Autoreactivity profiles of influenza hemagglutinin broadly neutralizing antibodies

Goran Bajic, Cees E. van der Poel, Masayuki Kuraoka, Aaron G. Schmidt, Michael C. Carroll, Garnett Kelsoe, Stephen C. Harrison

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Epitope-focused approaches for selective clonal induction of broadly neutralizing antibodies (bnAbs) inform most current vaccine strategies for influenza virus and other rapidly evolving pathogens. The two conserved epitopes on the influenza hemagglutinin (HA) - the “stem” and the receptor-binding site (RBS) on the “head” - are the focus of the current “universal” influenza vaccine development efforts. Because stem-directed serum bnAbs are much less abundant than head-directed ones, we hypothesized that the HA stem bnAbs may be autoreactive and thus eliminated through the mechanisms of self-tolerance. We compared autoreactivity profiles of a set of stem and head-directed bnAbs. Most of the stem bnAbs we examined bound autoantigens; several showed staining of HEp-2 cells. A smaller proportion of the head-directed bnAbs were polyreactive. Gene usage did not correlate with autoreactivity. We suggest that complex foreign antigens may often have surface patches resembling some host epitope; our results indicate that HA stem epitopes resemble a host epitope more frequently than does the RBS.

Original languageEnglish
Article number3492
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019
Externally publishedYes

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