Assessment of Smallpox Specific Immune Responses

根据RFA-AI-02-002的要求，这项提案寻求资金，用于研究以前在美国商业批准的天花疫苗(制备活痘苗病毒)中接种过天花疫苗的个人对天花(天花)的长期免疫力(例如免疫记忆或回忆)。在2001年9月11日之后，现在至关重要的是更好地确定普通人群和那些可能被归类为免疫受损并因此被认为具有较高感染风险的人的天花保护性免疫或抗病机制。虽然天花只被认为是一种具有历史意义的疾病，但自从它较早被根除以来，它已被认为是潜在生物恐怖活动的重要病原体。使用当前最先进的技术或方法对长期免疫进行调查，可能有助于确定哪些人更有准备充当“一线”。 响应者。此外，这些信息可能有助于确定一种更好的战略，使用目前可用的有限的、非普遍可用的疫苗材料。 具体目标1：评估以前接种过天花疫苗的健康个体的天花特异性长期免疫反应，并与供者年龄和自上次接种以来的时间相关。 假设：最初的儿童疫苗接种将与不同水平的天花特异性宿主免疫反应有关，这将随接种的免疫次数和自上次接种以来的时间而不同。 具体目标2：通过与NIAID DAIDS ACTG合作，评估艾滋病毒携带者和艾滋病毒携带者中针对天花的长期免疫反应，并与以前接种天花疫苗的个人的年龄和感染状况相关联。 假设：HIV感染、CD4或病毒载量状态、自上次接种疫苗以来的时间和宿主年龄都将与不同水平的天花特异性宿主免疫反应相关。 具体目标3：绘制和评估健康和免疫参与者中病毒特异性细胞介导性反应的CD4/CD8免疫亚群关键记忆成分。这一模型没有群体免疫或自然增强作用，这是广泛研究病原体特异性免疫记忆的独特机会。 假设：CD4或CD8细胞对各种免疫优势病毒表位的反应水平和/或频率将随年龄、自上次接种疫苗以来的时间或疾病(如HIV)的存在而变化。

This proposal, in response to RFA-AI-02-002, seeks funding to study long-lasting immunity (e.g. immunological memory or recall) to smallpox (variola) in individuals who were previously vaccinated in the United States commercially approved smallpox vaccine (preparation of live Vaccinia virus). In the aftermath of September 11, 2001, it is now critical to better define mechanisms of smallpox protective immunity or disease resistance in the general population and in those who may be classified immune compromised and therefore, considered at a higher risk of infection. Though smallpox was considered a disease of historical interest only, since its earlier eradication, it as been known to be a significant pathogen for potential bioterrorist activities. Investigation of long-lasting immunity using current state-of-the-art techniques or methodologies may help determine which individuals are better prepared to serve as "first-line" responders. In addition, this information may help determine a better strategy for use of limited, non-universally administrable vaccine material available today. Specific Aim 1: To assess smallpox-specific long-lasting immunologic responses and correlate to donor age and time since last vaccination in healthy individuals that have previously received a smallpox vaccination. Hypothesis: Initial childhood vaccine administration will be associated with differing levels of smallpox-specific host immune responses that will vary with number of immunizations given and the time since last vaccination. Specific Aim 2: To assess smallpox-specific long-lasting immunologic responses in HIV- and HIV+ individuals through collaboration with the NIAID DAIDS ACTG and correlate to age and infection status in individuals previously having smallpox vaccination. Hypothesis: HIV infection, CD4 or viral load status, time since last vaccination and host age will each be associated differing levels of smallpox-specific host immune responses. Specific Aim 3: To viral epitope map and evaluate the CD4/CD8 immune subset critical memory component of virus-specific cell-mediated responses in healthy and immune comprised study participants. Herd immunity or natural boosting is absent from this model, it represents a unique opportunity to extensively study pathogen specific immunological memory. Hypothesis: Response level and/or frequency of CD4 or CD8 cells to various immunodominant viral epitopes will change with age, time since last vaccination or presence of disease (e.g, HIV).