VACCINATION AGAINST INTRAPARTUM HIV-1 CLADE C TRANSMISSION

预防产时 HIV-1 C 类传播的疫苗接种

• 批准号: 8357404
• 负责人: JAMES GIBSON ELSE
• 金额: $ 8.92万
• 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/8357404
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Antibody Formation; Antigens; Cellular Immunity; Data; Dose; Funding; Gagging; Genetic; Grant; HIV; HIV Infections; HIV vaccine; HIV-1; Hybrids; Immune response; Infant; Link; Macaca mulatta; Modeling; Monkeys; National Center for Research Resources; Primates; Principal Investigator; Recombinants; Research; Research Infrastructure; Resources; SIV; Series; Site; Source; Specificity; Time; United States National Institutes of Health; Vaccinated; Vaccination; Vaccines; Viremia; Virus; cost; efficacy testing; gene cloning; gp160; intrapartum; neutralizing antibody; particle; simian human immunodeficiency virus; transmission process; vaccine candidate

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. We are using the rhesus macaque (RM) model of HIV infection and AIDS to develop potential vaccine strategies against HIV clade C (HIV-C), the world's most prevalent subtype. To test the efficacy of candidate vaccines, we have developed a series of hybrid viruses, termed simian-human immunodeficiency viruses (SHIVs), by combining genetic components of monkey AIDS virus (termed simian immunodeficiency virus (SIV)) with envelope genes cloned directly from recently transmitted HIV-C strains isolated from Zambian infants. SHIVs are then adapted to RM and large virus stocks are generated for mucosal challenges in the RM model. We vaccinated RM with recombinant SIV Gag-Pol particles, HIV-1 Tat and trimeric HIV-C gp160, which induced cross-neutralizing antibodies (nAbs) and robust cellular immune responses. After five low-dose mucosal challenges with a SHIV that encoded a heterologous R5 HIV-C envelope (22.1% divergence from the gp160 immunogen), 94% of controls became viremic, whereas one third of vaccinees remained virus-free. Upon high-dose SHIV rechallenge, all control RM became infected, whereas some vaccinees remained aviremic. Peak viremia was inversely correlated with both cellular immunity (p0.001) and cross-nAb titers (p0.001). These data simultaneously linked cellular as well as humoral immune responses with the degree of protection for the first time. 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。 我们正在使用HIV感染的恒河猴（RM）模型和AIDS来开发针对世界上最普遍的亚型HIV进化枝C（HIV-C）的潜在疫苗策略。 为了测试候选疫苗的疗效，我们通过将猴子艾滋病病毒的遗传成分（称为示例性的邻苯二醇免疫缺陷病毒（SIV））与直接从信封基因中直接克隆的信封基因相结合，从而形成了一系列称为Simian-Human免疫缺陷病毒（SHIVS）的混合病毒，称为Simian-Human免疫缺陷病毒（SHIVS）（SHIVS）。最近从赞比亚婴儿分离出的HIV-C菌株。然后，将SHIV适应RM，并在RM模型中生成大量病毒量以用于粘膜挑战。 我们用重组SIV GAG-POL颗粒，HIV-1 TAT和三聚体HIV-C GP160接种RM，它们诱导了交叉中和抗体（NABS）和可靠的细胞免疫反应。在五个低剂量的粘膜挑战中用SHIV编码了异源R5 HIV-C包膜（与GP160免疫原差异22.1％）后，94％的对照组成为了病毒性，而三分之一的疫苗却没有病毒。 高剂量的湿夫补偿后，所有控制RM都被感染了，而一些疫苗仍然是无毒的。 峰值病毒血症与细胞免疫（P0.001）和交叉NAB滴度（P0.001）成反比。 这些数据同时将细胞以及体液免疫反应与第一次保护程度联系起来。 我们还分析了这些动物中抗体反应的细特异性，以识别能够跨HIV菌株诱导广泛的跨中和抗体的特定位点，这是新的HIV疫苗的关键成分。