACUUCAGCCAGUUCAGCCGGGGAAUCACCAGAGUUUC UUGGCCCAAGUUCGCCGUCCCCAACCUGCAGAGCCUGACCAACCUCC UUAGCAGCAACUUAAGCUGGCUGAGCCUGGACGUGAGCGCCGCCUU CUACCACAUUCCUCUGCAUCCCGCCGCCAUGCCACACCUGCUCAUCG GCAGCAGCGGCCUGAGCCGGUACGUGGCACGGCUGAGCUCUAACAGC CGGAUCAACAACAACCAGUACGGCACCAUGCAGAACCUGCACGACAG UUGCAGCCGGCAGCUGUACGUGAGCCUGAUGCUGCUAUACAAGACC UACGGCUGGAAGCUGCACCUGUACAGCCACCCCAUCGUGCUGGGUUU CAGGAAGAUCCCCAUGGGCGUGGGUCUGAGCCCCUUCCUCCUGGCCC AGUUCACCAGCGCCAUCUGCUCCGUGGUUCGGCGGGCCUUCCCUCAC UGCCUGGCCUUCAGCUACAUGGACGACGUAGUUCUGGGCGCCAAGA GCGUGCAGCACCGGGAGAGCCUGUAUACCGCUGUGACAAACUUCCU GCUCAGCCUGGGCAUCCACUUAAACCCCAACAAGACCAAACGGUGGG GAUACAGCCUGAACUUCAUGGGCUACAUCAUCGGGAGCUGGGGCAC CCUGCCCCAGGACCACAUCGUGCAGAAGAUCAAGCACUGCUUCCGGA AACUGCCCGUCAACCGGCCCAUCGACUGGAAGGUGUGCCAGCGGAUC GUGGGCCUGCUGGGCUUCGCCGCUCCCUUCACCCAGUGCGGCUACCC CGCCCUGAUGCCUCUGUACGCCUGCAUCCAAGCUAAGCAAGCCUUCA CCUUCAGCCCCACCUACAAGGCCUUCCUGUCUAAGCAGUACAUGAAC CUGUACCCCGUGGCUAGGCAACGGCCCGGUCUGUGCCAGGUGUUCGC UGACGCCACCCCUACCGGCUGGGGCCUGGCCAUCGGCCAUCAGGCCA UGCGCGGCACAUUCGUAGCCCCACUGCCCAUCCACACCGCAGAGCUG CUGGCCGCCUGCUUCGCCCGGAGCCGAAGCGGAGCCAAACUAAUCGG CACCGACAAUAGCGUGGUGCUAAGCCGGAAGUACACCUCUUUCCCCU GGUUACUGGGCUGCACCGCCAACUGGAUCCUGCGGGGCACCAGCUUC GUGUACGUGCCGAGCGCCCUGAACCCAGCUGCGGAUCCUAGCGCUGG GCGGCUGGGACUGAGUCGGCCCCUCCUUCGGCUGCCAUUCCAACCCA CCACCGGCCGGACUAGCCUCUACGCCGUAAGCCCCAGCGUGCCCUCU CAUCUGCCCGUGCGGGUGCACUUCGCCAGCCCACUGCACGUUGCCUG GCGCCCGCCU 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRKLLLLDDGTEAGPLEEELPRLADADLNRRVAEDLNLGNLN VSIPWTHKVGNFTGLASSTVPIFNPEWQTPSFPKIHLQEDIINRCQQFVGPL TVNEKRRLKLIMPARFYPTHTKYLPLDKGIKPYYPDQVVNHYFQTRHYLH TLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVIKTSQRHGDESFCS QPSGILSRSSVGPCIRSQLKQSRLGLQPHQGPLASSQPGRSGSIRARAHPST RRYFGVEPSGSGHIDHSVNNSSSCLHQSAVRKAAYSHLSTSKRQSSSGHA VEFHCLPPSSAGSQSQGSVFSAWWLQFRNSKPASEYALSHLVNLREDWGP ADEHGEHHIRIPRTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGITRV SWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLIGSSG LSRYVARLSSNSRINNNQYGTMQNLHDSCSRQLYVSLMLLYKTYGWKLH LYSHP1VLGFRK1PMGVGLSPFLLAQFTSA1CSWRRAFPHCLAFSYMDDV VLGAKSVQHRESLYTAVTNFLLSLGIHLNPNKTKRWGYSLNFMGYIIGSW 392 Name Sequence SEQ ID NO: GTLPQDHIVQKIKHCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPAL MPLYACIQAKQAFTFSPTYKAFLSKQYMNLYPVARQRPGLCQVFADATPT GWGLAIGHQAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSWLS RKYTSFPWLLGCTANWILRGTSFVYVPSALNPAADPSAGRLGLSRPLLRLP FQPTTGRTSLYAVSPSVPSHLPVRVHFASPLHVAWRPP Pol 8mut (B) 2 SEQ ID NO:404 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:383, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7 mG(5 ’ )ppp(5 ’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU CUCGCAACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCCCCUGAGCUACCAGCACUUUCGUAAGCUCCUGUUGCUGGACGA GGAAGCCGGGCCUCUGGAGGAGGAGUUACCGAGGCUCGCUGACGAG GGCCUGAACAGACGGGUGGCCGAGGACCUUAAUCUGGGAAAUCUGA ACGUCUCUAUCCCUUGGACCCAUAAGGUGGGCAACUUCACCGGACUG GCUAGCUCAACGGUGCCCUGCUUCAACCCCAAGUGGCAGACCCCGAG CUUCCCCGACAUUCACCUGCAGGAGGACAUCGUGGACCGGUGCAAAC AGUUCGUGGGACCACUGACCGUAAACGAGAACCGACGGCUAAAGCU CAUCAUGCCCGCCCGCUUUUACCCCAACGUAACCAAGUACCUACCCC UGGACAAGGGCAUCAAGCCCUAUUACCCCGAAUACGUGGUCAACCAC UACUUCCAGACCCGGCACUACCUCCAUACCCUGUGGAAGGCUGGAAU CUUGUAUAAACGGGAGAGCACUCGCUCUGCUAGCUUCUUCGGCAGC CCCUACAGCUGGGAGCAGGACCUGCAACACGGCCGGUUAGUGUUUC AGACAAGCAAGCGGCACGGUGACAAGAGCUUCUGCCCUCAGUCUCCG GGCAUACUGCCACGGUCCAGCGUCGGUCCUUGUAUCCAGUCCCAAUU ACGGAAGAGUCGGCUCGGCCCUCAACCCGCCCAGGGCCAACUGGCCG GGCGGCAACAAGGCGGCUCCGGCAGCAUACGGGCACGCGUCCAUCCC UCUCCCUGGGGAAUCGUUGGAGUGGAGCCCAGCGGUUCCGGGCCCAC CCACAACUGCGCCAGCUCCUCUAGCAGCUGCCUGCACCAGAGCGCCG UGCGGAAAGCCGCUUAUUCGCUAAUCAGCACUAGCAAGGGCCACAG CAGUAGCGGCCACGCCGUGGAGUUGCACCACUUCCCUCCCAACAGCU CUCGGAGCCAGAGCCAAGGCCCCGUGCUGAGCGCCUGGUGGCUGCAG UUCCGAAACUCAGAGCCCGCCAGCGAGUACGCCCUGUGCCACAUUGU GAACCUGAUCGAGGAUUGGGGCCCCGCCACUGAGCACGGAGAACACC GGAUUCGGACCCCGCGGACACCUGCUCGAGUGACCGGCGGCGUGUUU CUGGUCGACAAGAACCCUCACAACACCACCGAGUCGAGACUGGUGGU GGACUUCUCCCAGUUCAGCCGGGGCAACACCCGAGUCAGCUGGCCCA AGUUCGCUGUGCCCAAUCUGCAGAGCCUGACUAACCUGCUGUCUAGC AAUCUGUCUUGGCUGAGCCUGGACGUGAGCGCUGCCUUCUACCACCU GCCUCUGCACCCAGCAGCCAUGCCCCACUUGCUGGUGGGUAGCAGCG GACUGAGUCGGUACGUGGCCCGGUUGAGCAGCAAUAGCCGGAUCAU CAACAACCAACACCGAACAAUGCAGAACCUGCACAACUCCUGUAGCC GAAACCUUUACGUGUCACUGAUGUUACUGUAUAAGACCUACGGCAG AAAGCUGCACCUUUAUAGUCACCCCAUCAUCCUGGGCUUUAGGAAG AUCCCCAUGGGCGUGGGCCUAAGCCCUUUUCUGCUCGCACAGUUCAC CAGCGCCAUCUGCUCUGUGGUGCGGCGGGCCUUCCCACACUGCCUCG CUUUCAGCUACAUGGACGACGUGGUGCUGGGCGCCAAGAGCGUGCA GCACCUGGAGAGCUUGUACGCUGCCGUGACCAACUUCCUGCUAAGCC UGGGCAUCCACCUCAAUCCCCACAAGACCAAGCGGUGGGGUUACAGC 383 Name Sequence SEQ ID NO: UUGAACUUCAUGGGCUACGUGAUCGGCAGUUGGGGAACCCUGCCCC AGGAACAUAUCGUGCAGAAGAUCAAGAUGUGCUUCAGGAAACUGCC CGUGAACCGUCCCAUCGACUGGAAGGUGUGCCAGCGGAUCGUGGGG CUGUUAGGCUUCGCCGCCCCUUUCACCCAGUGCGGCUAUCCCGCCCU CAUGCCUCUUUACGCCUGCAUCCAGGCCAAGCAGGCCUUCACCUUCA GCCCUACCUACAAGGCCUUUCUGAGCAAGCAGUACUUGAAUCUCUAC CCCGUUGCCCGACAGCGACCAGGUCUGUGUCAGGUGUUCGCCGACGC CACCCCUACCGGCUGGGGCCUCGCAAUCGGCCAUCGGGCCAUGCGCG GCACCUUCGUGAGCCCUCUGCCCAUCCACACCGCCGAGCUCCUAGCC GCGUGCUUUGCCAGGAGCCGUUCCGGCGCUAAGCUGAUAGGCACCG ACAACAGCGUGGUCCUGAGCCGGAAGUACACCUCCUUCCCCUGGCUU CUGGGCUGCGCCGCUAACUGGAUCCUGCGGGGCACCAGCUUCGUGUA CGUGCCUAGCGCCCUGAAUCCAGCCGCUGAUCCCUCCGCCGGCAGAC UGGGCCUGUACCGGCCCCUGCUGCGGCUGUUCUACAGACCGACCACA GGCCGGACCAGCCUCUACGCCGAUUCACCCUCCGUCCCCAGUCACUU ACCCGACCGGGUGCACUUCGCCAGCCCACUUCACGUCGCCUGGCGGC CUCCA 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCU UUGAAUAAAGUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRKLLLLDEEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIP WTHKVGNFTGLASSTVPCFNPKWQTPSFPDIHLQEDIVDRCKQFVGPLTV NENRRLKLIMPARFYPNVTKYLPLDKGIKPYYPEYWNHYFQTRHYLHTL WKAGILYKRESTRSASFFGSPYSWEQDLQHGRLVFQTSKRHGDKSFCPQS PGILPRSSVGPCIQSQLRKSRLGPQPAQGQLAGRQQGGSGSIRARVHPSPW GIVGVEPSGSGPTHNCASSSSSCLHQSAVRKAAYSLISTSKGHSSSGHAVE LHHFPPNSSRSQSQGPVLSAWWLQFRNSEPASEYALCHIVNLIEDWGPATE HGEHRIRTPRTPARVTGGVFLVDKNPHNTTESRLWDFSQFSRGNTRVSW PKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLS RYVARLSSNSRIINNQHRTMQNLHNSCSRNLYVSLMLLYKTYGRKLHLYS HPIILGFRKIPMGVGLSPFLLAQFTSAICSWRRAFPHCLAFSYMDDWLGA KSVQHLESLYAAVTNFLLSLGIHLNPHKTKRWGYSLNFMGYVIGSWGTLP QEHIVQKIKMCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYP ALMPL YACIQAKQAFTFSPTYKAFLSKQYLNLYPVARQRPGLCQVFADATPTGW GLAIGHRAMRGTFVSPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKY TSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLRLFYR PTTGRTSLYADSPSVPSHLPDRVHFASPLHVAWRPP 393 Pol 8mut (C) 2 SEQ ID NO:405 consists of from 5' end to 3' end: 5' UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:384, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCCCCUGUCCUACCAGCACUUCCGCAAACUUCUACUGCUCGACGACGAGG CCGGCCCACUGGAGGAGGAGCUUCCCCGCCUGGCAGACGAGGGCCUGAACAG ACGGGUGGCCGAGGACCUGAACCUGGGCAAUCUGAACGUGUCUAUCCCCUGG ACUCACAAGGUGGGCAACUUCACAGGCCUCGCAUCGAGCACCGUGCCCGUUU UCAACCCCGAGUGGCAGACUCCUAGCUUCCCGCACAUCCACCUGCAGGAGGA UAUAAUCAACCGGUGUCAGCAGUACGUGGGUCCACUGACCAUCAACGAGAA 384 Name Sequence SEQID NO: GCGGCGGCUGAAGCUGAUCAUGCCCGCCCGGUUCUAUCCCAAUCUGACCAAG UAUCUGCCCCUGGAUAAGGGUAUCAAACCUUACUACCCCGAGCACGCUGUGA ACCAUUACUUCAAGACCCGGCACUACCUGCACACCCUGUGGAAGGCCGGCAU CCUAUAUAAGCGGGAGACGACCCGGAGCGCUUCCUUCUGCGGAAGCCCCUAC AGCUGGGAGCAAGAGUUGCAGCACGGCCGGCUGGUGUUCCAGACCAGCACCC GACACGGCGACGAGAGCUUUUGUAGCCAGAGCAGCGGCAUCUUGUCUCGGA GCCCUGUAGGCCCGUGUGUGCGGAGCCAGCUGAAGCAGAGCCGGCUAGGCCU GCAACCCCAACAGGGUAGCUUAGCUCGGGGCAAGAGCGGCCGGAGCGGCAGC AUACGGGCCAGAGUGCAUCCAACCACCCGGCGGAGCUUCGGCGUGGAGCCUC CUGGUUCCGGGCACAUCGACAACAGCGCCUCCUCUACCUCUUCUUGCCUGCA UCAGUCAGCCGUGCGGAAGACUGCCUACAGUCACCUGAGCACCAGCAAGCGG CAGAGCUCUAGCGGCCACGCCGUGGAGCUGCACAACAUCCCACCAAGCAGCG CCCGGAGCCAAAGCGCCGGCCCCAUCUUCAGCGCCUGGUGGCUGCAGUUUCG GAACAGCAAGCCCGCCAGCGACUACGCCCUGACCCACAUCGUGAACUUGCUG GAGGACUGGGGCCCUGCAACGGAACACGGGGAACACAACAUACGGAUCCCAC GGACACCAGCGCGGGUCACUGGCGGCGUGUUUCUGGUGGACAAGAACCCGCA CAACACCACCGAGAGCAGACUGGUCGUGGACUUCAGCCAGUUCAGCAGAGGC AGCACCCACGUGUCCUGGCCCAAGUUCGCCGUGCCAAACCUGCAAAGCCUGA CCAACCUUUUAUCAUCGAAUUUGAGCUGGCUGAGUCUGGACGUGAGCGCCGC CUUCUACCACAUCCCUCUGCACCCCGCUGCCAUGCCCCACCUGCUGGUGGGC AGCAGCGGGCUCCAACGGUACGUGGCCCGACUCAGUUCCACUAGUCGCAACA UCAAUCAUCAACACGGCGCCAUGCAGGACCUGCACGACAGCUGCAGUCGGAA CCUGUACGUGUCUCUGCUGCUUCUGUACAAGACCUUCGGCCGCAAGUUGCAC CUGUACAGCCAUCCCAUCAUCCUGGGCUUUAGGAAGAUCCCCAUGGGCGUGG GCCUGAGCCCCUUCCUGCUGGCCCAGUUCACAAGCGCCAUCUGCAGCGUUGU ACGGCGGGCCUUCCCUCACUGCCUGGCAUUCAGCUACAUGGACGACGUGGUG CUGGGCGCCAAGAGCGUGCAGCACCUCGAGAGCCUGUUCACCAGCAUCACCA ACUUCCUGUUGUCCCUGGGAAUCCACCUCAACCCUAAUAAGACCAAACGGUG GGGCUACAGCCUGAACUUCAUGGGCUACGUGAUCGGGAGCUGGGGCACCCUG CCCCAGGAGCAUAUCGUCUUAAAGCUUAAGCAGUGCUUCCGAAAGCUGCCCG UGAACCGGCCCAUCGAUUGGAAAGUGUGCCAGCGGAUCGUCGGCUUGUUAG GCUUCGCCGCCCCAUUCACCCAGUGCGGGUACCCCGCCCUGAUGCCCUUGUA CGCCUGUAUCCAGAGCAAGCAGGCCUUCACCUUCAGCCCUACCUACAAGGCC UUCCUCUGCAAACAGUACCUGAAUCUCUACCCCGUGGCGCGGCAACGUUCGG GCCUGUGCCAGGUGUUCGCCGACGCCACCCCAACCGGCUGGGGCCUGGCCAU CGGUCACCGGGCCAUGCGCGGCACUUUCGUGGCCCCACUGCCCAUCCACACC GCCGAACUGCUUGCCGCCUGUUUCGCACGGAGUCGGAGCGGGGCCAAGCUGA UAGGCACCGACAACUCUGUAGUGCUGAGCCGGAAGUACACCUCCUUUCCCUG GCUGCUGGGUUGCGCCGCCAACUGGAUCCUGCGGGGCACUUCUUUCGUGUAC GUGCCUUCCGCGCUGAAUCCCGCCGCUGAUCCCUCCGCAGGCCGACUGGGCC UUUACCGGCCCCUGCUGCACCUCCCCUUCAGACCCACCACCGGACGGACCAG CCUGUACGCCGUGAGCCCCAGCGUGCCCAGCCACCUGCCCGACCGCGUGCAC UUCGCCAGCCCACUACACGUGGCCUGGAAGCCGCCG 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA GUCUGAGUGGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHK VGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTINEKRRLKLIMPA RFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFC GSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQ PQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPPGSGHIDNSASSTSSCLHQSAVRK TAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSAGPIFSAWWLQFRNSKPASDYALT E1IVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFS RGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLVGSS GLQRYVARLSSTSRNINHQHGAMQDLHDSCSRNLYVSLLLLYKTFGRKLHLYSHPI 394 Name Sequence SEQ ID NO: ILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLES LFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKLKQCFRKL PVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLC KQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAA CFARSRSGAKLIGTDNSWLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAAD PSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWKPP Pol 8mut (D) 2 SEQ ID NO:406 consists of from 5' end to 3’ end: 5’ UTR SEQ ID NO:89, mRNA ORF SEQ ID NO:385, and 3' UTR SEQ ID NO: 65. Chemical Modification 1-methylpseudouridine Cap 7mG(5’)ppp(5’)NlmpNp 5' UTR GGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 89 mRNA ORF AUGCCCCUGAGCUACCAGCACUUCCGGCGGCUGUUACUGCUCGACGACGAGG CCGGACCCCUGGAGGAGGAGCUCCCACGGCUCGCAGACGAGGACCUGAAUCG GCGGGUGGCCGAAGACCUCAACCUGGGCAAUCUGAACGUGAGCAUUCCCUGG ACCCACAAAGUGGGCAACUUCACCGGCCUGGCCAGCAGCACCGUGCCCGUAU UCAACCCUCACUGGAAGACACCCAGCUUCCCCAACAUUCACCUGCACCAGGA CAUCAUCAAGAAGUGCGAGCAGUUCGUGGGACCACUGACAGUGAACGAGAA ACGGAGGCUGCAGCUGAUCAUGCCAGCCCGGUUCUACCCCAAGGUGACCAAG UACCUGCCCCUGGACAAGGGCAUCAAGCCCUACUACCCCGAGCACCUUGUGA ACCACUACUUCCAGACCCGGCACUACCUGCACACCCUGUGGAAGGCCGGCAU CCUGUACAAGCGGGAGACAACCCACAGCGCGAGCUUCUGCGGCAGCCCCUAC AGCUGGGAGCAGGAGCUUCAGCACGGCGCCGAGAGCUUCCACCAGCAGAGCA GCGGGAUCCUGAGCCGGCCUCCAGUGGGCAGCUCUCUGCAAAGCAAGCACAG CAAGUCCAGACUGGGCCUACAGAGCCAGCAAGGCCACUUGGCAAGGAGGCAG CAGGGCCGGAGCUGGAGCAUCAGAGCCGGGAUCCACCCCACGGCACGUAGAC CUUUUGGCGUGGAGCCUAGCGGCAGCGGGCACAAUACCAACCUGGCCUCUAA GAGCGCCAGCUGCCUGUACCAGAGCCCUCUGCGGAAGGCUGCUUACCCCGCA GUGUCCACCUUCGAGAAGCACAGUAGCUCUGGCCACGCAGUGGAGCUGCACA ACCUGCCACCCAACUCUGCCCGGAGUCAAGGCGAGCGCCCCGUGUUCCCAGC UUGGUGGCUGCAGUUCCGCAACAGCAAGCCCGCCAGCGACUACGCCCUGAGC CACAUCGUGAACCUGUUAGAGGACUGGGGUCCUGCAGCCGAGCACGGUGAGC ACCACAUCCGGAUUCCACGCACACCUGCUCGGGUGACUGGCGGCGUGUUCCU GGUGGACAAGAAUCCCCACAACACCGCCGAGUCACGGCUGGUGGUGGACUUC AGCCAGUUCAGCCGGGGCAACUACCGGGUGAGUUGGCCCAAGUUCGCCGUGC CCAACCUGCAGAGCCUGACCAACCUCCUGAGCAGCAACCUGAGCUGGCUGAG CCUGGACGUGAGCGCCGCCUUCUACCAUCUUCCCCUGCAUCCCGCAGCCAUG CCCCACCUGCUGGUUGGCAGCAGCGGCCUUUCUAGGUACGUGGCCCGCCUGU CUAGCAACAGCCGGAUCUUCAACCACCAACGGGGCACCAUGCAGAACCUGCA CGACUACUGUAGCCGGAACCUGUACGUGAGCCUGCUGCUGUUAUACCAGACC UUCGGCCGGAAGCUGCACCUGUACAGCCACCCCAUCAUACUGGGUUUCCGGA AGAUCCCCAUGGGCGUGGGUCUGAGCCCCUUCUUGUUAGCCCAGUUCACCAG CGCCAUCUGCAGCGUUGUGCGGCGGGCAUUCCCACACUGCCUGGCCUUCAGC UACAUGGACGACGUAGUGCUGGGCGCCAAGAGCGUGCAGCACCUGGAGAGCC UGUUCACCGCCGUGACCAACUUCCUGCUCAGCCUGGGCAUCCACCUGAACCC CAACAAGACCAAGCGGUGGGGCUACAGCCUGAACUUCAUGGGCUACGUGAUC GGCUGCUACGGCAGCCUGCCCCAGGACCACAUCAUCCAGAAGAUCAAGGAGU GCUUCAGAAAGCUGCCCGUGAACCGGCCCAUCGACUGGAAGGUGUGCCAGCG GAUCGUGGGCCUGCUGGGCUUCGCCGCACCCUUCACCCAGUGCGGCUACCCC GCCCUGAAGCCCCUCUACGCUUGCAUCCAGAGCAGACAGGCCUUCACCUUCA GCCCCACUUACAAGGCCUUCCUGUGCAAGCAGUACCUGAAUUUAUAUCCAGU GGCACGGCAGAGGAGCGGUCUGUGCCAGGUGUUCGCCGACGCCACUCCCACC GGCUGGGGACUGGUGAUGGGCCACCAGGCCAUGAGAGGCACCUUCCUGGCCC CUCUGCCCAUCCACACAGCCGAAUUGCUGGCCGCCUGCUUUGCCCGCAGCAG 385 Name Sequence SEQ ID NO: AAGCGGAGCCAACAUCCUGGGCACCGACAAUAGCGUGGUGCUGAGCCGAAAG UACACCAGCUUUCCCUGGCUCCUCGGGUGUGCCGCGAACUGGAUCCUGCGGG GCACAAGCUUCGUGUACGUCCCCAGUGCCCUGAAUCCCGCCGCCGAUCCAAG CGCUGGCCGUCUCGGACUGUCACGGCCCCUGCUGAGACUGCCCUUCCGCCCU ACCACAGCtCCGAACCAGCCUGUACGCCGACAGCCCAAGCCtUGCCCACtCCACC UCCCGGAUCGGGUGCACUUCGCCAGCCCACUUCACGUUGCCUGGCGGCCACC U 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUAAA CtUCUGAGUCtGGCGGC 65 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSIPWTHK VGNFTGLASSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTVNEKRRLQLIMP ARFYPKVTKYLPLDKGIKPYYPEHLVNHYFQTRHYLHTLWKAGILYKRETTHSASF CGSPYSWEQELQHGAESFHQQSSGILSRPPVGSSLQSKHSKSRLGLQSQQGHLARR QQGRSWSIRAGIHPTARRPFGVEPSGSGHNTNLASKSASCLYQSPLRKAAYPAVST FEKHSSSGHAVELHNLPPNSARSQGERPVFPAWWLQFRNSKPASDYALSHIVNLLE DWGPAAEHGEHHIRIPRTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGNYRV SWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYV ARLSSNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFRKI PMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTAVT NFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQKIKECFRKLPVNRPI DWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQAFTFSPTYKAFLCKQYLNL YPVARQRSGLCQVFADATPTGWGLVMGHQAMRGTFLAPLPIHTAELLAACFARSR SGANTLGTDNSVVLSRKYTSFPWEEGCAANWIERGTSFVYVPSAENPAADPSAGRE GLSRPLLRLPFRPTTGRTSLYADSPSVPSHLPDRVHFASPLHVAWRPP 29 Pol 8mut (D) 3 SEQ ID NO: 108 consists of from 5' end to 3' end: 5' UTR SEQ ID NO: 94. mRNA ORF SEQ ID NO: 109, and 3' UTRSEQIDNO: 110. 108 Chemical Modification 1-methylpseudouridine Cap m7G(5')ppp(5’)G-2'-O-methyl 5' UTR AGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC 94 mRNA ORF AUGCCCCUGAGCUAUCAGCAUUUCCGGCGCCUGCUCCUGCUUGACGACGAGG CCGGCCCUCUGGAGGAGGAGCUCCCACGGCUGGCCGACGAGGACUUGAACCG GCGGGUGGCCGAGGAUCUGAACCUGGGCAACCUGAACGUGUCUAUCCCUUGG ACCCAUAAGGUGGGCAACUUCACCGGCCUGGCAAGCAGCACCGUGCCCGUCU UCAACCCUCACUGGAAGACCCCUUCCUUCCCCAAUAUCCACCUGCACCAGGA CAUCAUCAAGAAGUGCGAGCAGUUCGUGGGUCCCCUGACCGUGAACGAGAA GCGGCGGCUACAACUGAUCAUGCCCGCCCGGUUCUACCCUAAGGUCACCAAG UACCUGCCCCUGGACAAGGGAAUCAAGCCCUAUUACCCGGAGCACCUCGUGA ACCACUACUUCCAGACCCGGCACUACCUGCACACUCUGUGGAAGGCUGGCAU CCUGUACAAGCGGGAGACAACCCACAGCGCCAGCUUCUGCGGCAGCCCCUAC AGCUGGGAGCAGGAACUGCAGCACGGCGCUGAGAGCUUCCACCAGCAAAGCA GCGGAAUCCUGAGCAGGCCACCAGUGGGCAGCUCGCUGCAAAGCAAACAUAG CAAGAGCCGCCUGGGGCUCCAGAGCCAGCAAGGGCACCUGGCUCGGCGUCAG CAAGGUCGCAGUUGGAGCAUCCGGGCCGGCAUACAUCCGACCGCUCGACGGC CCUUCGGCGUGGAGCCCAGCGGAAGCGGCCAUAACACCAACCUGGCCUCUAA GAGUGCCAGCUGCCUGUACCAGAGCCCACUCCGGAAGGCAGCCUACCCCGCU GUGAGCACCUUCGAGAAACACAGCUCCAGCGGCCACGCCGUGGAGCUGCACA ACCUGCCUCCUAAUUCAGCCCGGUCACAAGGGGAGCGGCCCGUGUUCCCCGC CUGGUGGCUCCAGUUUCGGAACAGCAAGCCCGCCAGCGAUUACGCCCUGAGC CAUAUUGUGAACCUGCUCGAGGACUGGGGCCCCGCAGCAGAGCACGGGGAGC ACCACAUCCGGAUUCCUCGGACACCCGCACGGGUUACCGGCGGCGUGUUCCU GGUGGACAAGAAUCCUCACAACACAGCCGAGUCUCGCCUCGUGGUGGACUUC 109 Name Sequence SEQID NO: AGCCAGUUCAGCCGGGGCAACUACCGGGUGAGCUGGCCCAAAUUCGCCGUGC CCAACCUGCAGAGCCUCACUAACUUACUGUCCUCAAAUCUUUCCUGGCUGAG CCUGGACGUGAGCGCCGCCUUCUAUCAUUUGCCGCUGCACCCAGCCGCCAUG CCACACCUGCUGGUAGGCAGCAGCGGCCUCAGCCGGUACGUCGCCAGACUGA GCACtCAACAGCCGGAUAUUCAACCAUCAGCGGGGCACCAUGCACtAACCUACA CGACUACUGCAGCCGGAACCUGUACGUGAGCCUGCUGCUGUUAUACCAGACC UUCGGACGGAAGCUUCACCUGUAUAGCCACCCCAUCAUCCUAGGUUUCCGGA AGAUCCCCAUGGGCGUGGGCCUGAGCCCCUUUCUGCUCGCCCAAUUCACUAG CGCCAUCUGCAGUGUGGUGCGGCGGGCCUUCCCACAUUGUCUGGCCUUCAGC UACAUGGACGACGUAGUGCUGGGCGCCAAGAGCGUGCAGCACCUGGAGAGCC UGUUCACGGCGGUGACCAACUUCCUUCUGUCCCUGGGCAUCCACCUCAAUCC CAACAAGACCAAGCGGUGGGGCUACAGCCUGAACUUCAUGGGCUACGUGAUC GGCUGCUACGGCAGCCUGCCCCAGGACCACAUCAUCCAGAAGAUCAAGGAGU GUUUCCGCAAGCUGCCCGUGAAUCGGCCCAUCGACUGGAAGGUGUGCCAGCG GAUCGUAGGCCUCCUGGGUUUCGCCGCCCCAUUCACCCAGUGCGGCUAUCCC GCCUUGAAGCCCUUGUACGCUUGCAUCCAAAGCCGGCAAGCUUUCACCUUCA GCCCUACCUACAAGGCCUUCCUGUGCAAGCAAUACCUGAAUCUUUACCCCGU GGCCCGGCAGAGAUCCGGCCUGUGUCAGGUGUUCGCCGACGCCACUCCGACG GGGUGGGGCCUGGUUAUGGGCCACCAAGCCAUGCGCGGCACCUUCCUGGCCC CUCUACCCAUCCACACCGCCGAGCUUCUGGCCGCCUGCUUCGCAAGGUCAAG GAGCGGGGCCAACAUCCUGGGCACCGACAACAGCGUGGUUCUGAGUCGGAAG UACACCAGCUUCCCCUGGCUGUUGGGCUGCGCCGCCAACUGGAUCCUGCGUG GCACAAGCUUCGUGUACGUGCCCUCUGCCCUGAACCCUGCUGCCGAUCCGUC AGCGGGCCGUCUGGGCUUGAGCCGGCCCCUGUUGCGGCUGCCCUUCCGACCC ACCACUGGACGAACCUCACUCUACGCCGACAGCCCCAGCGUGCCCAGCCACC UGCCCGACCGGGUCCAUUUCGCCAGUCCCCUGCACGUGGCCUGGCGGCCACC U 3' UTR UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCC CCCAGCCCCUCCUCCCCUUCCUGCAUUUUGCCCCGUGGUCUUUGAAUAAAGU CUGAGUGGGCGGC 110 PolyA 100 nucleotides 411 Corresponding Protein MPLSYQHFRRLLLLDDEAGPLEEELPRLADEDLNRRVAEDLNLGNLNVSIPWTHK VGNFTGLASSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTVNEKRRLQLIMP ARFYPKVTKYLPLDKG1KPYYPEHLVNHYFQTRHYLHTLWKAG1LYKRETTHSASF CGSPYSWEQELQHGAESFHQQSSGILSRPPVGSSLQSKHSKSRLGLQSQQGHLARR QQGRSWSIRAGIHPTARRPFGVEPSGSGHNTNLASKSASCLYQSPLRKAAYPAVST FEKHSSSGHAVELHNLPPNSARSQGERPVFPAWWLQFRNSKPASDYALSHIVNLLE DWGPAAEHGEHHIRIPRTPARVTGGVFLVDKNPHNTAESRLVVDFSQFSRGNYRV SWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHLPLHPAAMPHLLVGSSGLSRYV ARLSSNSRIFNHQRGTMQNLHDYCSRNLYVSLLLLYQTFGRKLHLYSHPIILGFRKI PMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTAVT NFLLSLGIHLNPNKTKRWGYSLNFMGYVIGCYGSLPQDHIIQKIKECFRKLPVNRPI DWKVCQRIVGLLGFAAPFTQCGYPALKPLYACIQSRQAFTFSPTYKAFLCKQYLNL YPVARQRSGLCQVFADATPTGWGLVMGHQAMRGTFLAPLPIHTAELLAACFARSR SGANlLGTDNSVVLSRKYTSFPWLLGCAANWILRG'rSFVYVPSALNPAADPSAGRL GLSRPLLRLPFRPTTGRTSLYADSPSVPSHLPDRVHFASPLHVAWRPP 29 Table IB. Full Construct Sequences mRNA Name SEQ ID NO mRNA Sequence (all uracils in the mRNAs are Nl-methylpseudouracils) PreSlS2-LuS (A) 3 412 5'7MeGpppG2'OMeAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU CUCGCAACUAGCAAGCUUUUUGUUCUCGCCAUGCUGCGGCUGUUACUGCGGCACCACU UCCAUUGCCUGCUGCUGUGCGCCGUGUGGGCCACCCCUUGCCUGGCAGGCGGUUGGAG CUCUAAGCCGCGGAAGGGCAUGGGCACCAACUUAAGCGUGCCCAACCCACUGGGCUUC UUCCCCGACCAUCAGCUGGAUCCCGCCUUCGGGGCCAACUCAAACAACCCCGACUGGGA CUUCAACCCCAUCAAGGACCAUUGGCCCGCCGCCAACCAGGUGGGCGUGGGAGCCUUU GGACCCGGCUUGACCCCACCCCACGGCGGCAUCCUGGGCUGGAGCCCGCAAGCCCAGGG GAUUCUGACCACUGUGAGCACCAUCCCACCUCCCGCGUCCACCAAUCGGCAAAGUGGG CGGCAGCCCACUCCUAUCUCUCCGCCCUUGCGGGACUCCCAUCCUCAGGCUAUGCAGUG GAACAGCACCGCCUUUCACCAAGCCCUGCAGGACCCAAGGGUGCGGGGCCUGUACUUC CCCGCCGGAGGUAGCAGCUCUGGCACCGUGAACCCUGCCCCAAACAUCGCCAGCCAUAU AUCCAGCAUCUCGGCCCGGACUGGUGACCCCGUGACAAACGGCAGCGGAAGCGCCAUG