The novel adjuvant CoVaccineHT (TM) 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 (TM) 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 (TM) and virusspecific antibody and cellular immune responses were assessed. The addition of CoVaccineHT (TM) 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 (TM)-adjuvanted vaccine correlated with the magnitude of the virus-specific CD4+ T helper cell responses. CoVaccineHT (TM) did not have an effect on the magnitude of the CD8+ T cell response. In vitro, CoVaccineHT (TM) upregulated the expression of co-stimulatory molecules both on mouse and human dendritic cells and induced the secretion of pro-inflammatory cytokines TNF-alpha, IL-6, IL-1 beta and IL-12p70 in mouse- and IL-6 in human dendritic cells. Inhibition experiments indicated that the effect of CoVaccineHT (TM) is mediated through TLR4 signaling. These data suggest that CoVaccineHT (TM) also will increase the immunogenicity of an influenza A/H5N1 vaccine in humans. (C) 2009 Elsevier Ltd. All rights reserved.