Project 5

Kenneth Kaufman, Ph.D.

Reverse Genomics of Anti-Protective Antigen Responses

Protection from anthrax infection can be accomplished by immunization. However, the protective immune response generated towards anthrax varies between individuals. Our goal is to understand the genetics involved in the immune response following anthrax immunization. We are examining the entire human genome to identify the genes that play a role in regulating the anthrax immune response. As we identify the important genes in this process we look for polymorphisms in the DNA sequence that can cause individuals to develop strong or weak immune responses towards anthrax. In order to identify these polymorphisms we screen between 500,000 to over 1 million DNA markers per individual. Our samples come from United States military volunteers that have been immunized against anthrax. We use the results of clinical antibody assays to determine if individuals have strong or weak anthrax immune responses. We collect data on the ability of the immunized individuals to generate antibodies towards anthrax proteins and the ability to neutralize the anthrax toxin. Initially, we examine the entire human genome to identify regions that appear to be associated with the anthrax immunization. We then perform additional experiments to confirm and replicate the initial results and further define the regions of association. The next step will be to actually identify the polymorphism that alters the anthrax immune response. These experiments are only possible due to the hard work of our collaborators, Colonel Renata Engler who recruited the majority of samples at the Walter Reed Medical Center and the OMRF investigator Dr. Judith James who has performed all of the clinical assays on the samples. Our hope is that the results of these experiments will help identify individuals who would not be protected by the standard anthrax immunization and help in the development of more effective vaccinations.