Universal influenza vaccine
Immunogenic compositions for inducing a universal immune response to influenza, and particularly influenza A, by eliciting anti-neuraminidase antibodies which provide protection against heterologous influenza infection. Compositions comprising recombinant baculovirus expression vectors expressing neuraminidase in cultured insect cells dispersed in a pharmaceutically-acceptable carrier comprising insect cell culture media, and optional adjuvant. Methods of inducing immune responses against influenza, and particularly influenza A, by eliciting anti-neuraminidase antibodies in a host animal susceptible to infection.
1. An immunogenic composition for inducing an immune response that mitigates clinical disease in swine from influenza after administration, said composition comprising recombinant baculovirus expression vectors in cultured insect cells dispersed in a pharmaceutically-acceptable carrier comprising insect cell culture media, optional adjuvant, said recombinant baculovirus expression vectors expressing a therapeutically effective amount of neuraminidase, said neuraminidase being associated with the cell membrane of said insect cells and/or baculovirus viral membrane surfaces in said composition and presented on the surfaces of said membranes.
2. The immunogenic composition of claim 1 , wherein said clinical disease is lung damage or lung lesions in said swine.
3. The immunogenic composition of claim 2 , wherein said lung damage or lung lesions are reduced in said swine.
4. The immunogenic composition of claim 1 , wherein said clinical disease is reduced as measured by reduction in influenza viral titer in swine lung tissue.
5. The immunogenic composition of claim 1 , wherein said swine is less than 8 weeks of age.
6. The immunogenic composition of claim 1 , said recombinant baculovirus expression vectors expressing native, full-length neuraminidase protein.
7. The immunogenic composition of claim 1 , said recombinant baculovirus expression vectors expressing neuraminidase derived from sequences of H1N1, H3N1, H1N2, H3N2, H5N1, H5N2, H3N8, and/or H3N2.
8. The immunogenic composition of claim 1 , said composition comprising a first set of recombinant baculovirus expression vectors expressing neuraminidase subtype 1 and a second set of recombinant baculovirus expression vectors expressing neuraminidase subtype 2.
9. The immunogenic composition of claim 1 , wherein the influenza antigenic components in said composition consists of influenza neuraminidase-type proteins.
10. The immunogenic composition of claim 1 , wherein said composition is chemically inactivated.
11. The immunogenic composition of claim 1 , wherein said composition is unpurified.
12. The immunogenic composition of claim 1 , wherein said insect cells are Spodoptera frugiperda cells, Trichoplusia ni cells, Bombyx mori cells, or a cell line derived therefrom.
13. The immunogenic composition of claim 1 , wherein said cell culture medium is serum free culture medium.
14. The immunogenic composition of claim 1 , said pharmaceutically-acceptable carrier further comprising phosphate buffered saline.
15. The immunogenic composition of claim 1 , in unit dosage form.
16. The immunogenic composition of claim 1 , said composition being substantially free of influenza hemagglutinin.
17. The immunogenic composition of claim 1 , said composition being substantially free of one or more of matrix proteins M1 or M2, RNA polymerase subunits PB1, PB2, and PA, nucleoprotein NP, nonstructural proteins NS1 or NS2, or associated virus like particles.
18. A kit for stimulating a universal immune response in swine against influenza infection, said kit comprising:
an immunogenic composition according to claim 1 ; and
instructions for administering said composition to a host swine animal susceptible to influenza.
19. A method of stimulating an immune response in swine that mitigates clinical disease from influenza infection, said method comprising administering an effective amount of an immunogenic composition according to claim 1 to swine less than 8 weeks of age, wherein maternal antibodies in said swine do not interfere with said immunogenic composition or immune response.
20. The method of claim 19 , wherein said immune response mitigates clinical disease from homologous or heterologous influenza infection in said swine.
21. The method of claim 19 , wherein said clinical disease is lung damage or lung lesions in said swine.
22. The method of claim 21 , wherein said lung damage or lung lesions are reduced in said swine.
23. The method of claim 19 , wherein said clinical disease is reduced as measured by reduction in influenza viral titer in lung tissue of said swine.
24. The method of claim 19 wherein said effective amount comprises a therapeutically effective amount of neuraminidase expressed in said composition.
25. The method of claim 19 , said composition being administered intramuscularly, subcutaneously, intradermally, intravenously, or mucosally.
26. The method of claim 19 , said immune response comprising production or activation of antibodies, B cells and/or T cells, directed specifically to neuraminidase in said host animal.
27. The method of claim 19 , said immune response comprising production or activation of antibodies, B cells and/or T cells, directed to both neuraminidase subtype 1 and subtype 2 in said host animal.
28. The method of claim 19 , wherein said immunogenic composition provides a protective immune response in said host animal against H1N1, H3N1, H1N2, H3N2, H5N1, H5N2, H3N8, and/or H3N2.