Monoclonal antibody-based therapeutics for Argentine hemorrhagic fever

Viral hemorrhagic fevers (VHFs) pose continuing threats to public health. Most have limited treatment options or vaccines, which underscores a point of vulnerability in public health. Passive immunization is an attractive treatment strategy; for example, transfusion of the monoclonal antibody (mAb) cocktail ZMappTM was a lead approach during the 2014-2016 Ebola virus outbreak. Results of testing in humans with ZMappTM did not reach statistical significance, suggesting that further studies would be required to fine-tune the approach. A mAb derived from the blood of an Ebola survivor, mAb114, was also recently deployed for testing in humans in the ongoing Ebola virus outbreak in the Democratic Republic of Congo.

While these investigational therapies are promising, there remains a large, unmet need for therapies against all agents that cause VHFs. We chose to focus on Argentine hemorrhagic fever (AHF) caused by the arenavirus Junin because antibody transfusions have a well-established track record of successfully treating this infection. We will isolate mAbs from the blood of AHF survivors, characterize the molecular basis for their antiviral activity, and test these for therapeutic effect in small animal models. We will also determine if the antibodies we isolate cross-react with Machupo, Guanarito, Sabia, and Chapare viruses, which are related arenaviruses that cause VHFs in South America and lack effective therapies. Once completed, the work would position candidate mAbs for pre-clinical testing in non-human primates, thus facilitating their translation into human use.