Recombinant virus, composition comprising the same, and uses thereof
Immunogenic compositions comprising hemagglutinin (HA) variants and/or neuraminidase (NA) variants, which may be contained in an influenza A virus, and uses thereof for eliciting immune responses against influenza A virus.
1. A recombinant Influenza A virus (IAV), comprising:
a mutant neuraminidase (NA), which, as compared with its wild-type counterpart, (a) comprises a substitution at a position corresponding to residue 102 or 135 in SEQ ID NO:4, or (b) consists of the amino acid sequence of SEQ ID NO:2; wherein the mutant NA is defective in neuraminidase activity.
2. The recombinant IAV of claim 1 , wherein the mutant NA comprises the substitution at the position corresponding to residue 102 or 135 in SEQ ID NO:4.
3. The recombinant IAV of claim 2 , wherein the mutant NA comprises an amino acid sequence at least 85% identical to SEQ ID NO: 4.
4. The recombinant IAV of claim 1 , wherein the mutant NA consists of the amino acid sequence of SEQ ID NO:2.
5. An immunogenic composition, comprising the recombinant Influenza A virus (IAV) of claim 1 , and a pharmaceutically acceptable carrier.
6. The immunogenic composition of claim 5 , wherein the pharmaceutically acceptable carrier is an adjuvant.
7. A method for inducing immune responses against influenza A virus in a subject, the method comprising administering to a subject in need thereof an effective amount of the immunogenic composition of claim 5 .
8. The method of claim 7 , wherein the subject is a human subject.
9. The method of claim 8 , wherein the human subject is infected, suspected of being infected, or at risk for infection by an influenza A virus.
10. The method of claim 9 , wherein the influenza A virus is an H1N1 or H5N1 influenza A virus.
11. The method of claim 7 , wherein the immunogenic composition is administered to the subject via a route selected from the group consisting of oral administration, enteral administration, nasal administration, topical administration, and transmucosal administration.
12. The method of claim 7 , wherein the immunogenic composition is administered to the subject parenterally.