Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses

Nicholas C. Wu, Andrew J. Thompson, Juhye M. Lee, Wen Su, Britni M. Arlian, Jia Xie, Richard A. Lerner, Hui Ling Yen, Jesse D. Bloom, Ian A. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

The discovery and characterization of broadly neutralizing human antibodies (bnAbs) to the highly conserved stem region of influenza hemagglutinin (HA) have contributed to considerations of a universal influenza vaccine. However, the potential for resistance to stem bnAbs also needs to be more thoroughly evaluated. Using deep mutational scanning, with a focus on epitope residues, we found that the genetic barrier to resistance to stem bnAbs is low for the H3 subtype but substantially higher for the H1 subtype owing to structural differences in the HA stem. Several strong resistance mutations in H3 can be observed in naturally circulating strains and do not reduce in vitro viral fitness and in vivo pathogenicity. This study highlights a potential challenge for development of a truly universal influenza vaccine.

Original languageEnglish (US)
Pages (from-to)1335-1340
Number of pages6
JournalScience
Volume368
Issue number6497
DOIs
StatePublished - Jun 19 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

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