A THERAPEUTIC DNA VACCINE IN NONHUMAN PRIMATE AGAINST CHAGAS DISEASE

针对非人类灵长类动物的恰加斯病治疗性 DNA 疫苗

• 批准号: 7716293
• 负责人: ERIC DUMONTEIL
• 金额: $ 1.39万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-21 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716293
• 关键词: Acute; Adjuvant; Animals; Antigens; Appearance; Applications Grants; Autopsy; Biological Assay; Blood; Blood specimen; Chagas Disease; Chemistry; Chronic Phase; Colon; Computer Retrieval of Information on Scientific Projects Database; Control Animal; Count; DNA; DNA Vaccines; Development; Disease; Disease Progression; Dose; Funding; Genus Cola; Grant; Hand; Heart; Immune response; Immunohistochemistry; In Vitro; Infection; Inflammation; Injection of therapeutic agent; Institution; Liver; Lung; Macaca mulatta; Monitor; Monkeys; Mouse Strains; Organ; Parasitemia; Parasites; Peripheral Blood Mononuclear Cell; Pilot Projects; Plasmids; Polymerase Chain Reaction; Research; Research Personnel; Resources; Safety; Skeletal Muscle; Source; Stomach; Therapeutic; Therapeutic Effect; Tissue Sample; Tissues; Treatment Efficacy; Trypanosoma cruzi; United States National Institutes of Health; Vaccines; aluminum phosphate; diabetic; nonhuman primate; therapeutic vaccine; vaccine safety

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Previous studies showed that a DNA vaccine expressing Trypanosoma cruzi antigens TSA1 and Tc24, administered during the acute or chronic phase of the infection with T. cruzi could control at least partially the development of the disease in several strains of mice. In this pilot study, we thus aimed at evaluating the safety and efficacy of this DNA vaccine in rhesus monkeys. Six animals (6.5-14.8 kg) were infected via IV with 500,000 T. cruzi parasites/kg (Y strain), and three were treated with three IM injections of 500 ¿g of DNA vaccine encosing TSA1 and Tc24 with aluminium phosphate as an adjuvant at 3, 4, and 5 months post-infection. Three control animals received the same doses of empty plasmid. Treated and untreated animals were followed for a total of 6 months post-infection. Safety of the DNA vaccine treatment was assessed by monthly monitoring of blood counts and chemistry, all of which did not show any alteration, except for one animal which turned diabetic. Treatment efficacy was assessed by comparing disease development between treated and untreated animals. Two months after infection, all the animals were seroposivive for T. cruzi and/or presented parasitemia as indicated by a positive T. cruzi PCR in blood samples. Electrocardiographic reccordings at 4 and 6 months post infection were normal in both groups of monkeys. However, QT interval appeared longer in untreated animals compared to that of treated animals. All animals were sacrified at 6 months post infection. Necropsies indicated that all organs had a normal appearance, confirming the safety of the vaccine treatment. Histopathologic analysis of tissue sections indicated that there was minimal inflammation in the heart of monkeys from both groups. One treated monkey also presented minimal inflammation in the liver, and anonther one mild inflammation in the stomach. On the other hand, all the untreated animals presented minimal to mild inflammation in several tissues, such as colon, stomach, liver, lung, and skeletal muscle, suggesting a more severe disease in these animals. Further analysis, including in vitro PBMC stimulation for the analysis of the immune response, PCR assays to detect parasite DNA in tissue samples, and immunohistochemistry, are still underway. These first results indicate that the therapeutic vaccine used was safe and had some therapeutic effect on the control of disease progression in non-human primates. A NIH grant proposal for a full project expanding this pilot study will be submitted next semester.

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