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Sci Rep. 2019 Mar 5;9(1):3492. doi: 10.1038/s41598-019-40175-8.

Autoreactivity profiles of influenza hemagglutinin broadly neutralizing antibodies.

Author information

1
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA.
2
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA.
3
Department of Immunology, Duke University, Durham, North Carolina, 27710, USA.
4
Department of Microbiology, Harvard Medical School, Boston, Massachusetts, 02115, USA.
5
Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, 02139, USA.
6
Duke Human Vaccine Institute, Duke University, Durham, North Carolina, 27710, USA.
7
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA. harrison@crystal.harvard.edu.
8
Howard Hughes Medical Institute, Boston, Massachusetts, 02115, USA. harrison@crystal.harvard.edu.

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.

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