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

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

doi:10.1038/s41467-018-08165-y

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

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

Melbourne Sexual Health Centre

Research output: Contribution to journal › Article › Research › peer-review

36 Citations (Scopus)

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.

Original language	English
Article number	324
Number of pages	13
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-08165-y
Publication status	Published - 1 Dec 2019

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/s41467-018-08165-yLicence: CC BY

262177986-oaFinal published version, 1.3 MBLicence: CC BY

Cite this

@article{2b6ed4d7ccc14455834cf49d851cb5b6,

title = "Cross-lineage protection by human antibodies binding the influenza B hemagglutinin",

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.",

author = "Yi Liu and Tan, {Hyon Xhi} and Marios Koutsakos and Sinthujan Jegaskanda and Robyn Esterbauer and Danielle Tilmanis and Malet Aban and Katherine Kedzierska and Hurt, {Aeron C.} and Kent, {Stephen J.} and Wheatley, {Adam K.}",

year = "2019",

month = dec,

day = "1",

doi = "10.1038/s41467-018-08165-y",

language = "English",

volume = "10",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Cross-lineage protection by human antibodies binding the influenza B hemagglutinin. / Liu, Yi; Tan, Hyon Xhi; Koutsakos, Marios; Jegaskanda, Sinthujan; Esterbauer, Robyn; Tilmanis, Danielle; Aban, Malet; Kedzierska, Katherine; Hurt, Aeron C.; Kent, Stephen J.; Wheatley, Adam K.

In: Nature Communications, Vol. 10, No. 1, 324, 01.12.2019.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Cross-lineage protection by human antibodies binding the influenza B hemagglutinin

AU - Liu, Yi

AU - Tan, Hyon Xhi

AU - Koutsakos, Marios

AU - Jegaskanda, Sinthujan

AU - Esterbauer, Robyn

AU - Tilmanis, Danielle

AU - Aban, Malet

AU - Kedzierska, Katherine

AU - Hurt, Aeron C.

AU - Kent, Stephen J.

AU - Wheatley, Adam K.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85060156548&partnerID=8YFLogxK

U2 - 10.1038/s41467-018-08165-y

DO - 10.1038/s41467-018-08165-y

M3 - Article

C2 - 30659197

AN - SCOPUS:85060156548

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 324

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

HIV latency, pathogenesis and immunity

Cite this

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

Abstract

UN SDGs

Access to Document

Other files and links

Projects

HIV latency, pathogenesis and immunity

Cite this