USE OF RECALL IMMUNITY TO ENHANCE VACCINE EFFICACY IN THE ELDERLY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项试点研究，在灵长类动物模型上测试我们的回忆记忆免疫增强方案。它利用了圣安东尼奥一种独特的资源，一群年轻时接种过破伤风疫苗的老年狒狒。我们预测，这些动物将具有破伤风特异性的长寿命记忆T细胞，当动物年老时，这些T细胞能够在再次暴露于破伤风（或TTFC，免疫优势片段）时为B细胞提供“帮助”。此外，通过将一种新的抗原（狒狒种群从未见过）融合到TTFC中，我们预测这些记忆T细胞也将能够为这种新抗原特异性的B细胞提供帮助。我们建议使用鼠疫耶尔森菌LcrV蛋白作为检测抗原。这将为我们提供一个模型，我们可以在其中测试疫苗效力的三个参数：i)针对“新”抗原LcrV产生的抗体滴度；Ii)产生的抗体的保护潜能；iii)对回忆抗原（TTFC）和新抗原（LcrV）特异性T细胞的刺激量。如果回忆记忆增强是成功的，它将有许多潜在的应用，包括：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.