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Opportunity at U.S. Army Medical Research & Materiel Command (AMRMC)

The Development of Human Anti-Ricin Neutralizing Antibodies

Location

U.S. Army Medical Research Institute of Infectious Diseases, US Army Medical Research Insti Infec Diseases

RO# Location
97.20.00.B8269 Fort Detrick, MD 217025011

Advisers

Name E-mail Phone
Webb, Robert Paul robert.p.webb6.civ@mail.mil 301.619.6686

Description

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.

 

References

Pincus SH, Bhaskaran M, Brey RN, et al: Clinical and Pathological Findings Associated with Aerosol Exposure of Macaques to Ricin Toxin. Toxins 7: 2121-2133; 2015. doi:10.3390/toxins7062121

O’Hara JM, Brey RN, Mantis NJ: Comparative Efficacy of Two Leading Candidate Ricin Toxin A Subunit Vaccines in Mice. Clinical and Vaccine Immunology 20(6): 789-94, 2013. doi:10.1128/CVI.00098-13. Epub 2013 Mar 20

McLain DE, Horn TL, Detrisac CJ, et al: Progress in biological threat agent vaccine development: a repeat-dose toxicity study of a recombinant ricin toxin A-chain (rRTA) 1-33/44-198 vaccine (RVEc) in male and female New Zealand white rabbits. International Journal of Toxicology 30(2): 143-52, 2011. doi:10.1177/1091581810396730. Epub 2011 Mar 4

 

Keywords:
Ricin; scFv; Toxin; Monoclonal antibody; Vaccine; Yeast surface expression;

Eligibility

Citizenship:  Open to U.S. citizens, permanent residents and non-U.S. citizens
Level:  Open to Postdoctoral and Senior applicants
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