DENDRITIC CELL ACTIVATION BY ISS ODN FOR SIV IMMUNITY

ISS ODN 激活树突状细胞以增强 SIV 免疫能力

• 批准号: 8358061
• 负责人: Melissa J Robbiani
• 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/8358061
• 关键词: Adjuvant; Animals; Blood; Dendritic cell activation; Funding; Grant; HIV; Immune; Immunity; Immunization; Individual; Infection; Measures; Methodology; Modeling; National Center for Research Resources; Plasma; Primates; Principal Investigator; Research; Research Infrastructure; Resources; SIV; Source; Therapeutic; Tissues; Tonsil; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Viral; Viral Load result; Viremia; Virus Diseases; antiretroviral therapy; cost; nonhuman primate; rectal; therapeutic vaccine

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. BACKGROUND: HIV-infected individuals rely on antiretroviral therapy (ART) to control viral replication. Despite abundant demonstrable benefits, the multiple limitations of ART point to the potential advantages of therapeutic vaccination approaches that could provide sustained host control of viral replication after discontinuation of ART. We provide evidence from a non-human primate model that a therapeutic vaccine applied to the tonsils can maintain low viral loads after cessation of ART. METHODOLOGY/PRINCIPAL FINDINGS: Animals received 40 weeks of ART initiated 9 weeks after rectal SIVmac239 infection. During ART, animals were vaccinated (or not) with AT-2 inactivated SIVmac239 using CpG-C ISS-ODN (C274) or polyICLC as adjuvants. PolyICLC/AT-2 SIV vaccinated animals maintained viral loads 3¿10(3) copies/ml for up to 16 weeks post-ART, whereas the C274/AT-2 SIV vaccinated and non-vaccinated animals' viremia ranged between 1¿10(4)-4¿10(5) copies/ml (p0.03). Neutralizing Ab activity in plasma was increased by polyICLC/AT-2 tonsillar vaccination under ART, compared to controls (p0.03). Subsequent vaccination of all animals with polyICLC/AT-2 SIV in the absence of ART did not alter viral loads. Other immune parameters measured in blood and tissues were comparable between groups. CONCLUSIONS/SIGNIFICANCE: These results provide support for the potential benefit of mucosally delivered vaccines in therapeutic immunization strategies for control of AIDS virus infection.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 背景：HIV感染者依靠抗逆转录病毒治疗（ART）来控制病毒复制。尽管有大量可证实的益处，但ART的多重局限性表明了治疗性疫苗接种方法的潜在优势，该方法可以在ART停止后提供对病毒复制的持续宿主控制。我们提供了来自非人灵长类动物模型的证据，即应用于扁桃体的治疗性疫苗可以在ART停止后维持低病毒载量。方法学/主要发现：动物在直肠SIVmac 239感染后9周开始接受40周的ART。在ART期间，使用CpG-C ISS-0 DN（C274）或聚ICLC作为佐剂，用AT-2灭活的SIVmac 239接种（或不接种）动物。PolyICLC/AT-2 SIV接种动物在ART后长达16周内保持病毒载量3 <$10（3）拷贝/ml，而C274/AT-2 SIV接种和未接种动物的病毒血症范围为1 <$10（4）-4 <$10（5）拷贝/ml（p <0.03）。与对照组相比，ART下polyICLC/AT-2扁桃体接种增加了血浆中的中和Ab活性（p <0.03）。在不存在ART的情况下，所有动物随后接种polyICLC/AT-2 SIV未改变病毒载量。血液和组织中测量的其他免疫参数在组间相当。 结论/意义：这些结果为粘膜递送疫苗在控制艾滋病病毒感染的治疗性免疫策略中的潜在益处提供了支持。