Multisubunit herpesvirus vaccines and therapeutics

Abstract

The present disclosure relates generally to multisubunit nucleic acids comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from a herpesvirus. The multisubunit nucleic acid encodes a multisubunit peptide.

Description

[0001] Multisubunit Herpesvirus Vaccines and Therapeutics

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of priority to U.S. Provisional Patent Application serial number 63 / 664,831, filed on June 27, 2024, the entire contents of which are hereby incorporated herein by reference in its entirety.

[0004] REFERENCE TO A SEQUENCE LISTING XML

[0005] This application contains a Sequence Listing which has been submitted electronically in XML format. The Sequence Listing XML is incorporated herein by reference. Said XML file, created on June 23, 2025, is named PVM-00825.xml and is 21,579,741 bytes in size.

[0006] BACKGROUND

[0007] More than 100 herpesviruses are known, of them 8 herpesviruses (herpes simplex virus types 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, human herpesvirus 7, and Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8) routinely infect humans. It is said that all humans become infected with one or more herpesviruses during their lifetime. Herpesviruses cause a variety of diseases, for example, gingivostomatitits, genital herpes, herpetic keratitis, herpetic whitlows, neonatal herpes simplex virus infection, herpes simplex encephalitis, varicella or chickenpox, herpes zoster or shingles, congenital cytomegalic inclusion disease, cytomegalovirus mononucleosis, Epstein-Barr virus mononucleosis, exanthem subitem or roseola, and Kaposi sarcoma. HSV1 and HSV2 alone have been estimated to have infected 3.7 billion and 491 million people globally under the age of 50 respectively. After the primary infection, herpesviruses remain in the body in the latent form. Reactivation from latency is a major clinical concern in those individuals whose immune system is suppressed. Prophylactic and therapeutic interventions exist against the diseases caused by some of the herpesviruses, but they are inadequate. Therefore, effective vaccines and therapeutics against herpesviruses are an important necessity. SUMMARY

[0008] Accordingly, the present disclosure relates to a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a selfassembling sequence or a linker sequence, a target sequence, a linker sequence, and a selfassembling sequence or a combination thereof, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence. In some embodiments, the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality. In some embodiments, the target sequence, the linker sequence, and the self-assembling sequence or the linker sequence, the target sequence, the linker sequence, and the self-assembling sequence are in 5' to 3' order.

[0009] In some embodiments, provided herein is a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence. In some embodiments, the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality. In some embodiments, the target sequence, the linker sequence, and the self- assembling sequence are in 5' to 3' order.

[0010] In some embodiments, provided herein is a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a selfassembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence. In some embodiments, the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality. In some embodiments, the linker sequence, the target sequence, the linker sequence, and the self-assembling sequence are in 5' to 3' order.

[0011] In another aspect, provided herein is a vaccine comprising a multisubunit nucleic acid, wherein the multisubunit nucleic acid comprises a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a self-assembling sequence or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence. In some embodiments, the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality. In some embodiments, the target sequence, the linker sequence, and the selfassembling sequence or the linker sequence, the target sequence, the linker sequence, and the self- assembling sequence are in 5' to 3' order.

[0012] In another aspect, provided herein is a vaccine comprising a multisubunit nucleic acid, wherein the multisubunit nucleic acid comprises a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence. In some embodiments, the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality. In some embodiments, the target sequence, the linker sequence, and the self-assembling sequence are in 5' to 3' order.

[0013] In another aspect, provided herein is a vaccine comprising a multisubunit nucleic acid, wherein the multisubunit nucleic acid comprises a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence. In some embodiments, the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality. In some embodiments, the linker sequence, the target sequence, the linker sequence, and the selfassembling sequence are in 5' to 3' order.

[0014] In another aspect, provided herein is a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self- assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide. In some embodiments, the multisubunit nucleic acid further encodes a signal peptide on the aminoterminus of one or more of the polypeptides of the plurality. In some embodiments, the target peptide, the linker peptide, and the self-assembling peptide or the linker peptide, the target peptide, the linker peptide and the self-assembling peptide are in N-terminus to C- terminus order.

[0015] In another aspect, provided herein is a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide. In some embodiments, the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality. In some embodiments, the target peptide, the linker peptide, and the selfassembling peptide are in N-terminus to C-terminus order.

[0016] In another aspect, provided herein is a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide. In some embodiments, the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality. In some embodiments, the linker peptide, the target peptide, the linker peptide, and the self-assembling peptide are in N-terminus to C-terminus order.

[0017] In another aspect, provided herein is a vaccine comprising a multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self- assembling peptide or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide. In some embodiments, the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality. In some embodiments, the target peptide, the linker peptide, and the self-assembling peptide or the linker peptide, the target peptide, the linker peptide and the self- assembling peptide are in N-terminus to C-terminus order.

[0018] In another aspect, provided herein is a vaccine comprising a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide. In some embodiments, the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality. In some embodiments, the target peptide, the linker peptide, and the self- assembling peptide are in N-terminus to C-terminus order.

[0019] In another aspect, provided herein is a vaccine comprising a multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide. In some embodiments, the multisubunit nucleic acid further encodes a signal peptide on the aminoterminus of one or more of the polypeptides of the plurality. In some embodiments, the linker peptide, the target peptide, the linker peptide, and the self-assembling peptide are in N-terminus to C-terminus order.

[0020] In some embodiments, total number of the polynucleotide sequences are not more than 100. In some embodiments, total number of the polynucleotide sequences are between 2-5, 2-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-99.

[0021] In some embodiments, the multisubunit nucleic acid is a DNA or an RNA. In some embodiments, the RNA is an mRNA. In some embodiments, the mRNA is obtained or synthesized through a single IVT process or step.

[0022] In some embodiments, the linker sequence encodes a linker peptide. In some embodiments, the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof. In some embodiments, the linker peptide is an amino acid linker. In some embodiments, the linker peptide is a zipper motif. In some embodiments, the linker peptide is a foldon. In some embodiments, the linker peptide is a scaffold. In some embodiments, the linker peptide comprises an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker and a foldon. In some embodiments, the linker peptide comprises an amino acid linker and a scaffold. In some embodiments, the linker peptide comprises a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a foldon and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker, a zipper motif and a scaffold.

[0023] In some embodiments, the amino acid linker comprises 2 to 49 amino acids. In some embodiments, the amino acid linker is a glycine serine linker, a glycine proline linker, a glycine threonine linker, an alanine serine linker, any combination of two amino acids, or a combination thereof.

[0024] In some embodiments, the linker peptide has an amino acid sequence of any one of SEQ ID NOs: 12-51 or 19101-19105. In some embodiments, the self-assembling sequence encodes a self-assembling peptide. In some embodiments, the self-assembling peptide is lumazine synthase, MS2 coat protein, hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, hepatitis B core antigen (HBcAg) from Hepatitis B virus, human papillomavirus LI (HPV LI) protein, matrix protein Ml from influenza A virus, ferritin, riboflavin synthase, dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents or functional analogs thereof.

[0025] In some embodiments, the ferritin comprises ferritin subunit or ferritin peptide. In some embodiments, the ferritin peptide is obtained or derived from Listeria innocua or Helicobacter pylori. In some embodiments, the ferritin peptide is obtained or derived from Listeria innocua ferritin or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the ferritin peptide is obtained or derived from Helicobacter pylori ferritin, or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus, or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the lumazine synthase is obtained or derived from Aquifex species (for example, Aquifex aeolicus) or Bacillus species (for example, Bacillus subtilis), or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the MS2 coat protein is obtained or derived from Emesvirus zinderi, or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the self-assembling peptide has an amino acid sequence of any one of SEQ ID NOs: 1-11 or 19097-19100.

[0026] In some embodiments, the cleavage sequence encodes a cleavage peptide. In some embodiments, the cleavage sequence encodes one or more cleavage peptides. In some embodiments, the cleavage peptide comprises one or more cleavage peptides, for example, cleavage peptide- 1, cleavage peptide-2, and so on. In some embodiments, the one or more cleavage peptides are optionally connected to each other by a linker peptide. In some embodiments, the cleavage peptide is a golgi specific cleavage peptide, self cleaving peptide, or a combination thereof. In some embodiments, the cleavage peptide has an amino acid sequence of any one of SEQ ID NOs: 52-66. In some embodiments, the signal sequence encodes a signal peptide. In some embodiments, the signal peptide is present on the amino-terminus of the first polypeptide. In some embodiments, the multisubunit nucleic acid further encodes a second signal peptide on the amino-terminus of all or some polypeptides. In some embodiments, the signal peptide has an amino acid sequence of any one of SEQ ID NOs: 67-86.

[0027] In some embodiments, the target sequence encodes a target peptide. In some embodiments, the target peptide is encoded by a codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

[0028] In some embodiments, the herpesvirus is selected from the group comprising herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella- zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.

[0029] In some embodiments, the target peptide is a capsid protein of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the capsid protein has an amino acid sequence of any one of SEQ ID NOs: 87-772, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0030] In some embodiments, the target peptide is a tegument protein of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the tegument protein has an amino acid sequence of any one of SEQ ID NOs: 773-2566, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0031] In some embodiments, the target peptide is an envelope protein of a herpes simplex virus 1 (HSV1), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0032] In some embodiments, the target peptide is an envelope protein of a herpes simplex virus 2 (HSV2), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0033] In some embodiments, the target peptide is an envelope protein of a cytomegalovirus (CMV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 34 or gp34, glycoprotein 68 or gp68, UL131A, UL130, UL128, UL16, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0034] In some embodiments, the target peptide is an envelope protein of a Epstein-Barr virus (EBV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 350 or gp350, glycoprotein 220 or gp220, glycoprotein 42 or gp42, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0035] In some embodiments, the target peptide is an envelope protein of a varicella-zoster virus (VZV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0036] In some embodiments, the target peptide is an envelope protein of a human herpesvirus 6 (HHV6), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0037] In some embodiments, the target peptide is an envelope protein of a human herpesvirus 7 (HHV7), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0038] In some embodiments, the target peptide is an envelope protein of a Kaposi’s sarcoma-associated herpesvirus (KSHV), wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0039] In some embodiments, the envelope protein has an amino acid sequence of any one of SEQ ID NOs: 2567-3557 or 15725-19096, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0040] In some embodiments, the target peptide is a regulatory protein of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the regulatory protein has an amino acid sequence of any one of SEQ ID NOs: 3558-4041, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0041] In some embodiments, the target peptide is a B cell epitope of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the B cell epitope has an amino acid sequence of any one of SEQ ID NOs: 4042-7752, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0042] In some embodiments, the target peptide is a T cell epitope of a herpesvirus, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the T cell epitope has an amino acid sequence of any one of SEQ ID NOs: 7753-15724, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0043] In some embodiments, the target peptide has an amino acid sequence of any one of SEQ ID NOs: 87-15724 or 15725-19096, including its codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0044] In another aspect, provided herein is a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid according to any of the preceding embodiments or paragraphs. In some embodiments, the cationic lipid comprises an ionizable lipid. In some embodiments, the cationic lipid is present in an amount from 10 mol percent to 70 mol percent. In some embodiments, the phospholipid is present in an amount from 2 mol percent to 65 mol percent. In some embodiments, the sterol is present in an amount from 20 mol percent to 65 mol percent. In some embodiments, the PEG-lipid is present in an amount from 0.2 mol percent to 2.0 mol percent. In some embodiments, the lipid nanoparticle composition additionally comprises an ionizable polymer. In some embodiments, the ionizable polymer is present in an amount from 1 mol percent to 25 mol percent. In some embodiments, the ionizable polymer is selected from the group comprising a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, a polyethyleneimine, and / or their derivatives or a combination thereof. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or SM-102, or ALC-0315, or a combination thereof.

[0045] In some aspects, provided herein is a vaccine comprising a lipid nanoparticle, wherein the lipid nanoparticle comprises a cationic lipid, a phospholipid, a sterol, a PEG- lipid, and the multisubunit nucleic acid according to any of the preceding embodiments or paragraphs. In some embodiments, the cationic lipid comprises an ionizable lipid. In some embodiments, the cationic lipid is present in an amount from 10 mol percent to 70 mol percent. In some embodiments, the phospholipid is present in an amount from 2 mol percent to 65 mol percent. In some embodiments, the sterol is present in an amount from 20 mol percent to 65 mol percent. In some embodiments, the PEG-lipid is present in an amount from 0.2 mol percent to 2.0 mol percent. In some embodiments, the lipid nanoparticle composition additionally comprises an ionizable polymer. In some embodiments, the ionizable polymer is present in an amount from 1 mol percent to 25 mol percent. In some embodiments, the ionizable polymer is selected from the group comprising a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, a polyethyleneimine, and / or their derivatives or a combination thereof. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), or formula (VIII), or SM-102, or ALC-0315, or a combination thereof.

[0046] In another aspect, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the multisubunit nucleic acid disclosed herein.

[0047] In another aspect, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the multisubunit peptide disclosed herein.

[0048] In another aspect, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the lipid nanoparticle composition disclosed herein.

[0049] In another aspect, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof, the vaccine comprising the multisubunit nucleic acid disclosed herein.

[0050] In another aspect, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof, the vaccine comprising the multisubunit peptide disclosed herein.

[0051] In another aspect, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof, the vaccine comprising the lipid nanoparticle or lipid nanoparticle composition disclosed herein.

[0052] In another aspect, provided herein is use of the multisubunit nucleic acid disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0053] In another aspect, provided herein is use of the vaccine comprising the multisubunit nucleic acid disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0054] In another aspect, provided herein is use of the lipid nanoparticle composition disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0055] In another aspect, provided herein is use of the vaccine comprising the lipid nanoparticle or lipid nanoparticle composition disclosed herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject. In another aspect, provided herein is a multisubunit peptide encoded by the multisubunit nucleic acid disclosed herein.

[0056] In another aspect, provided herein is a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the signal peptide is present on the amino-terminus of the first polypeptide. In some embodiments, the signal peptide is present on the amino-terminus of some or each of the polypeptides.

[0057] In another aspect, provided herein is a polypeptide nanoparticle comprising at least 2 or up to 500 polypeptides disclosed herein. In some embodiments, the polypeptides are homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or a combination thereof. In some embodiments, the polypeptide nanoparticle is icosahedral, helical, spherical, rod-like, or a combination thereof.

[0058] In another aspect, provided herein is a multisubunit nucleic acid sequence comprising two or more polynucleotide sequences, wherein some or all polynucleotide sequences comprises either a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein one polynucleotide sequence is connected to another polynucleotide sequence by a cleavage sequence, wherein the multisubunit nucleic acid sequence includes a signal sequence upstream of one or more of the polynucleotide sequences, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

[0059] In some embodiments, the linker sequence connects the signal sequence with the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of all or some of the polynucleotide sequences. In some embodiments, the signal sequence is present upstream of the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of all polynucleotide sequences. In some embodiments, the linker sequence connects the target sequence with the self-assembling sequence in a polynucleotide sequence. In some embodiments, one linker sequence connects the cleavage sequence with the target sequence and another linker sequence connects the target sequence with the self-assembling sequence in a polynucleotide sequence. In some embodiments, the multisubunit nucleic acid sequence is a DNA or an RNA. In some embodiments, the multisubunit nucleic acid sequence is an mRNA. In some embodiments, the multisubunit nucleic acid sequence encodes a multisubunit peptide. In some embodiments, the multisubunit nucleic acid sequence is encapsulated or formulated in a lipid nanoparticle composition. In some embodiments, the multisubunit nucleic acid sequence is obtained or synthesized through one or more in vitro transcription (IVT) process. In some embodiments, the multisubunit nucleic acid sequence (for example, mRNA) is obtained or synthesized through a single in vitro transcription (IVT) process or step.

[0060] In some embodiments, the disclosure relates to a multisubunit nucleic acid sequence encoding a multisubunit peptide described herein.

[0061] In some embodiments, the disclosure relates to a vaccine comprising a multisubunit nucleic acid sequence encoding a multisubunit peptide described herein.

[0062] In some embodiments, the disclosure relates to a multisubunit nucleic acid sequence encoding a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a selfassembling peptide, or a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, a signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, a signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, a signal peptide is present upstream (amino-terminus) of all polypeptides.

[0063] In some embodiments, the disclosure relates to a vaccine comprising a multisubunit nucleic acid sequence encoding a multisubunit peptide, wherein the multisubunit peptide comprises two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, signal peptide is present upstream (amino-terminus) of all the polypeptides.

[0064] In some embodiments, the disclosure also relates to a multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, signal peptide is present upstream (amino-terminus) of all the polypeptides.

[0065] In some embodiments, the disclosure also relates to a vaccine comprising a multisubunit peptide, wherein the multisubunit peptide comprises two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, a signal peptide is present upstream (amino-terminus) of all or some of the polypeptides. In some embodiments, a signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, a signal peptide is present upstream (amino-terminus) of all the polypeptides.

[0066] In some embodiments, the linker peptide connects the signal peptide with the first polypeptide in a multisubunit peptide. In some embodiments, the linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide.

[0067] In some embodiments, the multisubunit peptide comprises homologous polypeptides. In some embodiments, the multisubunit peptide comprises heterologous polypeptides. In some embodiments, the multisubunit peptide comprises homologous polypeptides, or heterologous polypeptides. In some embodiments, the disclosure relates to a polypeptide nanoparticle comprising one or more homologous polypeptides, one or more heterologous polypeptides, one or more oligomeric complexes, one or more polypeptide clusters, or a combination thereof. In some embodiments, the homologous polypeptides, heterologous polypeptides, oligomeric complexes, or polypeptide clusters comprise either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polypeptides in a polypeptide nanoparticle may also have some residues (amino acids) of the cleavage peptide.

[0068] In some embodiments, the disclosure relates to a polypeptide nanoparticle formed from the self-assembly of two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polypeptides in the polypeptide nanoparticle may also have some residues (amino acids) of the cleavage peptide. In some embodiments, the polypeptide nanoparticle comprises of homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or combination thereof. In some aspects, provided herein is the multisubunit nucleic acid sequence described herein, encapsulated or formulated in a lipid nanoparticle composition. In some aspects, the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG lipid and the multisubunit nucleic acid sequence described herein. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0069] In some aspects, provided herein is a vaccine comprising the multisubunit nucleic acid sequences described herein, encapsulated or formulated in a lipid nanoparticle composition. In some aspects, the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG lipid and the multisubunit nucleic acid sequence described herein. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0070] In some other aspects, provide herein is the lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence described herein. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula

[0071] (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0072] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the multisubunit nucleic acid sequence as described herein.

[0073] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the multisubunit nucleic acid sequence as described herein.

[0074] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula

[0075] (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0076] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula

[0077] (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0078] In some aspects, the disclosure relates to use of a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula

[0079] (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0080] In some aspects, the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject. In some embodiments, the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0081] In some embodiments, the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus, including the codon optimized sequences, fragments, variants, mutants, comparable equivalents, or functional analogs thereof. In some embodiments, the target sequence is modified or unmodified.

[0082] In some embodiments, the target sequence encodes a target peptide obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the target sequence or target peptide is modified or unmodified. In some embodiments, the target peptide regulates or modulates cellular functions. In some embodiments, the target peptide has immunostimulatory or immunomodulatory effect.

[0083] In some embodiments, the self-assembling sequence encodes a self-assembling peptide. In some embodiments, the self-assembling peptide includes, but not limited to, lumazine synthase, MS2 coat protein, hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, hepatitis B core antigen (HBcAg) from hepatitis B virus, human papillomavirus LI (HPV LI) protein, matrix protein Ml from influenza A virus, ferritin, riboflavin synthase, dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0084] In some embodiments, ferritin comprises ferritin subunit or ferritin peptide. In some embodiments, the ferritin peptide is obtained or derived from Listeria innocua or Helicobacter pylori. In some embodiments, the ferritin peptide is a Listeria innocua ferritin or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the ferritin peptide is a Helicobacter pylori ferritin or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the lumazine synthase is obtained or derived from Aquifex species (for example, Aquifex aeolicus) or Bacillus species (for example, Bacillus subtilis), or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof. In some embodiments, the MS2 coat protein is obtained or derived from Emesvirus zinderi or its fragment, mutant, variant, comparable equivalent, or functional analogs thereof.

[0085] In some embodiments, the linker sequence encodes a linker peptide. In some embodiments, the linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, the linker peptide connects the signal peptide with the first polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, the linker peptide connects two signal peptides. In some embodiments, the linker peptide connects two cleavage peptides. The linker peptide may be an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof.

[0086] In some embodiments, the cleavage sequence encodes a cleavage peptide. In some embodiments, the cleavage peptide comprises one or more cleavage peptides. The cleavage peptide connects one polypeptide with another polypeptide, for example, adjacent polypeptide. The cleavage peptide carries a cleavage site. In some embodiments, the cleavage peptide carries one or more cleavage sites. In some embodiments, the cleavage peptide facilitates the action of cellular proteases to cleave the multisubunit peptide into individual polypeptides. In some embodiments, the cleavage peptide self cleaves into individual polypeptides. In some embodiments, the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide- 1, cleavage peptide-2 and so on), optionally connected via a linker. In some embodiments, the cleavage peptide self cleaves into individual polypeptides or is cleaved by the action of cellular proteases. In some embodiments, the cleavage peptide is a substrate for cellular proteases. In some embodiments, the cleavage peptide is a substrate for golgi specific proteases. In some embodiments, the cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide - 1, cleavage peptide-2 and so on), optionally linked by a linker peptide, wherein one cleavage peptide is a substrate for cellular proteases and the other cleavage peptide is a self cleaving peptide.

[0087] In some embodiments, the signal sequence encodes a signal peptide. The signal peptide is present upstream (amino-terminus) of one or more polypeptides in a multisubunit peptide. In some embodiments, the signal peptide is present upstream (amino-terminus) of the first polypeptide. In some embodiments, the signal peptide is present upstream (amino-terminus) of some polypeptides. In some embodiments, the signal peptide is present upstream (amino-terminus) of all polypeptides. In some embodiments, the signal peptide transports the multisubunit peptide to cell organelles. In some embodiments, the signal peptide transports the multisubunit peptide to golgi body or golgi apparatus. In some embodiments, the signal peptide is a golgi targeting signal peptide.

[0088] In some aspects, the present disclosure also includes a method of transforming a cell with the multisubunit nucleic acid sequence as described herein.

[0089] BRIEF DESCRIPTION OF THE DRAWINGS

[0090] Figure 1 - shows representative schematic illustration of multisubunit nucleic acid sequence wherein each polynucleotide sequence (PS) comprises a target sequence (TS), a linker sequence (LS), and a self-assembling sequence (SAS) or a linker sequence (LS), a target sequence (TS), a linker sequence (LS), and a self-assembling sequence (SAS), wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. Multiple polynucleotide sequences are connected through a cleavage sequence (CS) such that between any two polynucleotide sequences there is present a cleavage sequence. The multisubunit nucleic acid sequence has a signal sequence (SS) upstream of the first polynucleotide sequence. The letter ‘n’ in figure 1 represents any number between 1 to 98. The multisubunit nucleic acid sequence may additionally have 5’ cap and 3’ poly(A) tail. This multisubunit nucleic acid sequence encodes corresponding multisubunit peptide depicted in Figure 2.

[0091] Figure 2 - shows representative schematic illustration of multisubunit peptide wherein each polypeptide (PP) comprises a target peptide (TP), a linker peptide (LP), and a self-assembling peptide (SAP) or a linker peptide (LP), a target peptide (TP), a linker peptide (LP), and a self-assembling peptide (SAP), wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. Multiple polypeptides are connected through a cleavage peptide (CP) such that between any two polypeptides there is present a cleavage peptide. The multisubunit peptide has a signal peptide (SP) on the N-terminus of the first polypeptide. The letter ‘n’ represents any number between 1 to 98.

[0092] DESCRIPTION

[0093] The present disclosure relates to multisubunit nucleic acid sequences, multisubunit peptides, polypeptide nanoparticle, and their compositions for vaccine and therapeutic purpose against herpesviruses.

[0094] Unless defined otherwise, technical, and scientific terms used herein have the same meaning as commonly understood by one of person skill in the art. Some of the terms are defined briefly here below; the definitions should not be construed in a limiting sense.

[0095] The singular forms “a”, “an” and “the” as used in the specification also include plural aspects unless the context dictates otherwise. Similarly, any singular term used in the specification also mean plural or vice versa unless the context dictates otherwise. As used herein in the claim(s), when used in conjunction with the word “comprising”, the words “a” or “an” may mean one or more than one. As used herein “another” may mean at least a second or more.

