Immunogenicity And Cross-reactivity Of Adenovirus-vectored H7Subtype Influenza Vaccines In Mice

Since the end of March2013, the outbreak of a novel avian-origin H7N9virus was recognized in eastern China. The H7N9virus has not been detected in humans before, the human immune system would not be able to defend the H7N9infection, vaccination is the most effective and sensible measure to protect people against virus infection and to restrain its spread when face with the highly pathogenic H7N9. In addition, previously research suggested that vaccines containing avian H7N7(A/Netherlands/219/03) influenza viruses are poorly immunogenic and only used by increasing the amount of antigen, combination with adjuvants or other methods can induce desired immune response. However, the immunogenicity of H7N9is almost unknown. Consider the replication-deficient adenoviral vectors able to generate robust immune response, and research have found that adenoviral vectors encoding H5N1subtype influenza hemagglutinin (HA) can successfully induce humoral responses, providing broadly protection against homologous and heterologous H5influenza strains. Therefore, in order to compared the immunogenicity between the adenoviral vaccine encoding H7-HA and inactivated virus vaccine, in this study we developed two adenovirus (Ad5)-based vaccine candidates named Ad5-NL and Ad5-AH which encoding the HA gene from A/Netherlands/219/03(H7N7) and A/AnHui/1/2013(H7N9) influenza virus, respectively; meanwhile, we constructed two inactivated whole virus vaccines H7/NL/219/2003-PR8(NL-PR8) and H7N9/AH/1/13-PR8(AH-PR8) by reverse genetics technology, then immunized the mice and detective the HI titers, MN titers and cross-reactivity against other H7strains. Our results show that the adenoviral vaccines can induce stronger hemagglutination inhibition antibody and neutralizing antibody when compared to those of inactivated whole-virus vaccines. Both adenoviral vaccine (Ad5-AH) and inactivated whole-virus vaccine (AH-PR8) can induce higher humoral immune response than Ad5-NL and NL-PR8. This suggested that the immunogenicity of H7N9novel virus hemagglutinin is higher than H7N7. Meanwhile, the cross-reactivity induced by Ad5-AH also higher than Ad5-NL groups. Taken together, our research analyzed the immunogenicity of novel H7N9influenza virus, and these finding may provide a new thinking for development of H7N9vaccines and explore the possibility of replication-defective adenoviral vector vaccine used as H7N9candidate vaccines.