"Aging, Immunization, and TH17 Immunity in Host Defense"

“宿主防御中的衰老、免疫和 TH17 免疫”

基本信息

批准号：
7846810
负责人：
KEVIN P. HIGH
金额：
$ 15.86万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-01 至 2012-05-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Aging is accompanied by a decline in immune responsiveness that renders older adults highly susceptible to infectious diseases, and immunization vs. vaccine preventable illness such as influenza is less effective in seniors. A recently identified, vaccine-inducible branch of immunity, Th17 immunity appears to be well preserved, perhaps even favored in the immune system of older adult mice. We have preliminary data that both old T cells and old dendritic cells favor a Th17 immune response, and that, on the whole animal level, Th17 immune responses are favored in older animals when compared to young animals. In this proposal, we suggest using the Th17 immune response as a platform for vaccine development in older adult mice and evaluating the effect of Th17 immunity on host defense vs. influenza challenge. We will use two different vaccines to determine which best induces Th17 immunity. One is based on using irradiated Brucella abortus as a vector to carry influenza proteins. The other uses cytokine-coated, inactivated influenza virus to skew the Th response in a specific direction. The capacity of each vaccine platform to induce Th17 immunity and protect from typically fatal influenza virus challenge will be evaluated across the adult lifespan (2 mos to 18 mos). Once the most effective vaccine is established, additional experiments will investigate the role of Th17 in host defenses in both naive and immunized mice. Further, since induction of one Th type (e.g. Th1) inhibits the development of other Th types (e.g. Th17), the influence of Th17 immune induction on Th1 and Th2 immune responses will be determined. The longer-term goal of these studies is to test the feasibility of using a Th17- based vaccine platform in humans. PUBLIC HEALTH RELEVANCE: Older adults are highly susceptible to infectious diseases, and immunization against influenza and other vaccine preventable illnesses are less effective in seniors because host defenses wane with age. In this proposal, we will use a novel vaccine strategy to induce Th17 immunity, a newly discovered type of immunity that appears to be preserved into old age, to try to protect old adult mice from influenza infection. The longer- term goal of these studies is to test the feasibility of using a Th17-based vaccine platform in humans.

描述（由申请人提供）：衰老伴随着免疫反应性的下降，使老年人非常容易受到传染病的影响，而免疫与可预防疾病（如流感）的免疫接种对老年人的有效性较小。 Th17免疫力似乎已保存得很好，甚至可能在老年小鼠的免疫系统中受到青睐。我们有初步的数据表明，旧的T细胞和旧的树突状细胞都有利于Th17免疫反应，并且，在整个动物水平上，与幼小的动物相比，老年动物的Th17免疫反应受到青睐。在此提案中，我们建议使用TH17免疫反应作为老年小鼠疫苗开发的平台，并评估TH17免疫对宿主防御与流感挑战的影响。我们将使用两种不同的疫苗来确定哪种最佳诱导Th17免疫力。一种基于使用辐照的布鲁氏菌作为载体来携带流感蛋白。另一个使用细胞因子包染的，灭活的流感病毒在特定方向上偏向TH反应。每个疫苗平台诱导Th17免疫力和保护通常致命的流感病毒挑战的能力将在整个成人寿命（2 MOS至18 MOS）中进行评估。一旦建立了最有效的疫苗，其他实验将研究Th17在幼稚和免疫小鼠中宿主防御中的作用。此外，由于一种诱导（例如TH1）抑制了其他类型的发展（例如TH17），因此将确定Th17免疫诱导对TH1和TH2免疫反应的影响。这些研究的长期目标是测试在人类中使用基于Th17的疫苗平台的可行性。公共卫生相关性：老年人非常容易受到传染病的影响，对流感和其他可预防疾病的免疫接种在老年人中的效果较小，因为宿主防御能力随着年龄的增长而减弱。在此提案中，我们将使用一种新型的疫苗策略来诱导Th17免疫，这是一种新发现的免疫力，似乎保留到老年中，以试图保护老年小鼠免受流感感染的影响。这些研究的长期目标是测试在人类中使用基于Th17的疫苗平台的可行性。