[0096] It must be noted that the words “comprising” or any of its form such as “comprise” or “comprises”, “having” or any of its forms such as “have” or “has”, “including” or any of its forms such as “include” or “includes”, or “containing” or any of its forms such as “contain” or “contains” are open-ended and do not exclude additional unrecited elements or method steps. Wherever any quantity or range is stated one skilled in the art will recognize that quantity or range within 10 or 20 percent of the stated values can also be expected to be appropriate and reasonable and included within the scope of the invention.

[0097] Unless otherwise defined herein, scientific, and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skilled in the art. Generally, nomenclatures used in connection with, and techniques of, cell and tissue culture, molecular biology, immunology, microbiology, protein, adjuvant, pharmaceutical biotechnology, and biopharmaceutical manufacturing described herein are those well known and commonly used in the art. The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification.

[0098] The term “composition”, “formulation”, “lipid nanoparticle composition”, or “lipid nanoparticle” has been used interchangeably to mean a nanoparticle, nanostructure, vesicle, liposome, composition or formulation comprising one or more lipid components (for example, a cationic lipid, a phospholipid, a sterol, and a PEG-lipid), and / or an ionizable polymer component. In some embodiments, the lipid nanoparticle comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and a multisubunit nucleic acid. In some embodiments, the lipid nanoparticle comprises one or more lipid components, an ionizable polymer component, and a multisubunit nucleic acid. In some embodiments, the cationic lipid is represented by any one of formulas (I), formulas (II), formulas (III), formulas (IV), formulas (V), formulas (VI), formulas (VII), formulas (VIII), or a combination thereof. In some embodiments, the multisubunit nucleic acid associated with the lipid nanoparticle is a DNA, an mRNA, a micro RNA, a small interfering RNA, a small nucleolar RNA, a small nuclear RNA, a long non-coding RNA or a combination thereof. In some embodiments, the lipid nanoparticle composition contains one or more pharmaceutical carriers or excipients, such as but not limited to, buffering agents, stabilizers, tonicity modifiers, surfactants, chelating agents, salts, anti-oxidants, diluents, and / or preservatives or a combination thereof. The term lipid nanoparticle also denotes lipid nanoparticles that are devoid of any encapsulated multisubunit nucleic acid (empty lipid nanoparticles or ghost lipid nanoparticles). In some embodiments, the lipid nanoparticle composition comprises lipid nanoparticles with encapsulated multisubunit nucleic acid as well as empty lipid nanoparticles. The term “therapeutic”, “therapeutic agent”, “prophylactic”, “prophylactic agent”, or “drug” has been used interchangeably to mean a compound (such as multisubunit nucleic acid sequence) or composition (such as a lipid nanoparticle composition described herein) having a biological effect or a combination of biological effects that prevents, inhibits, eliminates or prevents the progression of a disease or other aberrant biological processes in a subject, for example, an animal or human.

[0099] The term “preventing” is art-recognized, and when used in relation to a condition, such as an infection is well understood in the art, and includes administration of a composition, which reduces the frequency or severity, or delays the onset, of one or more symptoms of the medical condition in a subject relative to a subject who does not receive the composition. Thus, the prevention of a condition, such as an infection, includes, for example, the reduction of the frequency or severity of one or more symptoms of the medical condition in a population of patients receiving a therapy relative to a control population that did not receive the therapy, e.g., by a statistically and / or clinically significant amount. Similarly, the prevention of an infection includes reducing the likelihood that a patient receiving a therapy will develop the infection or related symptoms, relative to a patient who does not receive the therapy.

[0100] The term “molar percent”, “mol percent”, “molar %”, or “mol %” have been used interchangeably to mean number of moles of a component expressed as percentage relative to total moles of all lipid components present in the lipid nanoparticle compositions described herein. For example, 50 mol % cationic lipid means, 50 mol % of cationic lipid is present in the lipid nanoparticle composition and other lipid components together constitute remaining 50 mol % such that the total amount of all the lipid components constitute 100 mol %. In some embodiments, mol % also denotes to mean number of moles of a component expressed as percentage relative to total moles of all lipid components (such as cationic lipid, phospholipid, sterol and PEG-lipid) and ionizable polymer component(s) present in the lipid nanoparticle composition described herein. For example, 50 mol % of cationic lipid means, 50 mol % of cationic lipid is present in the lipid nanoparticle composition and other lipids components and ionizable polymer components together constitute the remaining 50 mol % such that the total amount of all the lipid components and ionizable polymer components constitute 100 mol %.

[0101] The term “N / P ratio”, “N:P ratio”, “lipid to nucleic acid ratio”, or “cationic lipid to nucleic acid ratio” have been used interchangeably herein and means the ratio (molar ratio) of the positive charges in the cationic lipid relative to the negative charges in the nucleic acid (such as the multisubunit nucleic acid sequence disclosed herein) in a lipid nanoparticle. In some embodiments, the N / P ratio refers to the ratio of protonable nitrogen present in the cationic lipid relative to the phosphate present in the nucleic acid in a lipid nanoparticle. In some embodiments, the N / P ratio is between 1 to 18 (i.e., 1 :1 to 18:1). For example, a N / P ratio of 18 refers to the presence of 18 protonable nitrogen of the cationic lipid relative to 1 phosphate of the nucleic acid in a lipid nanoparticle.

[0102] The terms “antibody” and “antibodies” have been used interchangeably herein and means any antibody or antibody fragment (whether produced naturally or recombinantly) which retains antigen binding activity. This includes a monoclonal or polyclonal antibody, a single chain antibody, a Fab fragment of a monoclonal or polyclonal antibody, a chimeric antibody, a humanized antibody, a human antibody, a bispecific antibody, a multispecific antibody, or a nanobody.

[0103] The term “buffer” as used herein means those agents that maintains the pH of a solution in a desired range.

[0104] The term “cell” as used herein means a single cell or a population of cells or plurality of cells.

[0105] The term “biologically effective amount” or “therapeutically effective amount” as used herein means an amount of an agent, for example, a therapeutic, drug, therapeutic agent, prophylactic agent, diagnostic agent, composition, etc., that is sufficient, when administered to a subject suffering from or susceptible to an infection, disease, disorder, and / or condition, to treat, prevent, diagnose, improve symptoms of, and / or delay the onset of the infection, disease, disorder, and / or condition. A therapeutically effective amount herein may vary according to factors such as the disease state, age, sex, and weight of the patient.

[0106] As used herein, the term “treating” or “treatment” includes reducing, arresting, or reversing the symptoms, clinical signs, or underlying pathology of a condition to stabilize or improve a subject’s condition or to reduce the likelihood that the subject’s condition will worsen as much as if the subject did not receive the treatment. Treatment may be administered to a subject who does not exhibit signs of a disease and / or exhibits only early signs of the disease for the purpose of decreasing the risk of developing pathology associated with the disease. The term “subject” as used herein refers to an animal or human, for example, a living mammal and may be interchangeably used with the term “patient”. Examples of mammals include, but are not limited to, any member of the mammalian class: humans, non-human primates such as chimpanzees, and other apes and monkey species; farm animals such as cattle, horses, sheep, goats, swine; domestic animals such as rabbits, dogs, and cats; laboratory animals including rodents, such as rats, mice, ferrets, and guinea pigs, and the like. The term does not denote a particular age or gender.

[0107] As used herein, an individual “at risk” of developing a particular disease, disorder, or condition may or may not have detectable disease or symptoms of disease, and may or may not have displayed detectable disease or symptoms of disease prior to the treatment methods described herein. “At risk” denotes that an individual has one or more risk factors, which are measurable parameters that correlate with development of a particular disease, disorder, or condition, as known in the art. An individual having one or more of these risk factors has a higher probability of developing a particular disease, disorder, or condition than an individual without one or more of these risk factors.

[0108] The term “disease” as used herein, means an interruption, cessation, or disorder of body function, system, or organ. Non limiting examples of disease include malignant diseases, autoimmune diseases, inherited diseases, metabolic disorders, or infectious diseases.

[0109] The term “vaccine” as used herein means a substance or composition comprising an antigen or immunogen for eliciting an immune response in a subject against the antigen or the immunogen. The term vaccine is also understood to mean a substance or composition comprising an antigen or immunogen that activates or stimulates an immune cell. In some cases, the antigen or immunogen is a peptide, a protein, a polysaccharide, or a combination thereof. In some cases, the antigen or immunogen is encoded by a nucleic acid, for example, a DNA, an RNA, or an mRNA. In some embodiments, the vaccine comprises a nucleic acid that encodes an antigen or an immunogen. In some embodiments, the vaccine comprises a multisubunit nucleic acid as described herein.

[0110] As used herein, administration “conjointly” with another compound or composition includes simultaneous administration and / or administration at different times. Conjoint administration also encompasses administration as a co-formulation or administration as separate compositions, including at different dosing frequencies or intervals, and using the same route of administration or different routes of administration. The term “multisubunit nucleic acid sequence” or “multisubunit nucleic acid” have been used interchangeably herein and means two or more polynucleotide sequences wherein some or all polynucleotide sequences comprises either a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, or a combination thereof, wherein one polynucleotide sequence is connected to another polynucleotide sequence by a cleavage sequence, wherein the multisubunit nucleic acid sequence includes a signal sequence upstream of one or more polynucleotide sequences, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the signal sequence is present upstream of the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of some polynucleotide sequences. In some embodiments, the signal sequence is present upstream of each of the polynucleotide sequences. In some embodiments, the polynucleotide sequence comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polynucleotide sequence comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. Thus, in some embodiments, one linker sequence connects the cleavage sequence with the target sequence and another linker sequence connects the target sequence with the selfassembling sequence in a polynucleotide sequence. In some embodiments, the linker sequence connects the signal sequence with the polynucleotide sequence. As illustrated in figure 1 multisubunit nucleic acid sequence comprises multiple repeats of polynucleotide sequences wherein each polynucleotide sequence comprises either a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence and a self-assembling sequence, or a combination thereof, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus, such that total number of polynucleotide sequences in a multisubunit nucleic acid sequence are not more than 100. In some embodiments, the linker sequence connects the signal sequence with the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of each of some or all of the polynucleotide sequences. In some embodiments, the multisubunit nucleic acid sequence is obtained or synthesized through a single in vitro transcription (IVT) process or step. The multisubunit nucleic acid sequence encodes multisubunit peptide.

[0111] The terms “multisubunit peptide” as used herein means two or more polypeptides wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide and a selfassembling peptide, or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide upstream (amino-terminus) of one or more polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the signal peptide is present on the amino-terminus of the first polypeptide. In some embodiments, the signal peptide is present on the amino-terminus of some polypeptides. In some embodiments, the signal peptide is present on the aminoterminus of each of the polypeptides. In some embodiments, the polypeptide comprises a target peptide, a linker peptide, and a self- assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polypeptide comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. Thus, in some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a multisubunit peptide. In some embodiments, the multisubunit peptide either comprises a target peptide, a linker peptide, and a self- assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus, such that the total number of polypeptides in a multisubunit peptide are not more than 100. In some embodiments, the linker peptide connects the signal peptide with the polypeptide. In some embodiments, the signal peptide is present on the amino-terminus of each of some or all polypeptides. The multisubunit peptide may comprise homologous polypeptides or heterologous polypeptides.

[0112] The term “polynucleotide sequence” as used herein means a sequence of nucleotides that encodes a polypeptide.

[0113] The terms “protein” or “peptide” have been used interchangeably herein and mean a polymer of amino acids linked through peptide bonds, but do not imply any specific length. The term also includes fusion proteins, muteins, analogs or modified forms.

[0114] The term “polypeptide” as used herein means a sequence of amino acids that comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polypeptide comprises a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polypeptide comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polypeptide may have some residues (amino acids) of cleavage peptide. In some embodiments, the polypeptide comprises a signal peptide.

[0115] The term “target sequence” as used herein means a sequence of nucleotides that encodes a target peptide obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

[0116] The term “target peptide” as used herein means a sequence of amino acids obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the target peptides in two or more polypeptides are identical i.e., homologous polypeptides. In some other embodiments, the target peptides in two or more polypeptides are different i.e., heterologous polypeptides. The term “signal sequence” as used herein means a sequence of nucleotides that encodes a signal peptide.

[0117] The term “signal peptide” as used herein means a sequence of amino acids that transports the multisubunit peptide to specific cell organelles. In some embodiments the signal peptide transports the multisubunit peptide to golgi apparatus or golgi body. The signal peptide is present on the N-terminus (amino-terminus) of one or more polypeptides. In some embodiments, the signal peptide is present on the N-terminus of some or all polypeptides. In some embodiments, the signal peptide is present on the N-terminus of the first polypeptide. In some embodiments, the signal peptide is present on the N-terminus of some polypeptides. In some embodiments, the signal peptide is present on the N-terminus of all polypeptides. In some embodiments, the signal peptide is encoded by signal sequence. In some embodiments, the signal peptide is a golgi targeting signal peptide.

[0118] The term “cleavage sequence” as used herein means a sequence of nucleotides that encodes a cleavage peptide.

[0119] The term “cleavage peptide” as used herein means a sequence of amino acids that facilitates the action of cellular proteases to cleave the multisubunit peptide into individual polypeptides or self cleaves into individual polypeptides. The cleavage peptide is present between any two polypeptides. It connects one polypeptide with another polypeptide, for example, adjacent polypeptide. The cleavage peptide carries one or more cleavage sites. In some embodiments, the cleavage peptide is a substrate for proteases. In some embodiments, cleavage peptide undergoes self cleavage to result in individual polypeptides. In some embodiments, the cleavage peptide is a substrate for golgi specific proteases. In some embodiments, the cleavage peptide comprises one or more cleavage peptides, for example, cleavage peptide- 1, cleavage peptide-2 and so on. In some embodiments, the cleavage peptide optionally comprises a linker peptide between two cleavage peptides. In some embodiments, the cleavage peptide self cleaves into individual polypeptides or is cleaved by the action of cellular proteases. In some embodiments, the cleavage peptide is a substrate for cellular proteases. In some embodiments, the cleavage peptide is a substrate for golgi specific proteases. In some embodiments, the cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide- 1, cleavage peptide-2 and so on), optionally linked by a linker peptide, wherein one cleavage peptide is a substrate for cellular proteases and the other cleavage peptide is a self cleaving peptide. The term “linker sequence” as used herein means a sequence of nucleotides that encodes a linker peptide.

[0120] The term “linker peptide” or “peptide linker” have been used interchangeably to mean a sequence of amino acids that either connects the target peptide with the selfassembling peptide, connects the signal peptide with the target peptide, connects the cleavage peptide with the target peptide, connects the signal peptide with the polypeptide, or connects two cleavage peptides. In some embodiments, the linker peptide connects the signal peptide with the polypeptide. In some embodiments, the linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide. In some embodiments, one linker peptide connects cleavage peptide with the target peptide and another linker peptide connects the signal peptide with the target peptide. In some embodiments, the linker peptide connects two cleavage peptides. In some embodiments, the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof. In some embodiments, the linker peptide is an amino acid linker. In some embodiments, the linker peptide is a foldon. In some embodiments, the linker peptide is a zipper motif. In some embodiments, the linker peptide is a scaffold. In some embodiments, the linker peptide comprises an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker and a foldon. In some embodiments, the linker peptide comprises an amino acid linker and a scaffold. In some embodiments, the linker peptide comprises a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a foldon and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker, a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker, a foldon, and a scaffold.

[0121] The term “amino acid linker sequence” as used herein means a sequence of nucleotides that encodes an amino acid linker.

[0122] The term “amino acid linker” as used herein means a sequence of amino acids that provides structural integrity to polypeptide such that the components of the polypeptide remain, as far as possible, in their native or stable conformation. In some embodiments, amino acid linker also helps in orientation of a polypeptide such that the domains or epitopes on the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system in the absence of foldon or scaffold. In some embodiments, the amino acid linker connects two cleavage peptides. Some of the nonlimiting examples of amino acid linkers includes, glycine serine linker, glycine proline linker, glycine threonine linker, alanine serine linker, any combination of two amino acids or a combination thereof. In some embodiments, amino acid linker is about 2-49 amino acid long.

[0123] The term “glycine serine linker sequence” as used herein means a sequence of nucleotides that encodes a glycine serine linker.

[0124] The term “glycine serine linker” as used herein means a sequence of amino acid comprising one or more glycine (G) and serine (S) in any combinations without any preference of order or limitation on number of appearances of either glycine or serine. In some embodiments, the glycine serine linker is few amino acids in length to several amino acids in length.

[0125] The term “zipper sequence” as used herein means a sequence of nucleotides that encodes a zipper motif.

[0126] The term “zipper motif’ or “zipper peptide” as used herein means a sequence of amino acids that facilitates homologous polypeptides or heterologous polypeptides to come together or associate to form a polypeptide cluster.

[0127] The term “foldon sequence” as used herein means a sequence of nucleotides that encodes a foldon.

[0128] The term “foldon” as used herein means a sequence of amino acids that enables two or more homologous polypeptides to organise to form an oligomeric complex. In some embodiments, the foldon also helps in orientation of a polypeptide such that the domains or epitopes on the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.

[0129] The term “scaffold sequence” as used herein means a sequence of nucleotides that encodes a scaffold.

[0130] The term “scaffold” as used herein means a sequence of amino acids that provides structural and / or functional integrity or support to the target peptide and helps in orientation of target peptide such that the domains or epitopes of the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.

[0131] The term “oligomeric complex” as used herein means a complex formed by two or more homologous polypeptides. In some embodiments, the oligomeric complex has at least two homologous polypeptides, at least three homologous polypeptides, at least four homologous polypeptides, at least five homologous polypeptides, or at least six homologous polypeptides and so on.

[0132] The term “polypeptide cluster” as used herein means a complex formed by interaction of protein domains of two or more homologous polypeptides or two or more heterologous polypeptides orchestrated by the zipper motif. In some embodiments, the polypeptide cluster has at least two, at least three, at least four, at least five, at least six homologous polypeptides, heterologous polypeptides, or combination thereof.

[0133] The term “self- assembling sequence” as used herein means a sequence of nucleotides that encodes a self-assembling peptide.

[0134] The term “self-assembling peptide” as used herein means a sequence of amino acids that enables the polypeptides to self-assemble into a polypeptide nanoparticle.

[0135] The term “self-assembly” or “self-assemble” or “self-assembling” has been used interchangeably to means the ability of polypeptides to undergo multimerization to form a polypeptide nanoparticle. In some embodiments, the polypeptide nanoparticle has at least two polypeptides (dimer or 2-mer), at least three polypeptides (trimer or 3-mer), at least four polypeptides (tetramer or 4-mer), at least five polypeptides (pentamer or 5-mer), at least six polypeptides (hexamer or 6-mer), at least seven polypeptides (heptamer or 7-mer), at least eight polypeptides (octamer or 8-mer), and so on. In some embodiments, the polypeptide nanoparticle is up to 500-mers. In some embodiments, hydrogen bonds, disulfide bonds, hydrophobic interactions, electrostatic interactions, and / or Van der Waals forces combine to maintain self-assembled structure.

[0136] The term “multimerization” as used herein means association of two or more units of homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or their combination.

[0137] The term “polypeptide nanoparticle” as used herein means a nanoparticle formed by self-assembly of polypeptides. In some embodiments, the polypeptide nanoparticle comprises two or more homologous polypeptides, two or more heterologous polypeptides, one or more oligomeric complexes, one or more polypeptide clusters, or a combination thereof.

[0138] The term “homologous polypeptides” as used herein means polypeptides in a multisubunit peptide that have identical target peptides. For example, if two polypeptides in the multisubunit peptide have identical target peptides they are considered to be homologous polypeptides.

[0139] The term “heterologous polypeptide” as used herein means polypeptides in a multisubunit peptide that have different target peptides. For example, if two polypeptides in the multisubunit peptide have different or non-identical target peptides, they are considered to be heterologous polypeptides.

[0140] The term “upstream”, “amino-terminus”, or “N-terminus” has been used interchangeably in the context of amino acid sequences (protein, peptide, polypeptide, or any other sequence composed of amino acids) or the nucleic acid sequences (DNA, RNA or any other sequence composed of nucleotides) to mean amino end of an amino acid sequence or the 5-prime end of a nucleic acid sequence respectively.

[0141] The term “fragment” as used herein, whether in the context of a nucleic acid, nucleotide, protein, polypeptide, or peptide, means any length of the nucleic acid, protein, polypeptide, or peptide sequence except the full length of the respective nucleic acid, protein, polypeptide, or peptide sequence. Fragment includes such portions of nucleic acid, protein, polypeptide, or peptide that are capable of treating, preventing, diagnosing, improving symptoms of, and / or delay the onset of an infection, disease, disorder, and / or condition. A fragment is also understood to mean an immunogenic fragment of the protein, polypeptide or peptide, or a fragment of nucleic acid encoding an immunogenic fragment of the protein, peptide, or polypeptide.

[0142] The term “variant” as used herein, whether in the context of a nucleic acid, nucleotide, protein, polypeptide, or peptide sequence, means homologs, orthologs, paralogs, mutants or analogs of respective nucleic acid, protein, polypeptide, or peptide sequence.

[0143] The term “mutant” as used herein, whether in the context of a nucleic acid, nucleotide, protein, polypeptide, or peptide sequence, means a sequence which is not a wild type sequence. A mutant is also understood to mean a nucleic acid, nucleotide, protein, polypeptide, or peptide sequence that carries a mutation. The term “mutation” as used herein means, a change or modification in the sequence of nucleic acid or amino acid in comparison to a reference sequence and includes insertion, deletion, substitution, or a combination thereof. Mutations are introduced to impart desirable properties upon the nucleic acid, nucleotide, protein, polypeptide, or peptide sequence. This includes, for example, enabling the nucleic acid, nucleotide, protein, polypeptide, or peptide sequence to elicit an immune response while ensuring that any undesirable or deleterious effects are minimized or entirely removed.

[0144] The term “sequence” as used herein means nucleic acid sequences, nucleic acids, polynucleotides, amino acid sequences, proteins, polypeptides, or peptides, depending upon the context in which the term sequence is used, to mean a sequence of nucleotides or amino acids. In the context of nucleic acid, polynucleotide, or nucleotide sequence, the sequence is represented by a single letter code representing the nitrogenous base, for example A, T, G, C, or U. In the context of amino acid sequences, proteins, polypeptides, or peptides the sequence is represented by a single letter amino acid code as generally understood by persons skilled in the art. If the single letter amino acid code is represented by the letter “X”, it means the amino acid at that position is either absent or substituted by any other amino acid. In some embodiments, the sequences representing target sequence or target peptide, may contain a tag, for example, histidine tag, streptavidin tag etc, which may be deleted or removed from the respective sequence before employing the sequence in accordance with the present disclosure. In some embodiments, the sequences representing target sequence or target peptide may contain a signal sequence or signal peptide respectively, which may be deleted or removed from the respective sequence before employing the sequence in accordance with the present disclosure. The deleted or removed signal sequence or signal peptide may be employed in accordance with the present disclosure. The presence of tags, signal sequence or signal peptide, or other similar elements, may easily be recognized by those skilled in the art.

[0145] The term “percentage identity”, “percent identity”, “% age identity”, or “% identity” have been used interchangeably and means the extent of identity between two sequences (e.g. nucleic acid sequences or amino acid sequences). Percent identity can be determined by aligning two sequences, introducing gaps to maximize identity between the sequences. Percent identity should generally be calculated between the same types of sequences for example nucleic acids, i.e. for DNA sequences or RNA sequences or amino acid sequences. The alignment of sequences (nucleic acid or amino acid) can be performed with the appropriate pair wise sequence alignment programs. Identity can be calculated between two sequences by multiplying the number of matches in the pair by 100 and dividing by the length of the aligned region, including gaps. Gaps at the end of sequences are not included, and internal gaps are included in the length. In some embodiments, the nucleic acid sequence or the amino acid sequence, as the case may be, shares at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity with the sequences disclosed herein. In some embodiments, the nucleic acid sequence or the amino acid sequence, as the case may be, shares at least 50% to 60%, at least 60% to 70%, at least 70% to 80%, at least 80% to 90%, or at least 90% to 100% identity with the sequences disclosed herein.

[0146] The term “functional analog” or “functional analogue” have been used interchangeably, whether in the context of nucleic acid sequence or amino acid (protein or peptide) sequence, and mean all sequences which essentially performs similar function compared to the sequence being referred. For example, functional analogs of a target peptide include all sequences, irrespective of their percentage identity, which essentially perform at least one function similar to the function the target peptide performs.

