An HLAII-targeted DNA vaccine against influenza H7N9 protected mice and ferrets from a virus challenge

TL;DR

A DNA vaccine targeting HLAII molecules showed protection against influenza H7N9 in mice and ferrets, suggesting potential for human use.

Contribution

A novel DNA vaccine design that targets HLAII molecules for enhanced immune response against influenza.

Findings

Vaccinated mice showed robust neutralizing antibodies and protection against H7N1.

Ferrets developed neutralizing antibodies and T-cell responses after vaccination.

High-dose vaccination in ferrets provided complete protection from H7N9 clinical disease.

Abstract

Due to antigenic drift and shift, influenza A viruses may cause new future pandemics. Currently used seasonal influenza vaccines are of little use against novel viruses with pandemic potential. Genetic vaccines can be rapidly produced and could therefore mitigate pandemic outbreaks. Here, we present preclinical proof of protective efficacy of a DNA vaccine encoding a vaccine protein that targets influenza hemagglutinin (HA) to human leukocyte antigen class II (HLAII) molecules on antigen presenting cells (APC). Vaccination of mice raised robust levels of neutralizing antibodies, and protection against a lethal challenge with influenza H7N1 virus. In ferrets, we observed induction of neutralizing antibodies and T-cell responses after a single vaccination, with levels increasing after a second dose. Protection of vaccinated ferrets against a viral challenge with influenza H7N9 was dose dependent, with ferrets receiving the highest vaccine dose being completely protected from clinical disease. In sum, these results warrant progression to a human clinical Phase I trial.

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