title: CAF01 potentiates immune responses and efficacy of an inactivated influenza vaccine in ferrets.
abstract: Trivalent inactivated vaccines (TIV) against influenza are given to 350 million people every year. Most of these are non-adjuvanted vaccines whose immunogenicity and protective efficacy are considered suboptimal. Commercially available non-adjuvanted TIV are known to elicit mainly a humoral immune response, whereas the induction of cell-mediated immune responses is negligible. Recently, a cationic liposomal adjuvant (dimethyldioctadecylammonium/trehalose 6,6'-dibehenate, CAF01) was developed. CAF01 has proven to enhance both humoral and cell-mediated immune responses to a number of different experimental vaccine candidates. In this study, we compared the immune responses in ferrets to a commercially available TIV with the responses to the same vaccine mixed with the CAF01 adjuvant. Two recently circulating H1N1 viruses were used as challenge to test the vaccine efficacy. CAF01 improved the immunogenicity of the vaccine, with increased influenza-specific IgA and IgG levels. Additionally, CAF01 promoted cellular-mediated immunity as indicated by interferon-gamma expressing lymphocytes, measured by flow cytometry. CAF01 also enhanced the protection conferred by the vaccine by reducing the viral load measured in nasal washes by RT-PCR. Finally, CAF01 allowed for dose-reduction and led to higher levels of protection compared to TIV adjuvanted with a squalene emulsion. The data obtained in this human-relevant challenge model supports the potential of CAF01 in future influenza vaccines.
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Cyril Jean-Marie
authors.initials: CJ
authors.lastname: Martel
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Julie Juul
authors.initials: JJ
authors.lastname: Poulsen
authors.forename: Trine
authors.initials: T
authors.lastname: Hammer Jensen
authors.forename: Lars
authors.initials: L
authors.lastname: Andresen
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.forename: Lars Peter
authors.initials: LP
authors.lastname: Nielsen
authors.forename: Merete
authors.initials: M
authors.lastname: Blixenkrone-Møller
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Bent
authors.initials: B
authors.lastname: Aasted
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D005260:Female; D005289:Ferrets; D007110:Immunity, Active / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D008081:Liposomes / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; D008081:Liposomes; D015164:Vaccines, Inactivated