Neutralizing immunogen (NimIV) of rhinovirus and its use for vaccine applications
The invention relates to methods and compositions for preventing or treating human rhinovirus infection.
1. A protein comprising an isolated rhinovirus neutralizing immunogen IV (NimIV) peptide, wherein said NimIV peptide consists of a sequence selected from the group consisting of: PVIKKR (SEQ ID NO: 1), PVIKKRK (SEQ ID NO: 2), PVIKKRE (SEQ ID NO: 3), PVIKKRS (SEQ ID NO: 4), NTEPVIKKRKGDIKSY (SEQ ID NO: 10), and an 8-30 amino acid fragment of the C-terminal end of virus structural protein 1 (VP-1) of a human rhinovirus comprising one of said sequences, and said protein does not comprise flanking sequence with which said NimIV peptide is contiguous in a naturally occurring virus.
2. The protein of claim 1 , wherein the NimIV peptide is a human rhinovirus 14 (HRV14) NimIV peptide, a human rhinovirus 6 (HRV6) NimIV peptide, or a human rhinovirus 72 (HRV72) peptide.
3. A virus comprising the protein of claim 1 .
4. The virus of claim 3 , wherein the virus is a human rhinovirus.
5. The virus of claim 4 , wherein the human rhinovirus is of a serotype different from that of the human rhinovirus from which the NimIV peptide is derived.
6. The virus of claim 5 , wherein the NimIV peptide is present in said human rhinovirus in place of NimIV sequences originally present in said virus.
7. The virus of claim 4 , wherein the human rhinovirus is a human rhinovirus 14 (HRV14).
8. The virus of claim 3 , wherein the rhinovirus from which the NimIV peptide is derived is human rhinovirus 6 (HRV6) or human rhinovirus 72 (HRV72).
9. The virus of claim 4 , wherein the human rhinovirus is human rhinovirus 14 (HRV14) and said human rhinovirus from which the NimIV peptide is derived is human rhinovirus 6 (HRV6) or human rhinovirus 72 (HRV72).
10. The virus of claim 6 , wherein the VP1 protein of said virus is replaced with the VP1 protein of the human rhinovirus from which the NimIV peptide is derived.
11. The virus of claim 3 , wherein the virus comprises an inactivated human rhinovirus , to which the NimIV peptide is cross-linked.
12. The virus of claim 3 , wherein the virus comprises a hepatitis B core sequence to which NimIV sequences are fused.
13. A pharmaceutical composition comprising the peptide of claim 1 .
14. The pharmaceutical composition of claim 13 , wherein the peptide is comprised within a virus.
15. The pharmaceutical composition of claim 13 , further comprising one or more of a pharmaceutically acceptable diluent, excipient, carrier, or adjuvant.
16. The pharmaceutical composition of claim 15 , wherein the adjuvant is selected from the group consisting of a chitin microparticle and an aluminum compound.
17. The pharmaceutical composition of claim 13 , further comprising one or more additional human rhinovirus neutralizing immunogens.
18. A method of inducing an immune response to a rhinovirus in a subject, the method comprising administering to the subject a protein of claim 1 .
19. The method of claim 18 , wherein the subject does not have but is at risk of developing rhinovirus infection.
20. The method of claim 18 , wherein the subject has rhinovirus infection.
21. The protein of claim 1 , wherein said NimIV peptide is 8-25, 10-20, 14-19, 15-18, or 16-17 amino acids in length.
22. The protein of claim 1 , wherein said protein is a fusion protein comprising (a) more than one of said NimIV peptides, and/or (b) a sequence heterologous to said NimIV peptide.
23. The protein of claim 22 , wherein said heterologous sequence is a carrier protein.
24. The protein of claim 22 , wherein said more than one Nim IV peptides are derived from single or multiple human rhinovirus serotypes.
25. The protein of claim 1 , wherein said NimIV peptide sequence consists of a sequence selected from the group consisting of: CKNIVPVIKKRENITTY (HRV6; SEQ ID NO: 15), CNTEPVIKKRKGDIKSY (HRV14; SEQ ID NO: 16), and CNPKPVIKKREGDIKTY (HRV72; SEQ ID NO: 17).