CAGAUCUACGAGGGCAAGCUCACAGCCGAAGGCCUGCGGUUCGGCAUUGUGGCCUCAC GGGCCAACCACGCCCUGGUGGACCGGCUGGUAGAAGGCGCCAUUGACGCCAUCGUGCG GCACGGAGGACGGGAGGAGGACAUCACACUGGUGCGGGUGUGCGGCAGCUGGGAGAUC CCUGUGGCCGCUGGCGAACUUGCCCGGAAAGAGGAUAUCGACGCCGUGAUUGCCAUCG GCGUGCUUUGCCGGGGCGCUACCCCUAGCUUCGACUACAUUGCAAGCGAGGUGAGUAA GGGCCUGGCCGACCUGUCUCUGGAGCUGCGGAAGCCCAUUACCUUCGGCGUGAUCACC GCCGACACCCUGGAGCAGGCUAUCGAGGCUGCUGGCACCUGCCACGGCAACAAGGGUU GGGAGGCGGCACUGUGUGCCAUAGAGAUGGCCAACCUGUUCAAGAGCCUGCGGUAAAG CUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCCCCCCAGCCCCUCC UCCCCUUCCUGCAUUUUGGCGUGGUCUUUGAAUAAAGUCUGAGUGGGCGGCAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAUCUAG Core 149 (D) 3 413 5'7MeGpppG2'OMeAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU CUCGCAACUAGCAAGCUUUUUGUUCUCGCCAUGGACAUCGACCCCUACAAGGAGUUCG GCGCCACAGUGGAGCUGCUGAGCUUCCUGCCCAGCGACUUCUUCCCCAGCGUGCGGGA UCUGCUGGACACUGCCAGCGCCCUGUAUCGGGAGGCCCUAGAGAGCCCCGAGCACUGC AGCCCUCACCACACCGCUCUCCGGCAGGCCAUCCUGUGCUGGGGCGAGCUGAUGACCCU GGCAACGUGGGUGGGCGUGAACCUGGAGGACCCCGCCUCAAGAGAUCUGGUCGUGAGC UACGUGAACACCAACAUGGGCCUGAAGUUCCGGCAGCUGCUGUGGUUCCACAUCAGCU GCCUGACCUUCGGCCGGGAGACUGUGAUCGAGUACCUGGUGAGCUUCGGCGUGUGGAU CCGGACACCACCAGCCUACCGGCCUCCAAACGCCCCGAUCCUGAGCACCCUGCCCGAGA CUACCGUGGUGUAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGC CUCCCCCCAGCCCCUCCUCCCCUUCCUGCAUUUUGGCCCAGUGGUCUUUGAAUAAAGUC UGAGUGGGCGGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAUC UAG Pol_8mut (D)_3 414 5'7MeGpppG2'OMeAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUU CUCGCAACUAGCAAGCUUUUUGUUCUCGCCAUGCCCCUGAGCUAUCAGCAUUUCCGGC GCCUGCUCCUGCUUGACGACGAGGCCGGCCCUCUGGAGGAGGAGCUCCCACGGCUGGC CGACGAGGACUUGAACCGGCGGGUGGCCGAGGAUCUGAACCUGGGCAACCUGAACGUG UCUAUCCCUUGGACCCAUAAGGUGGGCAACUUCACCGGCCUGGCAAGCAGCACCGUGC CCGUCUUCAACCCUCACUGGAAGACCCCUUCCUUCCCCAAUAUCCACCUGCACCAGGAC AUCAUCAAGAAGUGCGAGCAGUUCGUGGGUCCCCUGACCGUGAACGAGAAGCGGCGGC UACAACUGAUCAUGCCCGCCCGGUUCUACCCUAAGGUCACCAAGUACCUGCCCCUGGA CAAGGGAAUCAAGCCCUAUUACCCGGAGCACCUCGUGAACCACUACUUCCAGACCCGG CACUACCUGCACACUCUGUGGAAGGCUGGCAUCCUGUACAAGCGGGAGACAACCCACA GCGCCAGCUUCUGCGGCAGCCCCUACAGCUGGGAGCAGGAACUGCAGCACGGCGCUGA GAGCUUCCACCAGCAAAGCAGCGGAAUCCUGAGCAGGCCACCAGUGGGCAGCUCGCUG CAAAGCAAACAUAGCAAGAGCCGCCUGGGGCUCCAGAGCCAGCAAGGGCACCUGGCUC GGCGUCAGCAAGGUCGCAGUUGGAGCAUCCGGGCCGGCAUACAUCCGACCGCUCGACG GCCCUUCGGCGUGGAGCCCAGCGGAAGCGGCCAUAACACCAACCUGGCCUCUAAGAGU GCCAGCUGCCUGUACCAGAGCCCACUCCGGAAGGCAGCCUACCCCGCUGUGAGCACCUU CGAGAAACACAGCUCCAGCGGCCACGCCGUGGAGCUGCACAACCUGCCUCCUAAUUCA GCCCGGUCACAAGGGGAGCGGCCCGUGUUCCCCGCCUGGUGGCUCCAGUUUCGGAACA GCAAGCCCGCCAGCGAUUACGCCCUGAGCCAUAUUGUGAACCUGCUCGAGGACUGGGG CCCCGCAGCAGAGCACGGGGAGCACCACAUCCGGAUUCCUCGGACACCCGCACGGGUU ACCGGCGGCGUGUUCCUGGUGGACAAGAAUCCUCACAACACAGCCGAGUCUCGCCUCG UGGUGGACUUCAGCCAGUUCAGCCGGGGCAACUACCGGGUGAGCUGGCCCAAAUUCGC CGUGCCCAACCUGCAGAGCCUCACUAACUUACUGUCCUCAAAUCUUUCCUGGCUGAGC CUGGACGUGAGCGCCGCCUUCUAUCAUUUGCCGCUGCACCCAGCCGCCAUGCCACACCU GCUGGUAGGCAGCAGCGGCCUCAGCCGGUACGUCGCCAGACUGAGCAGCAACAGCCGG AUAUUCAACCAUCAGCGGGGCACCAUGCAGAACCUACACGACUACUGCAGCCGGAACC UGUACGUGAGCCUGCUGCUGUUAUACCAGACCUUCGGACGGAAGCUUCACCUGUAUAG CCACCCCAUCAUCCUAGGUUUCCGGAAGAUCCCCAUGGGCGUGGGCCUGAGCCCCUUU CUGCUCGCCCAAUUCACUAGCGCCAUCUGCAGUGUGGUGCGGCGGGCCUUCCCACAUU GUCUGGCCUUCAGCUACAUGGACGACGUAGUGCUGGGCGCCAAGAGCGUGCAGCACCU GGAGAGCCUGUUCACGGCGGUGACCAACUUCCUUCUGUCCCUGGGCAUCCACCUCAAU CCCAACAAGACCAAGCGGUGGGGCUACAGCCUGAACUUCAUGGGCUACGUGAUCGGCU GCUACGGCAGCCUGCCCCAGGACCACAUCAUCCAGAAGAUCAAGGAGUGUUUCCGCAA GCUGCCCGUGAAUCGGCCCAUCGACUGGAAGGUGUGCCAGCGGAUCGUAGGCCUCCUG GGUUUCGCCGCCCCAUUCACCCAGUGCGGCUAUCCCGCCUUGAAGCCCUUGUACGCUU GCAUCCAAAGCCGGCAAGCUUUCACCUUCAGCCCUACCUACAAGGCCUUCCUGUGCAA GCAAUACCUGAAUCUUUACCCCGUGGCCCGGCAGAGAUCCGGCCUGUGUCAGGUGUUC GCCGACGCCACUCCGACGGGGUGGGGCCUGGUUAUGGGCCACCAAGCCAUGCGCGGCA CCUUCCUGGCCCCUCUACCCAUCCACACCGCCGAGCUUCUGGCCGCCUGCUUCGCAAGG UCAAGGAGCGGGGCCAACAUCCUGGGCACCGACAACAGCGUGGUUCUGAGUCGGAAGU ACACCAGCUUCCCCUGGCUGUUGGGCUGCGCCGCCAACUGGAUCCUGCGUGGCACAAG CUUCGUGUACGUGCCCUCUGCCCUGAACCCUGCUGCCGAUCCGUCAGCGGGCCGUCUG GGCUUGAGCCGGCCCCUGUUGCGGCUGCCCUUCCGACCCACCACUGGACGAACCUCACU CUACGCCGACAGCCCCAGCGUGCCCAGCCACCUGCCCGACCGGGUCCAUUUCGCCAGUC CCCUGCACGUGGCCUGGCGGCCACCUUAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCU UCUUGCCCCUUGGGCCUCCCCCCAGCCCCUCCUCCCCinJCCUGCAinnJUGCCCCGUGGU CUUUGAAUAAAGUCUGAGUGGGCGGCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAUCUAG Table 2. Naturally Occurring HBV Protein Sequence HBV protein Genotype Naturally Occurring Protein Sequence SEQ ID NO: HBV envelope antigen (Large) A2 strain MGGWSSKPRKGMGTNLSVPNPLGFFPDHQL DPAFGANSNNPDWDFNPIKDHWPAANQVG VGAFGPGLTPPHGGILGWSPQAQGILTTVSTI PPPASTNRQSGRQPTPISPPLRDSHPQAMQW NSTAFHQALQDPRVRGLYFPAGGSSSGTVNP APNIASHISSISARTGDPVTNMENITSGFLGPL LVLQAGFFLLTRILTIPQSLDSWWTSLNFLGG SPVCLGQNSQSPTSNHSPTSCPPICPGYRWMC LRRFTIFLFILLLCLIFLLVLLDYQGMLPVCPLI PGSTTTSTGPCKTCTTPAQGNSMFPSCCCTKP TDGNCTCIPIPS S WAFAKYL WEWAS VRFS WL SLLVPFVQWFVGLSPTVWLSAIWMMWYWG PSLYSIVSPFIPLLPIFFCLWVYI* * 5 HBV envelope antigen (Middle) A2 strain MQWNSTAFHQALQDPRVRGLYFPAGGSSSG TVNPAPNIASHISSISARTGDPVTNMENITSGF LGPLLVLQAGFFLLTRILTIPQSLDSWWTSLN FLGGSPVCLGQNSQSPTSNHSPTSCPPICPGY RWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLP VCPLIPGSTTTSTGPCKTCTTPAQGNSMFPSC CCTKPTDGNCTCIPIPSSWAFAKYLWEWASV 4 RFSWLSLLVPFVQWFVGLSPTVWLSAIWMM WYWGPSLYSIVSPFIPLLPIFFCLWVYI HBV envelope antigen (Small) A2 strain MENITSGFLGPLLVLQAGFFLLTRILTIPQSLD SWWTSLNFLGGSPVCLGQNSQSPTSNHSPTS CPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLL DYQGMLPVCPLIPGSTTTSTGPCKTCTTPAQ GNSMFPSCCCTKPTDGNCTCIPIPSSWAFAKY LWEWASVRFSWLSLLVPFVQWFVGLSPTVW LSAIWMMWYWGPSLYSIVSPFIPLLPIFFCLW VYI 3 HBV polymerase protein D strain MPLSYQHFRRLLLLDDEAGPLEEELPRLADE DLNRRVAEDLNLGNLNVSIPWTHKVGNFTG LYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCE QFVGPLTVNEKRRLQLIMPARFYPKVTKYLP LDKGIKPYYPEHLVNHYFQTRHYLHTLWKA GILYKRETTHSASFCGSPYSWEQELQHGAES FHQQSSGILSRPPVGSSLQSKHSKSRLGLQSQ QGHLARRQQGRSWSIRAGIHPTARRPFGVEP SGSGHNTNLASKSASCLYQSPLRKAAYPAVS TFEKHSSSGHAVELHNLPPNSARSQGERPVFP CWWLQFRNSKPCSDYCLSHIVNLLEDWGPC AEHGEHHIRIPRTPARVTGGVFLVDKNPHNT AESRLVVDFSQFSRGNYRVSWPKFAVPNLQS LTNLLSSNLSWLSLDVSAAFYHLPLHPAAMP HLLVGSSGLSRYVARLSSNSRIFNHQRGTMQ NLHDYCSRNLYVSLLLLYQTFGRKLHLYSHP IILGFRKIPMGVGLSPFLLAQFTSAICSWRRA FPHCLAFSYMDDWLGAKSVQHLESLFTAV TNFLLSLGIHLNPNKTKRWGYSLNFMGYVIG CYGSLPQDHIIQKIKECFRKLPVNRPIDWKVC QRIVGLLGFAAPFTQCGYPALKPLYACIQSR QAFTFSPTYKAFLCKQYLNLYPVARQRSGLC QVFADATPTGWGLVMGHQRMRGTFLAPLPI HTAELLAACFARSRSGANILGTDNSWLSRK YTSFPWLLGCAANWILRGTSFVYVPSALNPA DDPSRGRLGLSRPLLRLPFRPTTGRTSLYADS PSVPSHLPDRVHFASPLHVAWRPP 1 HBV core protein D strain MDIDPYKEFGATVELLSFLPSDFFPSVRDLLD TASALYREALESPEHCSPHHTALRQAILCWG ELMTLATWVGVNLEDPASRDLWSYVNTN MGLKFRQLLWFHISCLTFGRETVIEYLVSFG VWIRTPPAYRPPNAPILSTLPETTWRRRGRS PRRRRTPSPRRRRSQSPRRRRSQSRESQC 2 5          In some embodiments a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein (alone or in multimeric form as disclosed herein), wherein the polymerase protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1, 29, 368, 371 or 374. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, e.g., Pol_8mut. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a core protein, wherein the core protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 2, 26, 28, and 374. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a core protein, wherein the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, e.g., Core_149. In some embodiments, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28. In some embodiments, the core protein comprises the amino acid sequence of SEQ ID NO: 28. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding an envelope antigen, wherein the envelope antigen comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 3-5 and 16-25. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding an envelope protein, wherein the envelope protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 24, e.g., UL130sigP_PreSlS2_LuS. In some embodiments, the envelope protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the envelope protein comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a envelope antigen, wherein the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 3, e.g., Small protein. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the envelope antigen comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 24. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the core protein comprises the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 3. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the core protein comprises the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises the amino acid sequence of SEQ ID NO: 3. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a fusion protein comprising a core protein and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the fusion protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 27. In some embodiments, the polymerase protein comprises the ammo acid sequence of SEQ ID NO: 29, the fusion protein comprises the amino acid sequence of SEQIDNO: 27. In some embodiments, the vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a polymerase protein, a core protein, and an envelope antigen, wherein the polymerase protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 80% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 29, the core protein comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises an amino acid sequence having at least 99% identity to the amino acid sequence of SEQ ID NOS: 3 and 24. In some embodiments, the polymerase protein comprises the amino acid sequence of SEQ ID NO: 29, the core protein comprises the amino acid sequence of SEQ ID NO: 28, and the envelope antigen comprises the amino acid sequence of SEQ ID NOS: 3 and 24. The mRNA of the present disclosure encodes an HBV protein of interest, intended to raise an immune response to HBV infection. Thus, the HBV proteins of the present disclosure are antigenic, i.e., they are antigens. Antigenicity is the ability to be specifically recognized by antibodies generated as a result of an immune response to a given substance, such as an HBV protein of the present disclosure. Thus, an antigen is a protein capable of inducing an immune response (e.g., causing an immune system to produce antibodies against the antigen). In some embodiments, an antigen is an immunogen. Immunogenicity refers to the ability of a substance to induce cellular and humoral immune responses. The compositions of the present disclosure do not comprise antigens per se, but rather comprise mRNA that have an open reading frame encoding a protein antigen (referred to herein simply as a “HBV protein”) that once delivered to subject is expressed by cells in the subject. Delivery of the mRNA is achieved by formulating the mRNA in appropriate carriers or delivery vehicles (e.g., lipid nanoparticles) such that upon administration to cells, tissues or subjects, the mRNA is taken up by cells which, in turn, express the protein(s) encoded by the mRNA. It should be understood that the term “protein” encompasses peptides (and polypeptides shorter than a full-length protein), and the term “antigen” encompasses antigenic fragments. The vaccines of the present disclosure provide a unique advantage over traditional protein-based vaccination approaches in which protein antigens are purified or produced in vitro, e.g., recombinant protein production technologies. The vaccines of the present disclosure comprise mRNA encoding the desired HBV antigen(s), which when introduced into the body, i.e., administered to a mammalian subject (for example a human) in vivo, cause the cells of the body to express the desired antigen(s). In order to facilitate delivery of the mRNA to the cells of the body, the RNA is formulated (e.g., encapsulated) in a lipid nanoparticle. Upon delivery and uptake by cells of the body, the RNA is translated in the cytosol and the antigens are generated by the host cell machinery. The antigens are presented by the host cells and elicit an adaptive humoral and cellular immune response. Neutralizing antibodies are directed against the expressed antigens, and hence the antigens are considered relevant target antigens for vaccine development. Many proteins have a quaternary or three-dimensional structure, which includes more than one polypeptide or several polypeptide chains that associate into an oligomeric molecule. As used herein the term “subunit” refers to a single protein molecule, for example, a polypeptide or polypeptide chain resulting from processing of a nascent protein molecule, which subunit assembles (or “coassembles”) with other protein molecules (e.g., subunits or chains) to form a protein complex. Proteins can have a relatively small number of subunits and therefore be described as “oligomeric” or can consist of a large number of subunits and therefore be described as “multimeric”. The subunits of an oligomeric or multimeric protein may be identical, homologous or totally dissimilar and dedicated to disparate tasks. Proteins or protein subunits can further comprise domains. As used herein, the term “domain” refers to a distinct functional and / or structural unit within a protein. Typically, a “domain” is responsible for a particular function or interaction, contributing to the overall role of a protein. Domains can exist in a variety of biological contexts. Similar domains (i.e., domains sharing structural, functional and / or sequence homology) can exist within a single protein or can exist within distinct proteins having similar or different functions. A protein domain is often a conserved part of a given protein tertiary structure or sequence that can function and exist independently of the rest of the protein or subunit thereof. An extracellular protein domain is a part of a protein molecule that is located outside of a cell. It is typically exposed to the extracellular environment and can interact with other proteins, molecules, or the cell envelope. A transmembrane domain is a structural component of a protein that spans the lipid bilayer of a cell membrane. Transmembrane domains typically include one or more alpha helices or beta strands that cross the hydrophobic lipid bilayer of the cell membrane. As used herein, the term “antigen” is distinct from the term “epitope,” which is a substructure of an antigen. An epitope of a part of an antigen to which an antibody attaches. An epitope may be a peptide, for example, a 7-10 amino acid peptide, or a carbohydrate structure. The art describes protein antigens that are delivered to subjects or immune cells in isolated form, e.g., isolated proteins, however, the design, testing, validation, and production of protein antigens can be costly and time-consuming, especially when producing proteins at large scale. By contrast, mRNA technology is amenable to rapid design and testing of mRNA encoding a variety of antigens. Moreover, rapid production of mRNA coupled with formulation in appropriate delivery vehicles (e.g., lipid nanoparticles), can proceed quickly and can rapidly produce mRNA vaccines at large scale. Potential benefit also arises from the fact that antigens encoded by the mRNAs of the present disclosure are expressed by the cells of the subject, e.g., are expressed by the human body, and thus the subject, e.g., the human body, serves as the “factory” to produce the antigens which, in turn, elicits the desired immune response. The vaccines, as provided herein, may include an mRNA or multiple RNAs encoding two or more antigens of the same or different HBV strains. Thus, the vaccines of the present disclosure may be combination vaccines that target one or more antigens of the same strain / species, or one or more antigens of different strains / species, e.g., antigens that induce immunity to organisms that are found in the same geographic areas where the risk of HBV infection is high or organisms to which an individual is likely to be exposed to when exposed to HBV. Transmembrane Domains In some embodiments, the HBV proteins encoded by the mRNA vaccines comprises a heterologous transmembrane domain. A transmembrane domain is a region of a protein that spans the lipid bilayer of a biological membrane, such as a cell membrane. Transmembrane domains are composed of hydrophobic amino acids that are able to interact with the hydrophobic core of the membrane, anchoring the protein to the membrane and allowing it to interact with other proteins or molecules on either side of the membrane. A transmembrane domain is “heterologous” to a protein if the protein does not naturally occur with the transmembrane domain. For example, a viral transmembrane domain is heterologous to a bacterial protein or a protein comprising a bacterial domain, such as a bacterial extracellular domain. In some embodiments, the viral transmembrane domain is from an influenza virus protein, for example, an influenza virus neuraminidase transmembrane domain. Other viral transmembrane domains may also be used to anchor HBV proteins to a host cell membrane, including without limitation, the transmembrane domain from any of the following: human immunodeficiency virus (HIV) envelope glycoprotein (Env), hepatitis C virus (HCV) envelope glycoproteins El and E2, herpes simplex virus (HSV) glycoprotein D (gD), and other influenza virus proteins, such as hemagglutinin, neuraminidase and M2 protein. The open reading frames (ORFs) (e g., the first ORF, the second ORF, and the third ORF) including a nucleic acid sequence encoding HBV antigens (e g., HBV envelope antigen, HBV core protein. And HBV polymerase) of the disclosure, in some embodiments, include a nucleic acid sequence encoding a heterologous amino terminal (N terminal) transmembrane domain. In some embodiments, the ORFS include a nucleic acid sequence encoding a heterologous carboxyl terminal (C terminal) transmembrane domain. When presented at the cell envelope, the bacterial antigens are more conformationally accurate, thereby capable of eliciting a more effective immune response. In some embodiments, the ORFs comprise a nucleic acid sequence encoding a transmembrane segment of influenza neuraminidase protein. In some embodiments, the transmembrane segment of influenza neuraminidase protein comprises the amino acid sequence of: MNPNQKIITIGSVSLTISTICFFMQIAILITTVTLHFKQ (SEQ ID NO: 8) In some embodiments, t the ORFs comprise a nucleic acid sequence encoding a transmembrane segment of influenza neuraminidase protein. In some embodiments, the transmembrane segment of influenza hemagglutinin protein comprises the ammo acid sequence of: ILAIYSTVASSLVLLVSLGAISF (SEQ ID NO: 12) In some embodiments, the ORFs comprise a nucleic acid sequence encoding an HBV antigen(s) of the disclosure and a transmembrane domain. In some embodiments, the first ORF comprises an HBV small envelope antigen and a transmembrane domain. In some embodiments, the first ORF comprises an HBV envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8). In some embodiments, the first ORF comprises an HBV small envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8). In some embodiments, the first ORF comprises an HBV envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8) fused at the N terminal. In some embodiments, the first ORF comprises an HBV small envelope antigen and the transmembrane segment of influenza neuraminidase protein (SEQ ID NO: 8) fused at the N terminus. Signal Peptides In some embodiments, an mRNA has an open reading frame that encodes a signal peptide fused to the HBV protein. Signal peptides, comprising the N-terminal 15-60 amino acids of proteins, are typically needed for the translocation across the membrane on the secretory pathway and, thus, universally control the entry of most proteins both in eukaryotes and prokaryotes to the secretory pathway. In eukaryotes, the signal peptide of a nascent precursor protein (pre-protein) directs the ribosome to the rough endoplasmic reticulum (ER) membrane and initiates the transport of the growing peptide chain across it for processing. ER processing produces mature proteins, wherein the signal peptide is cleaved from precursor proteins, typically by an ER-resident signal peptidase of the host cell, or they remain uncleaved and function as a membrane anchor. A signal peptide may also facilitate the targeting of the protein to the cell membrane. A signal peptide may have a length of 15-60 amino acids. For example, a signal peptide may have a length of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, or 60 amino acids. In some embodiments, a signal peptide has a length of 20-60, 25-60, 30-60, 35- 60, 40-60, 45- 60, 50-60, 55-60, 15-55, 20-55, 25-55, 30-55, 35-55, 40-55, 45-55, 50-55, 15-50, 20-50, 25-50, 30-50, 35-50, 40-50, 45-50, 15-45, 2045, 25-45, 30-45, 35-45, 40-45, 15-40, 20-40, 25-40, 30-40, 35-40, 15-35, 20-35, 25-35, 30-35, 15-30, 20-30, 25-30, 15-25, 20-25, or 15-20 amino acids. Signal peptides from heterologous genes (which regulate expression of genes other than HBV proteins in nature) are known in the art and can be tested for desired properties and then incorporated into a nucleic acid of the disclosure. In some embodiments, the open reading frames (ORFs) (e.g., the first ORF, the second ORF, the third ORF) comprising nucleic acid sequences encoding the HBV antigens of the present disclosure further comprise a nucleic acid sequence encoding a signal peptide from cytomegalovirus. In some embodiments, the HBV cytomegalovirus signal peptide from cytomegalovirus ULI30 Protein. In some embodiments, cytomegalovirus ULI30 Protein signal peptide comprises the amino acid sequence of: MLRLLLRHHFHCLLLCAVWATPCLA (SEQ ID NO: 9) In some embodiments, the ORFs of the present disclosure further comprise a nucleic acid sequence encoding a signal peptide. In some embodiments, the first ORF comprises a nucleic acid sequence encoding an HBV small envelope antigen and a signal peptide. In some embodiments, the first ORF comprises a nucleic acid sequence encoding an HBV envelope antigen and the cytomegalovirus ULI30 Protein signal peptide (SEQ ID NO: 9). In some embodiments, the first ORF comprises a nucleic acid sequence encoding an HBV small envelope antigen and the cytomegalovirus ULI30 Protein signal peptide (SEQ ID NO: 9). N-Linked Glycan Site Mutations In some embodiments, the bacterial proteins encoded by the mRNA vaccines comprises one or more N-linked glycan site mutations. N-linked glycan site mutations refer to alterations in the amino acid sequence of a protein that affect the attachment of carbohydrate molecules, or glycans, at specific sites. N-linked glycans are attached to proteins at asparagine residues that are located in a specific amino acid sequence context (NxS / T / C, where x can be any amino acid except proline). These glycans can affect the structure, stability, and function of proteins and play important roles in many biological processes. Bacterial systems rarely glycosylate proteins; however, glycosylation does occur somewhat frequently in mammalian cells. To prevent glycosylation, the mRNA described herein, in some embodiments, encodes bacterial proteins wherein residues prone to N-linked glycosylation (e.g., asparagine) have been removed, modified, or substituted in order to prevent glycosylation. In some embodiments, the HBV antigens encoded by the mRNA of the disclosure comprise an HBV envelope antigen comprising one or more N-linked glycan site mutations. In some embodiments, the HBV small envelope antigen comprises one or more N-linked glycan site mutations. Fusion Proteins In some embodiments, an mRNA encodes a fusion protein. Thus, an encoded protein may include two or more proteins (e.g., protein and / or protein fragment) joined together with or without a linker. Fusion proteins, in some embodiments, retain the functional property of each independent (nonfusion) protein. In some embodiments, the mRNA encodes a fusion protein comprised of one or more HBV antigens. In some embodiments, the mRNA encodes a fusion protein comprised of two or more HBV antigens. In some embodiments, the fusion protein comprises an HBV envelope antigen comprising PreSl, PreS2, and a lumazine synthase domain. In some embodiments, the fusion protein comprises and HBV envelope antigen, and a lumazine synthase. In some embodiments, the fusion protein comprises an HBV envelope antigen that is PreSlPreS2. In some embodiments, the fusion protein comprises an HBV PreSlPreS2 and a lumazine synthase. In some embodiments, the fusion protein has prolonged presentation by antigen presenting cells (APC) to B cells in the context of germinal center reaction, which improves antigen-specific antibody response. Accordingly, the fusion proteins are highly immunogenic. In some embodiments, the fusion protein comprises an HBV envelope antigen and an HBV core protein. In some embodiments, the fusion protein comprises an HBV envelope antigen PreSlS2 and HBV core protein. In some embodiments, the HBV PreSl / S2 and core protein displays PreSlS2 as a large protein nanoparticle (90-mer or 120-mer) with benefits for B cell immune response and is monovalent. In some embodiments, the HBV envelope antigen PreSlS2 and HBV core protein is highly immunogenic. In some embodiments a single mRNA encoding fusion protein PreSlS2 and Core assembly domain (aa 1-149, also referred as Corel49), was designed to exploit the self-assembly property of core protein to generate a nanoparticulate antigen without using antigens from other organisms (such as Lumazine Synthase and Ferritin). The design was useful for displaying PreSl S2 as a large protein nanoparticle (90-mer or 120-mer) for inducing an effective B cell immune response. These mRNA are highly immunogenic in mice (Example 5). mRNA was also used to encode VLP (virus like particles) by combining Large (PreSl-PreS2-Small), Medium (PreS2-Small), and Small Envelope sequences at different ratios, which allowed for the assembly of antigen into large particulate antigen structures similar to the natural virion particles produced by infected cells. These mRNAs were highly immunogenic in mice, (Examples). Protein variants and alignment Some embodiments relate to proteins having one or more mutations (e.g., substitutions) relative to a reference amino acid sequence and / or numbered according to a listed amino acid sequence. Some embodiments relate to amino acid or nucleotide sequences having a specified percentage sequence identity to a comparator amino acid or nucleotide sequence, respectively. The term “identity” refers to a relationship between the sequences of two or more polypeptides (e.g. antigens) or polynucleotides (nucleic acids), as determined by comparing the sequences. Identity also refers to the degree of sequence relatedness between or among sequences as determined by the number of matches between strings of two or more amino acid residues or nucleic acid residues. “Percent (%) identity” or “percent (%) sequence identity” as it applies to polypeptide or polynucleotide sequences 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 percent sequence identity that a candidate sequence (e.g., as present in a claimed protein or nucleic acid) has to a comparator sequence (e.g., having a SEQ ID NO: specified herein) is calculated by (i) aligning the candidate sequence to the comparator sequence, (ii) determining the number of matching residues (amino acids or nucleotides) between the aligned candidate and comparator sequences, and (iii) dividing the number of matching residues by the length of the comparator sequence, including any gaps introduced into the comparator sequence when the two sequences are aligned. The skilled artisan will appreciate that to determine whether a candidate protein or nucleic acid comprises an amino acid sequence or nucleotide sequence with a given percentage sequence identity to a comparator sequence, the denominator (length of comparator sequence plus internal gaps) in calculating sequence identity need not include gaps shown at the ends of the comparator sequence in an alignment, as such gaps are added where a candidate sequence contains additional amino acids or nucleotides that extend beyond the portions that align to the N-terminal end and / or C-terminal end (amino acid sequences), or 5' end or 3' end (nucleotide sequences) of the comparator sequence. Where an alignment between two sequences is contemplated, the first sequence (e.g., candidate sequence) is aligned to the second sequence (e.g., comparator sequence) using the Needleman-Wunsch algorithm for global alignment of the two sequences. Needleman & Wunsch, J Mol Biol. 1970. 48:443-453. Where two protein sequences are aligned, the Needleman-Wunsch algorithm uses a BLOSUM62 substitution scoring matrix, a Gap Open penalty of 10, a Gap Extend penalty of 0.5, and no End Gap penalties. Where two nucleotide sequences are aligned, the alignment uses an DNAFULL substitution scoring matrix, a Gap Open penalty of 10, a Gap Extend penalty of 0.5, and no End Gap penalties. The skilled artisan will appreciate that at the time of filing the instant specification, these parameters are the default parameters of the EMBOSS Needle pairwise comparison tool provided by European Bioinformatics Institute (see ebi.ac.uk). Other suitable alignment programs may be used to obtain a global alignment using these parameters, such as BLAST, or the Needleman-Wunsch algorithm may be implemented in a scripting language (e.g., Python). Linkers and Cleavable Peptides In some embodiments, an mRNA that encodes a fusion protein further encodes a linker located between at least one or each domain of the fusion protein. The linker may be, for example, a cleavable linker or protease-sensitive linker. In some embodiments, the linker is selected from the group consisting of F2A linker, P2A linker, T2A linker, E2A linker, and combinations thereof (see, e.g., WO 2017 / 127750). This family of selfcleaving peptide linkers, referred to as 2A peptides, has been described in the art (see, e.g., Kim, J.H. et al. PLoS ONE 201 l;6:el8556). In some embodiments, the linker is an F2A linker. In some embodiments, the linker is a GS linker. GS linkers are polypeptide linkers that include glycine and serine amino acids repeats. They comprise flexible and hydrophilic residues and can be used to perform fusion of protein subunits without interfering in the folding and function of the protein domains, and without formation of secondary structures. In some embodiments, an mRNA encodes a fusion protein that comprises a GS linker that is 3 to 20 amino acids long. For example, the GS linker may have a length of (or have a length of at least) 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids. In some embodiments, a GS linker is (or is at least) 15 amino acids long (e.g., GGSGGSGGSGGSGGG (SEQ ID NO: 52)). In some embodiments, a GS linker is (or is at least) 8 amino acids long (e.g., GGGSGGGS (SEQ ID NO: 10)). In some embodiments, a GS linker is (or is at least) 7 amino acids long (e.g., GGGSGGG (SEQ ID NO: 11)). In some embodiments, a GS linker is (or is at least) 4 amino acid long (e.g., GGGS (SEQ ID NO: 14)). In some embodiments, the GS linker comprises (GGGS)n (SEQ ID NO: 365), where n is any integer from 1-5. In some embodiments, a GS linker is (or is at least) 4 amino acid long (e.g., GSGG (SEQ ID NO: 50)). In some embodiments, the GS linker comprises (GSGG)n (SEQ ID NO: 51), where n is any integer from 1-5. In some embodiments, a linker is a glycine linker, for example having a length of (or a length of at least) 3 amino acids (e.g., GGG). In some embodiments, a protein encoded by an mRNA includes two or more linkers, which may be the same or different from each other. The skilled artisan will appreciate that other art-recognized linkers may be suitable for use in the constructs of the disclosure (e.g., encoded by the nucleic acids of the disclosure). The skilled artisan will likewise appreciate that other polycistronic constructs (mRNA encoding more than one protein separately within the same molecule) may be suitable for use as provided herein. Stabilization Domains Protein stabilization domains are protein sequences or structures that can enhance the stability of a protein to various environmental stresses, such as temperature, pH, and proteolysis. Non-limiting examples of protein stabilization domains for use to stabilize an HBV protein expressed by an mRNA include: lumazine synthase, ferritin, and thioredoxin. In some embodiments, an HBV protein is fused to a lumazine synthase. Lumazine synthase is protein from bacteria and plants that can stabilize fusion partners by forming homodimers or oligomers, which can enhance the solubility and stability of the target protein. In some embodiments, an HBV protein is fused to ferritin. Ferritin is a protein found in animals, plants, and bacteria that can form a cage-like structure that can store and sequester iron ions, protecting the cell from oxidative damage. Fusion of a target protein with ferritin can improve its stability and solubility. In some embodiments, an HBV protein, e.g., an E protein is fused to thioredoxin. Thioredoxin is small protein found in bacteria and eukaryotes that can act as a reducing agent and stabilize proteins by forming disulfide bonds. Nucleic Acids Encoding HBV Proteins Nucleic acids comprise a polymer of nucleotides (nucleotide monomers). Thus, nucleic acids are also referred to as polynucleotides. Nucleic acids may be or may include, for example, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), threose nucleic acid (TNA), glycol nucleic acid (GNA), peptide nucleic acid (PNA), locked nucleic acid (LNA, including LNA having a P-D-ribo configuration, a-LNA having an a-L-ribo configuration (a diastereomer of LNA), 2'-amino-LNA having a 2'-amino functionalization, and 2'-amino- a-LNA having a 2'-amino functionalization), ethylene nucleic acid (ENA), cyclohexenyl nucleic acid (CeNA) and / or chimeras and / or combinations thereof. mRNA of the present disclosure comprises an open reading frame (ORF) encoding an HBV protein. In some embodiments, the mRNA further comprises a 5' untranslated region (UTR), 3' UTR, a poly(A) tail and / or a 5' cap analog. Messenger RNA Messenger RNA (mRNA) is RNA that encodes a (at least one) protein (a naturally-occurring, non-naturally-occurring, or modified polymer of amino acids) and can be translated to produce the encoded protein in vitro, in vivo, in situ, or ex vivo. As used herein, the term mRNA refers to conventional mRNA that does not include nucleic acid sequences encoding viral replicase proteins. The skilled artisan will appreciate that, except where otherwise noted, nucleic acid sequences set forth in the instant application may recite “T”s in a representative DNA sequence but where the sequence represents mRNA, the “T”s would be substituted for “U”s. Thus, any of the DNAs disclosed and identified by a particular sequence identification number herein also disclose the corresponding mRNA sequence complementary to the DNA, where each “T” of the DNA sequence is substituted with “U.” Naturally-occurring eukaryotic mRNA molecules can contain stabilizing elements, including, but not limited to, UTRs at their 5'-end (5' UTR) and / or at their 3'-end (3' UTR), in addition to other structural features, such as a 5'-cap structure or a 3'-poly(A) tail. Both the 5' UTR and the 3' UTR are typically transcribed from the genomic DNA and are elements of the premature mRNA. Characteristic structural features of mature mRNA, such as the 5'-cap and the 3'-poly(A) tail are usually added to the transcribed (premature) mRNA during mRNA processing. Untranslated Regions (UTRs) The mRNAs of the present disclosure may comprise one or more regions or parts which act or function as an untranslated region. A “5’ untranslated region” (UTR) refers to a region of an mRNA that is directly upstream (z.e., 5') from the start codon (i.e., the first codon of an mRNA transcript translated by a ribosome) that does not encode a polypeptide. A “3' untranslated region” (UTR) refers to a region of an mRNA that is directly downstream (i.e., 3') from the stop codon (ie., the codon of an mRNA transcript that signals a termination of translation) that does not encode a polypeptide. When RNA transcripts are being generated, the 5’ UTR may comprise a promoter sequence. Such promoter sequences are known in the art. It should be understood that such promoter sequences will not be present in a vaccine of the disclosure. Where mRNAs are designed to encode a (at least one) viral protein, the mRNA may comprise a 5’ UTR and / or 3’ UTR. UTRs of an mRNA are transcribed but not translated. In mRNA, the 5' UTR starts at the transcription start site and continues to the start codon but does not include the start codon; the 3' UTR starts immediately following the stop codon and continues until the transcriptional termination signal. There is a growing body of evidence about the regulatory roles played by the UTRs in terms of stability of the nucleic acid molecule and translation. The regulatory features of a UTR can be incorporated into the polynucleotides of the present disclosure to, among other things, enhance the stability of the molecule. The specific features can also be incorporated to ensure controlled down-regulation of the transcript in case they are misdirected to undesired organs sites. A variety of 5’ UTR and 3’ UTR sequences are known. It should also be understood that the mRNA of the present disclosure may include any 5’ UTR and / or any 3’ UTR. Exemplary UTR sequences include SEQ ID NOs: 53-65; however, other UTR sequences may be used or exchanged for any of the UTR sequences described herein. In some