USE OF RECALL IMMUNITY TO ENHANCE VACCINE EFFICACY IN THE ELDERLY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这是一项在灵长类动物模型中测试我们的记忆免疫增强协议的试点研究。它利用了圣安东尼奥可用的独特资源，这是一群年长的狒狒，他们在年轻的时候就接种了破伤风疫苗。我们预测，这些动物将拥有针对破伤风的长期记忆T细胞，当动物年老时，这些T细胞将能够在再次暴露于破伤风(或免疫优势片段TTFC)时为B细胞提供帮助。此外，通过融合一种新的抗原(以前从未被狒狒种群看到过)到TTFC，我们预测这些记忆T细胞也将能够为这种新抗原的特异性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。这将允许我们建立一个模型，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产生的抗体的效价；ii)产生的抗体的保护潜力；以及iii)针对TTFC与新抗原(LcrV)的特异性T细胞的刺激量。如果记忆增强是成功的，它将有许多潜在的应用，包括：用于生物防御或天然人类病原体的疫苗，癌症疫苗，自身免疫调节，尤其是用于改进疫苗方案和免疫疗法，用于我们老龄化的人口。

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.