DNA VACCINE FOR INDUCTION OF MUCOSAL IMMUNITY

用于诱导粘膜免疫的 DNA 疫苗

• 批准号: 8358091
• 负责人: Preston A Marx
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358091
• 关键词: Animals; Biopsy; Blood; Blood specimen; Control Animal; DNA; DNA Vaccines; Data; Duodenum; Female; Funding; Grant; Immune response; Immunization; Irrigation; Lung; Macaca; Macaca mulatta; Monitor; Mucosal Immune Responses; Mucosal Immunity; National Center for Research Resources; Pennsylvania; Plasma; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SIV; Sampling; Shipping; Ships; Source; Specific qualifier value; Time; United States National Institutes of Health; Universities; Vaccinated; Vaccination; Vagina; Viral load measurement; Virus Diseases; base; chemokine; cost; flu; plasmid DNA; research study; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We hypothesize that, with the inclusion of mucosal chemokines with the DNA plasmid immunizations, a stronger mucosal immune response will be induced and that this response will correspond to increased efficacy against SIV challenge. Experiment 1: Twenty female Indian origin Rhesus macaques (Macaca mulatta) were previously immunized five times with DNA and various chemokines. In 2010, all 20 immunized animals plus 6 unimmunized animals were intravaginally challenged with SIVsmE660 twice a week for two weeks. Blood samples and mucosal lavages (including washes of the duodenum, lung and vagina) were collected at specified times after challenge and shipped to the University of Pennsylvania for analysis of immune responses. Blood samples and mucosal biopsies (including duodenum and vagina) were also collected after challenge and analyzed at the TNPRC to monitor viral infection and immune responses. Results of the challenge are as follows: 5 of 6 unimmunized control animals, 3 of 5 animals treated with DNA only, 4 of 5 animals treated with DNA+cTack, 2 of 5 animals treated with DNA+Teck and 4 of 5 animals treated with DNA+Meck became infected. However, the peak plasma virus loads of the DNA+Meck animals were greatly reduced compared to the unimmunized controls. All animals (n=18) that became infected were euthanized in 2010; all uninfected animals (n=8) will be used in the next experiment. Experiment 2: Based on the data obtained from the challenge results in Experiment 1, 16 new Rhesus macaques and the 8 uninfected macaques from Experiment 1 are being used in this experiment. Animals will be vaccinated five times with either SIV DNA + Teck, Flu DNA +/- Meck or C.Diff DNA +/- Meck. After the last vaccination, all animals will be challenged with SIVsmE660. Blood and mucosal samples will be collected to monitor viral infection and immune response.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 我们假设，随着与DNA质粒免疫的粘膜趋化因子纳入粘膜趋化因子，将诱导更强的粘膜免疫反应，并且这种反应将与针对SIV挑战的疗效提高相对应。 实验1：以前用DNA和各种趋化因子免疫五十次，印度印度雄鹿猕猴（Macaca mulatta）被免疫五次。 在2010年，所有20只免疫动物加6种无免疫动物都受到静脉内挑战，每周两次SIVSME660，持续两周。 在挑战后指定的时间收集了血液样本和粘膜灌洗（包括十二指肠，肺和阴道的洗涤），并运往宾夕法尼亚大学以分析免疫反应。 还收集了挑战后的血液样本和粘膜活检（包括十二指肠和阴道），并在TNPRC进行分析以监测病毒感染和免疫反应。 挑战的结果如下：6种无免疫的对照动物中的5个，仅用DNA处理的5只动物中的3只用DNA+CTACK治疗的5只动物中有4只用DNA+TECK处理的5只动物中的2只动物中的5只动物和用DNA+Meck处理的5只动物中有4只动物被感染。 然而，与无免疫对照相比，DNA+MECK动物的峰血浆病毒载荷大大减少。 所有被感染的动物（n = 18）在2010年被安乐死；下一个实验将使用所有未感染的动物（n = 8）。 实验2：基于实验1中从挑战结果获得的数据，在本实验中使用了16个新的恒河猕猴和实验1的8个未感染的猕猴。 SIV DNA +TECK，流感DNA +/- MECK或C.DIFF DNA +/- MECK将接种五次动物。 最后一次疫苗接种后，所有动物将受到SIVSME660的挑战。 将收集血液和粘膜样品，以监测病毒感染和免疫反应。