embodiments, a 5' UTR of the present disclosure comprises a sequence selected from: GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGAGCCACC (SEQ ID NO: 53), GGGAAAUAAGAGAGAAAAGAAGAGUAAGAAGAAAUAUAAGACCCCGGCGC CGCCACC (SEQ ID NO: 54), GAGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUC GCAACUAGCAAGCUUUUUGUUCUCGCC (SEQ ID NO: 55), and GGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCGC AACUAGCAAGCUUUUUGUUCUCGCC (SEQ ID NO: 56). In some embodiments, a 5' UTR of the present disclosure comprises AGGAAAUCGCAAAAUUUGCUCUUCGCGUUAGAUUUCUUUUAGUUUUCUCG CAACUAGCAAGCUUUUUGUUCUCGCC (SEQ ID NO:94). In some embodiments, a 3' UTR of the present disclosure comprises a sequence selected from UGAUAAUAGGCUGGAGCCUCGGUGGCCAUGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA AAGUCUGAGUGGGCGGC (SEQ ID NO: 57), UGAUAAUAGGCUGGAGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA AAGUCUGAGUGGGCGGC (SEQ ID NO: 58), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAGAUUGAGUGUAGUGACUAGUGG UCUUUGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 59), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAUUGAGACUACGGGUGGUCUUUG AAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 60), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGCAUAGACACUACGUGGUCUUUGAA UAAAGUCUGAGUGGGCGGC (SEQ ID NO: 61), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAGAUUGAGUGUAGUGGUGGUCUU UGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 62), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGGAGAUUGAGUGUAGUGACGUGGUC UUUGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 63), UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAGUGGUCUUUGAAUAAAGUCUGAGUG GGCGGC (SEQ ID NO: 64), and UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCACCCGUACCCCCGUGGUCUUUGAAUA AAGUCUGAGUGGGCGGC (SEQ ID NO: 65). In some embodiments, a 3' UTR comprises, in 5'-to-3' order: (a) the nucleic acid sequence UAAAGCUCCCCGGGGGCCUCGGUGGCCUAGCUUCUUGCCCCUUGGGCCUCC CCCCAGCCCCUCCUCCCCUUCCUGCAG (SEQ ID NO: 66), (b) an identification and ratio determination (IDR) sequence, and (c) the nucleic acid sequence UGGUCUUUGAAUAAAGUCUGAGUGGGCGGC (SEQ ID NO: 67) IDR sequences are described herein in the section entitled “Identification and Ratio Determination (IDR) Sequences.” UTRs may also be omitted from the mRNA provided herein. A 5' UTR does not encode a protein (is non-coding). Natural 5' UTRs have features that play roles in translation initiation. They harbor signatures like Kozak sequences which are commonly known to be involved in the process by which the ribosome initiates translation of many genes. Kozak sequences have the consensus CCR(A / G)CCAUGG, where Risa purine (adenine or guanine) three bases upstream of the start codon (AUG), which is followed by another 'G'.5'UTR also have been known to form secondary structures which are involved in elongation factor binding. In some embodiments of the disclosure, a 5’ UTR is a heterologous UTR, i.e., is a UTR found in nature associated with a different ORF. In other embodiments, a 5’ UTR is a synthetic UTR, i.e., does not occur in nature. Synthetic UTRs include UTRs that have been mutated to improve their properties, e.g., which increase gene expression as well as those which are completely synthetic. Exemplary 5’ UTRs include Xenopus or human derived a-globin or b-globin (8278063; 9012219), human cytochrome b-245 a polypeptide, and hydroxy steroid (17b) dehydrogenase, and Tobacco etch virus (US8278063, US9012219). CMV immediate-early 1 (IE1) gene (US2014 / 0206753, WO2013 / 185069), the sequence GGGAUCCUACC (SEQ ID NO: 68) (WO2014 / 144196) may also be used. In other embodiments, a 5' UTR is a 5' UTR of a TOP gene lacking the 5' TOP motif (the oligopyrimidine tract) (e.g, WO2015 / 101414, WO2015 / 101415, WO2015 / 062738, WO2015 / 024667, WO2015 / 024667); 5' UTR element derived from ribosomal protein Large 32 (L32) gene (WO / 2015101414, WO2015101415, WO / 2015 / 06273 8), 5' UTR element derived from the 5' UTR of an hydroxysteroid (17-0) dehydrogenase 4 gene (HSD17B4) (WO2015024667), or a 5' UTR element derived from the 5' UTR of ATP5A1 (WO2015 / 024667) can be used. In some embodiments, an internal ribosome entry site (IRES) is used instead of a 5' UTR. A 3' UTR does not encode a protein (is non-coding). Natural or wild type 3' UTRs are known to have stretches of adenosines and uridines embedded in them. These AU rich signatures are particularly prevalent in genes with high rates of turnover. Based on their sequence features and functional properties, the AU rich elements (AREs) can be separated into three classes (Chen et al, 1995): Class I AREs contain several dispersed copies of an AUUUA motif within U-rich regions. C-Myc and MyoD contain class I AREs. Class II AREs possess two or more overlapping UUAUUUA(U / A)(U / A) nonamers. Molecules containing this type of AREs include GM-CSF and TNF-a. Class III ARES are less well defined. These U rich regions do not contain an AUUUA motif, c-Jun and Myogenin are two well-studied examples of this class. Most proteins binding to the AREs are known to destabilize the messenger, whereas members of the ELAV family, most notably HuR, have been documented to increase the stability of mRNA. HuR binds to AREs of all the three classes. Engineering the HuR specific binding sites into the 3' UTR of nucleic acid molecules will lead to HuR binding and thus, stabilization of the message in vivo. Introduction, removal or modification of 3' UTR AU rich elements (AREs) can be used to modulate the stability of mRNA of the disclosure. When engineering specific nucleic acids, one or more copies of an ARE can be introduced to make nucleic acids of the disclosure less stable and thereby curtail translation and decrease production of the resultant protein. Likewise, AREs can be identified and removed or mutated to increase the intracellular stability and thus increase translation and production of the resultant protein. Transfection experiments can be conducted in relevant cell lines, using nucleic acids of the disclosure and protein production can be assayed at various time points posttransfection. For example, cells can be transfected with different ARE-engineering molecules and by using an ELISA kit to the relevant protein and assaying protein produced at 6 hours, 12 hours, 1 day, 2 days, and 7 days post-transfection. Those of ordinary skill in the art will understand that 5’ UTRs that are heterologous or synthetic may be used with any desired 3’ UTR sequence. For example, a heterologous or synthetic 5’ UTR may be used with a synthetic 3’ UTR or with a heterologous 3’ UTR. Non-UTR sequences may also be used as regions or subregions within a nucleic acid. For example, introns or portions of introns sequences may be incorporated into regions of nucleic acid of the disclosure. Incorporation of intronic sequences may increase protein production as well as nucleic acid levels. Combinations of features may be included in flanking regions and may be contained within other features. For example, the ORF may be flanked by a 5' UTR which may contain a strong Kozak translational initiation signal and / or a 3' UTR which may include an oligo(dT) sequence for templated addition of a poly-A tail. 5' UTR may comprise a first polynucleotide fragment and a second polynucleotide fragment from the same and / or different genes such as the 5' UTRs described in US2010 / 0293625 and WO2015 / 085318A2, each of which is herein incorporated by reference. It should be understood that any UTR from any gene may be incorporated into the regions of a nucleic acid. Furthermore, multiple wild-type UTRs of any known gene may be utilized. It is also within the scope of the present disclosure to provide artificial UTRs which are not vanants of wild type regions. These UTRs or portions thereof may be placed in the same orientation as in the transcript from which they were selected or may be altered in orientation or location. Hence a 5' or 3' UTR may be inverted, shortened, lengthened, made with one or more other 5' UTRs or 3' UTRs. As used herein, the term “altered” as it relates to a UTR sequence, means that the UTR has been changed in some way in relation to a reference sequence. For example, a 3' UTR or 5' UTR may be altered relative to a wild-type / native UTR by the change in orientation or location as taught above or may be altered by the inclusion of additional nucleotides, deletion of nucleotides, swapping or transposition of nucleotides. Any of these changes producing an “altered” UTR (whether 3' or 5') comprise a variant UTR. In some embodiments, a double, triple or quadruple UTR such as a 5' UTR or 3' UTR may be used. As used herein, a “double” UTR is one in which two copies of the same UTR are encoded either in series or substantially in series. For example, a double beta-globin 3' UTR may be used as described in US2010 / 0129877, which is incorporated herein by reference. It is also within the scope of the present disclosure to have patterned UTRs. As used herein “patterned UTRs” are those UTRs which reflect a repeating or alternating pattern, such as ABABAB or AABBAABBAABB or ABCABCABC or variants thereof repeated once, twice, or more than 3 times. In these patterns, each letter, A, B, or C represent a different UTR at the nucleotide level. In some embodiments, flanking regions are selected from a family of transcripts whose proteins share a common function, structure, feature, or property. For example, polypeptides of interest may belong to a family of proteins which are expressed in a particular cell, tissue or at some time during development. The UTRs from any of these genes may be swapped for any other UTR of the same or different family of proteins to create a new polynucleotide. As used herein, a “family of proteins” is used in the broadest sense to refer to a group of two or more polypeptides of interest which share at least one function, structure, feature, localization, origin, or expression pattern. The untranslated region may also include translation enhancer elements (TEE). As a non-limiting example, the TEE may include those described in US 2009 / 0226470, herein incorporated by reference, and those known in the art. Open Reading Frames An open reading frame (ORF) is a continuous stretch of DNA or RNA beginning with a start codon (e.g., methionine (ATG or AUG)) and ending with a stop codon (e.g., TAA, TAG or TGA, or UAA, UAG or UGA). An ORF typically encodes a protein. It will be understood that the sequences disclosed herein may further comprise additional elements, e.g., 5' and / or 3' UTRs, but that those elements, unlike the ORF, need not necessarily be present in an mRNA of the present disclosure. 5’ End Capping In some embodiments, an mRNA comprises a 5' terminal cap. 5'-capping of polynucleotides may be completed concomitantly during an in vitro transcription reaction using, for example, the following chemical RNA cap analogs to generate the 5'-guanosine cap structure according to manufacturer protocols: 3'-O-Me-m7G(5')ppp(5') G [the ARCA cap];G(5')ppp(5')A; G(5')ppp(5')G; m7G(5')ppp(5')A; m7G(5')ppp(5')G (New England BioLabs, Ipswich, MA). 5'-capping of modified mRNA may be completed post-transcriptionally using, for example, a Vaccinia Virus Capping Enzyme to generate the “Cap 0” structure: m7G(5')ppp(5')G (New England BioLabs, Ipswich, MA). Cap 1 structure may be generated using both Vaccinia Virus Capping Enzyme and a 2'-0 methyl-transferase to generate: m7G(5')ppp(5')G-2'-O-methyl. Cap 2 structure may be generated from the Cap 1 structure followed by the 2'-O-methylation of the 5'-antepenultimate nucleotide using a 2'-0 methyl-transferase. Cap 3 structure may be generated from the Cap 2 structure followed by the 2'-O-methylation of the 5'-preantepenultimate nucleotide using a 2'-0 methyl-transferase. Enzymes may be derived from a recombinant source. Other cap analogs may be used. Polyadenylation Tailing A “poly(A) tail” is a region of mRNA that is downstream, e.g., directly downstream (i.e., 3'), from the 3' UTR that contains multiple, consecutive adenosine monophosphates. A poly(A) tail may contain 10 to 300 adenosine monophosphates (SEQ ID NO: 408). It can, in some instances, comprise up to about 400 adenine nucleotides. For example, a poly(A) tail may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290 or 300 adenosine monophosphates (SEQ ID NO: 409). In some embodiments, a poly(A) tail contains 50 to 250 adenosine monophosphates (SEQ ID NO: 410). In a relevant biological setting (e.g., in cells, in vivo) the poly(A) tail functions to protect mRNA from enzymatic degradation, e.g., in the cytoplasm, and aids in transcription termination, and / or export of the mRNA from the nucleus and translation. In some embodiments, the length of the 3'-poly(A) tail may be an essential element with respect to the stability of the individual mRNA. In some embodiments, a poly(A) tail has a length of about 50, about 100, about 150, about 200, about 250, about 300, about 350, or about 400 nucleotides. In some embodiments, a poly(A) tail has a length of 100 nucleotides (SEQ ID NO: 411). Additional Stabilizing Elements mRNA provided herein, in some embodiments, includes an additional stabilizing element. Stabilizing elements may include, for example, a histone stem-loop. A stemloop binding protein (SLBP), a 32 kDa protein has been identified. It is associated with the histone stem-loop at the 3'-end of the histone messages in both the nucleus and the cytoplasm. Its expression level is regulated by the cell cycle; it peaks during the S-phase, when histone mRNA levels are also elevated. The protein has been shown to be essential for efficient 3'-end processing of histone pre-mRNA by the U7 snRNP. SLBP continues to be associated with the stem-loop after processing, and then stimulates the translation of mature histone mRNAs into histone proteins in the cytoplasm. The RNA binding domain of SLBP is conserved through metazoa and protozoa; its binding to the histone stem-loop depends on the structure of the loop. The minimum binding site includes at least three nucleotides 5’ and two nucleotides 3' relative to the stem-loop. In some embodiments, an mRNA includes an open reading frame (coding region), a histone stem-loop, and optionally, a poly(A) sequence or polyadenylation signal. The poly(A) sequence or polyadenylation signal generally should enhance the expression level of the encoded protein. The encoded protein, in some embodiments, is not a histone protein, a reporter protein (e.g., Luciferase, GFP, EGFP, P-Galactosidase, EGFP), or a marker or selection protein (e.g., alpha-Globin, Galactokinase and Xanthine:guanine phosphoribosyl transferase (GPT)). In some embodiments, an mRNA includes the combination of a poly(A) sequence or polyadenylation signal and at least one histone stem-loop, even though both represent alternative mechanisms in nature, they act synergistically to increase the protein expression beyond the level observed with either of the individual elements. The synergistic effect of the combination of poly(A) and a histone stem-loop does not depend on the order of the elements or the length of the poly(A) sequence. In some embodiments, an mRNA does not include a histone downstream element (HDE). “Histone downstream element” (HDE) includes a purine-rich polynucleotide stretch of approximately 15 to 20 nucleotides 3' of naturally-occurring stem-loops, representing the binding site for the U7 snRNA, which is involved in processing of histone pre-mRNA into mature histone mRNA. In some embodiments, the nucleic acid does not include an intron. An mRNA may or may not contain an enhancer and / or promoter sequence, which may be modified or unmodified or which may be activated or inactivated. In some embodiments, the histone stem-loop is generally derived from histone genes and includes an intramolecular base pairing of two neighbored partially or entirely reverse complementary sequences separated by a spacer, consisting of a short sequence, which forms the loop of the structure. The unpaired loop region is typically unable to base pair with either of the stem loop elements. It occurs more often in RNA, as is a key component of many RNA secondary structures but may be present in single-stranded DNA as well. Stability of the stem-loop structure generally depends on the length, number of mismatches or bulges, and base composition of the paired region. In some embodiments, wobble base pairing (non-Watson-Crick base pairing) may result. In some embodiments, the at least one histone stem-loop sequence comprises a length of 15 to 45 nucleotides. In some embodiments, an mRNA has one or more AU-rich sequences removed. These sequences, sometimes referred to as AURES are destabilizing sequences found in the 3 ’UTR. The AURES may be removed from the mRNA. Alternatively, the AURES may remain in the mRNA. Sequence Optimization In some embodiments, an open reading frame encoding a protein of the disclosure is codon optimized. Codon optimization methods are known in the art. An open reading frame of any one or more of the sequences provided herein may be codon optimized. Codon optimization, in some embodiments, may be used to match codon frequencies in target and host organisms to ensure proper folding; bias GC content to increase mRNA stability or reduce secondary structures; minimize tandem repeat codons or base runs that may impair gene construction or expression; customize transcriptional and translational control regions; insert or remove protein trafficking sequences; remove / add post translation modification sites in encoded protein (e.g., glycosylation sites); add, remove or shuffle protein domains; insert or delete restriction sites; modify ribosome binding sites and mRNA degradation sites; adjust translational rates to allow the various domains of the protein to fold properly; or reduce or eliminate problem secondary structures within the polynucleotide. Codon optimization tools, algorithms and services are known in the art - non-limiting examples include services from GeneArt (Life Technologies), DNA2.0 (Menlo Park CA) and / or proprietary methods. In some embodiments, the open reading frame sequence is optimized using optimization algorithms. In some embodiments, a codon optimized sequence shares less than 95% sequence identity to a naturally-occurring or wild-type sequence open reading frame (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein antigen). In some embodiments, a codon optimized sequence shares less than 90% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares less than 85% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares less than 80% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares less than 75% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares