Adenovirus and Poxvirus Mediated Protection Against Mucosal SIV Infection

腺病毒和痘病毒介导的针对粘膜 SIV 感染的保护作用

基本信息

批准号：
8198143
负责人：
Dan H. Barouch
金额：
$ 37.47万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-15 至 2016-06-30
项目状态：
已结题

项目摘要

The earliest events following mucosal HIV-1 exposure represent a critical window of opportunity for vaccine-elicited immune responses to impact the acquisition and propagation of HIV-1 infection. However, very little is known about the biology of the eclipse phase of HIV-1 infection in humans, particularly the immunologic and virologic events that occur at the mucosal site of transmission. Given the difficulties in studying the earliest mucosal events of HIV-1 infection in humans, modeling these events in nonhuman primates is required. Such studies will provide insight into the early events of virus transmission and the capacity of immune responses to block or to attenuate these events. In this Project, we hypothesize that SIV-specific immune responses elicited by adenovirus and poxvirus vaccine vectors will substantially impact the early events following intravaginal (IVAG) SIV infection of rhesus monkeys. In particular, we hypothesize that vaccine-elicited mucosal immune responses at the site of inoculation will limit the initial local amplification of virus at the mucosal portal of entry during the eclipse phase of infection prior to systemic virus dissemination. The goal is to define precisely when and where innate and adaptive immune responses intercept the virus following IVAG SIV infection of both .naive and vaccinated animals. To evaluate these hypotheses, we propose the following Specific Aims: 1. To define the early virologic, immunologic, and pathologic events following IVAG SIV infection of naive, unvaccinated rhesus monkeys; 2. To evaluate the capacity of adenovirus vector-based vaccines to impact the early events following IVAG SIV infection of rhesus monkeys; and 3. To assess the capacity of poxvirus vector-based vaccines to impact the early events following IVAG SIV infection of rhesus monkeys.

粘膜HIV-1暴露后最早的事件代表了吸收疫苗的关键机会窗口对影响HIV-1感染的获取和传播的免疫反应。但是，很少关于人类HIV-1感染的Eclipse阶段的生物学已知，尤其是免疫学以及在传播的粘膜部位发生的病毒学事件。鉴于很难研究人类HIV-1感染最早的粘膜事件，对非人类灵长类动物中的这些事件进行建模是必需的。这样的研究将洞悉病毒传播的早期事件和能力对阻止或减弱这些事件的免疫反应。在这个项目中，我们假设腺病毒和痘病毒疫苗载体将显着影响腔内（IVAG）SIV后的早期事件恒河猴的感染。特别是，我们假设疫苗引起的粘膜免疫接种部位的反应将限制粘膜处病毒的初始局部扩增在全身病毒传播之前的日食感染阶段的进入门户。目标是精确定义何时何地定义先天和适应性免疫反应拦截病毒 IVAG SIV感染。为了评估这些假设，我们提出以下具体目的： 1。定义幼稚的IVAG SIV感染后的早期病毒，免疫和病理事件，未接种的恒河猴； 2。评估基于腺病毒载体的疫苗影响IVAG后早期事件的能力恒河猴的SIV感染；和 3。评估基于痘病毒载体的疫苗影响IVAG SIV后早期事件的能力恒河猴的感染。