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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，那里的艾滋病患者超过40%。百万人被感染。为南部非洲民众研制HIV-1疫苗和其他发展中国家是最高优先事项。目前的HIV-1疫苗旨在驱动 Th 1型和细胞毒性CD 8 + T细胞应答是开发中或开发中的候选疫苗的安全性。临床试验此外，发展中国家的居民也感染蠕虫抑制对ThHype疫苗的免疫应答和病毒抗原特异性扩增的寄生虫 C 04+和CDS+ T细胞应答。因此，蠕虫感染如何影响诱导 of neutrali;！：;产生抗体或对候选HIV-1疫苗产生强有力的T细胞应答是重要的在蠕虫感染人群中测试候选vaGCill 6之前调查的问题。在本申请中，我们提出检测对肠道脱落李斯特菌载体HIV-1的免疫应答疫苗在未感染和裂体感染的小鼠中的作用。我们选择李斯特菌载体是因为肠道是HIV-1复制的早期场所。除了蠕虫感染的影响，我们还将检查先前感染和重新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细胞应答对小鼠.我们还将确定是否再次感染与histosomes影响T细胞的记忆。我们也建议在Th 1型和Th 2型小鼠中检验这两个问题。的具体目标这一建议是：1）将根除小鼠体内的病毒感染，使其免疫系统接种后产生强烈的C 04+和CD 8 + T细胞和中和抗体应答，李斯特菌载体HIV·1候选疫苗？2)重组质粒是否会改变Llst~ria载体 HIV-1疫苗诱导的中和抗体还是T细胞记忆反应？