between 65% and 85% (e.g., between about 67% and about 85% or between about 67% and about 80%) sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon optimized sequence shares between 65% and 75% or about 80% sequence identity to a naturally-occurring or wild-type sequence (e.g., a naturally-occurring or wild-type mRNA sequence encoding an HBV protein). In some embodiments, a codon-optimized sequence encodes an antigen that is as immunogenic as, or more immunogenic than (e.g., at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 100%, or at least 200% more), than an HBV protein encoded by a non-codon-optimized sequence. When transfected into mammalian host cells, the modified mRNAs have a stability of between 12-18 hours, or greater than 18 hours, e.g., 24, 36, 48, 60, 72, or greater than 72 hours and are capable of being expressed by the mammalian host cells. In some embodiments, a codon optimized mRNA may be one in which the levels of G / C are enhanced. The G / C-content of nucleic acid molecules (e.g., mRNA) may influence the stability of the RNA. mRNA having an increased amount of guanine (G) and / or cytosine (C) residues may be functionally more stable than RNA containing a large amount of adenine (A) and thymine (T) or uracil (U) nucleotides. As an example, WO02 / 098443 discloses a pharmaceutical composition containing an mRNA stabilized by sequence modifications in the translated region. Due to the degeneracy of the genetic code, the modifications work by substituting existing codons for those that promote greater RNA stability without changing the resulting amino acid. The approach is limited to coding regions of the mRNA. Chemically Unmodified Nucleotides In some embodiments, an mRNA is not chemically modified and comprises the standard ribonucleotides consisting of adenosine, guanosine, cytosine and uridine. In some embodiments, nucleotides and nucleosides of the present disclosure comprise standard nucleoside residues such as those present in transcribed RNA (e.g., A, G, C, or U). In some embodiments, nucleotides and nucleosides of the present disclosure comprise standard deoxyribonucleosides such as those present in DNA (e.g., dA, dG, dC, or dT). Chemically Modified Nucleotides The compositions of the present disclosure comprise, in some embodiments, an RNA having an open reading frame encoding an HBV protein, wherein the nucleic acid comprises nucleotides and / or nucleosides that can be standard (unmodified) or modified as is known in the art. In some embodiments, nucleotides and nucleosides of the present disclosure comprise modified nucleotides or nucleosides. Such modified nucleotides and nucleosides can be naturally-occurring modified nucleotides and nucleosides or non-naturally-occurring modified nucleotides and nucleosides. Such modifications can include those at the sugar, backbone, or nucleobase portion of the nucleotide and / or nucleoside as are recognized in the art. In some embodiments, a naturally-occurring modified nucleotide or nucleotide of the disclosure is one as is generally known or recognized in the art. Non-limiting examples of such naturally-occurring modified nucleotides and nucleotides can be found, inter alia, in the widely recognized MODOMICS database. In some embodiments, a non-naturally-occurring modified nucleotide or nucleoside of the disclosure is one as is generally known or recognized in the art. Nonlimiting examples of such non-naturally-occurring modified nucleotides and nucleosides can be found, inter alia, in international publication numbers WO2013052523A1; WO2014093924A1; WO2015051173A2; WO2015051169A2; WO2015089511A2; or WO2017153936A1, each of which is herein incorporated by reference in its entirety. Hence, nucleic acids of the disclosure (e.g., DNA and RNA, such as mRNA) can comprise standard nucleotides and nucleosides, naturally-occurring nucleotides and nucleosides, non-naturally-occurring nucleotides and nucleosides, or any combination thereof. Nucleic acids of the disclosure (e.g., DNA and RNA, such as mRNA), in some embodiments, comprise various (more than one) different types of standard and / or modified nucleotides and nucleosides. In some embodiments, a particular region of a nucleic acid contains one, two or more (optionally different) types of standard and / or modified nucleotides and nucleosides. In some embodiments, a modified mRNA introduced to a cell or organism, exhibits reduced degradation in the cell or organism, respectively, relative to an unmodified nucleic acid comprising standard nucleotides and nucleosides. In some embodiments, a modified mRNA introduced into a cell or organism, may exhibit reduced immunogenicity in the cell or organism, respectively (e.g., a reduced innate response) relative to an unmodified nucleic acid comprising standard nucleotides and nucleosides. Nucleic acids (e.g., RNA, such as mRNA), in some embodiments, comprise nonnatural modified nucleotides that are introduced during synthesis or post-synthesis of the nucleic acids to achieve desired functions or properties. The modifications may be present on internucleotide linkages, purine or pyrimidine bases, or sugars. The modification may be introduced with chemical synthesis or with a polymerase enzyme at the terminal of a chain or anywhere else in the chain. Any of the regions of a nucleic acid may be chemically modified. The present disclosure provides for modified nucleosides and nucleotides of a nucleic acid (e.g., RNA, such as mRNA). A “nucleoside” refers to a compound containing a sugar molecule (e.g, a pentose or ribose) or a derivative thereof in combination with an organic base (e.g, a purine or pyrimidine) or a derivative thereof (also referred to herein as “nucleobase”). A “nucleotide” refers to a nucleoside, including a phosphate group. Modified nucleotides may by synthesized by any useful method, such as, for example, chemically, enzymatically, or recombinantly, to include one or more modified or non-natural nucleosides. Nucleic acids can comprise a region or regions of linked nucleosides. Such regions may have variable backbone linkages. The linkages can be standard phosphodiester linkages, in which case the nucleic acids would comprise regions of nucleotides. Modified nucleotide base pairing encompasses not only the standard adenosinethymine, adenosine-uracil, or guanosine-cytosine base pairs, but also base pairs formed between nucleotides and / or modified nucleotides comprising non-standard or modified bases, wherein the arrangement of hydrogen bond donors and hydrogen bond acceptors permits hydrogen bonding between a non-standard base and a standard base or between two complementary non-standard base structures, such as, for example, in those nucleic acids having at least one chemical modification. One example of such non-standard base pairing is the base pairing between the modified nucleotide inosine and adenine, cytosine or uracil. Any combination of base / sugar or linker may be incorporated into nucleic acids of the present disclosure. In some embodiments, modified nucleobases in nucleic acids (e.g., RNA, such as mRNA) comprise 1-methyl-pseudouridine (mly), 1-ethyl-pseudouridine (ely), 5-methoxy-uridine (mo5U), 5-methyl-cytidine (m5C), and / or pseudouridine (\| / ). In some embodiments, modified nucleobases in nucleic acids (e.g., RNA, such as mRNA) comprise 5-methoxymethyl uridine, 5-methylthio uridine, 1-methoxymethyl pseudouridine, 5-methyl cytidine, and / or 5-methoxy cytidine. In some embodiments, the polyribonucleotide includes a combination of at least two (e.g., 2, 3, 4 or more) of any of the aforementioned modified nucleobases, including but not limited to chemical modifications. In some embodiments, an mRNA of the disclosure comprises 1-methyl-pseudouridine (ml \p) substitutions at one or more or all uridine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises 1-methyl-pseudouridine (ml\| / ) substitutions at one or more or all uridine positions of the nucleic acid and 5-methyl cytidine substitutions at one or more or all cytidine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises pseudouridine (y) substitutions at one or more or all uridine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises pseudouridine (y) substitutions at one or more or all uridine positions of the nucleic acid and 5-methyl cytidine substitutions at one or more or all cytidine positions of the nucleic acid. In some embodiments, an mRNA of the disclosure comprises uridine at one or more or all uridine positions of the nucleic acid. In some embodiments, RNAs (e.g., mRNAs) are uniformly modified (e.g., fully modified, modified throughout the entire sequence) for a particular modification. For example, a nucleic acid can be uniformly modified with 1-methyl-pseudouridine, meaning that all uridine residues in the mRNA sequence are replaced with 1-methyl-pseudouridine. Similarly, a nucleic acid can be uniformly modified for any type of nucleoside residue present in the sequence by replacement with a modified residue such as those set forth above. The nucleic acids of the present disclosure may be partially or fully modified along the entire length of the molecule. For example, one or more or all or a given type of nucleotide (e.g., purine or pyrimidine, or any one or more or all of A, G, U, C) may be uniformly modified in a nucleic acid of the disclosure, or in a predetermined sequence region thereof (e.g., in the mRNA including or excluding the poly(A) tail). In some embodiments, all nucleotides X in a nucleic acid of the present disclosure (or in a sequence region thereof) are modified nucleotides, wherein X may be any one of nucleotides A, G, U, C, or any one of the combinations A+G, A+U, A+C, G+U, G+C, U+C, A+G+U, A+G+C, G+U+C or A+G+C. The nucleic acid may contain from about 1% to about 100% modified nucleotides (either in relation to overall nucleotide content, or in relation to one or more types of nucleotide, i.e., any one or more of A, G, U or C) or any intervening percentage (e.g., from 1% to 20%, from 1% to 25%, from 1% to 50%, from 1% to 60%, from 1% to 70%, from 1% to 80%, from 1% to 90%, from 1% to 95%, from 10% to 20%, from 10% to 25%, from 10% to 50%, from 10% to 60%, from 10% to 70%, from 10% to 80%, from 10% to 90%, from 10% to 95%, from 10% to 100%, from 20% to 25%, from 20% to 50%, from 20% to 60%, from 20% to 70%, from 20% to 80%, from 20% to 90%, from 20% to 95%, from 20% to 100%, from 50% to 60%, from 50% to 70%, from 50% to 80%, from 50% to 90%, from 50% to 95%, from 50% to 100%, from 70% to 80%, from 70% to 90%, from 70% to 95%, from 70% to 100%, from 80% to 90%, from 80% to 95%, from 80% to 100%, from 90% to 95%, from 90% to 100%, and from 95% to 100%). It will be understood that any remaining percentage is accounted for by the presence of unmodified A, G, U, or C. The mRNA may contain at a minimum 1% and at maximum 100% modified nucleotides, or any intervening percentage, such as at least 5% modified nucleotides, at least 10% modified nucleotides, at least 25% modified nucleotides, at least 50% modified nucleotides, at least 80% modified nucleotides, or at least 90% modified nucleotides. For example, the nucleic acids may contain a modified pyrimidine such as a modified uracil or cytosine. In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90% or 100% of the uracil in the nucleic acid is replaced with a modified uracil (e.g., a 5-substituted uracil). The modified uracil can be replaced by a compound having a single unique structure or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4 or more unique structures). In some embodiments, at least 5%, at least 10%, at least 25%, at least 50%, at least 80%, at least 90% or 100% of the cytosine in the nucleic acid is replaced with a modified cytosine (e.g., a 5-substituted cytosine). The modified cytosine can be replaced by a compound having a single unique structure or can be replaced by a plurality of compounds having different structures (e.g., 2, 3, 4 or more unique structures). Identification and Ratio Determination (IDR) Sequences An Identification and Ratio Determination (IDR) sequence is a sequence of a biological molecule (e.g., nucleic acid or protein) that, when combined with the sequence of a target biological molecule, serves to identify the target biological molecule. Typically, an IDR sequence is a heterologous sequence that is incorporated within or appended to a sequence of a target biological molecule and can be used as a reference to identify the target molecule. Thus, in some embodiments, a nucleic acid (e.g., mRNA) comprises (i) a target sequence of interest (e.g., a coding sequence encoding an antigenic peptide or protein); and (ii) a unique IDR sequence. An RNA species (e.g., RNA having a given coding sequence) may comprise an IDR sequence that differs from the IDR sequence of other RNA species (e.g., RNA(s) having different coding sequence(s)). Each IDR sequence thus identifies a particular RNA species, and so the abundance of IDR sequences may be measured to determine the abundance of each RNA species in a composition. Use of distinct IDR sequences to identify RNA species allows for analysis of multivalent RNA compositions (e.g., containing multiple RNA species) containing RNA species with similar coding sequences and / or lengths, which could otherwise be difficult to distinguish using PCR- or chromatography-based analysis of full-length RNAs. Each RNA species in a multivalent RNA composition may comprise an IDR sequence that is not a sequence isomer of an IDR sequence of another RNA species in a multivalent RNA composition (e.g., the IDR sequence does not have the same number of adenosine nucleotides, the same number of cytosine nucleotides, the same number of guanine nucleotides, and the same number of uracil nucleotides, as another IDR sequence in the composition, even if those sequences have different sequences). Having identical nucleotide compositions causes sequence isomers to have the same mass, presenting a challenge to distinguishing sequence isomers using mass-based identification methods (e.g., mass spectrometry). Each RNA species in a multivalent RNA composition may comprise an IDR sequence having a mass that differs from the mass of IDR sequences of each other RNA species in a multivalent RNA composition. For example, the mass of each IDR sequence may differ from the mass of other IDR sequences by at least 9 Da, at least 25 Da, at least 25 Da, or at least 50 Da. Use of IDR sequences with distinct masses allows RNA fragments comprising different IDR sequences to be distinguished using mass-based analysis methods (e.g., mass spectrometry), which do not require reverse transcription, amplification, or sequencing of RNAs. Each RNA species in an RNA composition may comprises an IDR sequence with a different length. For example, each IDR sequence may have a length independently selected from 0 to 25 nucleotides. The length of a nucleic acid influences the rate at which the nucleic acid traverses a chromatography column, and so the use of IDR sequences of different lengths on different RNA species allows RNA fragments having different IDR sequences to be distinguished using chromatography-based methods (e.g., LC-UV). IDR sequences may be chosen such that no IDR sequence comprises a start codon, ‘AUG’. Lack of a start codon in an IDR sequence prevents undesired translation of nucleotide sequences within and / or downstream from the IDR sequence. IDR sequences may be chosen such that no IDR sequence comprises a recognition site for a restriction enzyme. In one example, no IDR sequence comprises a recognition site for Xbal, ‘UCUAG’. Lack of a recognition site for a restriction enzyme (e.g., Xbal recognition site ‘UCUAG’) allows the restriction enzyme to be used in generating and modifying a DNA template for in vitro transcription, without affecting the IDR sequence or sequence of the transcribed RNA. Nucleic Acid Production Chemical Synthesis Solid-phase chemical synthesis. Nucleic acids the present disclosure may be manufactured in whole or in part using solid phase techniques. Solid-phase chemical synthesis of nucleic acids is an automated method wherein molecules are immobilized on a solid support and synthesized step by step in a reactant solution. Solid-phase synthesis is useful in site-specific introduction of chemical modifications in the nucleic acid sequences. The synthesis of nucleic acids of the present disclosure by the sequential addition of monomer building blocks may be carried out in a liquid phase. The synthetic methods discussed above each has its own advantages and limitations. Attempts have been conducted to combine these methods to overcome the limitations. Such combinations of methods are within the scope of the present disclosure. The use of solid-phase or liquid-phase chemical synthesis in combination with enzymatic ligation provides an efficient way to generate long chain nucleic acids that cannot be obtained by chemical synthesis alone. Ligation Assembling nucleic acids by a ligase may also be used. DNA or RNA ligases promote intermolecular ligation of the 5’ and 3’ ends of polynucleotide chains through the formation of a phosphodiester bond. Nucleic acids such as chimeric polynucleotides and / or circular nucleic acids may be prepared by ligation of one or more regions or subregions. DNA fragments can be joined by a ligase catalyzed reaction to create recombinant DNA with different functions. Two oligodeoxynucleotides, one with a 5’ phosphoryl group and another with a free 3’ hydroxyl group, serve as substrates for a DNA ligase. Purification Purification of the nucleic acids described herein may include, but is not limited to, nucleic acid clean-up, quality assurance and quality control. Clean-up may be performed by methods known in the arts such as, but not limited to, AGENCOURT® beads (Beckman Coulter Genomics, Danvers, MA), poly-T beads, LNATM oligo-T capture probes (EXIQON® Inc, Vedbaek, Denmark) or HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC). The term “purified” when used in relation to a nucleic acid such as a “purified nucleic acid” refers to one that is separated from at least one contaminant. A “contaminant” is any substance that makes another unfit, impure or inferior. Thus, a purified nucleic acid (e.g., DNA and RNA) is present in a form or setting different from that in which it is found in nature, or a form or setting different from that which existed prior to subjecting it to a treatment or purification method. A quality assurance and / or quality control check may be conducted using methods such as, but not limited to, gel electrophoresis, UV absorbance, or analytical HPLC. In some embodiments, the nucleic acids may be sequenced by methods including, but