| Literature DB >> 30943399 |
Pramila Rijal1, Sean C Elias2, Samara Rosendo Machado3, Julie Xiao3, Lisa Schimanski3, Victoria O'Dowd4, Terry Baker4, Emily Barry4, Simon C Mendelsohn2, Catherine J Cherry2, Jing Jin2, Geneviève M Labbé2, Francesca R Donnellan2, Tommy Rampling2, Stuart Dowall5, Emma Rayner5, Stephen Findlay-Wilson5, Miles Carroll5, Jia Guo6, Xiao-Ning Xu6, Kuan-Ying A Huang7, Ayato Takada8, Gillian Burgess4, David McMillan4, Andy Popplewell4, Daniel J Lightwood4, Simon J Draper2, Alain R Townsend9.
Abstract
We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano- to pico-molar range, similar to "affinity matured" antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies.Entities:
Keywords: E-S-FLU virus; Ebola virus; Ebola virus glycoprotein epitopes; affinity maturation; antibody binding kinetics; guinea pig model; human monoclonal antibodies; immunotherapy; therapeutic antibodies
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Year: 2019 PMID： 30943399 DOI： 10.1016/j.celrep.2019.03.020
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423