Induction of cross‐group broadly reactive antibody response by natural H7N9 avian influenza virus infection and immunization with inactivated H7N9 vaccine in chickens

Pre‐existing immunity against the conserved haemagglutinin (HA) stalk underlies the elicitation of cross‐group antibody induced by natural H7N9 virus infection and immunization in humans. However, whether broadly reactive antibodies can be induced by H7N9 infection and immunization in the absence of pre‐existing stalk‐specific immunity is unclear. In this study, antibody response induced by H7N9 virus infection and immunization with inactivated and viral‐vectored H7N9 vaccines in naïve chickens was analysed. The results showed that H7N9 infection and immunization with inactivated vaccine resulted in potent induction of haemagglutination‐inhibition (HI), virus neutralization (VN) and HA‐binding antibodies, whereas Newcastle disease virus (NDV)‐vectored H7N9 vaccine induced marginal HI and VN titres but high levels of HA‐binding antibody. In addition, H7N9 infection and immunization induced stalk‐specific antibodies in naïve chickens and these antibodies recognized different epitopes in the stalk. Virus infection and immunization with inactivated vaccine elicited antibodies cross‐reactive with both group 1 and group 2 HAs, while antibodies induced by NDV‐H7N9 vaccination showed a narrower cross‐reactivity within group 2. Moreover, only homologous neutralizing activity of the sera against H7N9 virus was observed, and cross‐binding antibodies did not show heterosubtypic neutralizing activity. Our results indicated that cross‐group binding but non‐neutralizing antibodies primarily targeting the stalk can be induced by natural H7N9 infection and immunization with inactivated vaccine in naïve chickens. This suggests that at least in a naïve chicken model, pre‐existing stalk‐specific immunity is not required for induction of broadly reactive antibodies. Additionally, H7N9‐based immunogens may be explored as vaccine candidates or as a prime component to induce broadly protective influenza immunity.