| Literature DB >> 26159721 |
Scott A Smith1, Laurie A Silva2, Julie M Fox3, Andrew I Flyak4, Nurgun Kose5, Gopal Sapparapu5, Solomiia Khomandiak, Solomiia Khomadiak2, Alison W Ashbrook6, Kristen M Kahle7, Rachel H Fong7, Sherri Swayne7, Benjamin J Doranz7, Charles E McGee8, Mark T Heise8, Pankaj Pal3, James D Brien3, S Kyle Austin3, Michael S Diamond3, Terence S Dermody6, James E Crowe9.
Abstract
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.Entities:
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Year: 2015 PMID： 26159721 PMCID： PMC4501771 DOI： 10.1016/j.chom.2015.06.009
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023