[0147] The term “comparable equivalent” in the context of nucleic acid sequences, amino acid sequences, proteins, polypeptides, or peptides, as disclosed herein, means structurally or functionally similar or identical nucleic acid sequences, amino acid sequences, proteins, polypeptides, or peptides compared to the nucleic acid sequences or amino acid sequences being referred.

[0148] The term “envelope protein” as used herein means a protein associated with the viral envelope, for example, anchored into, projecting from, or across the lipid layer of the viral envelope. Envelope proteins mediate attachment and fusion. In some embodiments, envelope proteins are glycosylated.

[0149] The term “capsid protein” or “nucleocapsid protein” as used herein means a protein that encapsidates or packages the viral genetic material or genome. The term is also understood to mean those proteins which are involved or participate in one or more of the following functions or activities, such as virus assembly, budding or release of virus, mediating attachment to and penetration into the host cells (especially in case of non- enveloped viruses), packaging the genome, etc. The capsid protein or nucleocapsid proteins are the proteins associated with viral capsid or viral nucleocapsid or viral core.

[0150] The term “matrix protein” as used herein means a protein that is found beneath the viral envelope, often acting as a bridge between nucleocapsid or core and the envelope.

[0151] The term “structural protein” as used herein means proteins that are components of the viral particle or structure, for example, capsid proteins, membrane or envelope proteins, proteins packaged within the virus particle etc.

[0152] The term “non-structural protein” as used herein means proteins that are encoded by the virus, but are not the component or part of the mature viral particle or structure, for example, enzymes, transcription factors etc.

[0153] The term “B cell epitope” as used herein means a protein determinant that is recognized by B cell receptors (BCR) and capable of specific binding to an antibody or immunoglobulin.

[0154] The term “T cell epitope” as used herein means a protein determinant derived from an antigen which is presented by an antigen presenting cell (APC) through major histocompatibility complex (MHC) for recognition by a T cell receptor (TCR).

[0155] The term “herpesvirus”, “human herpesvirus”, “HSV”, or “HHSV” have been used interchangeably and mean herpesviruses belonging to the family herpesviridae, including but not limited to, herpes simplex virus 1 or human herpesvirus 1 (HSV1 or HHV1), herpes simplex virus 2 or human herpesvirus 2 (HSV2 or HHV2), varicella-zoster virus or human herpesvirus 3 (VZV or HHV3), Epstein-Barr virus or human herpesvirus 4 (EBV or HHV4), cytomegalovirus or human herpesvirus 5 (CMV or HHV5), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), and Kaposi’s sarcoma-associated herpesvirus or human herpesvirus 8 (KSHV or HHV8).

[0156] The term “herpes simplex virus 1”, “herpes simplex virus type 1”, “human herpesvirus 1”, “HSV1”, or “HHSV1” has been used interchangeably to refer to herpes simplex virus 1 belonging to the subfamily Alphaherpesvirinae.

[0157] The term “herpes simplex virus 2”, “herpes simplex virus type 2”, “human herpesvirus 2”, “HSV2”, or “HHSV2” has been used interchangeably to refer to herpes simplex virus 2 belonging to the subfamily Alphaherpesvirinae.

[0158] The term “varicella-zoster virus”, “human herpesvirus 3”, “VZV”, or “HHV3” has been used interchangeably to refer to varicella-zoster virus belonging to the subfamily Alphaherpesvirinae. The term “Epstein-Barr virus”, “human herpesvirus 4”, “EBV”, or “HHV4” has been used interchangeably to refer to Epstein-Barr virus belonging to the subfamily Gammaherpesvirinae.

[0159] The term “cytomegalovirus”, “human herpesvirus 5”, “CMV”, or “HHV5” has been used interchangeably to refer to cytomegalovirus belonging to the subfamily Betaherpesvirinae.

[0160] The term “human herpesvirus 6”, or “HHV6” has been used interchangeably to refer to human herpesvirus 6 belonging to the subfamily Betaherpesvirinae.

[0161] The term “human herpesvirus 7”, or “HHV7” has been used interchangeably to refer to human herpesvirus 7belonging to the subfamily Betaherpesvirinae.

[0162] The term “Kaposi’s sarcoma-associated herpesvirus”, “Kaposi’s sarcoma virus”, “human herpesvirus 8”, “KSHV”, or “HHV8” has been used interchangeably to refer to Kaposi sarcoma-associated herpesvirus belonging to the subfamily Gammaherpesvirinae.

[0163] Multisubunit nucleic acid sequence and multisubunit peptide

[0164] In the present disclosure, a multisubunit nucleic acid sequence includes two or more polynucleotide sequences wherein some or all polynucleotide sequences comprises either a target sequence, a linker sequence, and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein one polynucleotide sequence is connected to the another polynucleotide sequence by a cleavage sequence, wherein the multisubunit nucleic acid sequence includes a signal sequence upstream of one or more polynucleotide sequences, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the signal sequence is present upstream of all or some polynucleotide sequences. In some embodiments, the signal sequence is present upstream of the first polynucleotide sequence. In some embodiments, the signal sequence is present upstream of some polynucleotide sequences. In some embodiments, the signal sequence is present upstream of each of the polynucleotide sequences. In some embodiments, the polynucleotide sequence comprises a target sequence, a linker sequence, and a selfassembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the polynucleotide sequence comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the multisubunit nucleic acid sequence comprises one polynucleotide sequence comprising a target sequence, a linker sequence and a self-assembling sequence, and another polynucleotide sequence comprising a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the multisubunit nucleic acid sequence either comprises a target sequence, a linker sequence and a self-assembling sequence, or a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence or a combination thereof, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus, such that the total number of polynucleotide sequences in a multisubunit nucleic acid sequence are not more than 100. In some embodiments, the linker sequence connects the signal sequence with the polynucleotide sequence. In some embodiments, one linker sequence connects the cleavage sequence with the target sequence and another linker sequence connects the target sequence with the self-assembling sequence in a polynucleotide sequence. Some exemplary illustrations of the multisubunit nucleic acid sequences are provided in figure 1 and their representative encoded multisubunit peptides are provided in figure 2 respectively.

[0165] The term “nucleic acid” as used herein means a polymer comprising two or more nucleotides for example, deoxyribonucleotides or ribonucleotides, either in an unmodified or modified form. The nucleic acid may be either single stranded or double stranded, linear, or circular. The term nucleic acid also encompasses fragments, variants, mutants, or codon optimized sequences of deoxyribonucleotides, ribonucleotides, or functional analogs thereof.

[0166] The term “nucleotide” as used herein means a ribonucleotide or deoxyribonucleotide. If the term nucleotide is used in the context of RNA, it refers to ribonucleotide, and if it is used in the context of DNA, it refers to deoxyribonucleotide. In some embodiments, the multisubunit nucleic acid sequence is a DNA, an RNA, or an mRNA. The multisubunit nucleic acid sequence may be few nucleotides long to several thousand nucleotides long.

[0167] Deoxyribonucleic acid (DNA)

[0168] The term “deoxyribonucleic acid” or “DNA” has been used interchangeably herein and means a polymer of deoxyribonucleotides. The DNA may be either single stranded or double stranded, linear, or circular.

[0169] In some embodiments, the multisubunit nucleic acid sequence is a DNA. In some embodiments, the DNA encodes a multisubunit peptide described herein.

[0170] Ribonucleic acid (RNA)

[0171] The term “ribonucleic acid” or “RNA” has been used interchangeably herein and means a polymer of ribonucleotides. The RNA may be either single stranded or double stranded, linear, or circular. The term RNA also includes messenger RNA (mRNA). In some embodiments, the multisubunit nucleic acid sequence is an mRNA.

[0172] In some embodiments, the mRNA encodes a multisubunit peptide as described herein.

[0173] In some embodiments, the mRNA is unmodified or modified or a combination of both. The modification may be in the nucleobase of the nucleotide, or sugar moiety of the nucleotide, or the phosphate of the nucleotide.

[0174] In some embodiments, mRNA is produced using recombinant expression system, or chemically synthesized or obtained through in vitro transcription. In some embodiments, the mRNA is obtained through a single in vitro transcription (IVT) process or step. In vitro transcription (IVT) is a laboratory process used to synthesize RNA molecules (for example, mRNA) from a DNA template enzymatically outside of a cell or in a cell free system. A single IVT process or step is understood to mean one complete cycle of an IVT reaction which produces mRNA molecules, each comprising at least two polynucleotide sequences, as described herein, as against multiple IVT reactions that produces separate mRNA molecules, each comprising a single polynucleotide sequence.

[0175] In some embodiments, the mRNA is circular. In other embodiments, the mRNA is linear. In some embodiments, the mRNA is self-amplifying or self-replicating. Selfamplifying or self-replicating mRNA as used herein means an mRNA that self-replicate upon delivery into the cells. Such mRNAs typically contain a replicase sequence, usually derived from an alphavirus, which enables amplification of the original strand of mRNA encoding the protein of interest upon delivery into the cells (Beissert, Tim et al. Molecular Therapy (2020) 28:119-128).

[0176] The present disclosure provides mRNAs which are few hundred nucleotides long to several thousand nucleotides long. State of the art discourages using long mRNAs for vaccines and therapeutics. Longer mRNA molecules are more susceptible to degradation, which can compromise their stability and reduce their effectiveness in experimental and therapeutic context. Besides, longer mRNAs are also harder to transcribe accurately as the RNA polymerase used during the IVT reaction is inherently vulnerable to introduce errors within the transcribed mRNA. Additionally, long mRNA molecules are more prone to form complex secondary and tertiary structures, which can interfere with their intended function, reduce their efficiency, complicates the production process, and may even lead to unintended outcomes. Therefore, longer mRNAs are avoided in the art owing to their inherent complexities and challenges.

[0177] In some embodiments, mRNA is few hundred nucleotides long to several thousand nucleotides long. In some embodiments, mRNA is about 0.5 kb, 1 kb, 1.5 kb, 2 kb, 2.5 kb, 3 kb, 3.5 kb, 4 kb, 4.5 kb, 5 kb, 5.5 kb, 6 kb, 6.5 kb, 7.0 kb, 7.5 kb, 8 kb, 8.5 kb, 9 kb, 9.5 kb, 10 kb, 10.5 kb, 11 kb, 11.5 kb, 12 kb, 12.5 kb, 13 kb, 13.5 kb, 14 kb, 14.5 kb, 15 kb, 16 kb, 17 kb, 18 kb, 19 kb, 20 kb, 21 kb, 22 kb, 23 kb, 24 kb, 25 kb, 26 kb, 27 kb, 28 kb, 29 kb, 30 kb in length, or a fraction thereof. In some embodiments, mRNA is about 0.5 to 30 kb, 0.5 to 25 kb, 0.5 to 20 kb in length, or any range therein. In some embodiments, mRNA is about 1 to 20 kb, 1 to 18 kb, 1 to 16 kb, 1 to 14 kb, 1 to 12 kb, 1 to 10 kb, 1 to 9 kb, 1 to 8 kb, 1 to 7 kb, 1 to 6 kb, 1 to 5 kb in length, or any range therein.

[0178] In some embodiments, mRNA is about 0.5 kb to about 1 kb, about 1 kb to about 2 kb, about 2 kb to about 3 kb, about 3 kb to about 4 kb, about 4 kb to about 5 kb, about 5 kb to about 6 kb, about 6 kb to about 7 kb, about 7 kb to about 8 kb, about 8 kb to about 9 kb, about 9 kb to about 10 kb, about 10 kb to about 11 kb, about 11 kb to about 12 kb, about 12 kb to about 13 kb, about 13 kb to about 14 kb, about 14 kb to about 15 kb, about 15 kb to about 16 kb, about 16 kb to about 17 kb, about 17 kb to about 18 kb, about 18 kb to about 19 kb, about 19 kb to about 20 kb, about 20 kb to about 21 kb, about 21 kb to about 22 kb, about 22 kb to about 23 kb, about 23 kb to about 24 kb, about 24 kb to about 25 kb, about 25 kb to about 26 kb, about 26 kb to about 27 kb, about 27 kb to about 28 kb, about 28 kb to about 29 kb, about 29 kb to about 30 kb in length, or any range therein.

[0179] Target Sequence and target peptide

[0180] The multisubunit nucleic acid sequence and the multisubunit peptide includes target sequence and target peptide respectively, wherein the target sequence and target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, target sequence and target peptide contains recurring target sequences and target peptides respectively. In some embodiments, the target sequence is a DNA or an RNA. In another embodiment, the target sequence is an mRNA. In some embodiments, the target sequence is modified or unmodified. The target sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof.

[0181] In some embodiments, the target sequence is a sequence of nucleotides that encodes a target peptide obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, functional analogs, or a combination thereof of a herpesvirus.

[0182] In some embodiments, the target peptide is identical in two or more polypeptides, for example homologous polypeptides. In some embodiments, the target peptide is different in two or more polypeptides, for example as in heterologous polypeptides.

[0183] In some embodiments, the target peptide is few amino acids long to several hundred amino acids long.

[0184] Herpesviruses

[0185] Herpesviruses belong to the family Herpesviridae, which includes a diverse group of viruses. They are characterized by their unique structure, ability to establish latency, and association with various human diseases. Herpesviruses are classified into three subfamilies viz., Alphaherpesvirinae [Alpha (a) Herpesviruses] - which includes herpes simplex virus (HSV) types 1 and 2, as well as varicella-zoster virus (VZV). Betaherpesvirinae [Beta ( ) Herpesviruses] - which includes cytomegalovirus (CMV) and human herpesvirus 6 (HHV6) and human herpesvirus 7 (HHV7). Gammaherpesvirinae [Gamma (y) Herpesviruses] - which includes Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV8) or Kaposi’s sarcoma-associated herpesvirus (KSHV).

[0186] Herpesviruses are enveloped, double stranded DNA viruses. All herpesviruses share a unique four-layered structure, a core containing the DNA, a capsid surrounding the core, a cluster of proteins called the tegument, and an outer lipid bilayer envelope. The genome encodes several proteins which can be broadly categorized into capsid proteins, tegument proteins, envelope proteins, and regulatory proteins.

[0187] In some embodiments, the target peptide is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.

[0188] In some embodiments, the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitopes, T cell epitopes, or a combination thereof of a herpesvirus, including mutants, derivatives, variants, comparable equivalents, or functional analogs thereof.

[0189] Capsid protein

[0190] In some embodiments, the target peptide is obtained or derived from capsid protein of a herpesvirus. In some embodiments, the capsid protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella- zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.

[0191] Table 1: Capsid proteins in different herpesviruses

[0192] In some embodiments, the capsid protein is selected from the group comprising major capsid protein, triplex monomer, triplex dimer, small capsid protein, portal protein, portal capping protein, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpesvirus.

[0193] Major capsid protein (MCP)

[0194] In some embodiments, the target peptide is obtained or derived from major capsid protein of a herpesvirus.

[0195] In some embodiments, the major capsid protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0196] Exemplary major capsid protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 87-157, 158-164, 165-188, 189-254, 255-259, 260, 261-277, or 278-287 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0197] In some embodiments, the major capsid protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0198] Given the amino acid sequences of the major capsid protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above major capsid protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the major capsid protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0199] Triplex monomer (TRI1)

[0200] In some embodiments, the target peptide is obtained or derived from triplex monomer of a herpesvirus.

[0201] In some embodiments, the triplex monomer is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0202] Exemplary triplex monomer includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 288-338, 339-344, 345-351, 352-371, 372-373, 374, 375-398, or 399-403 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0203] In some embodiments, the triplex monomer shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0204] Given the amino acid sequences of the triplex monomer, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above triplex monomer. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the triplex monomer is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0205] Triplex dimer (TRI2)

[0206] In some embodiments, the target peptide is obtained or derived from triplex dimer of a herpesvirus.

[0207] In some embodiments, the triplex dimer is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0208] Exemplary triplex dimer includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 404-434, 435, 436-438, 439-445, 446-447, 448, 449- 453, or 454-466 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0209] In some embodiments, the triplex dimer shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0210] Given the amino acid sequences of the triplex dimer, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above triplex dimer. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the triplex dimer is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0211] Small capsid protein (SCP)

[0212] In some embodiments, the target peptide is obtained or derived from small capsid protein of a herpesvirus.

[0213] In some embodiments, the small capsid protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof. Exemplary small capsid protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 467-468, 469-470, 471-473, 474-478, 479- 480, 481, 482-494, or 495-501 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0214] In some embodiments, the small capsid protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0215] Given the amino acid sequences of the small capsid protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above small capsid protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the small capsid protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0216] Portal protein (PORT)

[0217] In some embodiments, the target peptide is obtained or derived from portal protein of a herpesvirus.

[0218] In some embodiments, the portal protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0219] Exemplary portal protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 502-567, 568-574, 575-592, 593-646, 647-652, 653, 654-683, or 684-692 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma- associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the portal protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0220] Given the amino acid sequences of the portal protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above portal protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the portal protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0221] Portal capping protein (PCP)

[0222] In some embodiments, the target peptide is obtained or derived from portal capping protein of a herpesvirus.

[0223] In some embodiments, the portal capping protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0224] Exemplary portal capping protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 693-730, 731-734, 735-738, 739-742, 743- 747, 748, 749-762, or 763-772 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0225] In some embodiments, the portal capping protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0226] Given the amino acid sequences of the portal capping protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above portal capping protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the portal capping protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA. Tegument protein

[0227] In some embodiments, the target peptide is obtained or derived from tegument protein of a herpesvirus. In some embodiments, the tegument protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.

[0228] Table 2: Tegument proteins in different herpesviruses

[0229] In some embodiments, the tegument protein is selected from the group comprising virion protein kinase, largest tegument protein, LTP binding protein, encapsidation and egress protein, cytoplasmic egress tegument protein, CETP binding protein, cytoplasmic egress facilitator- 1, encapsidation chaperone protein, capsid transport tegument protein, cytoplasmic egress facilitator-2, putative membrane or tegument protein, tegument protein pp65, tegument protein ppl50, pp85 protein, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpesvirus.

[0230] Virion protein kinase (VPK)

[0231] In some embodiments, the target peptide is obtained or derived from virion protein kinase of a herpesvirus.

[0232] In some embodiments, the virion protein kinase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0233] Exemplary virion protein kinase includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 773-794, 795-796, 797, 798, 799, or 800-806 of a herpesvirus, for example, herpes simplex virus 1 (HSV1), varicella-zoster virus (VZV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0234] In some embodiments, the virion protein kinase shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0235] Given the amino acid sequences of the virion protein kinase, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above virion protein kinase. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the virion protein kinase is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA. Largest or large tegument protein (LTP)

[0236] In some embodiments, the target peptide is obtained or derived from largest tegument protein of a herpesvirus.

[0237] In some embodiments, the largest tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0238] Exemplary largest tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 807-941, 942-951, 952-1033, 1034-1265, 1266-1273, 1274, 1275-1453, or 1454-1475 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0239] In some embodiments, the largest tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0240] Given the amino acid sequences of the largest tegument protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above largest tegument protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the largest tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0241] LTP binding protein (LTPbp)

[0242] In some embodiments, the target peptide is obtained or derived from LTP binding protein of a herpesvirus.

[0243] In some embodiments, the LTP binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0244] Exemplary LTP binding protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1476-1549, 1550-1555, 1556-1564, 1565- 1567, 1568-1572, 1573, 1574-1586, or 1587-1598 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0245] In some embodiments, the LTP binding protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0246] Given the amino acid sequences of the LTP binding protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above LTP binding protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the LTP binding protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0247] Encapsidation and egress protein (EEP)

[0248] In some embodiments, the target peptide is obtained or derived from encapsidation and egress protein of a herpesvirus.

[0249] In some embodiments, the encapsidation and egress protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0250] Exemplary encapsidation and egress protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1599-1633, 1634-1636, 1637- 1643, 1644, 1645-1647, 1648, 1649-1655, or 1656-1660 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0251] In some embodiments, the encapsidation and egress protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0252] Given the amino acid sequences of the encapsidation and egress protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above encapsidation and egress protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the encapsidation and egress protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0253] Cytoplasmic egress tegument protein (CETP)

[0254] In some embodiments, the target peptide is obtained or derived from cytoplasmic egress tegument protein of a herpesvirus.

[0255] In some embodiments, the cytoplasmic egress tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0256] Exemplary cytoplasmic egress tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1661-1675, 1676, 1677-1678, 1679-1682, 1683-1686, 1687, 1688-1690, or 1691-1693 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0257] In some embodiments, the cytoplasmic egress tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0258] Given the amino acid sequences of the cytoplasmic egress tegument protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above cytoplasmic egress tegument protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the cytoplasmic egress tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0259] CETP binding protein (CETPbp)

[0260] In some embodiments, the target peptide is obtained or derived from CETP binding protein of a herpesvirus. In some embodiments, the CETP binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0261] Exemplary CETP binding protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1694-1729, 1730-1732, 1733-1738, 1739- 1741, 1742-1746, 1747, 1748-1751, or 1752-1760 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0262] In some embodiments, the CETP binding protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0263] Given the amino acid sequences of the CETP binding protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above CETP binding protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the CETP binding protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0264] Cytoplasmic egress facilitator-1 (CEF1)

[0265] In some embodiments, the target peptide is obtained or derived from cytoplasmic egress facilitator- 1 of a herpesvirus.

[0266] In some embodiments, the cytoplasmic egress facilitator- 1 is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0267] Exemplary cytoplasmic egress facilitator- 1 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1761-1782, 1783, 1784-1789, 1790-1794, 1795-1799, 1800, 1801-1803, or 1804-1809 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0268] In some embodiments, the cytoplasmic egress facilitator- 1 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0269] Given the amino acid sequences of the cytoplasmic egress facilitator- 1, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above cytoplasmic egress facilitator- 1. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the cytoplasmic egress facilitator- 1 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0270] Encapsidation chaperone protein (ECP)

[0271] In some embodiments, the target peptide is obtained or derived from encapsidation chaperone protein of a herpesvirus.

[0272] In some embodiments, the encapsidation chaperone protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0273] Exemplary encapsidation chaperone protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1810-1832, 1833-1834, 1835- 1839, 1840-1978, 1979-1981, 1982, 1983-1991, or 1992-1996 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0274] In some embodiments, the encapsidation chaperone protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0275] Given the amino acid sequences of the encapsidation chaperone protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above encapsidation chaperone protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the encapsidation chaperone protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0276] Capsid transport tegument protein (CTTP)

[0277] In some embodiments, the target peptide is obtained or derived from capsid transport tegument protein of a herpesvirus.

[0278] In some embodiments, the capsid transport tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0279] Exemplary capsid transport tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 1997-2053, 2054-2058, 2059- 2069, 2070-2073, 2074-2078, 2079, 2080-2091, or 2092-2106 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0280] In some embodiments, the capsid transport tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0281] Given the amino acid sequences of the capsid transport tegument protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above capsid transport tegument protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the capsid transport tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0282] Cytoplasmic egress facilitator-2 (CEF2)

[0283] In some embodiments, the target peptide is obtained or derived from cytoplasmic egress facilitator-2 of a herpesvirus.

[0284] In some embodiments, the cytoplasmic egress facilitator-2 is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof. Exemplary cytoplasmic egress facilitator-2 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2107-2147, 2148-2150, 2151- 2155, 2156-2195, 2196-2200, 2201, 2202-2210, or 2211-2221 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0285] In some embodiments, the cytoplasmic egress facilitator-2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0286] Given the amino acid sequences of the cytoplasmic egress facilitator-2, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above cytoplasmic egress facilitator-2. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the cytoplasmic egress facilitator-2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0287] Putative membrane or tegument protein

[0288] In some embodiments, the target peptide is obtained or derived from putative membrane or tegument protein of a herpesvirus.

[0289] In some embodiments, the putative membrane or tegument protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0290] Exemplary putative membrane or tegument protein includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2222-2238, 2239-2240, 2241- 2254, 2255-2258, 2259-2261, 2262, 2263-2265, or 2266-2271 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the putative membrane or tegument protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0291] Given the amino acid sequences of the putative membrane or tegument protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above putative membrane or tegument protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the putative membrane or tegument protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0292] Tegument protein pp65

[0293] In some embodiments, the target peptide is obtained or derived from tegument protein pp65 of a herpesvirus, for example, cytomegalovirus (CMV).

