Mosaic vaccines for serotype a foot-and-mouth disease virus
Synthetic foot-and-mouth disease virus (FMDV) mosaic polypeptides, and nucleic acid molecules encoding the mosaic polypeptides, are described. The mosaic polypeptides have greater T-cell epitope coverage than naturally occurring FMDV polypeptides, and include common FMDV epitopes, but exclude rare FMDV epitopes. When included as part of an FMDV genome, the mosaic polypeptides permit virus replication and assembly into FMDV particles. The mosaic polypeptide and nucleic acid compositions can be used to elicit immune responses that provide protection against a broad range of serotype A FMDV strains.
1. A synthetic polypeptide comprising an amino acid sequence at least 98% identical to SEQ ID NO: 2 or SEQ ID NO: 4.
2. The synthetic polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4.
3. A composition, comprising the synthetic polypeptide of claim 1 or claim 2 , further comprising a pharmaceutically acceptable carrier.
4. The composition of claim 3 , comprising a first synthetic polypeptide comprising the amino acid sequence of SEQ ID NO: 2, a second synthetic polypeptide comprising the amino acid sequence of SEQ ID NO: 4, and a pharmaceutically acceptable carrier.
5. The composition of claim 3 , further comprising an adjuvant.
6. A recombinant foot-and-mouth disease virus (FMDV) comprising a synthetic polypeptide having an amino acid sequence at least 98% identical to SEQ ID NO: 2 or SEQ ID NO: 4.
7. The recombinant FMDV of claim 6 , comprising a synthetic polypeptide comprising the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4.
8. A composition comprising the recombinant foot-and-mouth disease virus (FMDV) of claim 6 , and a pharmaceutically acceptable carrier.
9. An isolated nucleic acid molecule encoding the synthetic polypeptide of claim 1 .
10. The isolated nucleic acid molecule of claim 9 , comprising the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 3.
11. A vector comprising the isolated nucleic acid molecule of claim 9 .
12. The vector of claim 11 , further comprising coding sequences for FMDV L, VP4, P2 and P3 proteins, whereupon transfection of the vector into a permissive host cell, infectious FMDV is produced.
13. A method of eliciting an immune response against serotype A foot-and-mouth disease virus (FMDV) in a subject, comprising administering to the subject a composition comprising a synthetic polypeptide at least 98% identical to SEQ ID NO: 2 or SEQ ID NO: 4, thereby eliciting an immune response to serotype A FMDV.
14. The method of claim 13 , wherein the synthetic polypeptide comprises SEQ ID NO: 2 or SEQ ID NO: 4.
15. The method of claim 13 , wherein the composition comprising the synthetic polypeptide further comprises a pharmaceutically acceptable carrier.
16. The method of claim 13 , wherein the composition comprising the synthetic polypeptide further comprises an adjuvant.
17. The method of claim 13 , comprising administering to the subject a first composition comprising a synthetic polypeptide at least 98% identical to the amino acid sequence of SEQ ID NO: 2 and a second composition comprising a second synthetic polypeptide at least 98% identical to the amino acid sequence of SEQ ID NO: 4.
18. The method of claim 17 , wherein the first and second compositions are administered to the subject at different anatomical sites.