COMPARISON OF VACCINE REGIMENS: HIV-SIV RECOMBINANTS WITH PROTEIN BOOSTING

疫苗方案的比较：具有蛋白质增强作用的 HIV-SIV 重组体

• 批准号: 8357622
• 负责人: DAVID M ANDERSON
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 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/8357622
• 关键词: Acute; Adenoviruses; Animal Model; Animals; Antigens; Chronic Phase; Control Groups; Event; Funding; Grant; HIV; Immune response; Immunity; Immunization; Infection; Modeling; National Center for Research Resources; Phase; Primates; Principal Investigator; Proteins; Protocols documentation; Recombinants; Regimen; Research; Research Infrastructure; Resources; SIV; Source; United States National Institutes of Health; Vaccine Design; Vaccines; Viral; Viral Proteins; Viremia; Virus; Virus Replication; cost; gag Gene Products; immunogenic; protective efficacy; response; simian human immunodeficiency virus; tat Protein

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. Originally we sought to compare the same immunization protocol in both M. mulatta and M. fascicularis to determine if native viral protein, Tat alone could confer protection in either or both animal models. Although immunogenic, inactive Tat had not elicited protection against viral challenge in other studies; therefore it was important to determine if the active (native) molecule would be useful in vaccine design. Second, we wanted to determine if substitution of immunizations with Adenovirus recombinants encoding Tat followed by 2 Tat protein immunizations (Group II) is as effective as the multiple Tat protein immunization alone ( Group I). The ability of a vaccine to confer protective immunity with as few immunizations as possible is important, especially in the developing world. Third, we sought to evaluate two immunogens in combination, both aimed at blocking initial infection or early virus replication events, for their ability to blunt acute phase viremia (Group III). The immunogens were HIV Env and tat. Finally, cellular immune responses, especially to the SIV Gag protein, had been shown able to significantly reduce viremia in the chronic phase in the SHIV challenge model. Therefore, (Group IV) animals were immunized with gag protein. Together with appropriate control groups, these immunization regimens were to help elucidate and compare the response and protective efficacy of immunologically active viral gene products during immunization and after virus challenge.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 最初，我们试图比较穆拉塔分枝杆菌和束枝分枝杆菌的相同免疫方案，以确定是否仅有天然病毒蛋白TAT可以在其中一种或两种动物模型中提供保护。尽管具有免疫原性，但在其他研究中，非活性TAT并未引起对病毒攻击的保护；因此，确定活性(天然)分子是否对疫苗设计有用是很重要的。 其次，我们想要确定用编码TAT的重组腺病毒替代免疫，然后进行2次TAT蛋白免疫(组II)是否与单独使用多重TAT蛋白免疫(组I)一样有效。疫苗在尽可能少的免疫情况下提供保护性免疫的能力很重要，特别是在发展中国家。 第三，我们试图评估两种免疫原的组合，它们都旨在阻止初始感染或早期病毒复制事件，以了解它们钝化急性期病毒血症的能力(第三组)。免疫原为HIV、Env和Tat。 最后，细胞免疫反应，特别是对SIV Gag蛋白的免疫反应，已经被证明能够显著减少SIV挑战模型中慢性期的病毒血症。因此，(IV组)动物用Gag蛋白免疫。 与适当的对照组一起，这些免疫方案有助于阐明和比较免疫活性病毒基因产品在免疫期间和病毒攻击后的反应和保护效果。