An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections

Ha V. Dang; Yee Peng Chan; Young Jun Park; Joost Snijder; Sofia Cheliout Da Silva; Bang Vu; Lianying Yan; Yan Ru Feng; Barry Rockx; Thomas W. Geisbert; Chad E. Mire; Christopher C. Broder; David Veesler

doi:10.1038/s41594-019-0308-9

An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections

Ha V. Dang, Yee Peng Chan, Young Jun Park, Joost Snijder, Sofia Cheliout Da Silva, Bang Vu, Lianying Yan, Yan Ru Feng, Barry Rockx, Thomas W. Geisbert, Chad E. Mire, Christopher C. Broder, David Veesler

Microbiology And Immunology

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

58 Scopus citations

Abstract

Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.

Original language	English (US)
Pages (from-to)	980-987
Number of pages	8
Journal	Nature Structural and Molecular Biology
Volume	26
Issue number	10
DOIs	https://doi.org/10.1038/s41594-019-0308-9
State	Published - Oct 1 2019

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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title = "An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections",

abstract = "Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.",

author = "Dang, {Ha V.} and Chan, {Yee Peng} and Park, {Young Jun} and Joost Snijder and {Da Silva}, {Sofia Cheliout} and Bang Vu and Lianying Yan and Feng, {Yan Ru} and Barry Rockx and Geisbert, {Thomas W.} and Mire, {Chad E.} and Broder, {Christopher C.} and David Veesler",

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AU - Dang, Ha V.

AU - Chan, Yee Peng

AU - Park, Young Jun

AU - Snijder, Joost

AU - Da Silva, Sofia Cheliout

AU - Vu, Bang

AU - Yan, Lianying

AU - Feng, Yan Ru

AU - Rockx, Barry

AU - Geisbert, Thomas W.

AU - Mire, Chad E.

AU - Broder, Christopher C.

AU - Veesler, David

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.

AB - Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50–100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.

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An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections

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