[0294] In some embodiments, the tegument protein pp65 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0295] Exemplary tegument protein pp65 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 2272-2314 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0296] In some embodiments, the tegument protein pp65 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0297] Given the amino acid sequences of the tegument protein pp65, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above tegument protein pp65. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the tegument protein pp65 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0298] Tegument protein ppl50

[0299] In some embodiments, the target peptide is obtained or derived from tegument protein ppl50 of a herpesvirus, for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7). In some embodiments, the tegument protein pp 150 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7) comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0300] Exemplary tegument protein ppl50 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2315-2562, 2563-2564, or 2565 of a herpesvirus, for example, cytomegalovirus (CMV), human herpesvirus 6 (HHV6), or human herpesvirus 7 (HHV7), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0301] In some embodiments, the tegument protein ppl50 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0302] Given the amino acid sequences of the tegument protein ppl50, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above tegument protein ppl50. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the tegument protein ppl50 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA. pp85 protein

[0303] In some embodiments, the target peptide is obtained or derived from pp85 protein of a herpesvirus, for example, human herpesvirus 7 (HHV7).

[0304] In some embodiments, the pp85 protein is a full length protein or a fragment thereof of a herpesvirus, for example, human herpesvirus 7 (HHV7) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0305] Exemplary pp85 protein includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NO: 2566 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0306] In some embodiments, the pp85 protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof. Given the amino acid sequences of the pp85 protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above pp85 protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the pp85 protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0307] Envelope protein

[0308] In some embodiments, the target peptide is obtained or derived from envelope protein of a herpesvirus. In some embodiments, the envelope protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof

[0309] Table 3: Envelope proteins in different herpesviruses

[0310]

[0311] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, or glycoprotein E, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpes simplex virus 1 (HSV1). In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, or glycoprotein E, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a herpes simplex virus 2 (HSV2).

[0312] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 34 (gp34), glycoprotein 68 (gp68), UL128, UL130, UL131A, or UL16, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a cytomegalovirus (CMV).

[0313] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 350 (gp350), glycoprotein 220 (gp220), or glycoprotein 42 (gp42), including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a Epstein-Barr virus (EBV).

[0314] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a varicella-zoster virus (VZV).

[0315] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a human herpesvirus 6 (HHV6).

[0316] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a human herpesvirus 7 (HHV7).

[0317] In some embodiments, the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, or glycoprotein N, including mutants, derivatives, variants, comparable equivalents, or functional analogs, or a combination thereof of a Kaposi’s sarcoma-associated herpesvirus (KSHV). Glycoprotein B (gB)

[0318] In some embodiments, the target peptide is obtained or derived from glycoprotein B of a herpesvirus.

[0319] In some embodiments, the glycoprotein B is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0320] Exemplary glycoprotein B includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2567-2614, 2615-2623, 2624-2639, 2640-2737, 2738-2746, 2747 , 2748-2783, or 2784-2795 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0321] In some embodiments, the glycoprotein B shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0322] Given the amino acid sequences of the glycoprotein B, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein B. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein B is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0323] Glycoprotein H (gH)

[0324] In some embodiments, the target peptide is obtained or derived from glycoprotein H of a herpesvirus.

[0325] In some embodiments, the glycoprotein H is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0326] Exemplary glycoprotein H includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2796-2860, 2861-2869, 2870-2885, 2886-2967, 2968-2972, 2973, 2974-2982, or 2983-2997 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0327] In some embodiments, the glycoprotein H shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0328] Given the amino acid sequences of the glycoprotein H, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein H. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein H is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0329] Glycoprotein L (gL)

[0330] In some embodiments, the target peptide is obtained or derived from glycoprotein L of a herpesvirus.

[0331] In some embodiments, the glycoprotein L is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0332] Exemplary glycoprotein L includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 2998-3034, 3035-3037, 3038-3049, 3050-3103, 3104-3108, 3109, 3110-3123, or 3124-3127 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0333] In some embodiments, the glycoprotein L shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0334] Given the amino acid sequences of the glycoprotein L, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein L. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein L is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0335] Glycoprotein M (gM)

[0336] In some embodiments, the target peptide is obtained or derived from glycoprotein M of a herpesvirus.

[0337] In some embodiments, the glycoprotein M is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0338] Exemplary glycoprotein M includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3128-3170, 3171-3173, 3174-3187, 3188-3231, 3232-3233, 3234, 3235-3262, or 3263-3267 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0339] In some embodiments, the glycoprotein M shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0340] Given the amino acid sequences of the glycoprotein M, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein M. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein M is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0341] Glycoprotein N (gN)

[0342] In some embodiments, the target peptide is obtained or derived from glycoprotein N of a herpesvirus.

[0343] In some embodiments, the glycoprotein N is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof. Exemplary glycoprotein N includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3268-3283, 3284-3285, 3286-3292, 3293-3327, 3328-3229, 3330, 3331-3344, or 3345-3349 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0344] In some embodiments, the glycoprotein N shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0345] Given the amino acid sequences of the glycoprotein N, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein N. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein N is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0346] Glycoprotein C (gC)

[0347] In some embodiments, the target peptide is obtained or derived from glycoprotein C of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).

[0348] In some embodiments, the glycoprotein C is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0349] Exemplary glycoprotein C includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3350-3413 or 3414-3418 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0350] In some embodiments, the glycoprotein C shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof. Given the amino acid sequences of the glycoprotein C, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein C. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein C is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0351] Glycoprotein D (gD)

[0352] In some embodiments, the target peptide is obtained or derived from glycoprotein D of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).

[0353] In some embodiments, the glycoprotein D is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0354] Exemplary glycoprotein D includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3419-3444 or 3445-3446 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0355] In some embodiments, the glycoprotein D shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0356] Given the amino acid sequences of the glycoprotein D, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein D. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein D is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0357] Glycoprotein I (gl)

[0358] In some embodiments, the target peptide is obtained or derived from glycoprotein I of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2). In some embodiments, the glycoprotein I is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0359] Exemplary glycoprotein I includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3447-3521 or 3522-3529 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0360] In some embodiments, the glycoprotein I shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0361] Given the amino acid sequences of the glycoprotein I, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein I. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein I is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0362] Glycoprotein E (gE)

[0363] In some embodiments, the target peptide is obtained or derived from glycoprotein E of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).

[0364] In some embodiments, the glycoprotein E is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0365] Exemplary glycoprotein E includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 15725-16107 or 16108-16386 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the glycoprotein E shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0366] Given the amino acid sequences of the glycoprotein E, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein E. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein E is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0367] Glycoprotein 350 (gp350)

[0368] In some embodiments, the target peptide is obtained or derived from glycoprotein 350 of a herpesvirus, for example, Epstein-Barr virus (EBV).

[0369] In some embodiments, the glycoprotein 350 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0370] Exemplary glycoprotein 350 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3530-3554 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0371] In some embodiments, the glycoprotein 350 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0372] Given the amino acid sequences of the glycoprotein 350, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein 350. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein 350 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0373] Glycoprotein 220 (gp220)

[0374] In some embodiments, the target peptide is obtained or derived from glycoprotein 220 of a herpesvirus, for example, Epstein-Barr virus (EBV). In some embodiments, the glycoprotein 220 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0375] Exemplary glycoprotein 220 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 19093-19096 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0376] In some embodiments, the glycoprotein 220 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0377] Given the amino acid sequences of the glycoprotein 220, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein 220. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein 220 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0378] Glycoprotein 42 (gp42)

[0379] In some embodiments, the target peptide is obtained or derived from glycoprotein 42 of a herpesvirus, for example, Epstein-Barr virus (EBV).

[0380] In some embodiments, the glycoprotein 42 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0381] Exemplary glycoprotein 42 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3555-3557 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0382] In some embodiments, the glycoprotein 42 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0383] Given the amino acid sequences of the glycoprotein 42, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein 42. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein 42 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0384] Glycoprotein 34 (gp34)

[0385] In some embodiments, the target peptide is obtained or derived from glycoprotein 34 of a herpesvirus, for example, cytomegalovirus (CMV).

[0386] In some embodiments, the glycoprotein 34 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0387] Exemplary glycoprotein 34 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 16387-16680 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0388] In some embodiments, the glycoprotein 34 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0389] Given the amino acid sequences of the glycoprotein 34, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein 34. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein 34 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0390] Glycoprotein 68 (gp68)

[0391] In some embodiments, the target peptide is obtained or derived from glycoprotein 68 of a herpesvirus, for example, cytomegalovirus (CMV).

[0392] In some embodiments, the glycoprotein 68 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0393] Exemplary glycoprotein 68 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 16681-17065 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the glycoprotein 68 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0394] Given the amino acid sequences of the glycoprotein 68, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above glycoprotein 68. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the glycoprotein 68 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0395] UL128

[0396] In some embodiments, the target peptide is obtained or derived from UL128 of a herpesvirus, for example, cytomegalovirus (CMV).

[0397] In some embodiments, the UL128 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0398] Exemplary UL128 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 17066-17435 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0399] In some embodiments, the UL128 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0400] Given the amino acid sequences of the ULI 28, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above UL128. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the UL128 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0401] UL130

[0402] In some embodiments, the target peptide is obtained or derived from UL130 of a herpesvirus, for example, cytomegalovirus (CMV). In some embodiments, the UL130 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0403] Exemplary ULI 30 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 17436-18255 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0404] In some embodiments, the UL130 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0405] Given the amino acid sequences of the ULI 30, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above ULI 30. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the UL130 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0406] UL131A

[0407] In some embodiments, the target peptide is obtained or derived from UL131A of a herpesvirus, for example, cytomegalovirus (CMV).

[0408] In some embodiments, the UL131A is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0409] Exemplary UL131A includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 18256-18687 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0410] In some embodiments, the UL131A shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0411] Given the amino acid sequences of the ULI 31 A, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above UL131A. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the UL131A is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0412] UL16

[0413] In some embodiments, the target peptide is obtained or derived from ULI 6 of a herpesvirus, for example, cytomegalovirus (CMV).

[0414] In some embodiments, the ULI 6 is a full length protein or a fragment thereof of a herpesvirus, for example, cytomegalovirus (CMV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0415] Exemplary UL16 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 18688-19092 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0416] In some embodiments, the UL16 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0417] Given the amino acid sequences of the ULI 6, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above ULI 6. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the UL16 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0418] Regulatory protein

[0419] In some embodiments, the target peptide is obtained or derived from regulatory protein of a herpesvirus. In some embodiments, the regulatory protein is obtained or derived from herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicellazoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.

[0420] Table 4: Regulatory proteins in different herpesviruses

[0421] In some embodiments, the regulatory protein is selected from the group comprising multifunctional regulatory of expression, DNA polymerase, DNA polymerase processivity subunit, helicase-primase ATPase subunit, helicase-primase RNA pol subunit B, helicase- primase subunit C, single strand DNA binding protein, alkaline deoxyribonuclease, deoxyuridine triphosphatase, uracil-DNA glycosidase, ribonucleotide reductase large subunit, ribonucleotide reductase subunit 2, EBNA1, EBNA2, EBNA3, LMP1, LMP2, maturational protease, assembly protein, capsid transport nuclear protein, terminase ATPase subunit 1, terminase DNA binding subunit 2, terminase binding protein, nuclear egress membrane protein, nuclear egress lamina protein, including mutants, derivatives, variants, comparable equivalents, functional analogs, or a combination thereof of a herpesvirus. Multifunctional regulator of expression (MRE)

[0422] In some embodiments, the target peptide is obtained or derived from multifunctional regulator of expression of a herpesvirus, for example, human herpesvirus 6 (HHV6).

[0423] In some embodiments, the multifunctional regulator of expression is a full length protein or a fragment thereof of a herpesvirus, for example, human herpesvirus 6 (HHV6) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0424] Exemplary multifunctional regulator of expression includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3558-3560 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0425] In some embodiments, the multifunctional regulator of expression shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0426] Given the amino acid sequences of the multifunctional regulator of expression, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above multifunctional regulator of expression. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the multifunctional regulator of expression is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0427] Ribonucleotide reductase large subunit (RR1)

[0428] In some embodiments, the target peptide is obtained or derived from ribonucleotide reductase large subunit of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).

[0429] In some embodiments, the ribonucleotide reductase large subunit is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0430] Exemplary ribonucleotide reductase large subunit includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3561-3634 or 3635-3645 of herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0431] In some embodiments, the ribonucleotide reductase large subunit shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0432] Given the amino acid sequences of the ribonucleotide reductase large subunit, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above ribonucleotide reductase large subunit. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the ribonucleotide reductase large subunit is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0433] Ribonucleotide reductase subunit 2 (R1R2)

[0434] In some embodiments, the target peptide is obtained or derived from ribonucleotide reductase subunit 2 of a herpesvirus, for example, herpes simplex virus 1 (HSV1) or herpes simplex virus 2 (HSV2).

[0435] In some embodiments, the ribonucleotide reductase subunit 2 is a full length protein or a fragment thereof of a herpesvirus, for example, herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0436] Exemplary ribonucleotide reductase subunit 2 includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 3646-3670 or 3671-3673 of a herpesvirus, for example, herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0437] In some embodiments, the ribonucleotide reductase subunit 2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0438] Given the amino acid sequences of the ribonucleotide reductase subunit 2, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above ribonucleotide reductase subunit 2. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the ribonucleotide reductase subunit 2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0439] EBNA1

[0440] In some embodiments, the target peptide is obtained or derived from EBNA1 of herpesvirus, for example, Epstein-Barr virus (EBV).

[0441] In some embodiments, the EBNA1 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0442] Exemplary EBNA1 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3674-3684 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0443] In some embodiments, the EBNA1 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0444] Given the amino acid sequences of the EBNA1, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above EBNA1. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the EBNA1 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0445] EBNA2

[0446] In some embodiments, the target peptide is obtained or derived from EBNA2 of a herpesvirus, for example, Epstein-Barr virus (EBV).

[0447] In some embodiments, the EBNA2 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0448] Exemplary EBNA2 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3685-3694 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the EBNA2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0449] Given the amino acid sequences of the EBNA2, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above EBNA2. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the EBNA2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0450] EBNA3

[0451] In some embodiments, the target peptide is obtained or derived from EBNA3 of a herpesvirus, for example, Epstein-Barr virus (EBV).

[0452] In some embodiments, the EBNA3 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0453] Exemplary EBNA3 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 3695-4008 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0454] In some embodiments, the EBNA3 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0455] Given the amino acid sequences of the EBNA3, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above EBNA3. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the EBNA3 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0456] LMP1

[0457] In some embodiments, the target peptide is obtained or derived from LMP1 of herpesvirus, for example, Epstein-Barr virus (EBV). In some embodiments, the LMP1 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0458] Exemplary LMP1 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 4009-4017 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0459] In some embodiments, the LMP1 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0460] Given the amino acid sequences of the LMP1, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above LMP1. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the LMP1 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0461] LMP2

[0462] In some embodiments, the target peptide is obtained or derived from LMP2 of herpesvirus, for example, Epstein-Barr virus (EBV).

[0463] In some embodiments, the LMP2 is a full length protein or a fragment thereof of a herpesvirus, for example, Epstein-Barr (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0464] Exemplary LMP2 includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 4018-4032 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0465] In some embodiments, the LMP2 shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0466] Given the amino acid sequences of the LMP2, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above LMP2. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the LMP2 is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0467] Maturational protease (PR)

[0468] In some embodiments, the target peptide is obtained or derived from maturational protease of a herpesvirus, for example, human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7).

[0469] In some embodiments, the maturational protease is a full length protein or a fragment thereof of a herpesvirus, for example, human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7), or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0470] Exemplary maturational protease includes, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 4033-4034 or 4035 of a herpesvirus, for example, human herpesvirus 6 (HHV6) or human herpesvirus 7 (HHV7) respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0471] In some embodiments, the maturational protease shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0472] Given the amino acid sequences of the maturational protease, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above maturational protease. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the maturational protease is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0473] Assembly protein (AP (NP)d)

[0474] In some embodiments, the target peptide is obtained or derived from assembly protein of a herpesvirus, for example, human herpesvirus 7 (HHV7).

[0475] In some embodiments, the assembly protein is a full length protein or a fragment thereof of a herpesvirus, for example, human herpesvirus 7 (HHV7) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0476] Exemplary assembly protein includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NO: 4036 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0477] In some embodiments, the assembly protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0478] Given the amino acid sequences of the assembly protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above assembly protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the assembly protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0479] Nuclear egress membrane protein (NEMP)

[0480] In some embodiments, the target peptide is obtained or derived from nuclear egress membrane protein of a herpesvirus, for example, Epstein-Barr virus (EBV).

[0481] In some embodiments, the nuclear egress membrane protein is a full length protein or a fragment thereof of a herpesvirus, for example, an Epstein-Barr virus (EBV) or comparable equivalents, including mutants, derivatives, variants, functional analogs thereof.

[0482] Exemplary nuclear egress membrane protein includes, but not limited to, the one represented by the amino acid sequences having SEQ ID NOs: 4037-4041 or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0483] In some embodiments, the nuclear egress membrane protein shares at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, or variants thereof.

[0484] Given the amino acid sequences of the nuclear egress membrane protein, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above nuclear egress membrane protein. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the nuclear egress membrane protein is encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0485] In some embodiments, the target peptide is obtained or derived from DNA polymerase of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the DNA polymerase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0486] In some embodiments, the target peptide is obtained or derived from DNA polymerase processivity subunit of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the DNA polymerase processivity subunit is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0487] In some embodiments, the target peptide is obtained or derived from helicase - primase ATPase subunit of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the helicase-primase ATPase subunit is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0488] In some embodiments, the target peptide is obtained or derived from helicase- primase RNA pol subunit B of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the helicase-primase RNA pol subunit B is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0489] In some embodiments, the target peptide is obtained or derived from helicase- primase subunit C of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the helicase-primase subunit C is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof. In some embodiments, the target peptide is obtained or derived from single strand DNA binding protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the single strand DNA binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0490] In some embodiments, the target peptide is obtained or derived from alkaline deoxyribonuclease of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the alkaline deoxyribonuclease is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0491] In some embodiments, the target peptide is obtained or derived from deoxyuridine triphosphatase of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the deoxyuridine triphosphatase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0492] In some embodiments, the target peptide is obtained or derived from uracil-DNA glycosidase of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the uracil-DNA glycosidase is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0493] In some embodiments, the target peptide is obtained or derived from capsid transport nuclear protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the capsid transport nuclear protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0494] In some embodiments, the target peptide is obtained or derived from terminase ATPase subunit 1 of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the terminase ATPase subunit 1 is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0495] In some embodiments, the target peptide is obtained or derived from terminase DNA binding subunit 2 of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the terminase DNA binding subunit 2is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0496] In some embodiments, the target peptide is obtained or derived from terminase binding protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the terminase binding protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof.

[0497] In some embodiments, the target peptide is obtained or derived from nuclear egress lamina protein of a herpesvirus or comparable equivalents, including the codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the nuclear egress lamina protein is a full length protein or a fragment thereof of a herpesvirus or comparable equivalents, including mutant, derivatives, variants, or functional analogs thereof. B cell epitope

[0498] In some embodiments, the target peptide is obtained or derived from B cell epitope of a herpesvirus, including a fragment, mutant, derivative or variant thereof.

[0499] Exemplary B cell epitopes include, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 4042-4261, 4262-4546, 4547-4582, 4583-5034, 5035-5041, 5042-5043, 5044-7725, or 7726-7752 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0500] In some embodiments, the B cell epitopes share at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0501] Given the amino acid sequences of the B cell epitopes, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above B cell epitope. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the B cell epitopes are encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0502] T cell epitope

[0503] In some embodiments, the target peptide is obtained or derived from T cell epitope of a herpesvirus, including a fragment, mutant, derivative or variant thereof.

[0504] Exemplary T cell epitopes include, but not limited to, the one comprising amino acid sequences having SEQ ID NOs: 7753-8033, 8034-8293, 8294-8742, 8743-10004, 10005-14658, 14659-14660, 14661-15312, or 15313-15724 representing herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), or Kaposi’s sarcoma-associated herpesvirus (KSHV), respectively, or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof. In some embodiments, the T cell epitopes share at least 50% identity with the sequences described herein or comparable equivalents, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0505] Given the amino acid sequences of the T cell epitopes, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above T cell epitope. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the T cell epitopes are encoded by a target sequence which may be either a DNA, an RNA, or an mRNA.

[0506] Self-assembling sequence and self-assembling peptide

[0507] The multisubunit nucleic acid sequence and multisubunit peptide includes selfassembling sequence and self-assembling peptide respectively. The self-assembling sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a self-assembling peptide. The self-assembling sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof. In some embodiments, the selfassembling sequence is a DNA, an RNA, or an mRNA.

[0508] Any self-assembling peptide that is capable of self-assembling into a polypeptide nanoparticle can be employed in accordance with the present disclosure.

[0509] In some embodiments self-assembling peptide is a full-length protein or its fragment, mutants, or variant thereof.

[0510] In some embodiments, the self-assembling peptide includes, but not limited to, lumazine synthase, MS2 coat protein, hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, hepatitis B core antigen (HbcAg) from Hepatitis B virus, human papillomavirus LI (HPV LI) protein, matrix protein Ml from influenza A virus, ferritin, riboflavin synthase, a dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalent, or functional analogs thereof.

[0511] In some embodiments, the self-assembling peptide is a ferritin peptide.

[0512] Ferritin is one of the ubiquitous proteins found in nature. It is produced by all living organisms including archaea, bacteria, algae, higher plants, and animals. Each ferritin protein is generally composed of 12 or 24 subunits or peptides which selfassembles into a ferritin nanoparticle. In some aspects, the multisubunit nucleic acid sequence and multisubunit peptide includes ferritin sequence and ferritin peptide respectively. The ferritin sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a ferritin peptide. In some embodiments, the ferritin sequence is a DNA or an RNA or an mRNA.

