We will produce, safety test and determine the immunogenicity of (1) tissue culture and egg grown inactivated influenza vaccine administered with or without an adjuvant (Novasomes), (2) tissue culture & egg grown live as well as formal in inactivated """"""""cold recombinant"""""""" avian x human influenza virus vaccines administered with or without an adjuvant, and (3) baculovirus expressed recombinant VLP subunit avian influenza virus vaccines administered with or without adjuvant or with alum. Initial studies to determine feasibility of these types of vaccines will be determined by measuring the immune response elicited in a rat model following intramuscular inoculation. Should these initial I.M. studies prove immunogenic, studies will proceed to compare all three routes of administration, ie., intranasal, intradermal/subcutaneous via a needless syringe and I.M.. lmmunogenicity to the vaccine will be determined by: hemagglutination inhibition assay, virus specific antibody ELISA, gamma interferon production, Cytotoxic T-cell response, and HA & neuraminidase specific antibody response; and comparing them to that obtained with egg grown influenza virus. The vaccine method(s) that produces a vaccine that elicits an immune response equal to or greater than that of the egg grown virus will be used to produce pilot lot(s) of the avian/human reassortant virus(es) (provided by sponsor, sponsor collaborator). The pilot lots of both live and inactivated vaccines will have been produced and safety tested in accordance with cGMP guidelines which would be suitable for use in a Phase I study. A Phase I study or submission for a IND is not part of this proposal.
| Pushko, Peter; Tumpey, Terrence M; Bu, Fang et al. (2005) Influenza virus-like particles comprised of the HA, NA, and M1 proteins of H9N2 influenza virus induce protective immune responses in BALB/c mice. Vaccine 23:5751-9 |
