The Effect of Helminth Infection on HIV-1 Vaccines

蠕虫感染对 HIV-1 疫苗的影响

• 批准号: 7418170
• 负责人: Donald A Harn
• 金额: $ 37.1万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-19 至 2011-05-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7418170
• 关键词: AIDS vaccine development; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Antibodies; Antibody Formation; Antigens; Brazil; CD8B1 gene; Cells; China; Clinical Trials; Consensus; Country; Cytotoxic T-Lymphocytes; DNA Vaccines; Developed Countries; Developing Countries; Development; Eating; Epidemic; Frequencies; Generations; HIV-1; HIV-1 vaccine; Helminths; High Prevalence; Human; Immune; Immune response; Immune system; India; Individual; Infection; Joints; Life; Listeria; Memory; Mus; Parasites; Pharmaceutical Preparations; Population; Prevalence; Research Personnel; Schistosoma; Schistosoma mansoni; Schistosoma mansonii infection; Site; Southern Africa; T memory cell; T-Lymphocyte; Testing; Time; United Nations; Vaccinated; Vaccination; Vaccine Design; Vaccines; Viral; Virus; cytotoxic; immune function; immunoregulation; neutralizing antibody; pathogen; plasmid DNA; programs; repository; response; vaccine candidate; vaccine evaluation; vector

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?

在发展中国家，全球艾滋病流行最具毁灭性，MOFE超过40 百万人被感染。开发南部非洲人口的HIV-1疫苗 其他发展中国家是最高优先事项。电流HIV-1疫苗旨在驱动 Th1型和细胞毒性CD8+ T细胞屈服于发育中的候选疫苗 临床试验。此外，发展中国家的居民还吃了蠕虫 抑制免疫调查的寄生虫，并扩展病毒抗原特异性 C04+和CD+ T细胞响应。因此，蠕虫感染如何影响诱导 中性;！ 在测试被蠕虫感染人群中的候选杂物之前要进行的问题。在 我们提出的该应用程序旨在检查对肠道凹形李斯特菌载体HIV-1-1的免疫回报 幼稚和棘齿状小鼠中的疫苗。我们选择李斯特菌向量的事实，即 肠道是HIV-1复制的早期站点。除了蠕虫感染的影响外，我们还将 检查先前感染，然后再对嗜热寄生虫重新感染如何影响 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 在老鼠中。 。我们还将确定使用血块的改革是否影响T细胞记忆。我们也是 提案10在Th1型和Th2型小鼠中检查了这两个问题。特定目的 该提议是：1）在小鼠中消除血吸虫感染允许其免疫系统 安装强的C04+和CD8+ T Celi，并在疫苗接种后中和AB反应 李斯特菌载体HIV·1个候选疫苗？ 2）将用血块拟合llst〜ria vector重新感染 HIV-1疫苗诱导中和抗体ORT细胞记忆反应？