Induction of neutralizing antibodies to influenza A virus H7N9 by inactivated whole virus in mice and nonhuman primates

• The immunogenicity of hemagglutinin (HA) of newly emerged influenza A virus H7N9 need to be known.
• Inactivated whole-virion containing HA and NA of H7N9 in the PR8 background was evaluated.
• Antibody titers were assessed in different doses of HA alone, or with alum, and/or with a booster.
• Immunization could produce neutralizing antibodies in mice and rhesus macaques.
• Mice received sera from immunized animals could be protected from lethal challenge of H7N9 virus.

We evaluated the immunogenicity of hemagglutinin (HA) in the context of inactivated H7N9/AH/1/13-PR8 whole-virion. At 4 weeks after immunization with 15 μg HA, mice produced hemagglutination inhibition (HI) titers of 1:192 and neutralizing antibodies of 1:317. Aluminum hydroxide (alum), or a booster immunization, or both increased HI to 1:768, 1:384, 1:896 and neutralizing antibodies to 1:1868, 1:2302, 1:10,000, respectively. Macaques generated HI of 1:190 or 1:360 and virus neutralizing titers of 1:280 or 1:658 at 3 weeks after immunization with HA alone or with alum. Sera from immunized mice and macaques protected mice from infection of A/Anhui/1/2013 (H7N9), suggesting an H7N9 vaccine is immunologically feasible.