VACCINATION AGAINST INTRAPARTUM HIV-L CLADE C TRANSMISSION SUPPLEMENT

产时接种 HIV-L C 型传播补充剂

• 批准号: 8357549
• 负责人: JAMES GIBSON ELSE
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357549
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Antiviral Agents; Childhood; Dana-Farber Cancer Institute; Funding; Genetic; Grant; HIV; HIV Infections; HIV vaccine; Hybrids; Immunity; Infection; Life; Macaca mulatta; Modeling; National Center for Research Resources; Newborn Infant; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Route; SIV; Sampling; Series; Site; Source; Specificity; Testing; United States National Institutes of Health; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Viral Load result; Virus; Virus Diseases; cost; efficacy testing; gene cloning; interest; intrapartum; neutralizing antibody; transmission process; vaccine efficacy

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. In association with the Dana Farber Cancer Institute, we are using the rhesus macaque model of HIV infection and AIDS to develop potential vaccine strategies against the Clade C strain of HIV (HIV-C) the world's most prevalent strain. The grant supplement specifically seeks to determine the correlates of protection in a vaccinated Rhesus with long-lived antiviral immunity. For efficacy testing of potential vaccines, we have developed a series of hybrid viruses, (SHIVs) by combining genetic components of simian immunodeficiency virus with envelope genes cloned directly from Zambian pediatric samples. SHIVs are then adapted to rhesus macaques generating challenge stocks capable of inducing infection via mucosal routes and sustaining viral loads and disease to test vaccine efficacy. Of interest is the fact that the Env of SHIV1157ipd3 was isolated from a newborn who has maintained high CD4 levels in spite of high viral loads for 10 years while Env from SHIV2873Nip was isolated from a newborn that developed AIDS and died at 9 months, suggesting Env as a pathogenic determinant across species. Vaccine efficacy is purposely tested against challenges with SHIV-C isolates that are heterogonous to the isolates from which the vaccine antigens are developed to mimic reality field conditions. We are also analyzing the fine-specificity of the antibody responses in these animals to identify specific sites of envelope able to induce broadly cross-neutralizing antibodies across HIV strains, a key component of new HIV vaccines.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 我们与达纳法伯癌症研究所合作，利用艾滋病毒感染和艾滋病的恒河猴模型来开发针对世界上最流行的艾滋病毒 C 型菌株 (HIV-C) 的潜在疫苗策略。该补助金特别旨在确定接种疫苗的恒河猴的保护与长效抗病毒免疫力的相关性。为了测试潜在疫苗的功效，我们通过将猿猴免疫缺陷病毒的遗传成分与直接从赞比亚儿科样本克隆的包膜基因相结合，开发了一系列混合病毒（SHIV）。然后将 SHIV 适应恒河猴，产生能够通过粘膜途径诱导感染并维持病毒载量和疾病以测试疫苗功效的挑战种群。有趣的是，SHIV1157ipd3 的 Env 是从一名新生儿中分离出来的，该新生儿尽管病毒载量很高，10 年来仍保持高 CD4 水平，而 SHIV2873Nip 的 Env 是从一名患艾滋病并在 9 个月时死亡的新生儿中分离出来的，这表明 Env作为跨物种的致病决定因素。疫苗功效是专门针对 SHIV-C 分离株的挑战进行测试的，这些分离株与开发疫苗抗原的分离株是异源的，以模拟现实现场条件。我们还在分析这些动物中抗体反应的精细特异性，以确定能够诱导跨 HIV 毒株广泛交叉中和抗体的包膜特定位点，这是新型 HIV 疫苗的关键组成部分。