Enhanced Immune Response Against Influenza Virus by Priming with a DNA-based Vaccine

Available for licensing and commercial development are compositions and methods for enhancing an immune response to influenza viruses by priming with DNA-based vaccines encoding influenza proteins. The priming compositions contain DNA constructs with inserted nucleic acids encoding influenza virus hemagglutinin (HA) or an epitope-bearing domain thereof, while the boosting compositions are inactivated influenza vaccines. The DNA constructs are based on proprietary expression systems that increase protein expression relative to commonly used alternatives.

A potential influenza pandemic caused by H5N1 strains of avian influenza virus (bird flu) is a major global concern. The seasonal influenza caused by other subtypes of influenza is also a cause of concern. Vaccination is one of the most effective ways to minimize suffering and death from influenza. However, influenza vaccination does not reduce the risk of community-acquired pneumonia in elderly nor does it decrease the rate of influenza infection in children aged 6-23 months. Strategies to elicit protective immunity with greater potency and breadth therefore remain a priority. The present invention discloses the ability of gene-based priming with influenza hemagglutinin (HA) to prime for an increase in titer and cross-reactivity of the neutralizing antibody response after inactivated influenza virus vaccine boost. After priming with a DNA vaccine encoding HA from a H1N1 strain, boosting with a seasonal influenza vaccine containing this inactivated virus stimulated a 100-fold increase in the titer of H1 neutralizing antibodies. Of note, this combination immunization, in contrast to either component alone, elicited heterotypic neutralizing antibodies against a H5N1 strain. Similar priming was also observed with a DNA vaccine encoding an HA from a H5N1 strain, with the H5N1 subvirion vaccine boost. These results show that gene-based priming prior to vaccinating with the traditional influenza vaccine boost induced humoral immunity against different subtypes of influenza viruses that increases the potency and breadth of the neutralizing antibody response.