The novel adjuvant CoVaccineHT™ increases the immunogenicity of cell-culture derived influenza A/H5N1 vaccine and induces the maturation of murine and human dendritic cells in vitro

A candidate influenza H5N1 vaccine based on cell-culture-derived whole inactivated virus and the novel adjuvant CoVaccineHT™ was evaluated in vitro and in vivo. To this end, mice were vaccinated with the whole inactivated influenza A/H5N1 virus vaccine with and without CoVaccineHT™ and virus-specific antibody and cellular immune responses were assessed. The addition of CoVaccineHT™ increased virus specific primary and secondary antibody responses against the homologous and an antigenically distinct heterologous influenza A/H5N1 strain. The superior antibody responses induced with the CoVaccineHT™-adjuvanted vaccine correlated with the magnitude of the virus-specific CD4+ T helper cell responses. CoVaccineHT™ did not have an effect on the magnitude of the CD8+ T cell response. In vitro, CoVaccineHT™ upregulated the expression of co-stimulatory molecules both on mouse and human dendritic cells and induced the secretion of pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IL-12p70 in mouse- and IL-6 in human dendritic cells. Inhibition experiments indicated that the effect of CoVaccineHT™ is mediated through TLR4 signaling. These data suggest that CoVaccineHT™ also will increase the immunogenicity of an influenza A/H5N1 vaccine in humans.