The authors were interested in the isolation of therapeutic monoclonal antibodies from human volunteers vaccinated with recombinant adenovirus expressing Ebolavirus glycoprotein (EBOV-GP) and then boosted with modified vaccinia virus Ankara. 82 antibodies were isolated from peripheral B cells, almost half of which neutralised GP pseudotyped influenza virus. The antibody response was found to be diverse in terms of gene usage and epitope recognition. While they were close to the germline in sequence, some neutralising antibodies had binding affinities in the nano- to picomolar range, similar to affinity matured antibodies isolated from convalescent donors. They were able to recognise the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies that targeted the latter three non-overlapping epitopes given on day 3 of EBOV infection were found to completely protect guinea pigs. Therefore experimental vaccine trials can produce a number of therapeutic human monoclonal antibodies.
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