TY - JOUR
T1 - Exceptionally potent cross-reactive neutralization of Nipah and Hendra viruses by a human monoclonal antibody
AU - Zhu, Zhongyu
AU - Bossart, Katharine N.
AU - Bishop, Kimberly A.
AU - Crameri, Gary
AU - Dimitrov, Antony S.
AU - McEachern, Jennifer A.
AU - Feng, Yang
AU - Middleton, Deborah
AU - Wang, Lin Fa
AU - Broder, Christopher C.
AU - Dimitrov, Dimiter S.
PY - 2008/3/15
Y1 - 2008/3/15
N2 - 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 (sGHeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeVG, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG HeV. 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 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sGHeV and sGNiV. m102.4 bound a soluble form of NiV G (sGNiV) better than it bound sGHeV, and it neutralized NiV better than HeV, despite being originally selected against sGHeV. 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.
AB - 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 (sGHeV). One of these antibodies, m102, which exhibited the highest level of cross-reactive neutralization of both NiV and HeVG, was affinity maturated by light-chain shuffling combined with random mutagenesis of its heavy-chain variable domain and panning against sG HeV. 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 μg/mL, respectively. The virus-neutralizing activity correlated with the binding affinity of the antibody to sGHeV and sGNiV. m102.4 bound a soluble form of NiV G (sGNiV) better than it bound sGHeV, and it neutralized NiV better than HeV, despite being originally selected against sGHeV. 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.
UR - http://www.scopus.com/inward/record.url?scp=40949131046&partnerID=8YFLogxK
U2 - 10.1086/528801
DO - 10.1086/528801
M3 - Article
C2 - 18271743
AN - SCOPUS:40949131046
SN - 0022-1899
VL - 197
SP - 846
EP - 853
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -