The Effect of Helminth Infection on HIV-1 Vaccines

蠕虫感染对 HIV-1 疫苗的影响

基本信息

批准号：
7877043
负责人：
Donald A Harn
金额：
$ 37.22万
依托单位：
UNIVERSITY OF GEORGIA
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：
2009-06-19 至 2011-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7877043
关键词：
AIDS vaccine development AIDS/HIV problem Acquired Immunodeficiency Syndrome Antibodies Antibody Formation Antigens Bacterial Vaccines Brazil CD8B1 gene Cells China Clinical Trials Country Cytotoxic T-Lymphocytes DNA Vaccines Developing Countries Development Eating Epidemic HIV-1 HIV-1 vaccine Helminths High Prevalence Human Immune Immune response Immune system Immunosuppression India Individual Infection Joints Life Listeria Memory Modeling Mus Parasites Persons Pharmaceutical Preparations Population Praziquantel Prevalence Research Personnel Route Schistosoma Schistosoma mansoni Schistosoma mansonii infection Site Southern Africa T cell response 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 research study response vaccine candidate vector

项目摘要

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?

全球艾滋病流行在发展中国家最具破坏性，这些国家的人口超过 40 为南部非洲人口开发 HIV-1 疫苗。目前，其他发展中国家的首要任务是开发 HIV-1 疫苗。 Th1 型和细胞毒性 CD8+ T 细胞对正在开发或在研的候选疫苗有反应此外，发展中国家的居民也感染了蠕虫。抑制对 ThHype 疫苗的免疫反应和病毒抗原特异性扩展的寄生虫因此，C04+ 和 CDS+ T 细胞反应如何影响诱导。中和抗体或对候选 HIV-1 疫苗的强大 T 细胞反应是一个重要因素在蠕虫感染人群中测试候选 vaGCill6 之前需要调查的问题。在本应用中，我们建议检查对肠道排出的李斯特菌载体 HIV-1 的免疫反应我们选择李斯特菌载体来接种幼稚和血吸虫感染的小鼠。肠道是HIV-1复制的早期部位。除了蠕虫感染的影响外，我们还会发现。检查先前感染和随后再次感染蠕虫寄生虫如何影响李斯特菌载体 HIV-1 疫苗可诱导中和抗体和疫苗特异性 T 细胞反应我们还将确定血吸虫的再次感染是否会影响 T 细胞记忆。建议 10 在 Th1 型和 Th2 型小鼠中检查这两个问题。该建议是： 1）将根除小鼠体内的血吸虫感染，让其免疫系统建立强 C04+ 和 CD8+ T 细胞并中和疫苗接种后的抗体反应李斯特菌载体 HIV·1 候选疫苗？ 2) 血吸虫再次感染会改变李斯特菌载体吗？ HIV-1 疫苗诱导中和抗体或 T 细胞记忆反应？