Chikungunya virus envelope-specific human monoclonal antibodies with broad neutralization potency
Autor(es): Warter Lucile, Lee Chia Yin, Thiagarajan Rekha, Grandadam Marc, Lebecque Serge, Lin Raymond T P, Bertin-Maghit Sebastien, Ng Lisa F P, Abastado Jean-Pierre, Desprès Philippe, Wang Cheng-I, Nardin Alessandra
Resumo: Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics in Africa - Asia. Infection by CHIKV is often characterized by long-lasting, incapacitating arthritis, - some fatal cases have been described among elderly - newborns. Currently, there is no available vaccine or specific treatment against CHIKV. Blood B cells from a donor with history of CHIKV infection were activated, immortalized, amplified, - cloned. Two human mAbs against CHIKV, 5F10 - 8B10, were identified, sequenced, - expressed in recombinant form for characterization. In a plaque reduction neutralization test, 5F10 - 8B10 show mean IC(50) of 72 - 46 ng/ml, respectively. Moreover, both mAbs lead to a strong decrease in extracellular spreading of infectious viral particles from infected to uninfected cells. Importantly, the mAbs neutralize different CHIKV isolates from Singapore, Africa, - Indonesia, as well as O'nyong-nyong virus, but do not recognize other alphaviruses tested. Both mAbs are specific for the CHIKV envelope: 5F10 binds to the E2 glycoprotein ectodomain - 8B10 to E1 -/or E2. In conclusion, these two unique human mAbs strongly, broadly, - specifically neutralize CHIKV infection in vitro - might become possible therapeutic tools against CHIKV infection, especially in individuals at risk for severe disease. Importantly, these mAbs will also represent precious tools for future studies on host-pathogen interactions - the rational design of vaccines against CHIKV.
Imprenta: Journal of Immunology, v. 186, n. 5, p. 3258-3264, 2011
Identificador do objeto digital: 10.4049/jimmunol.1003139
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Molecular structure ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Serology ; Chikungunya virus - Viral infections ; Chikungunya virus - Serology ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2011