Cross-lineage protection by human antibodies binding the influenza B hemagglutinin

Yi Liu,Stephen J Kent,Hyon-Xhi Tan,Robyn Esterbauer,Sinthujan Jegaskanda,Malet Aban,Adam K Wheatley,Marios Koutsakos,Katherine Kedzierska,Danielle Tilmanis,Aeron C Hurt

doi:10.1038/s41467-018-08165-y

Abstract

Influenza B viruses (IBV) drive a significant proportion of influenza-related hospitalisations yet are understudied compared to influenza A. Current vaccines target the head of the viral hemagglutinin (HA) which undergoes rapid mutation, significantly reducing vaccine effectiveness. Improved vaccines to control IBV are needed. Here we developed novel IBV HA probes to interrogate humoral responses to IBV in humans. A significant proportion of IBV HA-specific B cells recognise both B/Victoria/2/87-like and B/Yamagata/16/88-like lineages in a distinct pattern of cross-reactivity. Monoclonal antibodies (mAbs) were reconstituted from IBV HA-specific B cells, including mAbs providing broad protection in murine models of lethal IBV infection. Protection was mediated by neutralising antibodies targeting the receptor binding domain, or via Fc-mediated functions of non-neutralising antibodies binding alternative epitopes including the IBV HA stem. This work defines antigenic cross-recognition between IBV lineages and provides guidance for the rational design of improved IBV vaccines for broad and durable protection.

Highlights

Influenza B viruses (IBV) drive a significant proportion of influenza-related hospitalisations yet are understudied compared to influenza A
Unlike influenza A viruses (IAV) where hemagglutination inhibition assay (HIA)+ antibodies are usually highly strain specific, we found anti-IBV Monoclonal antibodies (mAbs) elicited by seasonal vaccines generally recognised all strains tested within a respective IBV antigenic lineage spanning over 20 years of antigenic drift
IBV infections make up a significant proportion of the global influenza burden[1], with health authorities recommending simultaneous immunisation with both IBV lineages to combat increasing IBV diversity and minimise the chances of seasonal vaccine mismatch

Summary

Introduction

Influenza B viruses (IBV) drive a significant proportion of influenza-related hospitalisations yet are understudied compared to influenza A. Monoclonal antibodies (mAbs) were reconstituted from IBV HA-specific B cells, including mAbs providing broad protection in murine models of lethal IBV infection. This work defines antigenic crossrecognition between IBV lineages and provides guidance for the rational design of improved IBV vaccines for broad and durable protection. Two types of influenza viruses co-circulate in human populations, influenza A viruses (IAV) and influenza B viruses (IBV). Both IAV and IBV are formulated into current seasonal influenza vaccines. Vaccine effectiveness of seasonal influenza vaccines against IBV can often remain low even when antigenic match with circulating strains is good[11,12]. There remains a need for improved next-generation IBV vaccines to provide resilient and durable protection against a broad array of IBV strains

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Conclusion