not limited to reverse-transcriptase-PCR. Quantification In some embodiments, the nucleic acids of the present disclosure may be quantified in exosomes or when derived from one or more bodily fluid. Bodily fluids include peripheral blood, serum, plasma, ascites, urine, cerebrospinal fluid (CSF), sputum, saliva, bone marrow, synovial fluid, aqueous humor, amniotic fluid, cerumen, breast milk, broncheoalveolar lavage fluid, semen, prostatic fluid, cowper's fluid or pre-ejaculatory fluid, sweat, fecal matter, hair, tears, cyst fluid, pleural and peritoneal fluid, pericardial fluid, lymph, chyme, chyle, bile, interstitial fluid, menses, pus, sebum, vomit, vaginal secretions, mucosal secretion, stool water, pancreatic juice, lavage fluids from sinus cavities, bronchopulmonary aspirates, blastocyl cavity fluid, and umbilical cord blood. Alternatively, exosomes may be retrieved from an organ selected from the group consisting of lung, heart, pancreas, stomach, intestine, bladder, kidney, ovary, testis, skin, colon, breast, prostate, brain, esophagus, liver, and placenta. Assays may be performed using construct specific probes, cytometry, qRT-PCR, real-time PCR, PCR, flow cytometry, electrophoresis, mass spectrometry, or combinations thereof while the exosomes may be isolated using immunohistochemical methods such as enzyme linked immunosorbent assay (ELISA) methods. Exosomes may also be isolated by size exclusion chromatography, density gradient centrifugation, differential centrifugation, nanomembrane ultrafiltration, immunoabsorbent capture, affinity purification, microfluidic separation, or combinations thereof. These methods afford the investigator the ability to monitor, in real time, the level of nucleic acids remaining or delivered. This is possible because the nucleic acids of the present disclosure, in some embodiments, differ from the endogenous forms due to the structural or chemical modifications. In some embodiments, the nucleic acid may be quantified using methods such as, but not limited to, ultraviolet visible spectroscopy (UV / Vis). A non-limiting example of a UV / Vis spectrometer is a NANODROP® spectrometer (ThermoFisher, Waltham, MA). The quantified nucleic acid may be analyzed in order to determine if the nucleic acid may be of proper size, check that no degradation of the nucleic acid has occurred. Degradation of the nucleic acid may be checked by methods such as, but not limited to, agarose gel electrophoresis, HPLC based purification methods such as, but not limited to, strong anion exchange HPLC, weak anion exchange HPLC, reverse phase HPLC (RP-HPLC), and hydrophobic interaction HPLC (HIC-HPLC), liquid chromatography-mass spectrometry (LCMS), capillary electrophoresis (CE) and capillary gel electrophoresis (CGE). In Vitro Transcription cDNA encoding the polynucleotides described herein may be transcribed using an in vitro transcription (IVT) system. In vitro transcription of mRNA is known in the art and is described in International Publication WO 2014 / 152027, which is incorporated by reference herein in its entirety. In some embodiments, the RNA of the present disclosure is prepared in accordance with any one or more of the methods described in WO 2018 / 053209 or WO 2019 / 036682, each of which is incorporated by reference herein. In some embodiments, the mRNA transcript is generated using a non-amplified, linearized DNA template in an in vitro transcription reaction to generate the RNA transcript. In some embodiments, the template DNA is isolated DNA. In some embodiments, the template DNA is cDNA. In some embodiments, the cDNA is formed by reverse transcription of an RNA, for example, but not limited to HBV mRNA. In some embodiments, cells, e.g., bacterial cells, e.g., E. coli, e.g., DH-1 cells are transfected with the plasmid DNA template. In some embodiments, the transfected cells are cultured to replicate the plasmid DNA which is then isolated and purified. In some embodiments, the DNA template includes an RNA polymerase promoter, e.g., a T7 promoter located 5 ' to and operably linked to the gene of interest. In some embodiments, an in vitro transcription template encodes a 5' untranslated (UTR) region, contains an open reading frame, and encodes a 3' UTR and a poly (A) tail. The particular nucleic acid sequence composition and length of an in vitro transcription template will depend on the mRNA encoded by the template. In some embodiments, a nucleic acid (e.g., template DNA and / or RNA) includes 200 to 3,000 nucleotides. For example, a nucleic acid may include 200 to 500, 200 to 1000, 200 to 1500, 200 to 3000, 500 to 1000, 500 to 1500, 500 to 2000, 500 to 3000, 1000 to 1500, 1000 to 2000, 1000 to 3000, 1500 to 3000, or 2000 to 3000 nucleotides. An in vitro transcription system typically comprises a transcription buffer (e.g., with magnesium), nucleotide triphosphates (NTPs), an RNase inhibitor and a polymerase (e.g., T7 RNA polymerase). In some embodiments, one or more of the NTPs is a chemically modified NTP (e.g., with 1-methylpseudouridine or other chemical modifications described herein and / or known in the art). In some embodiments, the NTPs comprise adenosine triphosphate (ATP), cytidine triphosphate (CTP), uridine triphosphate (UTP), and guanosine triphosphate (GTP), or an analog of each respective NTP. The ratio of NTPs may vary. In some embodiments, the ratio of GTP: ATP:CTP:UTP is 1:1:1:1. In some embodiments, the amount of the GTP or an analogue thereof is greater than an amount of the UTP or an analogue thereof. In some embodiments, the amount of the GTP is greater than the amount of the UTP. In some embodiments, the amount of ATP is greater than the amount of UTP, and the amount of CTP is greater than the amount of UTP. In some embodiments, the amount of the GTP or an analogue thereof is greater than an amount of the UTP or an analogue thereof. In some embodiments, an IVT system comprises an at least 2:1 ratio of GTP concentration to ATP concentration, an at least 2:1 ratio of GTP concentration to CTP concentration, and an at least 4:1 ratio of GTP concentration to UTP concentration. In some embodiments, an IVT system comprises a 2:1 ratio of GTP concentration to ATP concentration, a 2:1 ratio of GTP concentration to CTP concentration, and a 4:1 ratio of GTP concentration to UTP concentration. In some embodiments, an IVT system comprises guanosine diphosphate (GDP). In some embodiments, an IVT system comprises an at least 3:1 ratio of GTP plus GDP concentration to ATP concentration, an at least 6:1 ratio of GTP plus GDP concentration to CTP concentration, and an at least 6:1 ratio of GTP plus GDP concentration to UTP concentration. The NTPs may be manufactured in house, may be selected from a supplier, or may be synthesized as described herein. The NTPs may be selected from, but are not limited to, those described herein including natural and unnatural (modified) NTPs. Any number of RNA polymerases or variants may be used in the method of the present disclosure. The polymerase may be selected from, but is not limited to, a phage RNA polymerase, e.g., a T7 RNA polymerase, a T3 RNA polymerase, a SP6 RNA polymerase, and / or mutant polymerases such as, but not limited to, polymerases able to incorporate modified nucleic acids and / or modified nucleotides, including chemically modified nucleic acids and / or nucleotides. Some embodiments exclude the use of DNase. An IVT system, in some embodiments, comprises magnesium buffer, dithiothreitol (DTT) spermidine, pyrophosphatase, and / or RNase inhibitor. In some embodiments, an IVT system omits an RNase inhibitor. An IVT system may be incubated at 25 degrees Celsius or at 37 degrees Celsius. Other temperatures may be used, depending in part on the polymerase (e.g., use of a variant polymerase). In some embodiments, the RNA transcript is capped via enzymatic capping. In some embodiments, the RNA comprises 5' terminal cap, for example, 7mG(5’)ppp(5’)NlmpNp. Alternative mRNA Sequences In some embodiments, the compositions of the present disclosure include mRNA that encodes an HBV protein variant. Protein variants are proteins (including full length proteins and peptides) that differ in their amino acid sequence relative to a naturally occurring or reference amino acid sequence. A protein variant may possess one or more substitutions, deletions, and / or insertions at certain positions within its amino acid sequence, as compared to a naturally occurring or reference amino acid sequence. Ordinarily, protein variants have at least 50% identity to a naturally occurring or reference sequence. In some embodiments, a protein variant has at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%, identity to a naturally occurring or reference sequence. Global sequence alignment and local sequence alignment are two common methods used to compare and analyze sequences of DNA, RNA, or protein. Global sequence alignment compares the entire length of two sequences and finds the best possible alignment of the entire length of the sequences. It is useful, for example, when the two sequences being compared are similar in length and share significant homology. Local sequence alignment, on the other hand, identifies regions of similarity between sequences, allowing for gaps and mismatches in the alignment. This method is useful for identifying short regions of homology within larger sequences, and can be used to identify functional domains, protein families, and binding sites. Local alignment can be computationally more efficient than global alignment, and can be applied to sequences of different lengths. Unless stated otherwise herein, “percent (%) identity” between two mRNA polynucleotides or between two proteins refers to percent (%) identity determined using a global sequence alignment, comparing the length of entire sequences (e.g., entire mRNA polynucleotide, entire open reading frame of an mRNA, or entire protein encoded by an mRNA, as described herein). A protein variant encoded by an mRNA of the disclosure may contain amino acid changes that confer any of a number of desirable properties, for example, that enhance its immunogenicity, enhance its expression, and / or improve its stability or PK / PD properties in a subject. Protein variants can be made using routine mutagenesis techniques and assayed as appropriate to determine whether they possess the desired property. Assays to determine expression levels and immunogenicity of proteins, including protein variants, are well known in the art. Similarly, PK / PD properties of a protein variant can be measured using art recognized techniques, for example, by determining expression of the protein variant in a vaccinated subject over time and / or by looking at the durability of an induced immune response. The stability of a protein variant encoded by an mRNA may be measured by assaying thermal stability or stability upon urea denaturation or may be measured using in silico prediction, for example. Methods for such experiments and in silico determinations are known in the art. Other methods for determining protein variant expression levels, immunogenicity and / or PK / PD properties of a protein variant may be used. In some embodiments, an mRNA comprises an open reading frame that includes a nucleic acid sequence encoding an HBV envelope antigen comprising the amino acid sequence of any one of the sequences provided herein or comprises an amino acid sequence that has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of the sequences provided herein. See, e.g., SEQ ID NOs: 30-42. In some embodiments, an mRNA comprises an open reading frame that encodes a polymerase protein comprising the amino acid sequence of any one of the sequences provided herein or comprises an amino acid sequence that has at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of the sequences provided herein. See, e.g., SEQ ID NOs: 47-48. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a core protein, wherein the core protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 43, 44, and 46. In some embodiments, a vaccine of the present disclosure comprises an mRNA comprising an open reading frame encoding a fusion protein comprising a core protein and an envelope antigen protein, wherein the fusion protein comprises an amino acid sequence having at least 80%, at least 85%, at least 90%, at least 95%, 80%-85%, 80%-90%, 80%-95%, 80%-99%, 80%-100%, 85%-90%, 85%-95%, 85%-99%, 85%-100%, 90%-95%, 90%-99%, 90%-100%, 95%-99%, 95%-100%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NO: 45, and 374. “Identity” refers to a relationship between two or among three or more sequences (e.g., amino acid sequences or nucleotide sequences) as determined by comparing the sequences to each other. Identity also refers to the degree of sequence relatedness between or among sequences as determined by the number of matches between or among strings of amino acids (polypeptides) or strings of nucleotides (polynucleotides). Identity is a measure of the percent of identical matches between the smaller of two or more sequences with gap alignments (if any) addressed by a particular mathematical model or computer program (e.g., “algorithms”). Identity of related polypeptides and polynucleotides can be readily calculated by known methods. “Percent (%) identity” as it applies to polypeptide or polynucleotide sequences is defined as the percentage of residues (amino acid or nucleic acid residues) in the candidate (first) polypeptide or polynucleotide sequence that are identical with the residues in a second polypeptide or polynucleotide sequence after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity. Methods and computer programs for the alignment are well known in the art. It is understood that identity depends on a calculation of percent identity but may differ in value due to gaps and penalties introduced in the calculation. Generally, variants of a particular polynucleotide or polypeptide have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% but less than 100% sequence identity to that particular naturally occurring or reference sequence as determined by sequence alignment programs and parameters described herein and known to those skilled in the art. Such tools for alignment include but are not limited to those of the BLAST suite (Altschul, S.F., et al. Nucleic Acids Res. 1997;25:3389-3402); and those based on the Smith-Waterman algorithm (Smith, T.F. & Waterman, M.S. J. Mol. Biol. 1981;147:195-197). A general global alignment technique based on dynamic programming is the Needleman-Wunsch algorithm (Needleman, S.B. & Wunsch, C.D. J. Mol. Biol. 1920;48:443-453). A Fast Optimal Global Sequence Alignment Algorithm (FOGSAA) also has been developed that purportedly produces global alignment of nucleotide and protein sequences faster than other optimal global alignment methods, including the Needleman-Wunsch algorithm. Other non-limiting examples of global alignment tools include Needle (from EMBOSS), Clustal Omega, MUSCLE (Multiple Sequence Comparison by Log-Expectation), MAFFT (Multiple Alignment using Fast Fourier Transform), and T-Coffee (Tree-based Consistency Objective Function for Alignment Evaluation). Polynucleotides and polypeptides containing substitutions, insertions and / or deletions (e.g., indels), and covalent modifications with respect to naturally occurring or reference sequence, for example, the polypeptide (e.g., protein) sequences disclosed herein, are included within the scope of this disclosure. For example, sequence tags or amino acids, such as one or more lysine(s), can be added to polypeptide sequences (e.g., at the N-terminal and / or C-terminal end). Sequence tags can be used for peptide detection, purification and / or localization. Lysines can be used to increase peptide solubility or to allow for biotinylation. Alternatively, amino acid residues located at the N-terminal and / or C-terminal regions of the amino acid sequence of a protein may optionally be deleted providing for truncated sequences. Certain amino acids (e.g., C-terminal or N-terminal amino acids) may be deleted depending on the use of the sequence, as for example, expression of the sequence as part of a larger sequence that is soluble or linked to a solid support. In some embodiments, sequences for (or encoding) signal sequences, termination sequences, transmembrane domains, linkers, multimerization domains (e.g., foldon regions) and the like are substituted with alternative sequences that achieve the same or a similar function. In some embodiments, cavities in the core of proteins can be filled to improve stability, e.g., by introducing larger amino acids. In other embodiments, buried hydrogen bond networks are replaced with hydrophobic resides to improve stability. In yet other embodiments, glycosylation sites are removed and replaced with appropriate residues. Such sequences are readily identifiable to one of skill in the art. It should also be understood that some of the sequences provided herein contain sequence tags or terminal peptide sequences (e.g., at the N-terminal or C-terminal ends) that may be deleted, for example, prior to use in the preparation of an mRNA vaccine. As recognized by those skilled in the art, protein fragments, functional protein domains, and homologous proteins are also considered to be within the scope of HBV proteins provided herein. For example, provided herein is any protein fragment of (meaning a polypeptide sequence at least one amino acid residue shorter than but otherwise identical to) a naturally occurring or reference sequence, provided that the fragment is immunogenic and confers a protective immune response to LD. In addition to protein variants that are identical to the naturally occurring or reference protein but are truncated, in some embodiments, a protein includes 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations (e.g., substitutions, insertions and / or deletions), as shown in any of the sequences provided or referenced herein. Protein variants can range in length from about 4, 6, or 8 amino acids to full length proteins. Lipid Compositions In some embodiments, the nucleic acids of in (e.g., formulated as) a lipid composition, such as a composition comprising a lipid nanoparticle. In some embodiments, nucleic acids of the present disclosure are in (e.g., formulated as) lipid nanoparticle (LNP) compositions. Lipid nanoparticles typically comprise an ionizable amino lipid, non-cationic lipid (e.g., a phospholipid), structural lipid, and PEG lipid components along with the nucleic acid cargo (i.e., mRNA) of interest. A lipid nanoparticles of the present disclosure can be generated using components, compositions, and methods as are generally known in the art, see for example