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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 缺乏关于预防艾滋病毒/SIV感染的机制的信息，仍然是开发安全有效的艾滋病疫苗的主要障碍之一。用减毒的SIV毒株接种猕猴已被证明是诱导对致病性SIV攻击的保护最有效的手段，并提供了最好的可用实验模型来确定具体的保护机制。我们小组以前的研究已经提供了证据，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，但还不能评估它们的相对重要性或新的适应性或先天免疫反应对保护的潜在贡献。这项研究的目的是利用一些新的技术来全面分析适应性免疫反应和先天免疫反应在SIVnef诱导的对阴道攻击的保护中的作用，SIVnef是HIV最重要的传播方式之一。SIVnef感染后2~5周，自然杀伤细胞、SIV特异性CD8阳性T细胞反应和抗体反应显著增加；这些反应与疫苗接种后5周对阴道SIVmac251攻击的最小保护作用有关。体液和细胞免疫反应在接种后5到20周显示出逐渐成熟的证据，与对阴道SIVmac251挑战的实质性保护有关，尽管仍不完全。这些研究结果全面描绘了针对慢病毒感染的保护性免疫的标志性特征。