USE OF RECALL IMMUNITY TO ENHANCE VACCINE EFFICACY IN THE ELDERLY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot study to test our recall memory immune enhancement protocol in a primate model. It takes advantage of a unique resource available in San Antonio, a cohort of aged baboons who were immunized against tetanus when they were young. We predict that these animals will have long-lived memory T cells specific for tetanus that will be able to provide ¿help¿ to B cells upon re-exposure to tetanus (or TTFC, the immunodominant fragment) when the animals are old. Moreover, by fusing a ¿new¿ antigen (never before seen by the baboon population) to TTFC, we predict that these memory T cells will be able to provide ¿help¿ to B cells specific for this ¿new¿ antigen as well. For the test antigen, we propose to use the LcrV protein from the human pathogen Yersinia pestis (plague). This will allow us a model in which we can test three parameters of vaccine efficacy: i) titer of the antibodyies produced to the ¿new¿ antigen, LcrV; ii) protective potentials of the antibodies produced; and iii) the amount of stimulation of T cells specific for the ¿recall¿ antigen (TTFC) vs. the ¿new¿ antigen (LcrV). If recall memory enhancement were successful, it would have numerous potential applications, including: vaccines for biodefense or for natural human pathogens, cancer vaccines, autoimmune regulation, and most particularly, for the improvement of vaccine protocols and immune-based therapies for use in our aging population.