TY - JOUR
T1 - An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections
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
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
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.
UR - http://www.scopus.com/inward/record.url?scp=85074205590&partnerID=8YFLogxK
U2 - 10.1038/s41594-019-0308-9
DO - 10.1038/s41594-019-0308-9
M3 - Article
C2 - 31570878
AN - SCOPUS:85074205590
SN - 1545-9993
VL - 26
SP - 980
EP - 987
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -