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.

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。 最初，我们试图比较穆拉塔（M. Mulatta）和筋膜分枝杆菌中的相同免疫方案，以确定天然病毒蛋白是否可以在动物模型中或两种动物模型中提供保护。尽管免疫原性，但在其他研究中没有引起对病毒挑战的保护；因此，确定活性（天然）分子是否在疫苗设计中有用很重要。 其次，我们想确定用编码TAT的腺病毒重组的免疫接种，然后进行2种TAT蛋白免疫（II组）与单独的多重TAT蛋白免疫（I II组）一样有效（I组）。 疫苗以尽可能少的免疫接种赋予保护性免疫的能力很重要，尤其是在发展中国家。 第三，我们试图评估两种旨在阻止初始感染或早期病毒复制事件的免疫原子，因为它们具有钝化急性期病毒血症的能力（第三组）。 免疫原是HIV Env和TAT。 最后，在SHIV挑战模型中，已经证明了能够在慢性期显着降低病毒血症的细胞免疫反应，特别是对SIV GAG蛋白。因此，（IV组）用GAG蛋白免疫动物。 这些免疫方案与适当的对照组一起，有助于阐明和比较免疫和病毒挑战后免疫主动病毒基因产物的反应和保护性疗效。