A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies

Abstract

Influenza viruses evade human adaptive immune responses due to continuing antigenic changes. This makes it necessary to re-formulate and re-administer current seasonal influenza vaccines on an annual basis. Our pan-influenza vaccination approach attempts to redirect antibody responses from the variable, immuno-dominant hemagglutinin head towards the conserved—but immuno-subdominant—hemagglutinin stalk. The strategy utilizes sequential immunization with chimeric hemagglutinin-based vaccines expressing exotic head domains, and a conserved hemagglutinin stalk. We compared a live-attenuated influenza virus prime followed by an inactivated split-virus boost to two doses of split-virus vaccines and assessed the impact of adjuvant on protection against challenge with pandemic H1N1 virus in ferrets. All tested immunization regimens successfully induced broadly cross-reactive antibody responses. The combined live-attenuated/split virus vaccination conferred superior protection against pandemic H1N1 infection compared to two doses of split-virus vaccination. Our data support advancement of this chimeric hemagglutinin-based vaccine approach to clinical trials in humans.

Influenza: Defending against a common enemy

A vaccine against influenza targets non-varying parts of surface proteins to overcome the virus’ attempt at evading detection. Influenza viruses possess rapidly shifting surface proteins, effectively camouflaging themselves. These changes are making it difficult for vaccines to elicit reliable antibody responses against the threat. A team of researchers led by Florian Krammer and Randy A. Albrecht, of the United States’ Icahn School of Medicine at Mount Sinai, now describes a vaccine regimen that repeatedly targets a conserved component of the virus’ surface, prompting a broadly protective immune response. The conserved domains of the viral surface proteins are traditionally a more difficult target for vaccines as the immune systems of vaccinees have a preference for the varying domains. The team’s data, generated from ferret experiments, supports an investigation into the efficacy of this approach in humans.