Induction of broadly cross-reactive stalk-specific antibody responses to influenza group 1 and group 2 hemagglutinins by natural H7N9 virus infection in humans

Lu Liu, Raffael Nachbagauer, Lingyan Zhu, Yang Huang, Xinci Xie, Shan Jin, Anli Zhang, Yanmin Wan, Ariana Hirsh, Di Tian, Xiaolin Shi, Zhaoguang Dong, Songhua Yuan, Yunwen Hu, Florian Krammer, Xiaoyan Zhang, Jianqing Xu

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background. The outbreak of novel avian H7N9 influenza virus infections in China in 2013 has demonstrated the continuing threat posed by zoonotic pathogens. Deciphering the immune response during natural infection will guide future 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 enzyme-linked immunosorbent assay, and novel chimeric hemagglutinin constructs were used to dissect the anti-stalk or -head humoral immune response. Results. H7N9 infection induced strong antibody responses against divergent H7 hemagglutinins. Interestingly, we also found induction of antibodies against heterosubtypic hemagglutinins from both group 1 and group 2 and a boost in heterosubtypic neutralizing activity in the absence of hemagglutination inhibitory activity. Kinetic monitoring revealed that heterosubtypic binding/neutralizing antibody responses typically appeared and peaked earlier than intrasubtypic responses, likely mediated by memory recall responses. Conclusions. Our results indicate that cross-group binding and neutralizing antibody responses primarily targeting the stalk region can be elicited after natural influenza virus infection. These data support our understanding of the breadth of the postinfection immune response that could inform the design of future, broadly protective influenza virus vaccines.

Original languageEnglish (US)
Pages (from-to)518-528
Number of pages11
JournalJournal of Infectious Diseases
Volume215
Issue number4
DOIs
StatePublished - Feb 15 2017
Externally publishedYes

Keywords

  • cross-reactive antibody
  • H7N9
  • influenza
  • stalk-reactive
  • universal influenza vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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