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 - 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 and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 5
ER -