A neutralizing monoclonal antibody targeting the acid-sensitive region in chikungunya virus E2 protects from disease
Autor(es): Selvarajah Suganya, Sexton Nicole R, Kahle Kristen M, Fong Rachel H, Mattia Kimberly-Anne, Gardner Joy, Lu Kai, Liss Nathan M, Salvador Beatriz, Tucker David F, Barnes Trevor, Mabila Manu, Zhou Xiangdong, Rossini Giada, Rucker Joseph B, S-ers David Avram, Suhrbier -reas, Sambri Vittorio, Michault Alain, Muench Marcus O, Doranz Benjamin J, Simmons Graham
Resumo: The mosquito-borne alphavirus, chikungunya virus (CHIKV), has recently reemerged, producing the largest epidemic ever recorded for this virus, with up to 6.5 million cases of acute - chronic rheumatic disease. There are currently no licensed vaccines for CHIKV - current anti-inflammatory drug treatment is often inadequate. Here we describe the isolation - characterization of two human monoclonal antibodies, C9 - E8, from CHIKV infected - recovered individuals. C9 was determined to be a potent virus neutralizing antibody - a biosensor antibody binding study demonstrated it recognized residues on intact CHIKV VLPs. Shotgun mutagenesis alanine scanning of 98 percent of the residues in the E1 - E2 glycoproteins of CHIKV envelope showed that the epitope bound by C9 included amino-acid 162 in the acid-sensitive region (ASR) of the CHIKV E2 glycoprotein. The ASR is critical for the rearrangement of CHIKV E2 during fusion - viral entry into host cells, - we predict that C9 prevents these events from occurring. When used prophylactically in a CHIKV mouse model, C9 completely protected against CHIKV viremia - arthritis. We also observed that when administered therapeutically at 8 or 18 hours post-CHIKV challenge, C9 gave 100% protection in a pathogenic mouse model. Given that targeting this novel neutralizing epitope in E2 can potently protect both in vitro - in vivo, it is likely to be an important region both for future antibody - vaccine-based interventions against CHIKV.
Imprenta: PLoS Neglected Tropical Diseases, v. 7, n. 9, p. e2423, 2013
Identificador do objeto digital: 10.1371/journal.pntd.0002423
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Antibodies ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine ; Chikungunya virus - Chikungunya fever ; Chikungunya virus - Epidemic ; Chikungunya virus - Immunology
Data de publicação: 2013
