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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 缺乏有关保护艾滋病毒/SIV感染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。 事实证明，猕猴对猕猴的疫苗接种是最有效的方法，可以保护针对致病性SIV挑战，并提供最佳的可用实验模型来定义负责保护的特定机制。 我们小组的先前研究提供了证据，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，但无法评估其相对重要性或新型适应性或先天免疫反应对保护的相对重要性或潜在贡献。 这项研究的目的是利用许多新型技术来全面分析适应性和先天免疫反应在介导SIV NEF诱导的防御阴道挑战的保护中的作用，这是HIV传播的最重要模式之一。 SIV NEF感染导致自然杀伤细胞，SIV特异性CD8阳性T细胞反应和抗体反应的显着增加，并在感染后的前2-5周内显着增加。这些反应与疫苗接种后5周的阴道SIVMAC251挑战有关。 体液和细胞免疫反应都显示出疫苗接种后5到20周的渐进式证据，这与对阴道SIVMAC251挑战的实质但仍然不完整有关。 这些研究结果对保护性免疫的特征进行了全面的描述。