Identifying novel monoclonal antibodies against Ebola virus

2017

Challenge

Ebola and Marburg hemorrhagic fevers are acute viral diseases that often lead to severe illness and death in humans. There are currently no vaccines or cures for these infections, which are caused by a group of viruses called filoviruses. The 2014 Ebola outbreak in West Africa demonstrated the unpredictable nature of filovirus transmission and the need for advanced planning in the development of vaccines and treatments.

Advance

IRP researchers identified and isolated two anti-Ebola monoclonal antibodies, mAb100 and mAb114, from a patient who had survived Ebola infection. In vitro experiments performed with cells outside the body found that these antibodies neutralized both older and more recent variants of Ebola virus and induced the immune system to destroy Ebola-infected cells. In addition, intravenous injections of mAb114 in non-human primates protected them from Ebola infection.

Impact

Because the global fight to contain the 2013-2016 Ebola outbreak in West Africa was hampered by the lack of an effective treatment or vaccine, the discovery of two potentially protective monoclonal antibodies against Ebola virus has important implications for developing treatment options in the event of a future outbreak.

Publications

Corti D, Misasi J, Mulangu S, Stanley DA, Kanekiyo M, Wollen S, Ploquin A, Doria-Rose NA, Staupe RP, Bailey M, Shi W, Choe M, Marcus H, Thompson EA, Cagigi A, Silacci C, Fernandez-Rodriguez B, Perez L, Sallusto F, Vanzetta F, Agatic G, Cameroni E, Kisalu N, Gordon I, Ledgerwood JE, Mascola JR, Graham BS, Muyembe-Tamfun JJ, Trefry JC, Lanzavecchia A, Sullivan NJ. (2016). Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. Mar 18;351(6279):1339-42.

Misasi J, Gilman MS, Kanekiyo M, Gui M, Cagigi A, Mulangu S, Corti D, Ledgerwood JE, Lanzavecchia A, Cunningham J, Muyembe-Tamfun JJ, Baxa U, Graham BS, Xiang Y, Sullivan NJ, McLellan JS. (2016). Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. Mar 18;351(6279):1343-6.