James Crowe
Faculty Member
Last active: 3/31/2019

Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus.

Smith SA, Silva LA, Fox JM, Flyak AI, Kose N, Sapparapu G, Khomandiak S, Khomadiak S, Ashbrook AW, Kahle KM, Fong RH, Swayne S, Doranz BJ, McGee CE, Heise MT, Pal P, Brien JD, Austin SK, Diamond MS, Dermody TS, Crowe JE
Cell Host Microbe. 2015 18 (1): 86-95

PMID: 26159721 · PMCID: PMC4501771 · DOI:10.1016/j.chom.2015.06.009

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.

Copyright © 2015 Elsevier Inc. All rights reserved.

MeSH Terms (17)

Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibodies, Viral Chemoprevention Chikungunya Fever Chikungunya virus Disease Models, Animal Humans Immunization, Passive Inhibitory Concentration 50 Mice Protein Binding Survival Analysis Treatment Outcome Viral Envelope Proteins Virus Internalization

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