Vaccine against RSV
Novel nucleic acid molecules encoding a pre-fusion RSV F protein or immunologically active part thereof are described, and the pre-fusion RSV F protein contains the amino acid sequence of SEQ ID NO: 1 or 2. Use of the nucleic acid molecules, or vectors containing the nucleic acid molecules, as a vaccine against respiratory syncytial virus (RSV) is also described.
1. A nucleic acid molecule encoding a respiratory syncytial virus (RSV) F protein, comprising the polynucleotide sequence of SEQ ID NO: 3 or 4.
2. A recombinant human adenovirus vector comprising a polynucleotide sequence encoding a respiratory syncytial virus (RSV) F protein having the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, wherein the recombinant human adenovirus has a deletion in the E1 region, a deletion in the E3 region, or a deletion in both the E1 and the E3 regions of the adenoviral genome.
3. The recombinant human adenovirus vector according to claim 2 , wherein the nucleic acid encoding the RSV F protein is codon optimized for expression in human cells.
4. The recombinant human adenovirus vector according to claim 2 , wherein the nucleic acid encoding the RSV F protein comprises the nucleic acid sequence of SEQ ID NO: 3 or 4.
5. The vector according to claim 2 , wherein the recombinant human adenovirus is of serotype 26 or 35.
6. The vector according to claim 2 , wherein the recombinant human adenovirus has a genome comprising the polynucleotide sequence of CTATCTAT (SEQ ID NO: 7) at its 5′ terminal end.
7. A pharmaceutical composition comprising the nucleic acid molecule according to claim 1 .
8. A pharmaceutical composition comprising the vector according to claim 2 .
9. A method for vaccinating a subject against RSV, the method comprising administering to the subject the pharmaceutical composition according to claim 7 .
10. The method according to claim 9 , further comprising administering the RSV F protein to the subject.
11. A method for reducing infection and/or replication of RSV in a subject, comprising administering to the subject a composition comprising the nucleic acid molecule encoding the RSV F protein according to claim 1 .
12. A method for reducing infection and/or replication of RSV in a subject, comprising administering to the subject a composition comprising the vector according to claim 2 .
13. An isolated host cell comprising the nucleic acid molecule encoding the RSV F protein according to claim 1 .
14. A method for making a vaccine against respiratory syncytial virus (RSV), comprising providing a recombinant human adenovirus that comprises a nucleic acid encoding a pre-fusion RSV F protein, propagating the recombinant adenovirus in a culture of host cells, isolating and purifying the recombinant adenovirus, and formulating the recombinant adenovirus in a pharmaceutically acceptable composition, wherein the pre-fusion RSV F protein comprises the amino acid sequence of SEQ ID NO: 1 or 2, wherein the recombinant human adenovirus has a deletion in the E1 region, a deletion in the E3 region, or a deletion in both the E1 and the E3 regions of the adenoviral genome.
15. An isolated recombinant nucleic acid that forms the genome of a recombinant human adenovirus that comprises a nucleic acid encoding a pre-fusion RSV F protein, comprising the nucleic acid sequence of SEQ ID NO: 3 or 4.
16. A method for vaccinating a subject against RSV, the method comprising administering to the subject a composition according to claim 8 .
17. The method according to claim 16 , further comprising administering the RSV F protein to the subject.
18. An isolated host cell comprising the recombinant human adenovirus vector according to claim 2 .
19. A pharmaceutical composition comprising the recombinant human adenovirus vector according to claim 4 .
20. A method for vaccinating a subject against RSV, the method comprising administering to the subject a composition according to claim 19 .
21. The vector according to claim 2 , wherein the RSV F protein has the amino acid sequence of SEQ ID NO: 2.
22. The method according to claim 14 , wherein the RSV F protein has the amino acid sequence of SEQ ID NO: 2.
23. A recombinant human adenovirus vector comprising a polynucleotide sequence encoding a respiratory syncytial virus (RSV) F protein having the amino acid sequence of SEQ ID NO: 2.
24. The vector according to claim 23 , wherein the recombinant human adenovirus is of serotype 26 or 35.
25. The vector according to claim 23 , wherein the recombinant human adenovirus has a genome comprising the polynucleotide sequence of CTATCTAT (SEQ ID NO: 7) at its 5 ' terminal end.
26. A pharmaceutical composition comprising the vector according to claim 23 .
27. A method for vaccinating a subject against RSV, the method comprising administering to the subject the pharmaceutical composition according to claim 26 .
28. The method according to claim 27 , further comprising administering the RSV F protein to the subject.
29. A method for reducing infection and/or replication of RSV in a subject, comprising administering to the subject a composition comprising the vector according to claim 25 .
30. An isolated host cell comprising the recombinant human adenovirus vector according to claim 23 .
31. A method for making a vaccine against respiratory syncytial virus (RSV), comprising propagating the recombinant human adenovirus vector of claim 23 in a culture of host cells, isolating and purifying the recombinant human adenovirus vector, and formulating the recombinant human adenovirus vector in a pharmaceutically acceptable composition.