TY - JOUR
T1 - Broadly neutralizing antibody cocktails targeting Nipah virus and Hendra virus fusion glycoproteins
AU - Dang, Ha V.
AU - Cross, Robert W.
AU - Borisevich, Viktoriya
AU - Bornholdt, Zachary A.
AU - West, Brandyn R.
AU - Chan, Yee Peng
AU - Mire, Chad E.
AU - Da Silva, Sofia Cheliout
AU - Dimitrov, Antony S.
AU - Yan, Lianying
AU - Amaya, Moushimi
AU - Navaratnarajah, Chanakha K.
AU - Zeitlin, Larry
AU - Geisbert, Thomas W.
AU - Broder, Christopher C.
AU - Veesler, David
N1 - Funding Information:
This study was supported by the National Institute of Allergy and Infectious Diseases (grant nos. DP1AI158186 and HHSN272201700059C to D.V. and grant nos. AI054715, AI077995 and AI142764 to C.C.B.), the National Institute of General Medical Sciences (grant no. GM120553 to D.V.), an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund (D.V.), a Pew Biomedical Scholars Award (D.V.) and the University of Washington Arnold and Mabel Beckman cryo-EM center.
Funding Information:
Operations support of the Galveston National Laboratory was supported by NIAID/NIH grant no. UC7AI094660.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/5
Y1 - 2021/5
N2 - Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50–100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses.
AB - Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses (HNVs) causing respiratory illness and severe encephalitis in humans, with fatality rates of 50–100%. There are no licensed therapeutics or vaccines to protect humans. HeV and NiV use a receptor-binding glycoprotein (G) and a fusion glycoprotein (F) to enter host cells. HNV F and G are the main targets of the humoral immune response, and the presence of neutralizing antibodies is a correlate of protection against NiV and HeV in experimentally infected animals. We describe here two cross-reactive F-specific antibodies, 1F5 and 12B2, that neutralize NiV and HeV through inhibition of membrane fusion. Cryo-electron microscopy structures reveal that 1F5 and 12B2 recognize distinct prefusion-specific, conserved quaternary epitopes and lock F in its prefusion conformation. We provide proof-of-concept for using antibody cocktails for neutralizing NiV and HeV and define a roadmap for developing effective countermeasures against these highly pathogenic viruses.
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U2 - 10.1038/s41594-021-00584-8
DO - 10.1038/s41594-021-00584-8
M3 - Article
C2 - 33927387
AN - SCOPUS:85105141418
SN - 1545-9993
VL - 28
SP - 426
EP - 434
JO - Nature Structural Biology
JF - Nature Structural Biology
IS - 5
ER -