U.S. Army Medical Research Institute of Infectious Diseases, US Army Medical Research Insti Infec Diseases
||Fort Detrick, MD 217025011
|Webb, Robert Paul
A postdoctoral research opportunity is available to support a Defense Threat Reduction Agency (DTRA) funded research project involving the isolation and testing of human antibodies that effectively neutralize ricin using antibody producing cells from human subjects vaccinated with a recombinant subunit ricin vaccine that is currently in clinical trials. Antibody-producing peripheral blood mononuclear cells (PBMCs) will be collected from vaccinated human subjects. RNA will be extracted from the PBMCs and converted to cDNA, which will be used in multiple PCR reactions to isolate antibody heavy and light chain hyper-variable, or Fv, sequences. These sequences will be randomly combined using PCR to produce single chain Fv fragments (scFv) libraries that will be screened for binding to the ricin toxin and purified recombinant ricin subunit proteins. Ricin binding affinity, epitope, and potential for neutralization will be determined for individual candidates, and individual scFv that show potential as neutralizing antibodies will be engineered to produce full-length IgG1. Full-length anti-ricin mAbs will be tested for protective efficacy against ricin intoxication using in vitro assays. If necessary, antibodies will be engineered for higher affinity and greater protective efficacy.
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