Optimal designs of an HA-based DNA vaccine against H7 subtype influenza viruses

The outbreak of a novel H7N9 influenza virus in 2013 has raised serious concerns for the potential of another avian-source pandemic influenza. Effective vaccines against H7N9 virus are important in the prevention and control of any major outbreak. Novel vaccination technologies are useful additions to existing approaches. In the current report, DNA vaccine studies were conducted to identify the optimal design of an H7 HAHA antigen using the HAHA gene from a previously reported H7N7 virus that is lethal in humans as the model antigen. New Zealand White rabbits were immunized with DNA vaccines expressing 1 of 3 forms of H7 HAHA antigen inserts encoding the HAHA gene from the same H7N7 virus. High-level H7 HAHA-specific IgG was detected by ELISASA, and functional antibodies were confirmed by hemagglutination inhibition assay and pseudotyped virus-based neutralization assay against viruses expressing HAHA antigens from either the previous H7N7 virus or the novel H7N9 virus. HAHA antigen design under the tissue plasminogen activator leader (tPA) was the most immunogenic. The data presented in the current report confirm the immunogenicity of the H7 HAHA antigen and provide useful guidance to prepare for an optimized H7 HAHA DNA vaccine to help to control the emerging H7N9 virus if and when it is needed.