IMMUNOMODULATOR-MEDIATED ENHANCEMENT OF ANTI-HIV-SPECIFIC IMMUNE RESPONSE

免疫调节剂介导的抗 HIV 特异性免疫反应的增强

• 批准号: 8357102
• 负责人: Miguel Otero
• 金额: $ 7.82万
• 依托单位: UNIVERSIDAD CENTRAL DEL CARIBE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357102
• 关键词: Agonist; Antigens; Biomedical Research; C57BL/6 Mouse; Cells; Cervical; Clinic; DNA; Exhibits; Funding; Gagging; Grant; HIV; HIV Infections; Human; Imiquimod; Immune response; Immunization; Immunoglobulin A; Immunomodulators; Interferon Type II; Interferons; Lung; Measures; Mediating; Mucosal Immune Responses; Mucous Membrane; Mus; National Center for Research Resources; Patients; Persons; Play; Principal Investigator; Protocols documentation; Recombinants; Reporting; Research; Research Infrastructure; Resources; Role; Route; Secretory Immunoglobulin A; Serum; Source; T-Lymphocyte; Testing; United States National Institutes of Health; Vaccination; Vaccines; Vaccinia; Vaccinium; Vagina; Viremia; base; cost; enzyme linked immunospot assay; human TLR7 protein; mucosal site; response; sex; transmission process

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. Mucosal transmission is the principal route of HIV infection. It has been shown that the mucosal early innate interferon response plays an important role against HIV infection. However, the mucosal immune response against HIV would be more effective if the neutralizing secretory immunoglobulins A and G response could be enhanced. It has been reported that highly exposed, persistently seronegative patients such as Gambian sex workers, and partners of HIV infected persons who have unprotected sexual relations exhibit higher Gag, Pol and Nef-specific T cell IFN-gamma responses in cervical mucosa, as compared to HIV-seropositive patients. Moreover, several groups have shown that Gag induces an HIV-specific T-cell and IgA immune responses at mucosal sites of lung and vaginal tract, besides that Gag, Nef, and Pol have been used in numerous mucosal immunization protocols. Therefore, the selection of Gag, Nef and Pol as antigens in combination with a mucosal immunization approach is expected to have a positive impact in the HIV-specific immune responses. DNA based vaccines are known to elicit both: cell- and humoral-mediated immune responses, however there is a need to increase the amplitude of their response in humans. On this project, we will determine the immunomodulatory effect of Imiquimod (a Toll-like receptor 7 agonist) in the enhancement of the HIV-specific immune response on a DNA vaccination platform, after vaccination of C57BL/6 mice. Cell- and humoral-mediated immune responses, as measured by ELISPOT and ICC analysis in these mice, will be correlated with control of viremia after qPCR analysis of serum from recombinant HIV-vaccinia infected mice. We hypothesize that Imiquimod, will enhance the HIV-gag, nef and pol specific mediated immune responses, after a DNA based mucosal immunization in mice. We therefore expect that these results could be moved easily and safely into the clinics, and therefore, could be tested in humans.

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。 粘膜传播是HIV感染的主要途径。已经表明，粘膜早期的先天干扰素反应对HIV感染起着重要作用。但是，如果可以增强中和中和中和中和中和中和的分泌免疫球蛋白A和G反应，则对HIV的粘膜免疫反应将更加有效。据报道，与HIV阳性患者相比，诸如冈比亚性工作者之类的高度暴露，持续的血清症患者，例如冈比亚性工作者和HIV性关系不受保护的人的HIV感染者的伴侣表现出较高的GAG，POL和NEF特异性T细胞IFN-GAMMA反应。此外，几个组表明，除了众多的粘膜免疫方案中，使用了肺和阴道粘膜部位的HIV特异性T细胞和IgA免疫反应，除了肺部和阴道的粘膜部位。因此，预计将GAG，NEF和POL作为抗原与粘膜免疫方法结合使用将对HIV特异性免疫反应产生积极影响。已知基于DNA的疫苗同时引起：细胞和体液介导的免疫反应，但是有必要增加其在人类中反应的幅度。在该项目上，我们将在C57BL/6小鼠接种后，将确定咪喹莫德（一种类似Toll样受体7激动剂）在DNA疫苗接种平台上增强HIV特异性免疫反应的免疫调节作用。通过ELISPOT和ICC分析在这些小鼠中测量的细胞和体液介导的免疫反应将与对病毒血症的控制相关，因为对重组HIV-VACCINIA感染小鼠的血清血清后，将与病毒血症的控制相关。我们假设在小鼠中基于DNA的粘膜免疫后，咪喹莫德将增强HIV，NEF和POL特异性介导的免疫反应。因此，我们希望这些结果可以轻松，安全地进入诊所，因此可以在人类中进行测试。