PROTECTION AGAINST VAGINAL CHALLENGE IN SIVDELTANEF-VACCINATED ANIMALS

接种 SIVDELTANEF 疫苗的动物免受阴道感染的保护

• 批准号: 7958387
• 负责人: Roger H Reeves
• 金额: $ 19.97万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958387
• 关键词: AIDS Vaccines; Animals; Antibody Formation; Attenuated; Characteristics; Computer Retrieval of Information on Scientific Projects Database; Development; Experimental Models; Funding; Goals; Grant; HIV; Immune response; Immunity; Infection; Institution; Macaca; Mediating; Natural Killer Cells; New England; Primates; Relative (related person); Research; Research Personnel; Resources; Role; SIV; Source; T-Lymphocyte; Techniques; United States National Institutes of Health; Vaccinated; Vaccination; Vagina; base; novel; response; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Lack of information on mechanisms of protection against HIV/SIV infection remains one of the leading obstacles to the development of a safe and effective AIDS vaccine. Vaccination of macaques with attenuated SIV strains has consistently proved to be the most effective means of inducing protection against pathogenic SIV challenge and offers the best available experimental model to define specific mechanisms responsible for protection. Previous studies from our group have provided evidence that SIV-specific CD8-positive T cell and humoral responses both contribute to protective immunity induced by SIVdeltanef but have not been able to assess their relative importance or the potential contributions of novel adaptive or innate immune responses to protection. The goal of this study is to utilize a number of novel techniques to carry out a comprehensive analysis of the role of adaptive and innate immune responses in mediating protection induced by SIVnef against vaginal challenge, one of the most important modes of HIV transmission. SIVnef infection resulted in significant increases in natural killer cells, SIV-specific CD8-positive T cell responses and antibody responses in the first 2-5 weeks after infection; these responses were associated with minimal protection against vaginal SIVmac251 challenge at 5 weeks after vaccination. Both humoral and cellular immune responses display progressive evidence of maturation from 5 to 20 weeks after vaccination, associated with substantial, though still incomplete, protection against vaginal SIVmac251 challenge. These studies results are yielding a comprehensive delineation of the signature characteristics of protective immunity against lentiviral infection.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 缺乏有关 HIV/SIV 感染保护机制的信息仍然是开发安全有效的艾滋病疫苗的主要障碍之一。 猕猴接种 SIV 减毒株已被一致证明是针对致病性 SIV 攻击诱导保护的最有效方法，并提供了最佳的实验模型来定义负责保护的具体机制。 我们小组之前的研究提供了证据，表明 SIV 特异性 CD8 阳性 T 细胞和体液反应都有助于 SIVdeltanef 诱导的保护性免疫，但无法评估它们的相对重要性或新型适应性或先天免疫反应对保护的潜在贡献。 本研究的目的是利用多种新技术，全面分析适应性和先天免疫反应在介导 SIV nef 诱导的针对阴道攻击（HIV 传播最重要的模式之一）的保护中的作用。 SIV nef感染导致感染后2-5周内自然杀伤细胞、SIV特异性CD8阳性T细胞反应和抗体反应显着增加；这些反应与疫苗接种后 5 周时针对阴道 SIVmac251 攻击的最低保护作用相关。 接种疫苗后 5 至 20 周，体液和细胞免疫反应都显示出逐渐成熟的证据，与针对阴道 SIVmac251 攻击的实质性（尽管仍不完全）保护相关。 这些研究结果全面描述了针对慢病毒感染的保护性免疫的特征。