Autor(es): Smith Scott A, Silva Laurie A, Fox Julie M, Flyak Andrew I, Kose Nurgun, Sapparapu Gopal, Khomandiak Solomiia, Khomadiak Solomiia, Ashbrook Alison W, Kahle Kristen M, Fong Rachel H, Swayne Sherri, Doranz Benjamin J, McGee Charles E, Heise Mark T, Pal Pankaj, Brien James D, Austin S Kyle, Diamond Michael S, Dermody Terence S, Crowe James E

Resumo: 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, - no effective therapeutics or vaccines are available. We isolated - characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad - ultrapotent neutralizing activity (IC50 < 10 ng/ml), - all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, - 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, - their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.

Imprenta: Cell Host & Microbe, v. 18, n. 1, p. 86-95, 2015

Identificador do objeto digital: 10.1016/j.chom.2015.06.009

Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Molecular structure ; Chikungunya virus - RNA ; Chikungunya virus - Antibodies ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Immunology

Data de publicação: 2015