Polyclonal epitope mapping reveals temporal dynamics and diversity of human antibody responses to H5N1 vaccination

Julianna Han, Aaron J. Schmitz, Sara T. Richey, Ya Nan Dai, Hannah L. Turner, Bassem M. Mohammed, Daved H. Fremont, Ali H. Ellebedy, Andrew B. Ward

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Novel influenza A virus (IAV) strains elicit recall immune responses to conserved epitopes, making them favorable antigenic choices for universal influenza virus vaccines. Evaluating these immunogens requires a thorough understanding of the antigenic sites targeted by the polyclonal antibody (pAb) response, which single-particle electron microscopy (EM) can sensitively detect. In this study, we employ EM polyclonal epitope mapping (EMPEM) to extensively characterize the pAb response to hemagglutinin (HA) after H5N1 immunization in humans. Cross-reactive pAbs originating from memory B cells immediately bound the stem of HA and persisted for more than a year after vaccination. In contrast, de novo pAb responses to multiple sites on the head of HA, targeting previously determined key neutralizing sites on H5 HA, expanded after the second immunization and waned quickly. Thus, EMPEM provides a robust tool for comprehensively tracking the specificity and durability of immune responses elicited by novel universal influenza vaccine candidates.

Original languageEnglish
Article number108682
JournalCell Reports
Volume34
Issue number4
DOIs
StatePublished - Jan 26 2021

Keywords

  • EMPEM
  • H5N1
  • electron microscopy
  • epitope
  • hemagglutinin
  • influenza virus
  • monoclonal antibody
  • polyclonal antibody

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