USE OF RECALL IMMUNITY TO ENHANCE VACCINE EFFICACY IN THE ELDERLY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。这是一项初步研究，以测试我们的回忆记忆免疫增强方案在灵长类动物模型。它利用了圣安东尼奥的一种独特资源，一群在年轻时接种过破伤风疫苗的老年狒狒。我们预测，这些动物将具有对破伤风特异性的长寿记忆T细胞，当动物年老时，这些记忆T细胞将能够在再次暴露于破伤风（或TTFC，免疫显性片段）时为B细胞提供帮助。此外，通过融合新的我们预测，这些记忆T细胞将能够为特异于这种新抗原的B细胞提供帮助。对于测试抗原，我们建议使用来自人类病原体鼠疫耶尔森氏菌（鼠疫）的LcrV蛋白。这将使我们能够建立一个模型，在该模型中，我们可以测试疫苗效力的三个参数：i）针对新抗原LcrV产生的抗体的滴度; ii）产生的抗体的保护潜力;以及iii）对回忆抗原（TTFC）与新抗原（LcrV）特异性的T细胞的刺激量。如果回忆记忆增强成功，它将有许多潜在的应用，包括：生物防御疫苗或天然人类病原体疫苗，癌症疫苗，自身免疫调节，最特别的是，用于改进疫苗方案和免疫治疗，以用于我们的老龄化人口。

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.