Neutralizing immunogen (NimIV) of rhinovirus and its uses for vaccine applications
The invention relates to methods and compositions for preventing or treating human rhinovirus infection.
1. An isolated nucleic acid molecule encoding a protein comprising:
(a) a first region comprising a 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
(b) contiguous flanking sequences that do not include sequences with which the first region is contiguous in a naturally occurring virus.
2. The isolated nucleic acid molecule 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 vector comprising the isolated NimIV nucleic acid molecule of claim 1 .
4. The vector of claim 3 , wherein the vector is a human rhinovirus vector.
5. The vector of claim 4 , wherein the human rhinovirus vector is of a serotype different from that of the rhinovirus from which the sequences encoding the NimIV peptide are derived.
6. The vector of claim 5 , wherein the sequences encoding the NimIV peptide are present in said human rhinovirus vector in place of NimIV sequences originally present in said vector.
7. The vector of claim 4 , wherein the human rhinovirus vector is a human rhinovirus 14 (HRV14) vector.
8. The vector of claim 3 , wherein the rhinovirus from which the sequences encoding the NimIV peptide are derived is human rhinovirus 6 (HRV6) or human rhinovirus 72 (HRV72).
9. The vector of claim 4 , wherein the human rhinovirus vector is a human rhinovirus 14 (HRV14) vector and said rhinovirus from which the sequences encoding the NimIV peptide are derived is human rhinovirus 6 (HRV6) or human rhinovirus 72 (HRV72).
10. The vector of claim 6 , wherein said vector comprises VP1 sequences and the VP1 sequences of said vector are replaced with the VP1 sequences of the rhinovirus from which the NimIV sequences are derived.
11. The vector of claim 3 , wherein the vector comprises a hepatitis B core sequence to which NimIV sequences are fused.
12. A pharmaceutical composition comprising the isolated nucleic acid molecule of claim 1 .
13. The pharmaceutical composition of claim 12 , wherein the isolated nucleic acid molecule is comprised within a vector.
14. The pharmaceutical composition of claim 12 , further comprising one or more of a pharmaceutically acceptable diluent, excipient, carrier, or adjuvant.
15. The pharmaceutical composition of claim 14 , wherein the adjuvant is selected from the group consisting of a chitin microparticle and an aluminum compound.
16. The pharmaceutical composition of claim 12 , further comprising sequences encoding one or more additional rhinovirus neutralizing immunogens.
17. A method of inducing an immune response to a rhinovirus in a subject, the method comprising administering to the subject an isolated NimIV nucleic acid molecule.
18. The method of claim 17 , wherein the subject does not have but is at risk of developing rhinovirus infection.
19. The method of claim 17 , wherein the subject has rhinovirus infection.
20. The isolated nucleic acid molecule of claim 1 , wherein said NimIV peptide is 8-25, 10-20, 14-19, 15-18, or 16-17 amino acids in length.
21. The isolated nucleic acid molecule of claim 1 , encoding a fusion protein comprising (a) more than one of said NimIV peptides, and/or (b) a sequence heterologous to said NimIV peptide.
22. The isolated nucleic acid molecule of claim 21 , wherein said heterologous sequence is a carrier protein.
23. The isolated nucleic acid molecule of claim 21 , wherein said more than one Nim IV peptides are derived from single or multiple human rhinovirus serotypes.
24. The isolated nucleic acid molecule 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).