Monoclonal antibody prophylaxis protects against lethal Ebola virus infection

Abstract

Abstract Pan-Ebolavirus neutralizing antibodies MBP087 and MBP047, derived from a human EBOV survivor, are protective in rodent models when administered therapeutically two days after infection. Mutations in the Fc region of hIgG, known as YTE and XTND, prolong the half-life of hIgG so we incorporated these mutations into the framework of MBP087 an MBP047 to determine if the longer half-lives could provide protection with an extended pretreatment prior to infection. Wildtype (wt) (C57Bl/6) and mFcRn−/− hFcRn tg+/+ mice were given a single dose of Nicotiana (N)-derived MBP087 or MBP047 bearing a wt antibody framework or with the YTE or XTND mutations. MBP087-N or MBP087-YTE-N protected 80–100% of hFcRn tg mice against EBOV when administered 30 or 60 days prior to infection. Surprisingly, both MBP087-N and MBP087-XTND-N were also highly protective (80%) in wt mice over the same 30 or 60d window, showing surprising longevity and potency. Interestingly, wt MBP047-N protected 80% of wt mice when administered 30d prior to infection but provided little protection over 60d, regardless of YTE or XTND mutations. These data indicate that the utility of pan-Ebolavirus neutralizing antibodies can be expanded from a therapeutic use to a prophylactic use 30–60d prior to exposure. Expanding the utility of antibodies to prophylaxis may be advantageous in cases where vaccines are lacking or contraindicated due to patient restrictions.