title: Chikungunya virus envelope-specific human monoclonal antibodies with broad neutralization potency.
abstract: Chikungunya virus (CHIKV) is an alphavirus responsible for numerous epidemics in Africa and Asia. Infection by CHIKV is often characterized by long-lasting, incapacitating arthritis, and some fatal cases have been described among elderly and 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, and cloned. Two human mAbs against CHIKV, 5F10 and 8B10, were identified, sequenced, and expressed in recombinant form for characterization. In a plaque reduction neutralization test, 5F10 and 8B10 show mean IC(50) of 72 and 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, and 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 and 8B10 to E1 and/or E2. In conclusion, these two unique human mAbs strongly, broadly, and specifically neutralize CHIKV infection in vitro and 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 and the rational design of vaccines against CHIKV.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore. lucile_warter@immunol.a-star.edu.sg
authors.forename: Lucile
authors.initials: L
authors.lastname: Warter
authors.forename: Chia Yin
authors.initials: CY
authors.lastname: Lee
authors.forename: Rekha
authors.initials: R
authors.lastname: Thiagarajan
authors.forename: Marc
authors.initials: M
authors.lastname: Grandadam
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.forename: Raymond T P
authors.initials: RT
authors.lastname: Lin
authors.forename: Sebastien
authors.initials: S
authors.lastname: Bertin-Maghit
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Philippe
authors.initials: P
authors.lastname: Desprès
authors.forename: Cheng-I
authors.initials: CI
authors.lastname: Wang
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nardin
mesh_terms: D018354:Alphavirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000502:physiology*; D057134:Antibodies, Neutralizing / Q000378:metabolism / Q000502:physiology*; D001666:Binding Sites, Antibody; D002461:Cell Line, Transformed; D002646:Chikungunya virus / Q000276:immunology* / Q000472:pathogenicity; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D007116:Immunization, Passive / Q000379:methods; D007074:Immunoglobulin G / Q000378:metabolism; D009500:Neutralization Tests / Q000379:methods*; D011994:Recombinant Proteins / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins