251647 Subunit Vaccines for Biodefense Toxins

Monday, October 31, 2011

Anastasiya Yermakova, BS , School of Public Health, Department of Biomedical Sciences, University at Albany, School of Public Health, Rensselaer, NY
Nicholas Mantis, PhD , Department of Biomedical Sciences, University at Albany, School of Public Health, Rensselaer, NY
Biological toxins such as anthrax, botulinum, and ricin are a serious biothreat concern requiring the development of effective countermeasures. The B subunit (RTB) of ricin toxin is a galactose-specific lectin that promotes attachment and entry of ricin into host cells. The A subunit (RTA) is an RNA N-glycosidase that selectively targets ribosomes and arrests protein synthesis. While RTB is an appealing target for vaccine development and immunotherapeutics, the degree to which RTB immunization elicits ricin-specific protective antibodies remains unresolved. In this study, I immunized mice with RTB and then challenged with 5xLD50s of ricin, administered intraperitoneally. Despite high RTB-specific serum antibody titers, groups of RTB-immunized mice were only partially immune to ricin challenge. Analysis of a collection of RTB-specific B cell hybridomas suggested that only a small fraction of antibodies against RTB have demonstrable neutralizing activity. One such monoclonal antibody (mAb), SylH3, was characterized and proven capable of protecting mice against toxin in vivo. I further localized distinct epitopes on the surface of RTB associated with neutralizing and non-neutralizing antibodies. Both neutralizing and non-neutralizing mAbs bind ricin with equal affinities, demonstrating that epitope specificity, not association with ricin holotoxin, is likely the primary determinant of antibody-mediated protection. For the first time, this information provides an immunologic basis for ricin vaccine and therapeutic design which can serve as a platform for countermeasures against a wide array of biodefense agents. I performed all animal work, antibody characterization, and epitope mapping. Affinity analysis of antibodies was performed by the Wadsworth Center Immunology Core.

Learning Areas:
Public health or related research

Learning Objectives:
Evaluate strategies for the design of vaccines for biodefense toxins. Identify an immunologic basis for vaccine and therapeutic design.

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I am a member of Delta Omega.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.