Abstract
Broadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection1. However, viral mutants that escape broadly neutralizing antibodies have been reported2,3. The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine4,5, which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool.
Highlights
This is a PDF file of a peer-reviewed paper that has been accepted for publication
Discovery of anchor epitope binding monoclonal antibodies (mAbs) To investigate the specificities of HA-specific antibodies, we generated 358 mAbs from plasmablasts and HA+ memory B cells (MBCs) isolated from volunteers that were vaccinated against or naturally infected with seasonal influenza viruses or were participants in a phase 1 clinical trial of chimeric HA (cHA) vaccine[4,5]
Demic H1N1 monovalent inactivated influenza vaccine (MIV), While A373 is distant from the anchor epitope, the A373V mutation was and cHA vaccine cohorts (Extended Data Fig. 1b), as these exposure shown to affect the conformation of the HA stalk[2], explaining the broad routes have previously been shown to induce antibody responses reduction of HA binding by antibodies targeting either stalk epitope
Summary
The content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. PR Broadly neutralizing antibodies (bnAbs) targeting epitopes of the influenza virus hemagglutinin (HA) have the potential to provide near universal protection against influenza virus infection[1]. The identification of bnAb classes that can neutralize viral escape mutants L is critical for universal influenza virus vaccine design. We report a distinct class of bnAbs targeting a discrete membrane-proximal anchor epitope of the HA stalk. Antibodies T targeting this anchor epitope utilize a highly restricted repertoire, which encodes for two public binding motifs that make extensive contacts with conserved residues in. Anchor epitope-targeting B cells are common in the A human memory B cell (MBC) repertoire and were recalled in humans by an oil-in-water
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