[0513] Any ferritin peptide that is capable of self-assembling into a nanoparticle can be employed in accordance with the present disclosure. In some embodiments, the ferritin peptide is obtained or derived from Helicobacter pylori ferritin, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof. In some embodiments, the ferritin peptide is obtained or derived from Listeria innocua ferritin, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0514] In some embodiments, the self-assembling peptide is lumazine synthase. In some embodiments, the lumazine synthase is obtained or derived from Aquifex species (for example, Aquifex aeolicus) or Bacillus species (for example, Bacillus subtil is), including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0515] In some embodiments, the self-assembling peptide is dihydrolipoyl acetyltransferase (E2p). In some embodiments, the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0516] In some embodiments, the self-assembling peptide is MS2 coat protein. In some embodiments, the self-assembling peptide is MS2 coat protein obtained or derived from Emesvirus zinderi, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

[0517] Exemplary self-assembling peptides includes, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including codon optimized sequences, fragments, mutants, variants, or functional analogs thereof: LSKDIIKLLNEQVNKEMNSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAK KLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDH ATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGI (SEQ ID NO: 1);

[0518] LSKDIIKLLNEQVNKEMNSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAK KLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDH ATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIRRKR (SEQ ID NO: 2);

[0519] LSKDIIKLLNEQVNKEMNSSNLYMSMSSWCYTHSLDGAGLFLFDHAAEEYEHAK KLIIFLNENNVPVQLTSISAPEHKFEGLTQIFQKAYEHEQHISESINNIVDHAIKSKDH ATFNFLQWYVAEQHEEEVLFKDILDKIELIGNENHGLYLADQYVKGIAKSRKS (SEQ ID NO: 3);

[0520] MQIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDCIVRHGGREEDITLVRVPGS WEIPVAAGELARKEDIDAVIAIGVLIRGATPHFDYIASEVSKGLANLSLELRKPITFG VITADTLEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR (SEQ ID NO: 4);

[0521] MTKKVGIVDTTFARVDMASIAIKKLKELSPNIKIIRKTVPGIKDLPVACKKLLEEEG CDIVMALGMPGKAEKDKVCAHEASLGLMLAQLMTNKHIIEVFVHEDEAKDDKEL DWLAKRRAEEHAENVYYLLFKPEYLTRMAGKGLRQGFEDAGPARE (SEQ ID NO: 5);

[0522] MTEKEKMLAEKWYDANFDQYLINERARAKDICFELNHTRPSATNKRKELIDQLFQ TTTDNVSISIPFDTDYGWNVKLGKNVYVNTNCYFMDGGQITIGDNVFIGPNCGFY TATHPLNFHHRNEGFEKAGPIHIGSNTWFGGHVAVLPGVTIGEGSVIGAGSVVTKD IPPHSLAVGNPCKVVRKIDNDLPSETLNDETIK (SEQ ID NO: 6);

[0523] MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFQGGAPTCPGQNSQSPT SNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTT GTGPCRTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSW LSLLVPFVQWFAGLSPTVWLSVIWMMWYRGPSLYNTLSPFLPLLPISFCLWVYI (SEQ ID NO: 7);

[0524] MIFVLGGCRHKLVCSPAPCNFFHLCLIISCSCPTVHASKLCLGWLWGMHIDPYKEF GASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELM NLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVS FGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSR ESQC (SEQ ID NO: 8);

[0525] MSLWLPSEATVYLPPVPVSKVVSTDEYVARTNIYYHAGTSRLLAVGHPYFPIKKP NNNKILVPKVSGLQYRVFRIHLPDPNKFGFPDTSFYNPDTQRLVWACVGVEVGRG QPLGVGISGHPLLNKLDDTENASAYAANAGVDNRECISMDYKQTQLCLIGCKPPI

[0526] GEHWGKGSPCTNVAVNPGDCPPLELINTVIQDGDMVDTGFGAMDFTTLQANKSE

[0527] VPLDICTSICKYPDYIKMVSEPYGDSLFFYLRREQMFVRHLFNRAGAVGENVPDDL

[0528] YIKGSGSTANLASSNYFPTPSGSMVTSDAQIFNKPYWLQRAQGHNNGICWGNQLF

[0529] VTVVDTTRSTNMSLCAAISTSETTYKNTNFKEYLRHGEEYDLQFIFQLCKITLTAD

[0530] VMTYIHSMNSTILEDWNFGLQPPPGGTLEDTYRFVTSQAIACQKHTPPAPKEDPLK

[0531] KYTFWEVNLKEKFSADLDQFPLGRKFLLQAGLKAKPKFTLGKRKATPTTSSTSTT

[0532] AKRKKRKL (SEQ ID NO: 9):

[0533] MSLLTEVETYVLSIVPSGPLKAEIAQRLEDVFAGKNTDLEALMEWLKTRPILSPLT

[0534] KGILGFVFTLTVPSERGLQRRRFVQNALNGNGDPNNMDRAVKLYRKLKREITFHG

[0535] AKEIALSYSAGALASCMGLIYNRMGAVTTEVAFGLVCATCEQIADSQHRSHRQM

[0536] VTTTNPLIRHENRMVLASTTAKAMEQMAGSSEQAAEAMEVASQARQMVQAMRA

[0537] IGTHPRSSAGLKDDLLENLQAYQKRMGVQMQRFK (SEQ ID NO: 10);

[0538] AAAKPATTEGEFPETREKMSGIRRAIAKAMVHSKHTAPHVTLMDEADVTKLVAII

[0539] RKKFKAIAAEKGIKLTFLPYVVKALVSALREYPVLNTAIDDETEEIIQKHYYNIGIA

[0540] ADTDRGLLVPVIKHADRKPIFALAQEINELAEKARDGKLTPGEMKGASCTITNIGS

[0541] AGGQWFTPVINHPEVAILGIGRIAEKPIVRDGEIVAAPMLALSLSFDHRMIDGATAQ

[0542] KALNH1KRLLSDPELLLM (SEQ ID NO: 11)

[0543] ASNFTQFVLVDNGGTGDVTVAPSNFANGVAEWISSNSRSQAYKVTCSVRQSSAQ

[0544] NRKYTIKVEVPKVATQTVGGVELPVAAWRSYLNMELTIPIFATNSDCELIVKAMQ

[0545] GLLKDGNPIPSAIAANSGIY (SEQ ID NO: 19097);

[0546] QIYEGKLTAEGLRFGIVASRFNHALVDRLVEGAIDCIVRHGGREEDITLVRVPGSW

[0547] EIPVAAGELARKEDIDAVIATGVLIRGATPHFDYIASEVSKGLAQLSLELRKPITFGV

[0548] ITADTLEQAIERAGTKHGNKGWEAALSAIEMANLFKSLR (SEQ ID NO: 19098):

[0549] NIIQGNLVGTGLKIGIVVGRFNDF1TSKLLSGAEDALLRHGVDTNDIDVAWVPGAF

[0550] EIPFAAKKMAETKKYDAirTLGTVIRGATTHYDYVCNEAAKGIAQAAQTTGVPVIF

[0551] GIVTTENIEQAIETAGTKAGNKGVDCAVSAIEMANLQRSFE (SEQ ID NO: 19099):

[0552] KTINSVDTKEFLNHQVANLNVFTVKIHQ1IIWYMRGHNFFTLHEKMDDLYSEFGE

[0553] QMDEVAERLLA1GGSPFSTLKEFLENASVEEAPYTKPKTMDQLMEDLVGTLELLR

[0554] DEYKQGIELTDKEGDDVTNDMLTAFKASIDKHTWMFKAFLGKAPLE (SEQ ID NO: 19100).

[0555] In some embodiments, the self-assembling peptide shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0556] Given the disclosed amino acid sequences of the self-assembling peptides, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above self- assembling peptides. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the self- assembling peptide is encoded by the self-assembling sequence which may be either a DNA, an RNA, or an mRNA.

[0557] Linker sequence and linker peptide

[0558] The multisubunit nucleic acid sequence and multisubunit peptide includes linker sequence and linker peptide respectively. The linker sequence comprises a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a linker peptide. The linker sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof. In some embodiments, the linker sequence is a DNA, an RNA, or an mRNA.

[0559] In some embodiments, the linker peptide connects the target peptide with the selfassembling peptide in a polypeptide. In some embodiments, the linker peptide connects the signal peptide with a polypeptide. In some other embodiments, the linker peptide connects the signal peptide with the first polypeptide. In some embodiments, one linker peptide connects the cleavage peptide with the target peptide and another linker peptide connects the target peptide with the self-assembling peptide in a polypeptide. In some embodiments, the linker peptide connects two cleavage peptides. Any suitable linker peptides can be employed in accordance with the present disclosure.

[0560] In some embodiments, the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold or a combination thereof. In some embodiments, the linker peptide is an amino acid linker. In some embodiments, the linker peptide is a zipper motif. In some embodiments, the linker peptide is a foldon. In some embodiments, the linker peptide is a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises a combination of an amino acid linker and a foldon. In some embodiments, the linker peptide comprises a combination of an amino acid linker and a scaffold. In some embodiments, the linker peptide comprises a combination of a zipper motif and a foldon. In some embodiments, the linker peptide comprises a combination of a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a combination of a foldon and a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker, a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker, a foldon, and a scaffold. In some embodiments, the linker peptide comprises a combination of a zipper motif, a foldon, and a scaffold. In some embodiments, the linker peptide comprises a combination of a zipper motif, a foldon, and a scaffold. In some embodiments, the linker peptide comprises a combination of an amino acid linker, a zipper motif, a foldon, and a scaffold.

[0561] In some embodiments, the amino acid linker comprises of about 2-49 amino acids, 2-40 amino acids, 2-30 amino acids, 2-20 amino acids, 2-15 amino acids, or 2-10 amino acids. In some embodiments, the amino acid linker comprises a glycine serine linker, a glycine proline linker, a glycine threonine linker, an alanine serine linker, any combination of two amino acid, or a combination thereof.

[0562] The glycine proline linker comprises of glycine (G) and proline (P) amino acids consecutively without any preference of order of appearance of either glycine or proline. In some embodiments, the glycine proline linker is 2-49 amino acids in length.

[0563] The glycine threonine linker comprises of glycine (G) and threonine (T) amino acids consecutively without any preference of order of appearance of either glycine or threonine. In some embodiments, the glycine threonine linker is 2-49 amino acids in length.

[0564] The alanine serine linker comprises of alanine (A) and serine (S) amino acids consecutively without any preference of order of appearance of either alanine or serine. In some embodiments, the alanine serine linker is 2-49 amino acids in length.

[0565] The glycine serine linker comprises of glycine (G) and serine (S) amino acids consecutively without any preference of order of appearance of either glycine or serine. In some embodiments, the glycine serine linker is 2-49 amino acids in length.

[0566] Exemplary amino acid linkers include, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or their combinations, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:

[0567] GSG (SEQ ID NO: 12);

[0568] GSGG (SEQ ID NO: 13); GGSGG (SEQ ID NO: 14);

[0569] GGSGGGGSGG (SEQ ID NO: 15);

[0570] GGSGGGGSGGGGSGG (SEQ ID NO: 16);

[0571] SGGSGG (SEQ ID NO: 17);

[0572] GGGGSGGGGS (SEQ ID NO: 18);

[0573] GGGGSGGGGSGGGGS (SEQ ID NO: 19);

[0574] PGG (SEQ ID NO: 19101).

[0575] In some embodiments, the amino acid linkers share at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0576] Given the disclosed amino acid sequences of the amino acid linkers, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above amino acid linkers. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the amino acid linker is encoded by an amino acid linker sequence which may be either a DNA, an RNA, or an mRNA.

[0577] In some embodiments, linker peptide is a zipper motif. A zipper motif comprises of a sequence of amino acids encoded by a zipper sequence. Zipper motifs are generally a class of protein-protein interaction domains that facilitates formation of a complex i.e., enables two, three, four, five, or six homologous or heterologous polypeptides to associate themselves into a polypeptide cluster. In some embodiments, the zipper motif is a leucine zipper, an isoleucine zipper, or any synthetic zipper.

[0578] Exemplary zipper motifs include, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including codon optimized sequences, fragments, mutants, variants, or functional analogs thereof:

[0579] RIARLEEKVKTLKAQNSELASTANMLREQVAQLK QKVMNY (SEQ ID NO: 19102); LTDTLQAETDQLEDKKSALQTEIANLLKEKEKLEFILAAY (SEQ ID NO: 19103);

[0580] RNAYLRKKIARLKKDNLQLERDEQNLEKIIANLRDEIARLENEVA (SEQ ID NO: 19104);

[0581] LVAQLENEVASLENENETLKKKNLHKKDLIAYLEKEIANLRKKIE (SEQ ID NO: 19105). In some embodiments, the zipper motif shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0582] Given the disclosed amino acid sequences of the zipper motifs, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above zipper motifs. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the zipper motif is encoded by a zipper sequence which may be either a DNA, an RNA or an mRNA.

[0583] In some embodiments, the linker peptide is a foldon. A foldon comprises of a sequence of amino acids encoded by a foldon sequence. The foldon sequence includes codon optimized sequences, fragments, mutants, variants, functional analogs, or a combination thereof. A foldon enables two or more homologous polypeptides to organise to form an oligomeric complex. In some embodiments, foldon also helps in orientation of a polypeptide such that the domains or epitopes on the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.

[0584] Exemplary foldons includes, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:

[0585] YIPEAPRDGQAYVRKDGEWVLLSTFL (SEQ ID NO: 20);

[0586] HENEISHHAKEIERLQKEIERHKQSIKKLKQSE (SEQ ID NO: 21).

[0587] In some embodiments, the foldon shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0588] Given the disclosed amino acid sequences of the foldons, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above foldons. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the foldon is encoded by a foldon sequence which may be either a DNA, an RNA, or an mRNA. In some embodiments, the linker peptide is a scaffold. A scaffold comprises of a sequence of amino acids encoded by a scaffold sequence. The scaffold sequence includes codon optimized sequences, fragments, mutants, variants, or a combination thereof. A scaffold provides structural and / or functional integrity or support to the target peptide and may also help in orientation of target peptide such that the domains or epitopes of the target peptide are exposed or displayed for interaction or communication with cells or biomolecules or immune system.

[0589] Exemplary scaffolds include, but not limited to, the ones represented by the following amino acid sequences or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:

[0590] VDNKFNKEMRNAYWEIALLPNLNNQQKRAFIRSLYDDPSQSANLLAEAKKLNDA QAPK (SEQ ID NO: 22);

[0591] QDSTSDLIPAPPLSKVPLQQNFQDNQFHGKWYVVGKAGNHDLREDKDPRKMQAT IYELKEDKSYNVTNVRFVHKKCNYRIWTFVPGSQPGEFTLGNIKSWPGLTSWLVR VVSTNYNQHAMVFFKRVYQNRELFEITLYGRTKELTNELKENFIRFSKSLGLPENH IVFPVPIDQCIDGSAWSHPQFEK (SEQ ID NO: 23);

[0592] VSDVPRDLEVVAATPTSLLISWDAPAVTVRYYRITYGETGGNSPVQEFTVPGSKST ATISGLKPGVDYTITVYAVTGRGDSPASSKPISINYRT (SEQ ID NO: 24);

[0593] GCPRILMRCKQDSDCLAGCVCGPNGFCG (SEQ ID NO: 25);

[0594] MRGSHHHHHHGSDLGKKLLEAARAGQDDEVRILMANGADVNATDNDGYTPLHL AASNGHLEIVEVLLKNGADVNASDLTGITPLHLAAATGHLEIVEVLLKHGADVNA YDNDGHTPLHLAAKYGHLEIVEVLLKHGADVNAQDKFGKTAFDISIDNGNEDLA EILQ (SEQ ID NO: 26);

[0595] MRGSHHHHHHGSVKVKFFWNGEEKEVDTSKIVWVKRAGKSVLFIYDDNGKNGY GDVTEKDAPKELLDMLARAEREKKL (SEQ ID NO: 27);

[0596] MLPAPKNLVVSEVTEDSARLSWDDPAAFYESFLIQYQESEKVGEAIVLTVPGSERS YDLTGLKPGTEYTVSIYGVHNVYKDTNMRGLPLSAIFTTGGHHHHHH (SEQ ID NO: 28);

[0597] ETDICKLPKDEGTCRDFILKWYYDPNTKSCARFWYGGCGGNENKFGSQKECEKV CAPV (SEQ ID NO: 29); MIPGGLSEAKPATPEIQEIVDKVKPQLEEKTNETYGKLEAVQYKTQVVAGTNYYI KVRAGDNKYMHLKVFKSLPGQNEDLVLTGYQVDKNKDDELTGF (SEQ ID NO: 30);

[0598] PCSAFEFHCLSGECIHSSWRCDGGPDCKDKSDEENCA (SEQ ID NO: 31);

[0599] MQIFVKTLTGKTITLEVEPSDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLS DYNIQKESTLHLVLRLRGG (SEQ ID NO: 32);

[0600] MGSIIFLEDRAFQGRIYGCTTDCPNLQPYFSRCNSIVVQSGCWMIYERPNYQGHQY FLRRGEYPDYQQWMGLSDSIRSCCLIPPHSGAYRMKIYDRDELRGQMSELTDDCL SVQDRFHLTEIHSLNVLEGSWILYEMPNYRGRQYLLRPGEYRRFLDWGAPNAKV GSLRRVMDLYLEHHHHHH (SEQ ID NO: 33);

[0601] AGHRIAWLLMMGHPRQQLAIIFGIGVSTLYRYFPA (SEQ ID NO: 34);

[0602] AFSKSEEARHSSLERECIEEICDHAEAWDIMM (SEQ ID NO: 35);

[0603] RECDYCGTDIEPGTGGMAVHGDGATTHFCSHRCAWDAMMGAEARNLEWTDTA R (SEQ ID NO: 36);

[0604] CSQNEYFDSLLHACIPCQLRCSGAPHRCAWDCMM (SEQ ID NO: 37);

[0605] EHIPGTLAARLSHRAAWDLMMHSLDASQGTATGPRGIFTAEDALKLVQLKQTGK

[0606] TFPTYKCGHRFAWDCMMGSGLNGAACFAVKIADLPVYSCECAIGFMGQRCEYKE (SEQ ID NO: 38);

[0607] ACYGHRCAWDCMMLGFSSGKCINSKCKCYK (SEQ ID NO: 39);

[0608] GEYVVEKVLDKRVVKGKVEYLLKWKGFSDEDNTWEPDENLDGHRLAWDFMM

[0609] ADVYEVEAILADRVNKNGINEYYIKWAGYDWYDNTWEPEQNLFGAGHRLAWW MMR (SEQ ID NO: 40);

[0610] AGTIKITQTRSAIGRLPAHKATLLGLGLRRIGHTVEREDGHRIAWDIMMVSFMVKV EG (SEQ ID NO: 41);

[0611] GIPCGESCGSPCISSAIGCSCKLINTNGSWHIVCYRN (SEQ ID NO: 42);

[0612] GKCPETFDAWYCLNDAHCFAVLINTNGSWHIVYSCECAIGFMGQRCEYKE (SEQ ID NO: 43);

[0613] QEEADRTVFVGNLEARVREEILYELFLQAGPLTKVTICKDREGKPKSFGFVCFKHP ESVSYAIALAGLINLNGSWIIVSGPSSG (SEQ ID NO: 44);

[0614] NEEDAGKMFVGGLSWDTSKKDLKDYFTKFGEVVDCTIKMDPNTGRSRGFGFILF KDAASVEKVLDAGLHNLNGSWIIPKKA (SEQ ID NO: 45);

[0615] SGNIFIKNLDKSIDNKALYDTFSAFGNILSCKVVCDEQGSKGYGFVHFETQEAAER AIAKMGLMNLNGSWVIVGRFKSRKE (SEQ ID NO: 46); PSRVVYLGSIPYDQTEEQILDLCSNVGPVINLKMMFDPQTGRSKGYAFIEFRDLESS ASAVGALGLYNLNGSWLICGYSSNSDISGVSLEHHHH (SEQ ID NO: 47);

[0616] LAILVFGYPETMANQVIAYFQEFGTILEDFEVLRKPQAMTVGLQDRQFVPIFSGNS WTKITYDNPASAVDALAEGLANFNGSWLLVIPYTKDAVERLQ (SEQ ID NO: 48); RLVNCNGSWLIGLDRPPYPGAKGEDIYNNVSRKAWDEWQKHQTMLINERRLNM MNAEDRKFLQQEMDKFLSGEDY (SEQ ID NO: 49);

[0617] FAVESIEKLRNRNGSWEILVKWRGWSPKYNTWEPEENIG (SEQ ID NO: 50); MRDFFVITNSLYNFNGSWYIKGAVLHVSPTQKRAFWVIADQENFIKQVNKNIEYV EKQASPAFLQRIVEIYQVKFEGKNVG (SEQ ID NO: 51).

[0618] In some embodiments, the scaffold shares at least 50% identity with the sequences described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0619] Given the disclosed amino acid sequences of the scaffold, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above scaffold. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the scaffold is encoded by the scaffold sequence which may be either a DNA, an RNA, or an mRNA.

[0620] In some embodiments, the linker peptide comprises an amino acid linker and a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker followed by a zipper motif. In some embodiments, the linker peptide comprises a zipper motif followed by an amino acid linker. In some embodiments, the linker peptide comprises an amino acid linker followed by a zipper motif and another an amino acid linker. In some embodiments, the linker peptide comprises a zipper motif followed by an amino acid linker, and another zipper motif.

[0621] In some embodiments, the linker peptide comprises an amino acid linker and a foldon. In some embodiments, the linker peptide comprises an amino acid linker followed by a foldon. In another embodiment, the linker peptide comprises a foldon followed by an amino acid linker. In some embodiments, the linker peptide comprises an amino acid followed by a foldon and another amino acid linker. In some embodiments, the linker peptide comprises a foldon followed by an amino acid linker and another foldon. In some embodiments, the linker peptide comprises an amino acid linker and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker followed by a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker. In some embodiments, the linker peptide comprises an amino acid linker followed by a scaffold and another amino acid linker. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker and another scaffold.

[0622] In some embodiments, the linker peptide comprises a zipper motif and a scaffold. In some embodiments, the linker peptide comprises a zipper motif followed by a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by a zipper motif. In some embodiments, the linker peptide comprises a scaffold followed by a zipper motif and another scaffold. In some embodiments, the linker peptide comprises a zipper motif followed by a scaffold and another zipper motif.

[0623] In some embodiments, the linker peptide comprises a foldon and a scaffold. In some embodiments, the linker peptide comprises a foldon followed by a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by a foldon. In some embodiments, the linker peptide comprises a foldon followed by a scaffold and another foldon. In some embodiments, linker peptide comprises a scaffold followed by a foldon and another scaffold.

[0624] In some embodiments, the linker peptide comprises an amino acid linker, a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker followed by a zipper motif, and a scaffold. In some embodiments, the linker peptide comprises a zipper motif followed by an amino acid linker, and a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker, and a zipper motif. In some embodiments, the linker peptide comprises a first amino acid linker followed by a zipper motif, a second amino acid linker followed by a scaffold, and a third amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, a second amino acid linker followed by a zipper motif, and a third amino acid linker. In some embodiments, the linker peptide comprises a scaffold followed by a first amino acid linker, and a zipper motif followed by a second amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, and a second amino acid linker followed by a zipper motif. In some embodiments, the linker peptide comprises an amino acid linker, a foldon and a scaffold. In some embodiments, the linker peptide comprises an amino acid linker followed by a foldon and a scaffold. In some embodiments, the linker peptide comprises a foldon followed by an amino acid linker, and a scaffold. In some embodiments, the linker peptide comprises a scaffold followed by an amino acid linker, and a foldon. In some embodiments, the linker peptide comprises a first amino acid linker followed by a foldon, a second amino acid linker followed by scaffold, and a third amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, a second amino acid linker followed by a foldon, and a third amino acid linker. In some embodiments, the linker peptide comprises a scaffold followed by a first amino acid linker, and a foldon followed by a second amino acid linker. In some embodiments, the linker peptide comprises a first amino acid linker followed by a scaffold, and a second amino acid linker followed by a foldon.

[0625] Cleavage sequence and cleavage peptide

[0626] The multisubunit nucleic acid sequence and multisubunit peptide includes cleavage sequence and cleavage peptide respectively. The cleavage sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a cleavage peptide. The cleavage sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof. In some embodiments, the cleavage sequence is a DNA, an RNA, or an mRNA.

[0627] The cleavage peptide connects one polypeptide with another polypeptide, for example, the adjacent polypeptide. The cleavage peptide carries one or more cleavage sites. In some embodiments, the cleavage peptide comprises one or more cleavage peptides, for example cleavage peptide- 1, cleavage peptide-2 and so on. In some embodiments, the cleavage peptide optionally comprises a linker peptide between two cleavage peptides.

[0628] In some embodiments, the cleavage peptide facilitates the action of cellular proteases to cleave the multisubunit polypeptide into individual polypeptides or self cleaves into individual polypeptides. In some embodiments, the resulting polypeptides comprises either a target peptide, a linker peptide and a self-assembling peptide or a linker peptide, target peptide, linker peptide and a self-assembling peptide or a combination thereof. In some embodiments, the polypeptide, in addition to these peptides, may also have some residues (amino acids) of cleavage peptide. Any cleavage peptide that is susceptible to the action of cellular proteases or a cleavage peptide that has the ability to undergo self cleavage can be employed in accordance with the present disclosure.

[0629] In some embodiments, the cleavage peptide is a substrate for cellular proteases. In some embodiments, the cleavage peptide is a substrate for golgi specific proteases. In some embodiments, the cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide comprises two or more cleavage peptides (for example, cleavage peptide- 1, cleavage peptide-2 and so on), optionally linked by a linker peptide, wherein one cleavage peptide is a substrate for cellular proteases and the other cleavage peptide is a self cleaving peptide. In some embodiments, the cleavage peptide is a golgi specific cleavage peptide i.e., susceptible to action of golgi specific proteases.

[0630] Exemplary cleavage peptide includes, but not limited to, the one represented by the following amino acid sequence or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:

[0631] RRKRSVS (SEQ ID NO: 52);

[0632] GIRRKRSVSH (SEQ ID NO: 53);

[0633] VQREKRAVGI (SEQ ID NO: 54);

[0634] SIRHKREPSV (SEQ ID NO: 55);

[0635] KRRQRRRPPQ (SEQ ID NO: 56);

[0636] KIRRRRDVVD (SEQ ID NO: 57);

[0637] HNRTKRSTDG (SEQ ID NO: 58);

[0638] RKRRKRELET (SEQ ID NO: 59);

[0639] THRTRRSTSD (SEQ ID NO: 60);

[0640] SRRKRRSAST (SEQ ID NO: 61);

[0641] NLRRRRDLVD (SEQ ID NO: 62);

[0642] LRRRRRDAGN (SEQ ID NO: 63);

[0643] ATNFSLLKQAGDVEENPGP (SEQ ID NO: 64);

[0644] EGRGSLLTCGDVEENPGP (SEQ ID NO: 65);

[0645] QCTNYALLKLAGDVESNPGP (SEQ ID NO: 66).

