CTA1‐3M2e‐DD; a universal influenza vaccine

Abstract

At present no vaccine against potentially pandemic influenza A virus infections exists. In the present study we provide compelling evidence that a targeted fusion protein based on the CTA1‐DD adjuvant and containing tandem repeats of the conserved M2e ectodomain epitope, CTA1‐3M2e‐DD, confers strong protective immunity against a lethal challenge infection with influenza A virus in mice. Intranasally immunized mice survived the challenge and showed a dramatic reduction in lung viral load and less morbidity, as assessed by loss of body weight and temperature decrease. The adjuvant component was highly effective for mucosal immunizations and readily promoted specific serum IgG1 and IgG2a as well as mucosal IgA antibody levels. Importantly, we found a hitherto unknown MHC class II restricted T cell epitope in the M2e peptide, resulting in strong anti‐M2e IFNg T cell responses, which may have significant impact on the efficacy of this universal anti‐influenza A virus vaccine. The CTA1‐3M2e‐DD stimulated stronger responses than the single CTA1‐M2e‐DD construct and comparable responses to a preparation of M2e‐virus like particles based on Hepatitis B virus core subunits. Taken together, CTA1‐3M2e‐DD combines a molecular adjuvant, a universal influenza A vaccine antigen and a targeting domain into a single recombinant protein.