vaxfectin and Orthomyxoviridae-Infections

Mice were immunized either with unadjuvanted seasonal trivalent influenza vaccine (TIV) or TIV formulated with Vaxfectin, a cationic lipid-based adjuvant. Increasing doses of Vaxfectin resulted in increased hemagglutination-inhibition or anti-TIV ELISA antibody titers, with up to a 200-fold increase obtained with 900 microg of Vaxfectin. A >or=10-fold dose-sparing effect was demonstrated with Vaxfectin formulations. Vaxfectin preferentially increased IgG2 titers compared to IgG1 titers, resulting in a balanced IgG isotype distribution. Lower doses of Vaxfectin (30 microg) did not enhance antibody responses, but increased the number of IFN-gamma secreting T-cells by up to 18-fold. The data demonstrate that Vaxfectin enhances Th1 responses with protein-based seasonal influenza vaccine, and suggest that cellular or humoral immune responses may be preferentially induced by modifying the Vaxfectin:antigen ratio in the vaccine formulation.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Viral; Antibody Formation; Antigens, Viral; Cations; Cells, Cultured; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Hemagglutination Inhibition Tests; Immunity, Cellular; Immunity, Humoral; Immunoglobulin G; Influenza Vaccines; Interferon-gamma; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Orthomyxoviridae Infections; Phosphatidylethanolamines; Spleen; Th1 Cells

Plasmid DNA (pDNA) vaccines represent an alternative to conventional inactivated influenza vaccines that are likely to experience supply constraints during a pandemic. Several Vaxfectin-formulated pDNA vaccines were tested in mice and ferrets for efficacy against a lethal challenge with the highly pathogenic A/Vietnam/1203/04 (H5N1) influenza virus strain; the vaccines encoded influenza A virus hemagglutinin (HA), and/or nucleoprotein (NP), and M2 protein. Complete protection from death and disease was achieved in mice and ferrets with 2 doses of a Vaxfectin-formulated vaccine containing H5 HA, NP, and M2 plasmids and in ferrets with only 1 dose. A Vaxfectin-formulated vaccine containing NP and M2 pDNA provided significant protection against death in mice and provided some benefit in ferrets (i.e., 17% survival, delayed time to illness and death, and significant reduction in viral load compared with that in negative control animals). These experiments support the clinical testing of pDNA vaccine candidates that may ultimately increase global vaccine supply options during pandemics.

Topics: Animals; Antibodies, Viral; Body Weight; Chemistry, Pharmaceutical; Ferrets; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Mice; Mice, Inbred BALB C; Nasal Lavage Fluid; Orthomyxoviridae Infections; Phosphatidylethanolamines; Plasmids; Time Factors; Vaccines, DNA