Medical Countermeasure Development for Viral Induced Encephalitis Using Single DomainAntibodies

Alphaviruses, infection with which may cause encephalitis and death, are recognized as potential biological warfare agents. There are noapproved medical countermeasures against Alphaviruses. In Phase I, using Abzymes proprietary in vivo Self-Diversifying Camelid SingleDomain Antibody Library (SDALib) platform, broadly reactive single domain camelid VHH antibodies against equine encephalitis viral (EEV)protein E3E2 and VHH antibodies against human transferrin receptor TfR were isolated. Isolated EEV E3E2/E2 and TfR antibodies will serve as afoundation for developing bispecific EEVxTfR capable of traversing the blood brain barrier or BBB (phase I extension) and effective ascountermeasures for live EEV exposure in small animal studies (phase II). Antibodies capable of protecting animals from live viral challenge willbe selected for large scale production. Stable high-yield producer mammalian cell lines for affordable large scale antibody production will laythe foundation for subsequent Phase III studies.