Exceptionally potent cross-reactive neutralization of Nipah and Hendra viruses by a human monoclonal antibody.
We have previously identified neutralizing human monoclonal antibodies against Nipah virus (NiV) and Hendra virus (HeV) by panning a large nonimmune antibody library against a soluble form of the HeV attachment-envelope glycoprotein G (sG HeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeV G, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sGHeV. One of the selected antibody Fab clones, m102.4, had affinity of binding to sGHeV that was equal to or higher than that of the other Fabs; it was converted to IgG1 and tested against infectious NiV and HeV. It exhibited exceptionally potent and cross-reactive inhibitory activity with 50% inhibitory concentrations below 0.04 and 0.6 microg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sG HeV and sG NiV. m102.4 bound a soluble form of NiV G (sG NiV) better than it bound sG HeV, and it neutralized NiV better than HeV, despite being originally selected against sG HeV. These results suggest that m102.4 has potential as a therapeutic agent for the treatment of diseases caused by henipaviruses. It could be also used for prophylaxis and diagnosis, and as a research reagent.
Zhu
Zhongyu
Z
Protein Interactions Group, Center for Cancer Research Nanobiology Program, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, MD 21702-1201, USA. zhongyuzhu@ncifcrf.gov
Bossart
Katharine N
KN
Bishop
Kimberly A
KA
Crameri
Gary
G
Dimitrov
Antony S
AS
McEachern
Jennifer A
JA
Feng
Yang
Y
Middleton
Deborah
D
Wang
Lin-Fa
LF
Broder
Christopher C
CC
Dimitrov
Dimiter S
DS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005909:Glioblastoma; D006207:Half-Life; D006367:HeLa Cells; D045404:Hendra Virus / Q000276:immunology / Q000502:physiology*; D045464:Henipavirus Infections / Q000276:immunology* / Q000821:virology; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D009500:Neutralization Tests; D045405:Nipah Virus / Q000276:immunology / Q000502:physiology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D014759:Viral Envelope Proteins