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

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

Posted 17 Jun 2020
bioRxiv DOI: 10.1101/2020.06.16.155754

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. Here, we employed 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 over a year post vaccination. In contrast, de novo pAb responses to multiple sites on the head of HA, which targeted 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. ### Competing Interest Statement A.H.E. is a consultant for InBios and Fimbrion Therapeutics. The Ellebedy laboratory received funding under sponsored research agreements from Emergent BioSolutions. All other authors declare no competing interests.

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