[0646] In some embodiments, the cleavage peptide shares at least 50% identity with the sequence described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0647] Given the disclosed amino acid sequences of the cleavage peptide, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above cleavage peptide. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the cleavage peptide is encoded by a cleavage sequence which may be either a DNA, an RNA, or an mRNA.

[0648] Signal sequence and signal peptide

[0649] The multisubunit nucleic acid sequence and multisubunit peptide includes a signal sequence and a signal peptide respectively. The signal sequence comprises of a sequence of nucleotides, either deoxyribonucleotides or ribonucleotides, that encodes a signal peptide. The signal sequence includes codon optimized sequences, fragments, mutants, variants, comparable equivalents, functional analogs, or a combination thereof. In some embodiments, the signal sequence is a DNA, an RNA, or an mRNA.

[0650] The signal peptide is present upstream (N-terminus or amino-terminus) of one or more polypeptides. In some embodiments, the signal peptide is present on the N-terminus of all or some polypeptides. In some embodiments, the signal peptide is present on the N- terminus of the first polypeptide. In some embodiments, the signal peptide is present upstream (N-terminus) of some polypeptides. In some embodiments, the signal peptide is present upstream (N-terminus) of each of the polypeptides.

[0651] In some embodiments, the signal peptide transports the multisubunit peptide to cell organelles. In some embodiments, the signal peptide transports the multisubunit peptide to golgi body or golgi apparatus / complex. Any signal peptide that transports the multisubunit peptide to golgi bodies can be employed in accordance with the present disclosure. In some embodiments, the signal peptide is a golgi targeting signal peptide i.e., directs the multisubunit peptide to golgi complex.

[0652] Exemplary signal peptide includes, but not limited to, the one represented by the following amino acid sequence or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof:

[0653] MPSSVSWGILLLAGLCCLVPVSLAEDPQGDAA (SEQ ID NO: 67); MGSSVSWGILLLAGLCCLVPVSLAEDPQGDAA (SEQ ID NO: 68); MASSVSWGILLLAGLCCLVPVSLAEDPQGDAA (SEQ ID NO: 69);

[0654] MDMRAPAGIFGFLLVLFPGYRS (SEQ ID NO: 70);

[0655] MKWVTFISLLFLFSSAYS (SEQ ID NO: 71);

[0656] MDWTWRVFCLLAVTPGAHP (SEQ ID NO: 72);

[0657] MAWSPLFLTLITHCAGSWA (SEQ ID NO: 73);

[0658] MTRLTVLALLAGLLASSRA (SEQ ID NO: 74);

[0659] MARPLCTLLLLMATLAGALA (SEQ ID NO: 75);

[0660] MRSLVFVLLIGAAFA (SEQ ID NO: 76);

[0661] MSRLFVFILIALFLSAIIDVMS (SEQ ID NO: 77);

[0662] MGMRMMFIMFMLVVLATTVVS (SEQ ID NO: 78);

[0663] MRAFLFLTACISLPGVFG (SEQ ID NO: 79);

[0664] MKFQSTLLLAAAAGSALA (SEQ ID NO: 80);

[0665] MASSLYSFLLALSIVYIFVAPTHS (SEQ ID NO: 81);

[0666] MKTHYSSAILPILTLFVFLSINPSHG (SEQ ID NO: 82);

[0667] MESVSSLFNIFSTIMVNYKSLVLALLSVSNLKYARG (SEQ ID NO: 83);

[0668] MKAAQILTASIVSLLPIYTSA (SEQ ID NO: 84);

[0669] MIKLKFGVFFTVLLSSAYA (SEQ ID NO: 85);

[0670] MGVKVLFALICIAVAEA (SEQ ID NO: 86).

[0671] In some embodiments, the signal peptide shares at least 50% identity with the sequence described herein above or comparable equivalents, or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, or functional analogs thereof.

[0672] Given the disclosed amino acid sequences of the signal peptide, a person skilled in the art would be able to deduce all possible DNA or RNA sequences that encodes the above signal peptide. Such DNA or RNA sequences are deemed to be incorporated in this disclosure. In some embodiments, the signal peptide is encoded by a signal sequence which may be either a DNA, an RNA, or an mRNA.

[0673] Synthesis of multisubunit nucleic acid sequences

[0674] Multisubunit nucleic acid sequence according to the present disclosure can be either a DNA or an RNA or an mRNA. The multisubunit nucleic acid sequence as described herein can be synthesized by molecular biology or genetic engineering techniques well known in the art, for example, using recombinant expression system, chemical synthesis, or in vitro transcription (IVT).

[0675] In some embodiments, the multisubunit nucleic acid sequence is obtained through a single IVT process or step. In some embodiments, the multisubunit nucleic acid sequence obtained through single IVT process or step is an mRNA. In some embodiments, the multisubunit nucleic acid sequence is obtained or synthesized through a single in vitro transcription (IVT) process or step.

[0676] In some embodiments, the multisubunit nucleic acid sequence is a messenger RNA (mRNA). The mRNA encodes a multisubunit peptide as described herein.

[0677] Typically, an mRNA includes at least a coding region (which encodes the multisubunit peptide), a 5’ UTR, a 3’ UTR, a 5’ cap and a 3’ poly(A) tail. UTR (untranslated regions) flanks the coding region or open reading frame (ORF). The 5’ UTR and the 3’ UTR are sections of the mRNA before the start codon and after the stop codon respectively. The 5’ UTR has a cap (5’ cap) consisting of altered nucleotides. mRNA also contains a poly adenylated region at its 3’ end having adenine nucleotides called poly(A) tail.

[0678] In some embodiments, the mRNA is unmodified or modified or a combination of both. The modification may be in the nucleobase of the nucleotide, or sugar moiety of the nucleotide, or the phosphate of the nucleotide. In some embodiments, unmodified mRNA comprises naturally occurring nucleosides, for example, adenosine, guanosine, cytidine, and uridine. mRNA comprises one or more modified nucleosides, for example, adenosine analog, guanosine analog, cytidine analog, or uridine analog.

[0679] In some embodiments, the one or more modified nucleosides is a nucleoside analog selected from 2-aminoadenosine, 3-methyl adenosine, 7-deazaadenosine, 7- deazaguanosine, 8-oxoadenosine, or 8-oxoguanosine or a combination thereof.

[0680] In some embodiments, the one or more modified nucleosides is a uridine analog selected from propynyl-uridine, pseudouridine, C5 -bromouridine, C5-fluorouridine, C5- iodouridine, C5-propynyl-uridine, 5-aza-uridine, 2-thio-5-aza-uridine, 2-thio-uridine, 4- thio-pseudouridine, 2-thio-pseudouridine, 5-hydroxy-uridine, 3-methyl-uridine, 5- carboxymethyl-uridine, 1 -carboxymethyl-pseudouridine, l-methyl-3-(3-amino-3- carboxypropyl)pseudouridine, 2-thio-2 ’ -O-methyl-uridine, 5 -methoxycarbonylmethyl-2 ’ - O-methyl-uridine, 5-carboxymethylaminomethyl-2 ’ -O-methyl-uridine, 3 ,2 ’ -O-dimethyl- uridine, 5-propynyl-uridine, 1-propynyl-pseudouridine, 5-taurinomethyl-uridine, 1- taurinomethyl-pseudouridine, 5 -taurinomethyl-2-thio-uridine, 1 -taurino-4-thio- pseudouridine, 1-methyl-pseudouridine, 4-thio-l-methyl-pseudouridine, 2-thio- 1-methyl- pseudouridine, 1 -methyl- 1 deaza-pseudouridine, 2-thio- 1 -methyl- 1 -deaza-pseudouridine, dihydro-uridine, dihydro-pseudouridine, 2-thio-dihydro-uridine, 2-thio-dihydro- pseudouridine, 2-methoxy-uridine, 2-methoxy-4-thio-uridine, 4-methoxy-pseudouridine, or 4-methoxy-2-thio-pseudouridine, or a combination thereof.

[0681] In some embodiments, the one or more modified nucleosides is a cytidine analog selected from 5-methylcytidine, C5-propynyl-cytidine, C5-methylcytidine, pseudoisocytidine, 1-methyl-pseudoisocytidine, pyrrolo-pseudoisocytidine, 4-thio- pseudoisocytidine, 4-thio- 1 -methyl-pseudoisocytidine, 4-thio- 1 -methyl- 1 -deaza- pseudoisocytidine, 1 -methyl- 1-1 deaza-pseudoisocytidine, 4-methoxy- 1 -methyl- pseudoisocytidine, or a combination thereof.

[0682] Methods for making modified nucleosides are well known in the art.

[0683] In some embodiments, the modified nucleoside is pseudouridine, for example, 1- methyl-pseudouridine, 1-propynyl-pseudouridine, 1-carboxymethyl-pseudouridine, 1- methyl-3-(3-amino-3-carboxypropyl)pseudouridine, 4-methoxy-pseudouridine, or 4- methoxy-2-thio-pseudouridine 4-thio-pseudouridine, 2-thio-pseudouridine, 4-thio-l- methyl-pseudouridine, 2-thio- 1-methyl-pseudouridine, dihydro-pseudouridine, or a combination thereof.

[0684] In some embodiments, mRNA is produced using recombinant expression system, chemically synthesized, or obtained through in vitro transcription.

[0685] In some embodiments, the multisubunit nucleic acid sequence is obtained or synthesized through a single IVT process or step. mRNAs according to the present disclosure may be synthesized via in vitro transcription (IVT). Briefly, IVT is typically performed with a DNA template containing a promoter, a pool of ribonucleotide triphosphates, a buffer system that may include DTT and magnesium ions, and an appropriate RNA polymerase (e.g., T3, T7, or SP6 RNA polymerase), DNase I, pyrophosphatase, and / or RNase inhibitor. The exact conditions may vary according to the specific application. Methods of making mRNA through IVT reaction is well known in the art (see for example, Beckert, Bertrand and Masquida, Benoit Methods in Molecular Biology (2011) 703, 29-41 ; Brunelle, Julie L. and Green Rachel Methods in Enzymology (2013) 530, 101-114; Kamakaka, Rohinton T. and Kraus W. Lee Current Protocols in Cell Biology (1999) 11.6.1-11.6.17; Kanwal, Fariha et al. Cellular Physiology and Biochemistry (2018) 48:1915-1927; WO2018157153; W02020185811; W02022082001).

[0686] In some embodiments, the in vitro transcription occurs in a single batch. In some embodiments, IVT reaction includes capping and tailing reactions either co- transcriptionally or separately. A cap analog is added to the in vitro transcription reaction and will be incorporated at the 5’ end of the mRNA during the reaction. Alternative method of capping involves adding the cap post-transcriptionally through an enzymatic reaction. The poly (A) tail can be incorporated into the DNA template sequence, and thus the poly (A) tail will be incorporated into the mRNA by T7 RNA polymerase during the in vitro transcription. Alternative method of tailing involves adding the poly (A) tail post- transcriptionally through an enzymatic reaction. In some embodiments, capping and tailing reactions are performed co-transcriptionally i.e., during the IVT reaction. In some embodiments, capping and tailing reactions are performed separately from IVT reaction i.e., post transcriptionally. mRNA produced as a result of IVT reaction may be purified using techniques well known in the art, such as, centrifugation, filtration and / or chromatographic techniques. The purification of mRNA may be accomplished before capping and tailing steps are performed or after capping and tailing. The synthesized mRNA may be purified by ethanol precipitation or filtration or chromatography methods. In some embodiments, tangential flow filtration is used to purify mRNA. In some embodiments, mRNA is purified by chromatographic step. In other embodiments, mRNA is purified by a combination of filtration and chromatography steps.

[0687] In some embodiments, a suitable mRNA sequence is an mRNA sequence encoding a protein, peptide, polypeptide. In some embodiments, a suitable mRNA sequence is codon optimized for efficient expression in a host cell or organism. Codon optimization typically includes modifying a naturally-occurring or wild-type nucleic acid sequence encoding a peptide, polypeptide, or protein to achieve the highest possible expression of peptide, polypeptide, protein, or an antibody without altering the amino acid sequence.

[0688] In some embodiments, the mRNA is circular. In other embodiments, the mRNA is linear.

[0689] In some embodiments, the mRNA is self-amplifying or self-replicating.

[0690] In some embodiments, mRNA is few hundred nucleotides long to several thousand nucleotides long. In some embodiments, mRNA is about 0.5 kb, 1 kb, 1.5 kb, 2 kb, 2.5 kb, 3 kb, 3.5 kb, 4 kb, 4.5 kb, 5 kb, 5.5 kb, 6 kb, 6.5 kb, 7.0 kb, 7.5 kb, 8 kb, 8.5 kb, 9 kb, 9.5 kb, 10 kb, 10.5 kb, 11 kb, 11.5 kb, 12 kb, 12.5 kb, 13 kb, 13.5 kb, 14 kb, 14.5 kb, 15 kb, 16 kb, 17 kb, 18 kb, 19 kb, 20 kb, 21 kb, 22 kb, 23 kb, 24 kb, 25 kb, 26 kb, 27 kb, 28 kb, 29 kb, 30 kb in length, or a fraction thereof. In some embodiments, mRNA is about 0.5 to 30 kb, 0.5 to 25 kb, 0.5 to 20 kb in length, or any range therein. In some embodiments, mRNA is about 1 to 20 kb, 1 to 18 kb, 1 to 16 kb, 1 to 14 kb, 1 to 12 kb, 1 to 10 kb, 1 to 9 kb, 1 to 8 kb, 1 to 7 kb, 1 to 6 kb, 1 to 5 kb in length, or any range therein.

[0691] In some embodiments, mRNA is about 0.5 kb to about 1 kb, about 1 kb to about 2 kb, about 2 kb to about 3 kb, about 3 kb to about 4 kb, about 4 kb to about 5 kb, about 5 kb to about 6 kb, about 6 kb to about 7 kb, about 7 kb to about 8 kb, about 8 kb to about 9 kb, about 9 kb to about 10 kb, about 10 kb to about 11 kb, about 11 kb to about 12 kb, about 12 kb to about 13 kb, about 13 kb to about 14 kb, about 14 kb to about 15 kb, about 15 kb to about 16 kb, about 16 kb to about 17 kb, about 17 kb to about 18 kb, about 18 kb to about 19 kb, about 19 kb to about 20 kb, about 20 kb to about 21 kb, about 21 kb to about 22 kb, about 22 kb to about 23 kb, about 23 kb to about 24 kb, about 24 kb to about 25 kb, about 25 kb to about 26 kb, about 26 kb to about 27 kb, about 27 kb to about 28 kb, about 28 kb to about 29 kb, about 29 kb to about 30 kb in length, or any range therein.

[0692] The multisubunit nucleic acid sequence as described herein, express multisubunit peptide.

[0693] Polypeptide nanoparticle

[0694] The multisubunit peptide, encoded by the multisubunit nucleic acid, comprises multiple repeats of polypeptide comprising either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, target peptide, a linker peptide, and a selfassembling peptide, or a combination thereof, interspersed with cleavage peptide (see illustration in figures), wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In some embodiments, the total number of polypeptides present in a multisubunit peptide are up to 100 polypeptides. In some embodiments, one or more polypeptides in the multisubunit peptide has identical target peptides (homologous polypeptides). In some embodiments, one or more polypeptides in the multisubunit peptide has different target peptides (heterologous polypeptides). A multisubunit peptide as described herein is encoded by the multisubunit nucleic acid sequence as described herein. Each multisubunit peptide comprises two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. The polypeptides are connected with each other through a cleavage peptide. The multisubunit peptide includes a signal peptide upstream (N-terminus) of one or more polypeptides. In some embodiments, the multisubunit peptide includes a signal peptide upstream (N- terminus) of each of all or some polypeptides. In some embodiments, the multisubunit peptide optionally includes a signal peptide upstream (N-terminus) of each polypeptide. In some embodiments, the multisubunit peptide includes a signal peptide upstream (N- terminus) of some polypeptides. In some embodiments, the multisubunit peptide includes a signal peptide upstream (N-terminus) of all polypeptides.

[0695] The signal peptide transports the multisubunit peptide to golgi body or golgi apparatus. The cellular proteases act on the cleavage sites present in the cleavage peptides or the cleavage peptide undergoes self cleavage and cleaves the multisubunit peptide into individual polypeptides comprising either a target peptide, a linker peptide, and a selfassembling peptide, or a linker peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a signal peptide, a target peptide, a linker peptide, and a selfassembling peptide, or a signal peptide, a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, or a combination thereof, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. The polypeptides may additionally also have some residues (amino acids) of the cleavage peptide.

[0696] In some embodiments, the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof.

[0697] In some embodiments, the polypeptides are homologous polypeptides.

[0698] In some embodiments, two or more homologous polypeptides organise to form an oligomeric complex. In some embodiments, the oligomeric complex comprises at least two homologous polypeptides, at least three homologous polypeptides, at least four homologous polypeptides, at least five homologous polypeptides, or at least six homologous polypeptides and so on.

[0699] In some embodiments, the polypeptides are heterologous polypeptides.

[0700] In some embodiments, the homologous polypeptides or the heterologous polypeptides organise to form a polypeptide cluster.

[0701] A polypeptide nanoparticle is formed by self-assembly of two or more homologous polypeptides, two or more heterologous polypeptides, one or more oligomeric complexes, one or more polypeptide clusters, or their combination.

[0702] In some embodiments, a polypeptide nanoparticle comprises homologous polypeptides, heterologous polypeptides, oligomeric complexes, polypeptide clusters, or a combination thereof.

[0703] In some embodiments, the polypeptide nanoparticles are symmetrical, non- symmetrical, asymmetrical, or a combination thereof.

[0704] In some embodiments, the polypeptide nanoparticles are icosahedral, helical, spherical, rod-like, or a combination thereof.

[0705] In some embodiments, the polypeptide nanoparticles are enveloped or nonenveloped or a combination thereof.

[0706] In some embodiments, the polypeptide nanoparticles are single layered or multilayered or a combination thereof.

[0707] In some of the embodiments, the polypeptide nanoparticle comprises at least 2 or up to 500 polypeptides.

[0708] In some embodiments, the polypeptide nanoparticle comprises polypeptides between 2-5, 2-10, 2-20, 20-40, 40-60, 60-80, 80-100, 100-120, 120-140, 140-160, 160- 180, 180-200, 200-220, 220-240, 240-260, 260-280, 280-300, 300-320, 320-340, 340-360, 360-380, 380-400, 400-420, 420-440, 440-460, 460-480, or 480-500.

[0709] In some embodiments, the polypeptide nanoparticle comprises polypeptides between 2-5, 2-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-99.

[0710] In one of the embodiments, the polypeptide nanoparticle comprises at least 2 or up to 500 homologous polypeptides.

[0711] In some embodiments, the polypeptide nanoparticle comprises at least 2 or up to 500 heterologous polypeptides.

[0712] Ill In some embodiments, the polypeptide nanoparticle comprises two or more oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0713] In some embodiments, the polypeptide nanoparticle comprises two or more polypeptide clusters such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0714] In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides and some heterologous polypeptides such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0715] In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides and some oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0716] In some embodiments, the polypeptide nanoparticle comprises some heterologous polypeptides and some oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0717] In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides and some polypeptide clusters such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0718] In some embodiments, the polypeptide nanoparticle comprises some heterologous polypeptides and some polypeptide clusters such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0719] In some embodiments, the polypeptide nanoparticle comprises some polypeptide clusters and some oligomeric complexes such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0720] In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides, some heterologous polypeptides, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0721] In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides, some heterologous polypeptides, some polypeptide clusters, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500. In some embodiments, the polypeptide nanoparticle comprises some homologous polypeptides, some polypeptide clusters, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0722] In some embodiments, the polypeptide nanoparticle comprises some heterologous polypeptides, some polypeptide clusters, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0723] In some embodiments, the polypeptide nanoparticle comprises some heterologous polypeptides, some homologous polypeptides, some polypeptide clusters, some oligomeric complexes, or their combination such that the total number of polypeptides in the polypeptide nanoparticle are not more than 500.

[0724] Lipid nanoparticles (LNP) composition

[0725] The multisubunit nucleic acid sequences as described herein may be encapsulated or formulated in a lipid nanoparticle composition.

[0726] In some embodiments, the lipid nanoparticle composition comprises lipid components, ionizable polymer, or a combination thereof and a multisubunit nucleic acid sequence as described herein.

[0727] In some embodiments, the lipid nanoparticle composition comprises lipid components such as a cationic lipid, a phospholipid, a sterol, a PEG-lipid and a multisubunit nucleic acid sequence as described herein.

[0728] In another embodiment, the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and a multisubunit nucleic acid sequence as described herein.

[0729] In some embodiments, a vaccine comprising the lipid nanoparticle composition is provided herein.

[0730] Lipid Components

[0731] Lipid components of the lipid nanoparticle compositions may include one or more lipids, such as a cationic lipid, a phospholipid, a sterol, and a PEG-lipid. Cationic lipid

[0732] Cationic lipid refers to a lipid that has a net positive charge at a selected pH. Cationic lipids generally comprise a hydrophilic head group that carries the charge and a hydrophobic tail.

[0733] In some embodiments, the cationic lipid is a cationic lipid with an amine head group. The amine head group can be primary, secondary, tertiary or quaternary. The cationic lipid may comprise one (monoamine) or more (polyamine) such amine groups.

[0734] In some embodiments, the cationic lipids are positively charged at pH below the pKa of the cationic lipid. In certain embodiments, the cationic lipids are neutral i.e., when pH is same or above the pKa of the cationic lipid. In some embodiments, the cationic lipids are positively charged at acidic pH i.e., pH 1.0 to pH 6.9. In certain embodiments, the cationic lipids are neutral at certain pH i.e., around physiological pH (pH 7.0 to pH 7.5). A cationic lipid that can exist in a positively charged or neutral form depending on the pH is commonly referred to as ionizable lipid. In some embodiments, the cationic lipids are ionizable such that they can exist in a positively charged or neutral form depending on the pH. In some embodiments, the cationic lipids are positively charged irrespective of the pH.

[0735] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid disclosed in US provisional applications viz., 63 / 575930; 63 / 575934; 63 / 575938; 63 / 575939; and 63 / 575942.

[0736] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (I) formula (I) or isomer, or salt thereof, wherein:

[0737] Ri and R2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or Ri and R2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;

[0738] R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;

[0739] Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5, Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;

[0740] Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;

[0741] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R2is absent; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.

[0742] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (II) formula (II) or isomer, or salt thereof, wherein:

[0743] == represents either a single bond or a double bond;

[0744] Ri and R2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or

[0745] Ri and R2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;

[0746] R3 and R4 are independently chosen from, branched or unbranched, C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;

[0747] Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, Ls, Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;

[0748] Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;

[0749] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R2is absent; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent. In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (III) formula (III) or isomer, or salt thereof, wherein:

[0750] Ri and R2 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or

[0751] Ri and R2 may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;

[0752] R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;

[0753] Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5 Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;

[0754] Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-; A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatom, or C5-10 heteroaryl containing 1-4 heteroatom; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R2is absent; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.

[0755] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (IV) formula (IV) or isomer, or salt thereof, wherein:

[0756] == represents either a single bond or a double bond;

[0757] Ri and R2are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, or

[0758] Ri and R2may combine together to form a saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;

[0759] R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2.26 alkenyl, C2.26alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26; Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, Ls, Le, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;

[0760] Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;

[0761] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatom, or C5-10 heteroaryl containing 1-4 heteroatom; C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N provided that when Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, or S, one of Ri or R2is absent; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.

[0762] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (V) formula (V) or isomer, or salt thereof, wherein:

[0763] R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26; (Rio)qis chosen from H, -OH, optionally substituted Ci-io alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-L7-R5, and -NReR?, wherein q is an integer ranging from 0 to 5;

[0764] Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, and L7 is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene;

[0765] Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;

[0766] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, heteroaryl is independently optionally substituted with one or more substituent.

[0767] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (VI) formula (VI) or isomer, or salt thereof, wherein:

[0768] R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26; each of Li, L2, L3, and L4 is either absent or independently chosen from C1-10 alkylene, C2- 10 alkenylene, and C2-10 alkynylene; Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and OP(O)(O-)O-;

[0769] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, heteroaryl is independently optionally substituted with one or more substituent.

