Single domain antibodies as medical countermeasures for viral induced encephalitis

Alphavirus infection, which may cause encephalitis and death, are recognized as potential biological warfare agents. There are no approved medical countermeasures against diseases caused by Alphaviruses. In this project, thermostable single domain antibodies capable of crossing the blood brain barrier (BBB) and neutralizing encephalitic viruses will be developed using Abzymes proprietary in vivo Self-Diversifying Camelid Single Domain Antibody Library (SDALib) platform.Camelid SDALib will provide a diverse array of single domain antibodies, without the need for animal immunization.Since this is a non-animal system, the platform can generate diverse antibodies against toxins, pathogens, self-antigens, and the like which are by nature difficult to obtain.In Phase I, high-affinity single domain antibodies targeting equine encephalitis virus-like particles (VLP) will be developed.The ability of isolated single domain antibodies to cross blood-brain barrier will be demonstrated using an in vitro BBB system.In Phase II, antibody candidates will be humanized and further evaluated as a medical countermeasure against viral infection in a small mammal study.Antibodies from selected clones will be produced in large quantity.Non-clinical GLP pharmacokinetic and pharmacodynamics data will be obtained laying the foundation for subsequent Phase III studies.