A New Option for Treating Ebola

The recent West African Ebola virus outbreak highlighted the need for effective therapies against this pathogen. Research has shown that a cocktail of three mouse-derived monoclonal antibodies (mAbs), Zmapp, could be effective in treating nonhuman primates infected with Ebola (NEJM JW Infect Dis Oct 2014 and Nature 2015; 514:47), work that led researchers to explore the potential efficacy of human-derived mAbs.

The investigators found that a survivor of a 1995 Ebola virus outbreak retained potent virus-neutralizing antibody 11 years after infection. The researchers created immortalized cell lines from this individual's peripheral blood mononuclear cells and tested mAbs derived from the cell lines in vitro against Ebola virus. Four of these mAbs showed both high-level binding and inhibition activity against Ebola virus. Further testing of the two most neutralizing antibodies showed that both also mediated antibody-dependent cell-mediated cytotoxicity toward Ebola virus–infected cells. Treating three rhesus macaques with a combination of the two mAbs 24 hours after Ebola virus challenge protected all three animals. Giving monotherapy with the more-active mAb was also found to protect three of three macaques from Ebola virus challenge when given either 1 or 5 days postinfection.