PCT / US2016 / 052352; PCT / US2016 / 0683 00; PCT / US2017 / 037551; PCT / US2015 / 027400; PCT / US2016 / 047406; PCT / US2016000129; PCT / US2016 / 014280; PCT / US2017 / 038426; PCT / US2014 / 027077; PCT / US2014 / 055394; PCT / US2016 / 52117; PCT / US2012 / 069610; PCT / US2017 / 027492; PCT / US2016 / 059575; PCT / US2016 / 069491; PCT / US2016 / 069493; and PCT / US2014 / 66242, all of which are incorporated by reference herein in their entirety. In some embodiments, a lipid nanoparticle comprises at least one ionizable amino lipid, at least one non-cationic lipid, at least one sterol, and / or at least one polyethylene glycol (PEG)-modified lipid. In some embodiments, a lipid nanoparticle comprises 20-60 mole percent (mol%) ionizable amino lipid, 5-25 mol% non-cationic lipid, 25-55 mol% structural lipid, and 0.5-15 mol% PEG-modified lipid. In some embodiments, a lipid nanoparticle comprises 20-60 mol% ionizable amino lipid, 5-30 mol% non-cationic lipid, 10-55 mol% structural lipid, and 0.5-15 mol% PEG-modified lipid. In some embodiments, a lipid nanoparticle comprises 40-50 mol% ionizable lipid, optionally 45-50 mol%, for example, 45-46 mol%, 46-47 mol%, 47-48 mol%, 48-49 mol%, or 49-50 mol% for example about 45 mol%, 45.5 mol%, 46 mol%, 46.5 mol%, 47 mol%, 47.5 mol%, 48 mol%, 48.5 mol%, 49 mol%, or 49.5 mol%. In some embodiments, a lipid nanoparticle comprises 20-60 mol% ionizable amino lipid. For example, a lipid nanoparticle may comprise 20-50 mol%, 20-40 mol%, 20-30 mol%, 30-60 mol%, 30-50 mol%, 30-40 mol%, 40-60 mol%, 40-50 mol%, or 5060 mol% ionizable amino lipid. In some embodiments, a lipid nanoparticle comprises 20 mol%, 30 mol%, 40 mol%, 50 mol%, or 60 mol% ionizable amino lipid. In some embodiments, a lipid nanoparticle comprises 35 mol%, 36 mol%, 37 mol%, 38 mol%, 39 mol%, 40 mol%, 41 mol%, 42 mol%, 43 mol%, 44 mol%, 45 mol%, 46 mol%, 47 mol%, 48 mol%, 49 mol%, 50 mol%, 51 mol%, 52 mol%, 53 mol%, 54 mol%, or 55 mol% ionizable amino lipid. In some embodiments, a lipid nanoparticle comprises 45-55 mol% ionizable amino lipid. For example, lipid nanoparticle may comprise 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, or 55 mol% ionizable amino lipid. Ionizable amino lipids In some embodiments, the ionizable lipid is a compound of Formula (IL*) R2 / VM R1 KM'xR3 IN (IL*) or a salt thereof, wherein: R1 is -OH, -NRn-C4-io cycloalkenyl optionally substituted with one or more oxo or -N(Rn RN ); Rn is H or Ci-6 alkyl; Rn is H or Ci-6 alkyl; Rn is H or Ci-6 alkyl; o is 1, 2, 3, or 4; 5            n is 4, 5, 6, 7, or 8; m is 4, 5, 6, 7, or 8; M is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R2; M’ is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R3; R2a R2b , „AJ\ / r2c R is                  or-(Ci-6 alkylene)-(C3-8 cycloalkyl)-Ci-6 alkyl; 10           R2a is -H or Ci-io alkyl; R2b is -H or Ci-io alkyl; R2c is Ci-8 alkyl or C2-8 alkenyl; ^Y^Y^R3' R3 is R3a R3b ; R3a is H or C1-10 alkyl; 15           R3b is H or C1-8 alkyl; and R3c is C1-10 alkyl or C2-8 alkenyl. In some embodiments, the ionizable lipid is of Formula (IL**-I): (IL**-I) 20 or a salt thereof, wherein: R1 is -OH; 0 is 2, 3, or 4; n is 4, 5, 6, 7, or 8; M is -C(=O)-O-*, wherein * indicates attachment to R2; m is 6, 7, or 8; M’ is -C(=O)-O-*, wherein * indicates attachment to R3; R2c is C4-8 alkyl; R3a is C7-10 alkyl; and R3c is C3-5 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*MII): R2c (IL* Mil) or a salt thereof, wherein: R1 is NRn-C4-io cycloalkenyl optionally substituted with one or more oxo or -N(RnRn”); Rn is H; Rn is C1-2 alkyl; Rn” is H; 0 is 2, 3, or 4; n is 6, 7, or 8; M is -C(=O)-O-*, wherein * indicates attachment to R2; m is 6, 7, or 8; M’ is -C(=O)-O-*, wherein * indicates attachment to R3; R2a is C7-10 alkyl; R2c is C4-6 alkyl; R3a is C1-3 alkyl; and R3c is C4-6 alkyl. In some embodiments, the ionizable lipid is of Formula (IL**-IV): (IL**-IV) or a salt thereof, wherein: R1 is OH; 0 is 2, 3, or 4; n is 6, 7, or 8; M is -C(=O)-O-*, wherein * indicates attachment to R2; m is 6, 7, or 8; M’ is -C(=O)-O-*, wherein * indicates attachment to R3; R2b is C3-5 alkyl; R2c is C2-4 alkyl; R3a is C7-10 alkyl; and R3c is C4-6 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-I): (IL*-Ia) or a salt thereof, wherein: R1, o, m, n, M, M’, R , and R3c are as defined for variable IL*; and R3a is Ci-8 alkyl. In some embodiments, ionizable lipid is of Formula (IL*-Ia): (IL*-Ia) or a salt thereof, wherein: R1, o, m, n, M, M’, R2c, and R3c are as defined for Formula IL*; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-Ia’): (ILMa’) or a salt thereof, wherein: o, M, M’, R2e and R3c are as defined for variable IL*; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIa): (IL*-na) or a salt thereof, wherein: R1, o, m, n, M, M’, R2c, and R3c are as defined for Formula IL*; and R3ais Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IF): (IL*-IF) or a salt thereof, wherein: o, M, M’, R2c and R3c are as defined for variable IL*; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-III): (IL*-III) or a salt thereof, wherein: R1, o, m, n, M, M’, R2c, and R3" are as defined for variable IL*; R2a is a Ci-8 alkyl; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIa): R3a (IL*-IIIa) or a salt thereof, wherein: R1, o, m, n, M, M’, R2e, and R3c are as defined for variable IL*; R2b is a Cns alkyl; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIa): R3a (IL*-IIIa) or a salt thereof, wherein: R1, o, M, M’, R2c, and R3c are as defined for variable IL*; R2a is a C1-8 alkyl; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIa’): R3a (ILMIIa’) or a salt thereof, wherein: R1, o, M, M’, R2c, and R3c are as defined for variable IL*; R2a is a Ci-8 alkyl; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIb): R2a (IL*-IIIb) or a salt thereof, wherein: R1, o, M, M’, R2c, and R3c are as defined for variable IL*; 5           R2a is a Ci-8 alkyl; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IIIb’): 10                                            (IL*-IIIb’) or a salt thereof, wherein: R1, o, M, M’, R2e, and R3c are as defined for variable IL*; R2a is a Ci-8 alkyl; and R3a is Ci-8 alkyl. 15 In some embodiments, the ionizable lipid is of Formula (IL*-IV): (IL*-IV) or a salt thereof, wherein: R1, o, m, n, M, M’, R2c, and R3c are as defined for variable IL*; R2b is a Ci-8 alkyl; and R3ais C1-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-IVa): (ILMVa) or a salt thereof, wherein: R1, o, m, n, M, M’, R2c, and R3c are as defined for variable IL*; R2b is a Ci-8 alkyl; and R3a is Ci-8 alkyl. In some embodiments, the ionizable lipid is of Formula (IL*-Iva’): (ILMVa) or a salt thereof, wherein: o, M, M’, R2c, and R3c are as defined for variable IL*; R2a is a Ci-8 alkyl; and R3a is Ci-8 alkyl. Variables o, R1, RN, RN\ RN" of Ionizable Lipid In some embodiments of the ionizable lipid, o is 1. In some embodiments of the ionizable lipid, o is 2. In some embodiments of the ionizable lipid, o is 3. In some embodiments of the ionizable lipid, o is 4. In some embodiments of the ionizable lipid, R1 is -OH. In some embodiments of the ionizable lipid, RN is H. In some embodiments of the ionizable lipid, RN is methyl. In some embodiments of the ionizable lipid, RN is ethyl. In some embodiments of the ionizable lipid, R1 is -NRN-cyclobutenyl, wherein the cyclobutenyl is optionally substituted with one or more oxo or -N(Rn Rn ). In some embodiments of the ionizable lipid, RN is H. In some embodiments of the ionizable lipid, RN is methyl. In some embodiments of the ionizable lipid, RN is ethyl. In some embodiments of the ionizable lipid, RN is H. In some embodiments of the ionizable lipid, RN is methyl. In some embodiments of the ionizable lipid, RN is ethyl. In some embodiments of the ionizable lipid, RN is H and RN is methyl. °w° n-ch3 In some embodiments of the ionizable lipid, R1 is H H . 0^° N N-CH3 In some embodiments of the ionizable lipid, R1 is Variables m and n of the Ionizable Lipid In some embodiments of the ionizable lipid, m is 4. In some embodiments of the ionizable lipid, m is 5. In some embodiments of the ionizable lipid, m is 6. In some embodiments of the ionizable lipid, m is 7. In some embodiments of the ionizable lipid, m is 8. In some embodiments of the ionizable lipid, m is 4. In some embodiments of the ionizable lipid, n is 5. In some embodiments of the ionizable lipid, n is 6. In some embodiments of the ionizable lipid, n is 7. In some embodiments of the ionizable lipid, n is 8. In some embodiments of the ionizable lipid, n is 5 and m is 7. In some embodiments of the ionizable lipid, n is 7 and m is 7. In some embodiments of the ionizable lipid, m is 6 and n is 6. Variables M and M ’ In some embodiments of the ionizable lipid, M is -O-C(=O)-*, wherein * indicates attachment to R2. In some embodiments of the ionizable lipid, M is -C(=O)-O-* wherein * indicates attachment to R2 In some embodiments of the ionizable lipid, M’ is -O-C(=O)-*, wherein * indicates attachment to R3. In some embodiments of the ionizable lipid, M’ is -C(=O)-O-* wherein * indicates attachment to R3. In some embodiments of the ionizable lipid, M is -O-C(=O)-*, wherein * indicates attachment to R2, and M’ is -C(=O)-O-* wherein * indicates attachment to R3 Variables R2, R2a, R2b, R2c In some embodiments of the ionizable lipid, R2 is R2a R2b X -R2c In some embodiments of the ionizable lipid, R2a is hydrogen. In some embodiments of the ionizable lipid, R2a is methyl. In some embodiments of the ionizable lipid, R2a is ethyl. In some embodiments of the ionizable lipid, R2a is propyl. In some embodiments of the ionizable lipid, R2a is butyl. In some embodiments of the ionizable lipid, R2a is pentyl. In some embodiments of the ionizable lipid, R2a is hexyl. In some embodiments of the ionizable lipid, R2a is heptyl. In some embodiments of the ionizable lipid, R2a is octyl. In some embodiments of the ionizable lipid, R2b is hydrogen. In some embodiments of the ionizable lipid, R2b is methyl. In some embodiments of the ionizable lipid, R2b is ethyl. In some embodiments of the ionizable lipid, R2b is propyl. In some embodiments of the ionizable lipid, R2b is butyl. In some embodiments of the ionizable lipid, R2b is pentyl. In some embodiments of the ionizable lipid, R2b is hexyl. In some embodiments of the ionizable lipid, R2b is heptyl. In some embodiments of the ionizable lipid, R2b is octyl. In some embodiments of the ionizable lipid, R2a is hydrogen and R2b is hydrogen. In some embodiments of the ionizable lipid, R2a is hexyl and R2b is hydrogen. In some embodiments of the ionizable lipid, R2a is octyl and R2b is hydrogen. In some embodiments of the ionizable lipid, R2a is hydrogen and R2b is butyl. In some embodiments of the ionizable lipid, R2c is methyl. In some embodiments of the ionizable lipid, R2c is ethyl. In some embodiments of the ionizable lipid, R2c is propyl. In some embodiments of the ionizable lipid, R2e is butyl. In some embodiments of the ionizable lipid, R2c is pentyl. In some embodiments of the ionizable lipid, R2c is hexyl. In some embodiments of the ionizable lipid, R2e is heptyl. In some embodiments of the ionizable lipid, R2c is octyl. In some embodiments of the ionizable lipid, R2 is -(Ci-6 alkylene)-(C3-s cycloalkyl)-Ci-6 alkyl. In some embodiments of the ionizable lipid, R2 is -(Ci-6 alkylene)-(cyclohexyl)-Ci-6 alkyl. In some embodiments of the ionizable lipid, R2 is -(Ci-6 alkylene)-(cyclopentyl)-Ci-6 alkyl. Variables R3, R3a, R3b, and R3c In some embodiments of the ionizable lipid, R3 is R3a R3b . In some embodiments of the ionizable lipid, R3a is hydrogen. In some embodiments of the ionizable lipid, R3a is methyl. In some embodiments of the ionizable lipid, R3a is ethyl. In some embodiments of the ionizable lipid, R3a is propyl. In some embodiments of the ionizable lipid, R3a is butyl. In some embodiments of the ionizable lipid, R3a is pentyl. In some embodiments of the ionizable lipid, R3a is hexyl. In some embodiments of the ionizable lipid, R3a is heptyl. In some embodiments of the ionizable lipid, R3a is octyl. In some embodiments of the ionizable lipid, R3b is hydrogen. In some embodiments of the ionizable lipid, R3b is methyl. In some embodiments of the ionizable lipid, R3b is ethyl. In some embodiments of the ionizable lipid, R3b is propyl. In some embodiments of the ionizable lipid, R3b is butyl. In some embodiments of the ionizable lipid, R3b is pentyl. In some embodiments of the ionizable lipid, R3b is hexyl. In some embodiments of the ionizable lipid, R3b is heptyl. In some embodiments of the ionizable lipid, R3b is octyl. In some embodiments of the ionizable lipid, R3a is octyl and R3h is hydrogen. In some embodiments of the ionizable lipid, R3a is ethyl and R3b is hydrogen. In some embodiments of the ionizable lipid, R3a is hexyl and R3b is hydrogen. In some embodiments of the ionizable lipid, R3c is methyl. In some embodiments of the ionizable lipid, R3c is ethyl. In some embodiments of the ionizable lipid, R3c is propyl. In some embodiments of the ionizable lipid, R3c is butyl. In some embodiments of the ionizable lipid, R3c is pentyl. In some embodiments of the ionizable lipid, R3c is hexyl. In some embodiments of the ionizable lipid, R3c is heptyl. In some embodiments of the ionizable lipid, R3c is octyl. It is understood that, for an ionizable lipid, variables o, R1, RN, RN , RN , m, n, M, M’, R2, R2a, R2b, R2e, R3, R3a, R3b, and R3e can each be, where applicable, selected from the groups described herein, and any group described herein for any of variables o,.R’, Rn, Rn , RN , m, n, M, M’, R2, R2a, R2b, R2c, R3, R3a, R3b, and R3c can be combined, where applicable, with any group described herein for one or more of the remainder of variables o, R1, Rn, Rn , Rn , m, n, M, M’, R2, R2a, R2b, R2c, R3, R3a, R3b, and R3c. In some embodiments, the ionizable lipid is a compound selected from: In some embodiments, the ionizable lipid is In some embodiments, the ionizable lipid is In some embodiments, the ionizable lipid is Without wishing to be bound by theory, it is understood that an ionizable lipid may have a positive or partial positive charge at physiological pH. Such lipids may be referred to as cationic or ionizable (amino)lipids. Lipids may also be zwitterionic, i.e., neutral molecules having both a positive and a negative charge. mRNA-Lipid Adduct It has been determined that certain ionizable lipids are susceptible to the formation of lipid-polynucleotide adducts. In particular, ionizable lipids that comprise a tertiary amine group may decompose into one or both of a secondary amine and a reactive aldehyde species capable of interacting with polynucleotides (such as mRNA) to form an ionizable lipid-polynucleotide adduct impurity that can be detected by reverse phase ion pair chromatography (RP-IP HPLC). For example, oxidation of the tertiary amine may lead to N-oxide formation that can undergo acid / base-catalyzed hydrolysis at the amine to generate aldehydes and secondary amines which may form adducts with mRNA. Thus, in some aspects, the ionizable lipid-polynucleotide adduct impurity is an aldehyde-mRNA adduct impurity. It also has been determined that such adducts may disrupt mRNA translation and impact the activity of lipid nanoparticle (LNP) formulated mRNA products. Thus, it can be advantageous to prepare and use LNP compositions with a reduced content of ionizable lipid-polynucleotide adduct impurity, such as wherein less than about 20%, less than about 10%, less than about 5%, or less than about 1%, of the mRNA is in the form of ionizable lipid-polynucleotide adduct impurity, as may be measured by RP-IP HPLC. Thus, in accordance with some aspects, an LNP composition is provided wherein less than about 10%, less than about 5%, or less than about 1%, of the mRNA is in the form of ionizable lipid-polynucleotide adduct impurity, including less than 10%, less than 5%, or less than 1%, as may be measured by RP-IP HPLC. In some aspects, an amount of lipid aldehydes in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of N-oxide compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of transition metals, such as Fe, in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of alkyl halide compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of anhydride compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of ketone compounds in the composition is less than about 50 ppm, including less than 50 ppm. Additionally or alternatively, in some aspects an amount of conjugated diene compounds in the composition is less than about 50 ppm, including less than 50 ppm. In some aspects, the composition is stable against the formation of ionizable lipidpolynucleotide adduct impurity. In some aspects, an amount of ionizable lipidpolynucleotide adduct impurity in the composition increases at an average rate of less than about 2% per day when stored at a temperature of about 25 °C or below, including at an average rate of less than 2% per day. In some aspects, an amount of ionizable lipidpolynucleotide adduct impurity in the composition increases at an average rate of less than about 0.5% per day when stored at a temperature of about 5 °C or below, including at an average rate of less than 0.5% per day. In some aspects, an amount of ionizable lipid-polynucleotide adduct impurity in the composition increases at an average rate of less than about 0.5% per day when stored at a refrigerated temperature, optionally wherein the refrigerated temperature is about 5 °C. Lipid vehicle (e.g., LNP) compositions with a reduced content of ionizable lipidpolynucleotide adduct impurity can be prepared by methods that inhibit formation of one or both of N-oxides and aldehydes. Such methods may comprise treating a composition comprising an ionizable lipid comprising a tertiary amine group to inhibit formation of one or both of N-oxides and aldehydes, such as by treating the composition with a reducing agent; treating the composition with a chelating agent; adjusting the pH of the composition; adjusting the temperature of the composition; and adjusting the buffer in the composition. Such methods may comprise, prior to combining the ionizable lipid with a polynucleotide, one or more of treating the ionizable lipid with a scavenging agent; treating the ionizable lipid with a reductive treatment agent; treating the ionizable lipid with a reducing agent; treating the ionizable lipid with a chelating agent; treating the polynucleotide with a reducing agent; and treating the polynucleotide with a chelating agent. In accordance with any of the foregoing, the scavenging agent, reductive treatment agent, and / or reducing agent may be an agent that reacts with aldehyde, ketone, anhydride and / or diene compounds. A scavengi...

