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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)980-987
Number of pages8
JournalNature Structural and Molecular Biology
Volume26
Issue number10
DOIs
StatePublished - Oct 1 2019

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Hendra Virus
Nipah Virus
Virus Diseases
Henipavirus
Glycoproteins
Antibodies
Implosive Therapy
Cryoelectron Microscopy
Virus Internalization
Zoonoses
Encephalitis
Humoral Immunity
Disease Outbreaks
Epitopes
Vaccines
Monoclonal Antibodies
Membranes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Dang, H. V., Chan, Y. P., Park, Y. J., Snijder, J., Da Silva, S. C., Vu, B., ... Veesler, D. (2019). An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. Nature Structural and Molecular Biology, 26(10), 980-987. https://doi.org/10.1038/s41594-019-0308-9

An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. / Dang, Ha V.; Chan, Yee Peng; Park, Young Jun; Snijder, Joost; Da Silva, Sofia Cheliout; Vu, Bang; Yan, Lianying; Feng, Yan Ru; Rockx, Barry; Geisbert, Thomas W.; Mire, Chad E.; Broder, Christopher C.; Veesler, David.

In: Nature Structural and Molecular Biology, Vol. 26, No. 10, 01.10.2019, p. 980-987.

Research output: Contribution to journalArticle

Dang, HV, Chan, YP, Park, YJ, Snijder, J, Da Silva, SC, Vu, B, Yan, L, Feng, YR, Rockx, B, Geisbert, TW, Mire, CE, Broder, CC & Veesler, D 2019, 'An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections', Nature Structural and Molecular Biology, vol. 26, no. 10, pp. 980-987. https://doi.org/10.1038/s41594-019-0308-9
Dang, Ha V. ; Chan, Yee Peng ; Park, Young Jun ; Snijder, Joost ; Da Silva, Sofia Cheliout ; Vu, Bang ; Yan, Lianying ; Feng, Yan Ru ; Rockx, Barry ; Geisbert, Thomas W. ; Mire, Chad E. ; Broder, Christopher C. ; Veesler, David. / An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections. In: Nature Structural and Molecular Biology. 2019 ; Vol. 26, No. 10. pp. 980-987.
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