The Effect of Helminth Infection on HIV-1 Vaccines

艾滋病在世界范围内的流行在发展中国家是最具破坏性的，在这些国家，Mofe超过40 数以百万计的人被感染。为南部非洲人群开发HIV-1疫苗 和其他发展中国家是重中之重。目前设计的HIV-1疫苗旨在推动 Th1型和细胞毒性CD8+T细胞对正在研发或正在研发的候选疫苗的反应 临床试验。此外，发展中国家的居民进食也感染了蠕虫。 抑制ThH型疫苗免疫应答和病毒抗原性扩张的寄生虫 C04+和CDS+T细胞应答。因此，蠕虫感染是如何影响诱导的？ 中和抗体或强大的T细胞对候选HIV-1疫苗的反应是一个重要的 在蠕虫感染人群中检测候选VAGCill6s之前要调查的问题。在……里面 在这项应用中，我们建议检查肠道去激活的李斯特菌载体HIV-1的免疫反应 幼鼠和血吸虫感染小鼠的疫苗。我们之所以选择李斯特氏菌，是因为 肠道是HIV-1复制的早期部位。除了蠕虫感染的影响外，我们还将 检查先前感染，然后再次感染蠕虫寄生虫如何影响 李斯特菌载体HIV-1疫苗诱导中和抗体和疫苗特异性T细胞反应 在老鼠身上。。我们还将确定再次感染血吸虫是否会影响T细胞记忆。我们也 建议10在Th1型和Th2型小鼠身上研究这两个问题。的具体目标 这项建议是：1)根除小鼠的血吸虫感染是否会使它们的免疫系统 在接种疫苗后建立强大的C04+和CD8+T细胞和中和抗体反应 李斯特菌载体HIV·1候选疫苗？2)血吸虫再感染会改变载体吗？ HIV-1疫苗诱导中和抗体ORT细胞记忆反应？

The worldwide AIDS epidemic is most devastating in developing countries, where mOfe than 40 million people are Infected. Development of an HIV-1 vaccine for POPulations In southern Africa and other developing countries is the highest priority. Currentiy HIV-1 vaccines designed to drive Th1-type and cytotoxic CD8+ T cell fesponses afe the candidate vaccines in development or in clinical trials. In addition, inhabitants in developing countries aTe also infected with helminth parasites which suppress immune responses to ThHype vaccines and expansion of viral antigenspecific C04+ and CDS+ T cell responses. Therefore, how helminth Infection impacts the induction of neutrali;!:;ing antibodies or robust T cell responses to candidate HIV-1 vaccines is an Important question to investigate prior to testing of candidate vaGCill6s in helminth infected populations. In this application we propose to examine immune responses to a gut-deUvered Listeria vector HIV-1 vaccine in naIVe and schIStosome infected mice. We chose Listeria vectors do to the fact that the gut is the ear1y site of HIV-1 replication. In addition to the impact of helminth infection, we will also examine how prior infection and then re -Infectlon with helminth parasites impacts the ability of Listeria vector HIV-1 vaccines to induce neutralizing antibody and vaccine specific T cell responses in mice . . We will also determine if reinfection with schistosomes impacts T cell memory. We also propose 10 examine both of these questions in Th1-type and Th2-type mice. The specifiC aims of this proposal are: 1) Will eradication of schistosome infection In mice allow their immune systems to mount strong C04+ and CD8+ T celi and neutralizing ab responses follOWing vaccination with Listeria vector HIV·1 candidate vaccines? 2) Will re· lnfection with schistosomes alter Llst~ria vector HIV-1 vaccine induced neutralizing antibody orT cell memory responses?