[0770] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (VII) formula (VII) or isomer, or salt thereof, wherein:

[0771] == represents either a single bond or a double bond;

[0772] R3 and R4 are independently chosen from, branched or unbranched, C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;

[0773] (Rio)qis chosen from H, -OH, -CH2OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-Ls-Rs, and - NReR?, wherein q is an integer ranging from 0 to 5;

[0774] Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5, L7, and Ls is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, and C2-10 alkynylene; Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;

[0775] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;

[0776] Z is -CH2-, O, N, or S;

[0777] Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.

[0778] In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid represented by formula (VIII) formula (VIII) or isomer, or salt thereof, wherein:

[0779] R3 and R4 are independently chosen from branched or unbranched C1-26 alkyl, C2-26 alkenyl, C2-26 alkynyl, -(CH2)m-A-(CH2)n-(CH3)y, and -CH((CH2)m-A-(CH2)n-(CH3)y)2, wherein each of m, n, and y is independently an integer ranging from 0 to 26;

[0780] (Rio)qis chosen from H, -OH, -CH2OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, C5-10 heteroaryl containing 1-4 heteroatoms, -O-Ls-Rs, and - NReR?, wherein q is an integer ranging from 0 to 4;

[0781] Rs, Re, and R7 are independently chosen from H, -OH, C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, and C5-10 heteroaryl containing 1-4 heteroatoms; each of Li, L2, L3, L4, L5, L7, and Ls is either absent or independently chosen from C1-10 alkylene, C2-10 alkenylene, or C2-10 alkynylene;

[0782] Xi and X2 are independently chosen from -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, - C(S)NH-, -NHC(S)-, -C(S)O-, -OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, and - OP(O)(O-)O-;

[0783] A is H, a bond, saturated or unsaturated C3-10 cycloalkyl, Ce-io aryl, saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, or C5-10 heteroaryl containing 1-4 heteroatoms;

[0784] Z is -CH2-, O, N, or S;

[0785] Ai is -CH2-, -C(O)O-, -OC(O)-, -C(O)NH-, -NHC(O)-, -C(S)NH-, -NHC(S)-, -C(S)O-, - OC(S)-, -OC(O)NH-, -NHC(O)O-, -OP(O)(OH)O-, S, or N; and wherein each alkyl, alkenyl, alkynyl, alkylene, alkenylene, alkynylene, cycloalkyl, aryl, heterocycloalkyl, or heteroaryl is independently optionally substituted with one or more substituent.

[0786] In some embodiments, the cationic lipid represented by formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), or formula (VIII) are substituted with substituents independently chosen from H, OH, Cl, Br, I, O, S, N, P, optionally substituted C1-6 alkoxy, optionally substituted C1-6 alkyl, optionally substituted C2-6 alkenyl, optionally substituted C2-6 alkynyl, optionally substituted saturated or unsaturated C3-10 cycloalkyl, optionally substituted Ce-io aryl, optionally substituted saturated or unsaturated C3-10 heterocycloalkyl containing 1-4 heteroatoms, optionally substituted C5-10 heteroaryl containing 1-4 heteroatoms or combination thereof. In some embodiments, substituent may further be substituted with H, -OH, Cl, Br, I, or Ci- 6 hydroxyalkyl.

[0787] In some embodiments, N:P ratio or cationic lipid to nucleic acid ratio in LNP formulation is between 1 to 18, between 1 to 17, between 1 to 16, between 1 to 15, between 1 to 14, between 1 to 13, between 1 to 12, between 1 to 11, between 1 to 10, between 1 to 9, between 1 to 8, between 1 to 7, between 1 to 6, between 1 to 5, between 1 to 4, between 1 to 3, between 1 to 2, or any range therein.

[0788] In some embodiments, N:P ratio or cationic lipid to nucleic acid ratio in LNP formulation is about 18, about 17, about 16, about 15, about 14, about 13, about 12, about 11, about 10, about 9, about 8, about 7, about 6, about 5, about 4, about 3, about 2, about 1, or any portion or fraction thereof. In some embodiments, other exemplary cationic lipid for use in the lipid nanoparticle compositions include, but are not limited to, N,N-dioleyl-N,N- dimethylammonium chloride (DODAC); N-(2,3-dioleyloxy)propyl)-N,N,N- trimethylammonium chloride (DOTMA); N,N-distearyl-N,N-dimethylammonium bromide(DDAB); N-(2,3dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP); 3-(N — (N’,N’-dimethylaminoethane)-carbamoyl)cholesterol (DC-Chol), N-(l- (2,3-dioleoyloxy)propyl)N-2-(sperminecarboxamido)ethyl)-N,N- dimethylammoniumtrifluoracetate (DOSPA), dioctadecylamidoglycyl carboxyspermine (DOGS), 1,2-dioleoyl- 3 -dimethylammonium propane (DODAP), N,N-dimethyl-2,3-dioleoyloxy)propylamine (DODMA), N-(l ,2-dimyristyloxyprop-3-yl)-N,N-dimethyl-N-hydroxyethyl ammonium bromide (DMRIE), l,2-dilinoleyloxy-N,N-dimethylaminopropane (Dlin-DMA), 3- dimethylamino-2-(cholest-5-en-3-beta-oxybutan-4-oxy)-l-(cis,cis-9,12-oc- tadecadienoxy)propane (Clin-DMA), 2-[5’-(cholest-5-en-3-beta-oxy)-3’-oxapentoxy)-3- dimethyl-l-(cis,cis-9’,12’-octadecadienoxy)propane (CpLin-DMA), 2,3-Dilinoleoyloxy- N,N-dimethylpropylamine (Dlin-DAP), l,2-N,N’-Dilinoleylcarbamyl-3- dimethylaminopropane (Dlincarb-DAP), l,2-Dilinoleoylcarbamyl-3- dimethylaminopropane (Dlin-CD AP) , 2 ,2-dilinoleyl-4-dimethylaminomethyl- [1,3]- dioxolane (Dlin-K-DMA), heptatriaconta-6,9,28,31-tetraen-19-yl 4- (dimethylamino)butanoate (Dlin-MC3-DMA), heptadecane-9-yl 8-[2-hydroxyethyl-(6- oxo-6-undecoxyhexyl)amino]octanoate (SM-102), 6-[6-(2-hexyldecanoyloxy)hexyl-(4- hydroxybutyl)amino]hexyl 2-hexyldecanoate (ALC-0315), nonyl 8-[(8-heptadecan-9- yloxy-8-oxooctyl)-(2-hydroxyethyl)amino]octanoate (SLP-0001), or a combination thereof.

[0789] Methods of making cationic lipid and / or ionizable lipid or imparting the cationic lipid the ability to behave as an ionizable lipid are well known in the art (WO2005121348; W02009127060; W02009086558; W02010042877; W02010144740; WO2011075656; WO2017049245; WO2017075531; WO2018118102; WO2015199952; ReynierP. et al. Journal of Drug Targeting (2004) 12: 25-38; Sabnis, Staci et al. Molecular Therapy (2018) 26: 1509-1519). In some embodiments, the cationic lipid present in the lipid nanoparticle composition comprises a cationic lipid disclosed in published patent application viz., WO2019 / 152557; WO2019 / 232095; WO2021 / 077067; WO2019 / 089828; US2019 / 0240354; US2010 / 0130588 ; US2021 / 0087135; US2021 / 0128488 ; US2020 / 0121809; US2013 / 0108685; US2013 / 0195920; US2015 / 0005363; US2014 / 0308304; US 2017 / 0210697; and US2013 / 0053572.

[0790] The proportion of cationic lipid present in the lipid nanoparticle compositions is from about 10 mol % to about 70 mol % or any range therein.

[0791] In some embodiments, the proportion of cationic lipid present in the lipid nanoparticle compositions is from about 10 mol % to about 70 mol %, from about 10 mol % to about 65 mol %, from about 10 mol % to about 60 mol %, from about 10 mol % to about 55 mol %, from about 10 mol % to about 50 mol %, or any range therein.

[0792] In some embodiments, the proportion of cationic lipid present in the lipid nanoparticle compositions is about 10 mol %, about 11 mol %, about 12 mol %, about 13 mol %, about 14 mol %, about 15 mol %, about 16 mol %, about 17 mol %, about 18 mol %, about 19 mol %, about 20 mol %, about 21 mol %, about 22 mol %, about 23 mol %, about 24 mol %, about 25 mol %, about 26 mol %, about 27 mol %, about 28 mol %, about 29 mol %, about 30 mol %, about 31 mol %, about 32 mol %, about 33 mol %, about 34 mol %, about 35 mol %, about 36 mol %, about 37 mol %, about 38 mol %, about 39 mol %, about 40 mol %, about 41 mol %, about 42 mol %, about 43 mol %, about 44 mol %, about 45 mol %, about 46 mol %, about 47 mol %, about 48 mol %, about 49 mol %, about 50 mol %, about 51 mol %, about 52 mol %, about 53 mol %, about 54 mol %, about 55 mol %, about 56 mol %, about 57 mol %, about 58 mol %, about 59 mol %, about 60 mol %, about 61 mol %, about 62 mol %, about 63 mol %, about 64 mol %, about 65 mol %, about 66 mol %, about 67 mol %, about 68 mol %, about 69 mol %, about 70 mol %, or any portion or fraction thereof. In some embodiments, the proportion of cationic lipid present in the lipid nanoparticle compositions is about 10 mol% to about 20 mol%, about 20 mol% to about 30 mol%, about 30 mol% to about 40 mol%, about 40 mol% to about 50 mol%, about 50 mol% to about 60 mol%, about 60 mol% to about 70 mol%, or any range therein.

[0793] Phospholipids

[0794] Phospholipid includes a lipid containing a hydrophilic head with a phosphate group and a hydrophobic tail composed of fatty acid chains attached to a glycerol or sphingosine backbone. Exemplary phospholipids for use in the lipid nanoparticle compositions include, but are not limited to, l,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC), 1,2- dimyristoyl-sn-glycero-phosphocholine (DMPC), 1 ,2-dioleoyl-sn-glycero-3- phosphocholine (DOPC), l,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2- distearoyl-sn-glycero-3-phosphocholine (DSPC), 1 ,2-diundecanoyl-sn-glycero- phosphocholine (DUPC), l-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2- di-O-octadecenyl-sn-glycero-3-phosphocholine (18:0 Diether PC), l-oleoyl-2- cholesterylhemisuccinoyl-sn-glycero-3-phosphocholine (OchemsPC), 1 -hexadecyl-sn- glycero-3-phosphocholine (C16 Lyso PC), l,2-dilinolenoyl-sn-glycero-3-phosphocholine, 1 ,2-diarachidonoyl-sn-glycero-3-phosphocholine, 1 ,2-didocosahexaenoyl-sn-glycero-3- phosphocholine, l,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), 1,2- diphytanoyl-sn-glycero-3-phosphoethanolamine (ME 16.0 PE), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine, l,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine, 1,2- dilinolenoyl-sn-glycero-3-phosphoethanolamine, l,2-diarachidonoyl-sn-glycero-3- phosphoethanolamine, 1 ,2-didocosahexaenoyl-sn-glycero-3-phosphoethanolamine, 1 ,2- dioleoyl-sn-glycero-3-phospho-rac-(l -glycerol) sodium salt (DOPG), l-myristoyl-2- stearoyl-sn-glycero-3-phosphocholine (MSPC), l-palmitoyl-2-myristoyl-sn-glycero-3- phosphocholine (PMPC), l-palmitoyl-2-stearoyl-sn-glycero-3-phosphocholine (PSPC), 1- stearoyl-2-myristoyl-sn-glycero-3-Phosphocholine (SMPC), l-Stearoyl-2-palmitoyl-sn- glycero-3-phosphocholine (SPPC), l-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine (SOPC), l-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC), sphingomyelin, or a combination thereof.

[0795] The proportion of phospholipid present in the lipid nanoparticle compositions is from about 2 mol % to about 65 mol %, from about 5 mol % to about 65 mol %, from about 10 mol % to about 65 mol %, from about 10 mol % to about 55 mol %, from about 10 mol % to about 50 mol %, or any range therein.

[0796] In some embodiments, the proportion of phospholipid present in the lipid nanoparticle compositions is about 65 mol %, about 60 mol %, about 55 mol %, about 50 mol %, about 45 mol %, about 44 mol %, about 43 mol %, about 42 mol %, about 41 mol %, about 40 mol %, about 39 mol %, about 38 mol %, about 37 mol %, about 36 mol %, about 35 mol %, about 34 mol %, about 33 mol %, about 32 mol %, about 31 mol %, about 30 mol %, about 29 mol %, about 28 mol %, about 27 mol %, about 26 mol %, about 25 mol %, about 24 mol %, about 23 mol %, about 22 mol %, about 21 mol %, about 20 mol %, about 19 mol %, about 18 mol %, about 17 mol %, about 16 mol %, about 15 mol %, about 14 mol %, about 13 mol %, about 12 mol %, about 11 mol %, about 10 mol %, about 9 mol %, about 8 mol %, about 7 mol %, about 6 mol %, about 5 mol %, about 4 mol %, about 3 mol %, about 2 mol %, or any portion or fraction thereof.

[0797] Sterol

[0798] Lipid nanoparticle composition disclosed herein may include sterol and / or sterol derivatives. The term “sterol” as used herein include, but not limited to, cholesterol, sitosterol, fecosterol, ergosterol, campesterol, stigmasterol or their derivatives. In some embodiments, lipid nanoparticle composition comprises cholesterol and / or cholesterol derivatives. Non- limiting examples of cholesterol and cholesterol derivatives include 5 a- cholestanol, 5P-coprostanol, cholesteryl-(2’-hydroxy)-ethyl ether, cholesteryl- (4’- hydroxy)-butyl ether, 6-ketocholestanol, 5a-cholestane, cholestenone, 5a-cholestanone, 5P-cholestanone, cholesteryl decanoate, or mixtures thereof. Methods of making cholesterol and cholesterol derivatives are well known in the art.

[0799] The proportion of sterol present in the lipid nanoparticle compositions may be from about 20 mol % to about 65 mol % or any range therein.

[0800] In some embodiments, the proportion of sterol present in the lipid nanoparticle compositions is from about 20 mol % to about 65 mol %, from about 25 mol % to about 65 mol %, from about 30 mol % to about 65 mol %, from about 31 mol % to about 60 mol %, from about 32 mol % to about 60 mol %, from about 33 mol % to about 60 mol %, from about 34 mol % to about 60 mol %, from about 35 mol % to about 60 mol %, or any range therein.

[0801] In some embodiments, the proportion of sterol present in the lipid nanoparticle compositions is about 65 mol %, about 60 mol %, about 55 mol %, about 50 mol %, about 45 mol %, about 44 mol %, about 43 mol %, about 42 mol %, about 41 mol %, about 40 mol %, about 39 mol %, about 38 mol %, about 37 mol %, about 36 mol %, about 35 mol %, about 34 mol %, about 33 mol %, about 32 mol %, about 31 mol %, about 30 mol %, about 29 mol %, about 28 mol %, about 27 mol %, about 26 mol %, about 25 mol %, about 24 mol %, about 23 mol %, about 22 mol %, about 21 mol %, about 20 mol %, or any portion or fraction thereof. PEG-lipid

[0802] The term PEG-lipid, pegylated lipid, PEG linked lipid, PEG conjugated lipid, PEG- lipid conjugate, PEG modified lipid have been used interchangeably to mean polyethylene glycol linked to a lipid moiety. The lipid moiety may be linked directly to the PEG molecule or through a linker. In some embodiments, a PEG-lipid comprises a PEG- modified phosphatidylethanolamines, PEG-modified phosphatidic acids, PEG-modified ceramides, PEG-modified dialkylamines, PEG-modified diacylglycerols, PEG-modified dialkylglycerols, and / or PEG-modified cholesterol, and / or mixtures thereof. The methods of making PEG-lipid are well known to persons skilled in the art.

[0803] In some embodiments, PEG-lipid is selected from mPEG-Dimyristoyl glycerol (mPEG-DMG), mPEG-N,N-Ditetradecylacetamide (mPEG-DTA or ALC0159), mPEG- Cholesterol (mPEG-CLS), mPEG-DSPE, mPEG-DMPE, mPEG-DPPE, mPEG-DLPE, mPEG-DOPE, mPEG-DPPC, mPEG-DSPC, l,2-Distearoyl-sn-Glycero-3- Phosphoethanolamine with conjugated methoxyl poly(ethylene glycol) (mPEG-DSPE), l,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (mPEG2000-DMG), a- (3 ’ - { [ 1 ,2-di(myristyloxy)propanoxy]carbonylamino }propyl)-co-methoxy, polyoxyethylene (mPEG2000C-DMG), or mixtures thereof.

[0804] The PEG moiety of the PEG-lipid may comprise an average molecular weight ranging from 0.5 kDa to 10 kDa. In some embodiments, the PEG-lipid has an average molecular weight of about 0.5 kDa to 5 kDa, about 0.5 kDa to 4 kDa, 0.5 kDa to 3 kDa, 0.5 kDa to 2 kDa. In preferred embodiments, the PEG-lipid has an average molecular weight of about 0.5 kDa to about 2 kDa.

[0805] The proportion of PEG-lipid present in the lipid nanoparticle compositions may be from about 0.2 mol % to about 2.0 mol % or any range therein.

[0806] In some embodiments, the proportion of PEG-lipid present in the lipid nanoparticle compositions is from about 0.2 mol % to about 2.0 mol %, from about 0.2 mol % to about 1.9 mol %, from about 0.2 mol % to about 1.8 mol %, from about 0.2 mol % to about 1.7 mol %, from about 0.2 mol % to about 1.6 mol %, from about 0.2 mol % to about 1.5 mol %, or any range therein.

[0807] In some embodiments, the proportion of PEG-lipid present in the lipid nanoparticle compositions is about 0.2 mol %, about 0.3 mol %, about 0. 4 mol %, about 0.5 mol %, about 0.6 mol %, about 0.7 mol %, about 0.8 mol %, about 0.9 mol %, about 1.0 mol %, about 1.1 mol %, about 1.2 mol %, about 1.3 mol %, about 1.4 mol %, about 1.5 mol %, about 1.6 mol %, about 1.7 mol %, about 1.8 mol %, about 1.9 mol %, about 2.0 mol %, or any portion or fraction thereof.

[0808] In some embodiments, the lipid nanoparticle composition additionally contains an ionizable polymer.

[0809] Ionizable polymer

[0810] As used herein the term “polymer” means a compound formed from a plurality of repeating units called monomers. Polymers are produced through a process called polymerization wherein two or more monomers are linked through chemical bonds to form the polymer. In some embodiments, the polymer is branched or unbranched. In some embodiments, the polymer is homopolymer, i.e., comprising same type of repeat units or monomers, or heteropolymer, i.e., comprising more than one type of repeat units or monomers. The terms heteropolymer and copolymer have been used interchangeably herein.

[0811] The term “Ionizable polymer” as used herein means, a polymer that can exist in a positively charged or neutral form depending on the pH of the solution or environment, for example, ionizable polymer will be cationic (positively charged) when pH of the solution is below the pKa of the ionizable polymer and neutral (no charge) when pH of the solution is same or above the pKa of the ionizable polymer. In some embodiments, ionizable polymer is positively charge in acidic pH i.e., pH 1.0 to pH 6.9. In some embodiments, ionizable polymer is neutral (no charge) around physiological pH (pH 7.0 to pH 7.5).

[0812] In some embodiments, the ionizable polymer is a biocompatible polymer or biodegradable polymer. The term “biocompatible polymer” and “biodegradable polymer” have been used interchangeably to mean a polymer that is substantially free from any deleterious effects when introduced into a living or biological system. Such polymers are capable of undergoing degradation when introduced into the living or biological systems and are not expected to produce significant toxicity or immunological response.

[0813] In some embodiments, the lipid nanoparticle compositions comprise an ionizable polymer. The ionizable polymer may be selected from a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, a polyethyleneimine, their derivatives, or a combination thereof. In some embodiments, the ionizable polymer is positively charged at acidic pH i.e., pH 1.0 to 6.9 and is neutral around physiological pH (pH 7.0 to 7.5).

[0814] The proportion of ionizable polymer present in the lipid nanoparticle compositions may be from about 1 mol % to about 25 mol %.

[0815] In some embodiments, the proportion of ionizable polymer present in the lipid nanoparticle compositions is from about 1 mol % to about 25 mol %, from about 1 mol % to about 24 mol %, from about 1 mol % to about 23 mol %, from about 1 mol % to about 22 mol %, from about 1 mol % to about 21 mol %, from about 1 mol % to about 20 mol %, from about 1 mol % to about 19 mol %, from about 1 mol % to about 18 mol %, from about 1 mol % to about 17 mol %, from about 1 mol % to about 16 mol %, from about 1 mol % to about 15 mol %, or any range therein.

[0816] In some embodiments, the proportion of ionizable polymer present in the lipid nanoparticle compositions is about 1 mol %, about 2 mol %, about 3 mol %, about 4 mol %, about 5 mol %, about 6 mol %, about 7 mol %, about 8 mol %, about 9 mol %, about 10 mol %, about 11 mol %, about 12 mol %, about 13 mol %, about 14 mol %, about 15 mol %, about 16 mol %, about 17 mol %, about 18 mol %, about 19 mol %, about 20 mol %, about 21 mol %, about 22 mol %, about 23 mol %, about 24 mol %, about 25 mol %, or any portion or fraction thereof.

[0817] In some embodiments, the preferred ionizable polymer comprises a chitosan, chitosan derivatives, cellulose derivatives, a poly-L-lysine (PLL), a protamine, polyethyleneimine, and / or their derivatives, or a combination thereof.

[0818] Method of treatment

[0819] In some aspects, provided herein is a method of beating or preventing a disease, comprising administering to a subject in need thereof the multisubunit nucleic acid sequence as described herein.

[0820] In some aspects, provided herein is a method of heating or preventing a disease, comprising administering to a subject in need thereof the lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein.

[0821] In some aspects, provided herein is a method of heating or preventing a disease, comprising administering to a subject in need thereof the lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0822] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein.

[0823] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof the lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid and the multisubunit nucleic acid sequence as described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0824] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the multisubunit nucleic acid as described herein.

[0825] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid as described herein.

[0826] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein.

[0827] In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid as described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof. In some aspects, provided herein is a method of treating or preventing a disease, comprising administering to a subject in need thereof a vaccine comprising the lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0828] In some aspects, the disclosure relates to use of the multisubunit nucleic acid as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0829] In some aspects, the disclosure relates to use of a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0830] In some aspects, the disclosure relates to use of a lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0831] In some aspects, the disclosure relates to use of a lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0832] In some aspects, the disclosure relates to use of a lipid nanoparticle composition comprising an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid sequence as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0833] In some embodiments, the disclosure relates to use of a vaccine comprising multisubunit nucleic acid as described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject. In some embodiments, the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0834] In some embodiments, the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0835] In some embodiments, the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

[0836] In some embodiments, the disclosure relates to use of a vaccine comprising a lipid nanoparticle composition, wherein the lipid nanoparticle composition comprises an ionizable polymer, a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid described herein, in the manufacture of a medicament for the treatment or prevention of a disease in a subject, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or a combination thereof.

[0837] In some embodiments, the disease is gingivostomatitits, genital herpes, herpetic keratitis, herpetic whitlows, neonatal herpes simplex virus infection, herpes simplex encephalitis, varicella or chickenpox, herpes zoster or shingles, congenital cytomegalic inclusion disease, cytomegalovirus mononucleosis, Epstein-Barr virus mononucleosis, exanthem subitem or roseola, or Kaposi sarcoma caused by herpesviruses.

[0838] In some embodiments, the multisubunit nucleic acid sequence is present in biologically effective amount or therapeutically effective amount. In some embodiments, the biologically effective amount of the multisubunit nucleic acid sequence is between 0.1 pg to 2000 pg, 0.1 pg to 1800 pg, 0.1 pg to 1600 pg, 0.1 pg to 1400 pg, 0.1 pg to 1200 pg, 0.1 pg to 1000 pg, 0.1 pg to 950 pg, 0.1 pg to 900 pg, 0.1 pg to 850 pg, 0.1 pg to 800 pg, 0.1 pg to 750 pg, 0.1 pg to 700 pg, 0.1 pg to 650 pg, 0.1 pg to 600 pg, 0.1 pg to 550 pg, 0.1 pg to 500 pg, 0.1 pg to 450 pg, 0.1 pg to 400 pg, 0.1 pg to 350 pg, 0.1 pg to 300 pg, 0.1 pg to 250 pg 0.1 pg to 200 pg, 0.1 pg to 175 pg, 0.1 pg to 150 pg, 0.1 pg to 125 pg, 0.1 pg to 100 pg, 0.1 pg to 90 pg, 0.1 pg to 80 pg, 0.1 pg to 70 pg, 0.1 pg to 60 pg,

[0839] 0.1 pg to 50 pg, 0.1 pg to 40 pg, 0.1 pg to 30 pg, 0.1 pg to 20 pg, 0.1 pg to 10 pg, 0.1 pg to 5 pg, or any range therein.

