COMBINATION VACCINE/MICROBICIDE EFFICACY ASSESSMENT IN THE SHIV/MACAQUE MODEL

SHIV/猕猴模型中的联合疫苗/杀菌剂功效评估

• 批准号: 8172988
• 负责人: CECILIA C CHENG-MAYER
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172988
• 关键词: Animals; Cells; Combined Vaccines; Computer Retrieval of Information on Scientific Projects Database; Dose; Female; Funding; Gagging; Grant; Infection; Institution; Left; Macaca; Macaca mulatta; Modeling; Protocols documentation; Research; Research Personnel; Resources; SIV; Source; Systemic infection; United States National Institutes of Health; Vaccinated; Vaccines; Virus; microbicide

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. We completed repeat IVAG challenge of the eight DNA/Ad5 SIV gag-pol vaccinated and eight unvaccinated female Indian rhesus macaques (RM). We modified the challenge protocol as follows to assure that 100% of the unvaccinated macaques will be infected: 10 challenges with 300 TCID50, 5 challenges with 1000 TCID50 and 5 challenges with 3000 TCID50 of cell-free SHIVSF162P3 for a total of 20 exposures. Using this escalated dose challenge protocol, all 8 macaques in the control unvaccinated group were infected, with a range of 3-18 exposures needed to establish systemic infection. Six of the eight vaccinated macaques were also infected, with 1-17 inoculations needed for infection, while two remained uninfected after 20 exposures. Analysis of the cumulative proportion of uninfected macaques as a function of the number of weekly intravaginal exposures showed that the survival curve for the vaccinated group shifted to the left of the control curve from the 1st to 3rd exposure, reflecting the fact that two of the vaccinated macaques were infected after 1 and 2 virus exposures, whereas a minimum of three exposures was required to infect animals in the unvaccinated group. The vaccine survival curve diverged from that of the control after the 5th exposure, becoming maximal from the 9th to the 16th exposure. This latter observation, together with the fact the 2 of the 8 vaccinated macaques remained uninfected after 20 challenges is suggestive of a "leaky vaccine" effect.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们完成了8只DNA/Ad 5 SIV gag-pol疫苗接种和8只未接种的雌性印度恒河猴（RM）的重复IVAG攻击。我们对攻毒方案进行了如下修改，以确保100%未接种疫苗的猕猴将被感染：300 TCID 50攻毒10次，1000 TCID 50攻毒5次，3000 TCID 50无细胞SHIVSF 162 P3攻毒5次，共暴露20次。使用该递增剂量攻毒方案，对照未接种组中的所有8只猕猴均被感染，需要3-18次暴露以建立全身感染。 8只接种疫苗的猕猴中有6只也被感染，感染需要1-17次接种，而2只在20次接种后仍未感染。未感染猕猴的累积比例作为每周阴道内暴露次数的函数的分析显示，从第1次至第3次暴露，接种组的存活曲线向对照曲线的左侧移动，反映了2只接种猕猴在1次和2次病毒暴露后感染的事实，而感染未接种组的动物需要至少三次暴露。疫苗存活曲线在第5次暴露后偏离对照，在第9次至第16次暴露时达到最大值。后一种观察结果以及8只接种的猕猴中有2只在20次攻击后仍未感染的事实表明了“疫苗泄漏”效应。