Early studies have suggested that the passive administration of monoclonal antibodies (mAbs) may be a potential therapeutic approach for Ebolavirus disease (EVD). However, all mAbs and mAb cocktails that have entered clinical development so far are specific for a single member of the Ebolavirus genus, Ebolavirus (EBOV), and have been found to be ineffective against outbreak-causing Bundibugyo (BDBV) and Sudan viruses (SUDV). The authors developed MBP134, a cocktail of two broadly neutralising human mAbs, ADI-15878 from an EVD survivor and ADI-23774 from the same survivor but specificity-matured for SUDV GP binding affinity. They found that MBP134 potently neutralise all ebolaviruses and demonstrates greater protective efficacy than ADI-15878 alone in EBOV-challenged guinea pigs. A second-generation cocktail, MBP134AF, that was specifically engineered to harness natural killer (NK) cells led to additional efficacy, compared with its precursor, against EBOV and SUDV in guinea pigs. MBP134AF is therefore an optimised mAb cocktail that could be examined as a pan-ebolavirus therapeutic in nonhuman primates.
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