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-alpha, IL-6, IL-1beta 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.
Bodewes
R
R
Department of Virology, Erasmus Medical Center, Dr. Molewaterplein 50, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Geelhoed-Mieras
M M
MM
Heldens
J G M
JG
Glover
J
J
Lambrecht
B N
BN
Fouchier
R A M
RA
Osterhaus
A D M E
AD
Rimmelzwaan
G F
GF
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D007252:Influenza Vaccines