Claims

1. A composition comprising a lipid nanoparticle and one or more messengerribonucleic acids (mRNAs), wherein the one or more mRNAs comprise:a first open reading frame (ORF) comprising a nucleic acid sequence encoding a hepatitis B virus (HBV) envelope protein;a second ORF comprising a nucleic acid sequence encoding an HBV core protein; anda third ORF comprising a nucleic acid sequence encoding an HBV polymerase protein.

2. The composition of claim 1, wherein the HBV envelope protein comprises a Pre SI domain and a PreS2 domain.

3. The composition of claim 2, wherein the PreSl domain and a PreS2 domain further comprise a lumazine synthase domain.

4. The composition of any one of claims 1-3, wherein the HBV core protein comprises a Core_149 protein.

5. The composition of any one of claims 1-4, wherein the HBV polymerase protein comprises a Polymerase8mut.

6. The composition of any one of claims 1-5, further comprising a fourth ORF comprising a nucleic acid sequence encoding a Small domain of HBV Envelope protein.

7. The composition of any one of claims 1-5, wherein the composition comprisesthree different mRNAs, and wherein the first ORF is present in a first mRNA, the second ORF is present in a second mRNA, and the third ORF is present in a third mRNA.

8. The composition of any one of claims 1-7, wherein the HBV envelope antigen comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to an amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25.

9. The composition of any one of the preceding claims, wherein the HBV envelope antigen comprises the amino acid sequence of any one of SEQ ID NOs: 3-7, or 16-25.

10. The composition of any one of the preceding claims, wherein the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 30-42.

11. The composition of any one of the preceding claims, wherein the ORF encoding the HBV envelope antigen comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos: 30-42.

12. The composition of any one of the preceding claims, wherein the first ORF further comprises a nucleic acid sequence encoding a signal peptide.

13. The composition of any one of the preceding claims, wherein the HBV core protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99% or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28.

14. The composition of any one of the preceding claims, wherein the HBV core protein comprises the amino acid sequence of any one of SEQ ID NOs: 2, 26, or 28.

15. The composition of any one of the preceding claims, wherein the HBV core protein comprises SEQ ID NO:2, SEQ ID NO:28, or a protein that differs from SEQ ID NO:2 or SEQ ID NO:28 by 1-10 amino acids.

16. The composition of claim 15 wherein the HBV core protein is SEQ ID NO:2 or SEQIDNO:28.

17. The composition of any one of the preceding claims, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of any one of SEQ ID Nos: 43, 44 or 46.

18. The composition of claim 17, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of any one of SEQ ID Nos:43, 44 or 4619. The composition of any one of the preceding claims, wherein the HBV polymerase protein comprises an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, 96%, 97%, 98%, 99%, or 100% identity to the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO:29.

20. The composition of claim 19, wherein the HBV polymerase protein is a protein that differs from SEQ ID NO: 1 or SEQ ID NO:29 by 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acids.

21. The composition of claim 20, wherein the different amino acids are present in a terminal protein domain, a spacer domain, a reverse transcriptase domain, and / or a RNase H domain of the HBV polymerase protein.

22. The composition of any one of the preceding claims, wherein the HBV polymerase protein is SEQ ID NO: 1 or SEQ ID NO:29.

23. The composition of any one of the preceding claims, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identity to a nucleic acid sequence of SEQ ID NO:47 or SEQIDNO:48.

24. The composition of claim 23, wherein the ORF encoding the HBV core protein comprises a nucleic acid sequence comprising a nucleic acid sequence of SEQ ID NO:47 or SEQ ID NO:48.

25. The composition of claim 1, wherein the composition comprises:a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:24;a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:28; anda third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:29.

26. The composition of claim 1, wherein the composition comprises:a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:24;a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:28; anda third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising an amino acid sequence having at least 95% identity to the amino acid sequence of SEQ ID NO:29.

27. The composition of claim 1, wherein the composition comprises:a first mRNA comprising the first ORF, wherein the first ORF encodes a first polypeptide comprising the amino acid sequence set forth in SEQ ID NO:24;a second mRNA comprising the second ORF, wherein the second ORF encodes a second polypeptide comprising the amino acid sequence set forth in SEQ ID NO:28; anda third mRNA comprising the third ORF, wherein the third ORF encodes a third polypeptide comprising the amino acid sequence set forth in SEQ ID NO:29.

28. The composition of any one of the preceding claims, wherein the mRNA comprises a chemical modification.

29. The composition of any of the preceding claims, wherein the lipid nanoparticle comprises an ionizable lipid, a neutral lipid, a sterol, and a PEG-modified lipid.

30. The composition of claim 29, wherein the lipid nanoparticle comprises 40-55 mol% of the ionizable lipid, 30-45 mol% of the sterol, 5-15 mol% of the neutral lipid, and 1-5 mol% of the PEG-modified lipid.

31. The composition of claim 29 or 30, wherein the ionizable lipid is a lipid of Formula (IL*):R2Atm / VNR1               3IX(IL*)or a salt thereof, wherein:R1 is -OH, -NRn-C4-io cycloalkenyl optionally substituted with one or more oxo or -N(Rn RN );Rn is H or Ci-6 alkyl;Rn is H or Ci-6 alkyl;Rn is H or Ci-6 alkyl;o is 1, 2, 3, or 4;n is 4, 5, 6, 7, or 8;m is 4, 5, 6, 7, or 8;M is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R2;M’ is -C(=O)-O-* or -O-C(=O)-*, wherein * indicates attachment to R3;R2a R2b.   / k^L.R20R is                  or-(Ci-6 alkylene)-(C3-8 cycloalkyl)-Ci-6 alkyl;R2a is -H or Ci-10 alkyl;R2b is -H or Ci-io alkyl;R2c is Ci-8 alkyl or C2-8 alkenyl;^Y^Y^r30R3js R3a R3b .R3a is H or Ci-10 alkyl;R3b is H or Ci-8 alkyl; andR3c is Ci-10 alkyl or C2-8 alkenyl.

32. The composition of claim 29 or 30, wherein the ionizable lipid is Compound (I-33. The composition of claim 29 or 30, wherein:the ionizable lipid is Compound (1-25)the neutral lipid is l,2-distearoyl-sn-glycero-3-phosphocholine (DSPC); the sterol is cholesterol; andthe PEG-modified lipid is PEG2000-DMG.

34. A method of treating HBV disease in a human subject in need thereof, the methodcomprising administering to the human subject one or more doses of the composition of any one of the preceding claims in an effective amount to produce an immune response to an HBV.

35. The method of claim 34, wherein the HBV disease is chronic HBV disease.

36. The method of claim 34 or 35, comprising administering a single dose of thecomposition to the human subject.

37. The method of claim 34 or 35, comprising administering at least one prime dose and at least one booster dose of the composition to the human subject.

38. The method of claim 34 or 35, comprising administering at least two prime doses and at least two booster doses of the composition to the human subject.

39. The method of claim 34 or 35, comprising administering at least three prime doses and at least two booster doses of the composition to the human subject.

40. The method of claim 34 or 35, comprising administering three prime doses and two booster doses of the composition to the human subject.

41. The method of any one of claims 34-40, wherein the treatment produces sustained undetectable HBsAg and HBV DNA in the human subject.

42. The method of any one of claims 34-40, wherein the treatment produces HBsAg seroconversion in the human subject.

43. The method of any one of claims 34-40, wherein the treatment produces a functional cure in the human subject.

44. The method of any one of claims 34-43, wherein the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD4+ cell activity against HBV.

45. The method of any one of claims 34-44, wherein the treatment induces a cell mediated immune response and the cell mediated immune response is an increase in CD 8+ cell activity against HBV.

46. The method of any one of claims 34-45, further comprising administering PEG-IFN monotherapy and / or nucleos(t)ide analogues (NUCs) to the human subject prior to initiation of treatment with the composition.

47. The method of claim 46, wherein the PEG-IFN monotherapy and / or the NUCs are administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition.

48. The method of any one of claims 34-47, further comprising administering an siRNA that targets HBV to the human subject prior to initiation of treatment with the composition.

49. The method of claim 48, wherein the siRNA that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition.

50. The method of any one of claims 34-49, further comprising administering an antisense oligonucleotide that targets HBV to the human subject prior to initiation of treatment with the composition.

51. The method of claim 50, wherein the antisense oligonucleotide that targets HBV is administered to the human subject for at least 3 months, at least 6 months, at least 9 months, or at least one year prior to initiation of treatment with the composition.

52. The method of any one of claims 34-51, further comprising administering to the human subject at least one immunostimulatory antibody or at least one mRNA encoding at least one immunostimulatory antibody.

53. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-OX40 antibody.

54. The method of claim 53, wherein the agonist anti-OX40 antibody is tavohmab, MOXR-0916, PF-04518600, GSK3174998, BMS-986178, INCAGN01949, or 9B12.

55. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-CD27 antibody.

56. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-4-IBB antibody.

57. The method of claim 52, wherein the at least one immunostimulatory antibody is an agonist anti-GITR antibody.

58. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist of an immune checkpoint molecule.

59. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-PD-1 antibody.

60. The method of claim 59, wherein the antagonist anti-PD-1 antibody is nivolumab, pembrolizumab, cemiplimab, spartalizumab, camrelizumab, cetrelimab, toripalimab, sintilimab, retifanlimab, AB122, AMP-224, JTX-4014, BGB-108, BCD-100, BAT1306, LZM009, AK105, HLX10, or TSR-042.

61. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-PD-Ll antibody.

62. The method of claim 61, wherein the antagonist anti-PD-Ll antibody is atezolizumab, avelumab, durvalumab, tislelizumab, BMS-935559, MEDI4736, FAZO53,KN035, CS1001, SHR-1316, CBT-502, A167, STI-A101, CK-301, BGB-A333, MSB-2311, HLX20, or LY3300054.

63. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-CTLA-4 antibody.

64. The method of claim 63, wherein the antagonist anti-CTLA-4 antibody is ipilimumab, tremelimumab, AGEN1884, or CP-675,206.

65. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-LAG-3 antibody.

66. The method of claim 65, wherein the antagonist anti-LAG-3 antibody is relatlimab, LAG525, or INCAGN2385.

67. The method of claim 52, wherein the at least one immunostimulatory antibody is an antagonist anti-PD-L2 antibody.

68. A composition comprising a messenger ribonucleic acid (mRNA) comprising an open reading frame encoding a polypeptide comprising an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ IDNOs: 1-7, 16-26, or 28-29.

69. A polypeptide comprising an amino acid sequence comprising at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to the amino acid sequence of any one of SEQ ID NOs: 1-7, 16-26, or 2829.

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