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 | |
| Publication status | Published - 1 Dec 2019 |
Cite this
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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
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 324
ER -