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Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses.
Cell; 169(5): 878-890.e15, 2017 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-28525755
ABSTRACT
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes. Only a few somatic hypermutations are required for broad antiviral activity, and germline-approximating variants display enhanced GPCL recognition, suggesting that such antibodies could be elicited more efficiently with suitably optimized GP immunogens. Our findings inform the development of both broadly effective immunotherapeutics and vaccines against filoviruses.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Sobreviventes / Doença pelo Vírus Ebola / Vacinas contra Ebola / Anticorpos Neutralizantes / Anticorpos Antivirais Limite: Animais / Feminino / Humanos Idioma: Inglês Revista: Cell Ano de publicação: 2017 Tipo de documento: Artigo País de afiliação: Estados Unidos