[0840] In some embodiments, the biologically effective amount of the multisubunit nucleic acid sequence is from about 0.1 pg to 1000 pg, 0.1 pg to 950 pg, 0.1 pg to 900 pg, 0.1 pg to 850 pg, 0.1 pg to 800 pg, 0.1 pg to 750 pg, 0.1 pg to 700 pg, 0.1 pg to 650 pg, 0.1 pg to 600 pg, 0.1 pg to 550 pg, 0.1 pg to 500 pg, or any range therein.

[0841] In some embodiments, the biologically effective amount of the multisubunit nucleic acid sequence is 0.1 pg, 0.2 pg, 0.3 pg, 0.4 pg, 0.5 pg, 0.6 pg, 0.7 pg, 0.8 pg, 0.9 pg, 1 pg, 2 pg, 3 pg, 4 pg, 5 pg, 6 pg, 7 pg, 8 pg, 9 pg, 10 pg, 15 pg, 20 pg, 25 pg, 30 pg, 35 pg, 40 pg, 45 pg, 50 pg, 55 pg, 60 pg, 65 pg, 70 pg, 75 pg, 80 pg, 85 pg, 90 pg, 95 pg, 100 pg, 110 pg, 120 pg, 130 pg, 140 pg, 150 pg, 160 pg, 170 pg, 180 pg, 190 pg, 200 pg, 220 pg, 240 pg, 260 pg, 280 pg, 300 pg, 350 pg, 400 pg, 450 pg, 500 pg, 600 pg, 700 pg, 800 pg, 900 pg, 1000 pg, 1100 pg, 1200 pg, 1300 pg, 1400 pg, 1500 pg, 1600 pg, 1700 pg, 1800 pg, 1900 pg, 2000 pg, or any portion or fraction thereof.

[0842] In one aspect, provided herein is a nucleic acid comprising a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a self- assembling sequence or a linker sequence, a target sequence, a linker sequence and a self-assembling sequence or a combination thereof, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In another aspect, provided herein is a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self- assembling sequence or a second linker sequence, a second target sequence, a third linker sequence, and a second self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence or the second target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In another aspect, provided herein a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In yet another aspect, provided herein is a multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus. In one aspect, provided herein is a multisubunit nucleic acid comprising a first plurality of polynucleotide sequences and a second plurality of polynucleotide sequences, each polynucleotide sequence of the first plurality comprises a first target sequence, a first linker sequence, and a first selfassembling sequence, wherein each p...

Claims

What is claimed:

1. A multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein some or all polynucleotide sequences of the plurality comprises either a target sequence, a linker sequence, and a self-assembling sequence or a linker sequence, a target sequence, a linker sequence and a self-assembling sequence or a combination thereof, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

2. A multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

3. A multisubunit nucleic acid comprising a plurality of polynucleotide sequences, wherein each polynucleotide sequence of the plurality comprises a linker sequence, a target sequence, a linker sequence, and a self-assembling sequence, wherein each polynucleotide sequence of the plurality is connected to an adjacent polynucleotide sequence of the plurality by a cleavage sequence, and wherein the multisubunit nucleic acid further comprises a signal sequence upstream of one or more of the polynucleotide sequences of the plurality, wherein the target sequence is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

4. The multisubunit nucleic acid according to any one of the preceding claims, wherein the target sequence, the linker sequence, and the self-assembling sequence or the linker sequence, the target sequence, the linker sequence, and the self-assembling sequence are in 5’ to 3’ order.

5. A multisubunit nucleic acid encoding a plurality of polypeptides, wherein some or all polypeptides of the plurality comprises either a target peptide, a linker peptide, and a self-assembling peptide or a linker peptide, a target peptide, a linker peptide and a selfassembling peptide or a combination thereof, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

6. A multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a target peptide, a linker peptide, and a selfassembling peptide, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

7. A multisubunit nucleic acid encoding a plurality of polypeptides, wherein each polypeptide of the plurality comprises a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide, wherein each polypeptide of the plurality is connected to an adjacent polypeptide of the plurality by a cleavage peptide, and wherein the multisubunit nucleic acid further encodes a signal peptide on the amino-terminus of one or more of the polypeptides of the plurality, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

8. The multisubunit nucleic acid according to any one of the claims 5-7, wherein the target peptide, the linker peptide, and the self-assembling peptide or the linker peptide, the target peptide, the linker peptide, and the self-assembling peptide are in N-terminus to C- terminus order.

9. The multisubunit nucleic acid according to any one of the preceding claims, wherein the herpesvirus is selected from the group comprising herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), or a combination thereof.

10. The multisubunit nucleic acid according to any one of the preceding claims, wherein total number of the polynucleotide sequences or the polypeptides are not more than 100.

11. The multisubunit nucleic acid according to claim 10, wherein total number of the polynucleotide sequences or the polypeptides are between 2-5, 2-10, 10-20, 20-30, 30-40, 40-50, 50-60, 60-70, 70-80, 80-90, or 90-99.

12. The multisubunit nucleic acid according to any one of the preceding claims, wherein the multisubunit nucleic acid is a DNA or an RNA.

13. The multisubunit nucleic acid according to claim 12, wherein the RNA is an mRNA.

14. The multisubunit nucleic acid according to claim 13, wherein the mRNA is 1 to 20 kb, 1 to 18 kb, 1 to 16 kb, 1 to 14 kb, 1 to 12 kb, 1 to 10 kb, 1 to 9 kb, 1 to 8 kb, 1 to 7 kb,1 to 6 kb, 1 to 5 kb in length, or any range therein.

15. The multisubunit nucleic acid according to any one of the claims 13-14, wherein the mRNA is obtained through a single IVT process or step.

16. The multisubunit nucleic acid according to any one of the claims 1-4 and 9-15, wherein the linker sequence encodes a linker peptide.

17. The multisubunit nucleic acid according to any one of the claims 5-16, wherein the linker peptide is an amino acid linker, a zipper motif, a foldon, a scaffold, or a combination thereof.

18. The multisubunit nucleic acid according to claim 17, wherein the linker peptide is the amino acid linker.

19. The multisubunit nucleic acid according to claim 18, wherein the amino acid linker comprises 2 to 49 amino acids.

20. The multisubunit nucleic acid according to any one of the claims 18-19, wherein the amino acid linker is a glycine serine linker, a glycine proline linker, a glycine threonine linker, an alanine serine linker, any combination of two amino acids, or a combination thereof.

21. The multisubunit nucleic acid according to claim 17, wherein the linker peptide is the zipper motif.

22. The multisubunit nucleic acid according to claim 17, wherein the linker peptide is the foldon.

23. The multisubunit nucleic acid according to claim 17, wherein the linker peptide is the scaffold.

24. The multisubunit nucleic acid according to any one of the claims 17-20, wherein the linker peptide comprises the amino acid linker and the zipper motif.

25. The multisubunit nucleic acid according to any one of the claims 17-20, wherein the linker peptide comprises the amino acid linker and the foldon.

26. The multisubunit nucleic acid according to any one of the claims 17-20, wherein the linker peptide comprises the amino acid linker and the scaffold.

27. The multisubunit nucleic acid according to any one of the claims 17-20, wherein the linker peptide comprises the amino acid linker, the zipper motif, and the scaffold.

28. The multisubunit nucleic acid according to any one of the claims 17-20, wherein the linker peptide comprises the amino acid linker, the foldon, and the scaffold.

29. The multisubunit nucleic acid according to claim 17, wherein the linker peptide comprises the zipper motif and the scaffold.

30. The multisubunit nucleic acid according to claim 17, wherein the linker peptide comprises the foldon and the scaffold.

31. The multisubunit nucleic acid according to any one of the claims 5-30, wherein the linker peptide has an amino acid sequence of any one of SEQ ID NOs: 12-51 or 19101- 19105.

32. The multisubunit nucleic acid according to any one of the claims 1-4 and 9-31, wherein the self-assembling sequence encodes a self-assembling peptide.

33. The multisubunit nucleic acid according to any one of the claims 5-32, wherein the self-assembling peptide is a lumazine synthase, an MS2 coat protein, a hepatitis B surface antigen (HBsAg) from Hepatitis B Virus, a hepatitis B core antigen (HbcAg) from Hepatitis B virus, a human papillomavirus LI (HPV LI) protein, a matrix protein Ml from influenza A virus, a ferritin, a riboflavin synthase, a dihydrolipoyl acetyltransferase (E2p), or a combination thereof, including their codon optimized nucleic acid sequences, fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

34. The multisubunit nucleic acid according to any one of the claims 32-33, wherein the self-assembling peptide is a ferritin comprising a ferritin subunit or a ferritin peptide, adihydrolipoyl acetyltransferase (E2p), a lumazine synthase, an MS2 coat protein, or a combination thereof.

35. The multisubunit nucleic acid according to claim 34, wherein the ferritin peptide is obtained or derived from Helicobacter pylori ferritin or Listeria innocua ferritin, the lumazine synthase is obtained or derived from Aquifex aeolicus or Bacillus subtilis, the MS2 coat protein is obtained or derived from Emesvirus zinderi, and the dihydrolipoyl acetyltransferase (E2p) is obtained or derived from Bacillus stearothermophilus.

36. The multisubunit nucleic acid according to any one of the claims 5-35, wherein the self-assembling peptide has an amino acid sequence of any one of SEQ ID NOs: 1-11 or 19097-19100.

37. The multisubunit nucleic acid according to any one of the claims 1-4 and 9-36, wherein the cleavage sequence encodes one or more cleavage peptide.

38. The multisubunit nucleic acid according to any one of the claims 5-37, wherein the one or more cleavage peptides are optionally connected to each other by a linker peptide.

39. The multisubunit nucleic acid according to claim 38, wherein the cleavage peptide is a golgi specific cleavage peptide, a self cleaving peptide, or a combination thereof.

40. The multisubunit nucleic acid according to any one of the claims 5-39, wherein the cleavage peptide has an amino acid sequence of any one of SEQ ID NOs: 52-66.

41. The multisubunit nucleic acid according to any one of the claims 1-4 and 9-40, wherein the signal sequence encodes a signal peptide.

42. The multisubunit nucleic acid according to any one of the claims 5-41, wherein the signal peptide is present on the amino-terminus of one or more of the polypeptides of the plurality.

43. The multisubunit nucleic acid according to claim 42, wherein the multisubunit nucleic acid further encodes a second signal peptide on the amino-terminus of all or some polypeptides of the plurality.

44. The multisubunit nucleic acid according to any one of the claims 5-43, wherein the signal peptide has an amino acid sequence of any one of SEQ ID NOs: 67-86.

45. The multisubunit nucleic acid according to any one of the claims 1-4 and 5-44, wherein the target sequence encodes a target peptide.

46. The multisubunit nucleic acid according to any one of the claims 5-45, wherein the target peptide is encoded by a codon optimized nucleic acid sequence, or fragments, mutants, variants, comparable equivalents, or functional analogs thereof.

47. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a herpes simplex virus 1 (HSV1).

48. The multisubunit nucleic acid according to claim 47, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof of a herpes simplex virus 1 (HSV1).

49. The multisubunit nucleic acid according to claims 48, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2567-2614; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2796-2860; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 2998-3034; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3128-3170; e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3268-3283;f) the glycoprotein C comprises an amino acid sequence of any one of SEQ ID NOs: 3350-3413; g) the glycoprotein D comprises an amino acid sequence of any one of SEQ ID NOs: 3419-3444; h) the glycoprotein I comprises an amino acid sequence of any one of SEQ ID NOs: 3447-3521, and i) the glycoprotein E comprises an amino acid sequence of any one of SEQ ID NOs: 15725-16107.

50. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a herpes simplex virus 2 (HSV2).

51. The multisubunit nucleic acid according to claim 50, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein C, glycoprotein D, glycoprotein I, glycoprotein E, or a combination thereof of a herpes simplex virus 2 (HSV2).

52. The multisubunit nucleic acid according to claims 51, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2615-2623; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2861-2869; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3035-3037; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3171-3173; e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3284-3285; f) the glycoprotein C comprises an amino acid sequence of any one of SEQ ID NOs: 3414-3418; g) the glycoprotein D comprises an amino acid sequence of any one of SEQID NOs: 3445-3446;h) the glycoprotein I comprises an amino acid sequence of any one of SEQ ID NOs: 3522-3529, and i) the glycoprotein E comprises an amino acid sequence of any one of SEQ ID NOs: 16108-16386.

53. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a cytomegalovirus (CMV).

54. The multisubunit nucleic acid according to claim 53, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 34, glycoprotein 68, UL131A, UL130, UL128, UL16, or a combination thereof of a cytomegalovirus (CMV).

55. The multisubunit nucleic acid according to claim 54, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2640-2737; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2886-2967; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3050-3103; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3188-3231; e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3293-3327; f) the glycoprotein 34 comprises an amino acid sequence of any one of SEQ ID NOs: 16387-16680; g) the glycoprotein 68 comprises an amino acid sequence of any one of SEQ ID NOs: 16681-17065; h) the UL131A comprises an amino acid sequence of any one of SEQ ID NOs: 18256-18687; i) the UL130 comprises an amino acid sequence of any one of SEQ ID NOs:17436-18255;j) the UL128 comprises an amino acid sequence of any one of SEQ ID NOs: 17066-17435; and k) the UL16 comprises an amino acid sequence of any one of SEQ ID NOs: 18688-19092.

56. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of an Epstein-Barr virus (EBV).

57. The multisubunit nucleic acid according to claim 56, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, glycoprotein 350, glycoprotein 220, glycoprotein 42, or a combination thereof of an Epstein-Barr virus (EBV).

58. The multisubunit nucleic acid according to claim 57, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2748-2783; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2974-2982; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3110-3123; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3235-3262; e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3331-3344; f) the glycoprotein 350 comprises an amino acid sequence of any one of SEQ ID NOs: 3530-3554; g) the glycoprotein 220 comprises an amino acid sequence of any one of SEQ ID NOs: 19093-19096, and h) the glycoprotein 42 comprises an amino acid sequence of any one of SEQ ID NOs: 3555-3557.

59. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a varicella-zoster virus (VZV).

60. The multisubunit nucleic acid according to claim 59, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof of a varicella-zoster virus (VZV).

61. The multisubunit nucleic acid according to claim 60, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2624-2639; b) glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2870-2885; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3038-3049. d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3174-3187; and e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3286-3292.

62. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a human herpesvirus 6 (HHV6).

63. The multisubunit nucleic acid according to claim 62, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof of a human herpesvirus 6 (HHV6).

64. The multisubunit nucleic acid according to claim 63, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2738-2746; b) the glycoprotein H comprises an amino acid sequence of any one of SEQID NOs: 2968-2972;c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3104-3108; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3232-3233; and e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3328-3229.

65. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a human herpesvirus 7 (HHV7).

66. The multisubunit nucleic acid according to claim 65, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L, glycoprotein M, glycoprotein N, or a combination thereof of a human herpesvirus 7 (HHV7).

67. The multisubunit nucleic acid according to claim 66, wherein: a) the glycoprotein B comprises an amino acid sequence of SEQ ID NOs: 2747; b) the glycoprotein H comprises an amino acid sequence of SEQ ID NOs: 2973; c) the glycoprotein L comprises an amino acid sequence of SEQ ID NOs: 3109; d) the glycoprotein M comprises an amino acid sequence of SEQ ID NOs: 3234; and e) the glycoprotein N comprises an amino acid sequence of SEQ ID NOs: 3330.

68. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from envelope protein of a Kaposi’s sarcoma-associated herpesvirus (KSHV).

69. The multisubunit nucleic acid according to claim 68, wherein the envelope protein is selected from the group comprising glycoprotein B, glycoprotein H, glycoprotein L,glycoprotein M, glycoprotein N, or a combination thereof of a Kaposi’s sarcoma- associated herpesvirus (KSHV).

70. The multisubunit nucleic acid according to claim 69, wherein: a) the glycoprotein B comprises an amino acid sequence of any one of SEQ ID NOs: 2784-2795; b) the glycoprotein H comprises an amino acid sequence of any one of SEQ ID NOs: 2983-2997; c) the glycoprotein L comprises an amino acid sequence of any one of SEQ ID NOs: 3124-3127; d) the glycoprotein M comprises an amino acid sequence of any one of SEQ ID NOs: 3263-3267; and e) the glycoprotein N comprises an amino acid sequence of any one of SEQ ID NOs: 3345-3349.

71. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from capsid protein of a herpesvirus.

72. The multisubunit nucleic acid according to claim 71, wherein the capsid protein is selected from the group comprising major capsid protein, triplex monomer, triplex dimer, small capsid protein, portal protein, portal capping protein, or a combination thereof of a herpesvirus.

73. The multisubunit nucleic acid according to any one of the claims 71-72, wherein the capsid protein comprises an amino acid sequence of any one of SEQ ID NOs: 87-772.

74. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from tegument protein of a herpesvirus.

75. The multisubunit nucleic acid according to claim 74, wherein the tegument protein is selected from the group comprising largest tegument protein, LTP binding protein, encapsidation and egress protein, cytoplasmic egress tegument protein, CETP binding protein, cytoplasmic egress facilitator- 1, encapsidation chaperone protein, capsid transporttegument protein, cytoplasmic egress facilitator-2, putative membrane or tegument protein, tegument protein pp65, tegument protein ppl50, or pp85 protein, or a combination thereof of a herpesvirus.

76. The multisubunit nucleic acid according to any one of the claims 74-75, wherein the tegument protein comprises an amino acid sequence of any one of SEQ ID NOs: 773- 2566.

77. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from regulatory protein of a herpesvirus.

78. The multisubunit nucleic acid according to claim 77, wherein the regulatory protein is selected from the group comprising multifunctional regulatory of expression, DNA polymerase, DNA polymerase processivity subunit, helicase-primase ATPase subunit, helicase-primase RNA pol subunit B, helicase-primase subunit C, single strand DNA binding protein, alkaline deoxyribonuclease, deoxyuridine triphosphatase, uracil-DNA glycosidase, ribonucleotide reductase large subunit, ribonucleotide reductase subunit 2, EBNA1, EBNA2, EBNA3, LMP1, LMP2, maturational protease, assembly protein, capsid transport nuclear protein, terminase ATPase subunit 1, terminase DNA binding subunit 2, terminase binding protein, nuclear egress membrane protein, nuclear egress lamina protein, or a combination thereof of a herpesvirus.

79. The multisubunit nucleic acid according to any one of the claims 77-78, wherein the regulatory protein comprises an amino acid sequence of any one of SEQ ID NOs: 3558-4041.

80. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from B cell epitope of a herpesvirus.

81. The multisubunit nucleic acid according to claim 80, wherein the B cell epitope comprises an amino acid sequence of any one of SEQ ID NOs: 4042-7752.

82. The multisubunit nucleic acid according to claim 46, wherein the target peptide is obtained or derived from T cell epitope of a herpesvirus.

83. The multisubunit nucleic acid according to claim 82, wherein the T cell epitope comprises an amino acid sequence of any one of SEQ ID NOs: 7753-15724.

84. The multisubunit nucleic acid according to any one of the claims 5-83, wherein the target peptide has an amino acid sequence of any one of SEQ ID NOs: 87-15724 or 15725- 19096.

85. A lipid nanoparticle composition comprising a cationic lipid, a phospholipid, a sterol, a PEG-lipid, and the multisubunit nucleic acid according to any one of the preceding claims.

86. The lipid nanoparticle composition according to claim 85, wherein the cationic lipid is present in an amount from 10 mol percent to 70 mol percent.

87. The lipid nanoparticle composition according to claim 85, wherein the phospholipid is present in an amount from 2 mol percent to 65 mol percent.

88. The lipid nanoparticle composition according to claim 85, wherein the sterol is present in an amount from 20 mol percent to 65 mol percent.

89. The lipid nanoparticle composition according to claim 85, wherein the PEG-lipid is present in an amount from 0.2 mol percent to 2.0 mol percent.

90. The lipid nanoparticle composition according to claim 85, additionally comprising an ionizable polymer.

91. The lipid nanoparticle composition according to claim 90, wherein the ionizable polymer is present in an amount from 1 mol percent to 25 mol percent.

92. The lipid nanoparticle composition according to any one of the claims 85-91, wherein the cationic lipid is represented by any one of formula (I), formula (II), formula (III), formula (IV), formula (V), formula (VI), formula (VII), formula (VIII), or SM-102, or ALC-0315 or a combination thereof.

93. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (I).

94. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (II).

95. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (III).

96. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (IV).

97. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (V).

98. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (VI).

99. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (VII).

100. The lipid nanoparticle composition according to any one of the claims 85-92, wherein the cationic lipid is represented by formula (VIII).

101. A multisubunit peptide encoded by the multisubunit nucleic acid according to any one of the claims 1-84.

102. A multisubunit peptide comprising two or more polypeptides, wherein some or all polypeptides comprises either a target peptide, a linker peptide, and a self-assembling peptide, or a linker peptide, a target peptide, a linker peptide, and a self-assembling peptide or a combination thereof, wherein one polypeptide is connected to another polypeptide by a cleavage peptide, wherein the multisubunit peptide includes a signal peptide on the amino-terminus of one or more of the polypeptides, wherein the target peptide is obtained or derived from capsid protein, tegument protein, envelope protein, regulatory protein, B cell epitope, T cell epitope, or a combination thereof of a herpesvirus.

103. The multisubunit peptide according to claim 102, wherein the herpesvirus is selected from the group comprising herpes simplex virus 1 (HSV1), herpes simplex virus 2 (HSV2), varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV6), human herpesvirus 7 (HHV7), Epstein-Barr virus (EBV), Kaposi’s sarcoma- associated herpesvirus (KSHV) or a combination thereof.

104. A polypeptide nanoparticle comprising at least 2 or up to 500 polypeptides according to any one of the claims 5-84 or according to any one of the claims 102-103.

105. The polypeptide nanoparticle according to claim 104, comprising a homologous polypeptide, a heterologous polypeptide, an oligomeric complex, a polypeptide cluster, or a combination thereof.

106. The polypeptide nanoparticle according any one of the claims 104-105, wherein the polypeptide nanoparticle is icosahedral, helical, spherical, rod-like, or a combination thereof.

107. A vaccine comprising the multisubunit nucleic acid according to any one of the claims 1-84.

108. A vaccine comprising the polypeptide nanoparticle according to any one of the claims 104-106.

109. A vaccine comprising the lipid nanoparticle composition according to any one of the claims 85-100.

110. A method of treating or preventing a disease, comprising administering to a subject in need thereof, the multisubunit nucleic acid according to any one of the claims 1-84 or the vaccine according to any one of the claims 107-108.

111. A method of treating or preventing a disease, comprising administering to a subject in need thereof, the lipid nanoparticle composition according to any one of the claims 85- 100 or the vaccine according to claim 109.

112. The method according to any one of the claims 110-111, wherein the disease is gingivostomatitits, genital herpes, herpetic keratitis, herpetic whitlows, neonatal herpes simplex virus infection, herpes simplex encephalitis, varicella or chickenpox, herpes zoster or shingles, congenital cytomegalic inclusion disease, cytomegalovirus mononucleosis, Epstein-Barr virus mononucleosis, exanthem subitem or roseola, or Kaposi sarcoma.

113. Use of the multisubunit nucleic acid according to any one of the claims 1-84 or the vaccine according to any one of the claims 107-108, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

114. Use of the lipid nanoparticle composition according to any one of the claims 85- 100 or the vaccine according to claim 109, in the manufacture of a medicament for the treatment or prevention of a disease in a subject.

115. The use according to any one of the claims 113-114, wherein the disease is gingivostomatitits, genital herpes, herpetic keratitis, herpetic whitlows, neonatal herpes simplex virus infection, herpes simplex encephalitis, varicella or chickenpox, herpes zoster or shingles, congenital cytomegalic inclusion disease, cytomegalovirus mononucleosis, Epstein-Barr virus mononucleosis, exanthem subitem or roseola, or Kaposi sarcoma.