Natural H7N9 infection in humans boosts cross-group stalk-specific antibody responses broadly cross-reactive to heterosubtypic influenza hemagglutinins from both group 1 and group 2

Abstract

Abstract Background The outbreak of novel avian H7N9 influenza virus infections in China in 2013 has demonstrated the continuing threat posed by zoonotic pathogens. To decipher the responses during natural infection will enlighten the vaccine development. Methods We assessed the induction of heterosubtypic cross-reactive antibodies induced by H7N9 infection against a large panel of recombinant hemagglutinins and neuraminidases by quantitative ELISA, and novel chimeric hemagglutinin constructs were employed to dissect the anti-stalk or head humoral response. Results H7N9 infection induced strong antibody responses against divergent H7 hemagglutinins. Interestingly, we also found the induction of antibodies against heterosubtypic hemagglutinins from both group 1 and group 2 and a boost in heterosubtypic neutralizing activity but not in hemagglutination inhibitory activity. Kinetic monitoring revealed that heterosubtypic binding/neutralizing antibody responses typically appeared and peaked earlier than intrasubtypic responses as stalk-specific memory responses. Conclusions Our results indicate cross-group binding and neutralizing antibody responses primarily targeting at stalk region could be elicited after influenza natural infection and probably with proper immunogen in the presence of preexisting responses. These data support our understanding of the breadth of the post-infection immune response that could inform the design of future, broadly protective influenza virus vaccines.