IMMUNOGENICITY AND PROTECTION OF LIVE ATTENUATED SIV239 DELTA NEF IN RHESUS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 目的：利用SIV减毒活疫苗作为一个独特的机会， 有效的抗免疫缺陷病毒免疫反应。 进展： 我们用SIV减毒活毒株免疫了8只恒河猴 SIVmac2392009年春，我们监测了SIV特异性 使用多种测定来检测该群组中的免疫应答。接种疫苗的动物， 沿着8个幼稚对照，经直肠内（i.r.）重复，低 在2009年秋天，一批未克隆的“蜂群”病毒SIVsmE 660。我们找到这样一 与未经处理的对照组相比，SIVsmE 660的获得显著减少（Log- 秩检验; p=0.023）。在十次粘膜攻击后，我们检测到 8只接种动物中仅5只存在攻毒株。相比之下， 在这10次攻击后，8只对照动物感染了SIVsmE 660。 此外，SIVsmE 660感染的接种动物控制了急性病毒峰值， 复制显著优于幼稚对照（Mann-Whitney检验; p=0.038）。 5名SIVsmE 660疫苗接种者中有4名迅速控制了病毒复制 感染后第4周。不幸的是，这四只接种疫苗的动物中有两只 在感染的慢性阶段控制病毒复制。整体测序 对这些动物中的循环病毒的分析表明， 在疫苗和攻毒株之间发生，可能导致 增加了这些动物体内的病毒复制。总的来说，我们的研究结果表明，一个良好的- 设计的艾滋病毒疫苗既可以降低感染率， 复制的 该研究使用WNPRC病毒学和免疫学服务。 出版物： Reynolds MR，Weiler AM，Piaskowski SM，Kolar HL，Hessell AJ，Weiker M，Weisgrau KL， Le n EJ，Rogers WE，Makowsky R，McDermott AB，波义耳R，Wilson NA，Allison DB， Burton DR，Koff WC，Watkins DI.接种猴免疫缺陷疫苗的猕猴 病毒SIVmac 239 Δ nef在重复后延迟获得和控制复制 低剂量异源SIV攻击。J Virol。2010年9月; 84（18）：9190-9。Epub 2010年6月30日。PMID：20592091，PMCID：PMC2937616。

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. Objective: To use live-attenuated SIV vaccines as a unique opportunity to study effective anti-immunodeficiency virus immune responses. PROGRESS: We vaccinated eight rhesus macaques with the live-attenuated SIV strain SIVmac239nef in the spring of 2009. We monitored the development of SIV-specific immune responses in this cohort using a variety of assays. The vaccinated animals, along with eight naive controls, were challenged intrarectally (i.r.) with repeated, low doses of the uncloned "swarm" virus SIVsmE660 in the fall of 2009. We detected a significant reduction in acquisition of SIVsmE660 in comparison to na¿ve controls (Log- rank test; p=0.023). After ten mucosal challenges we detected replication of the challenge strain in only five of the eight vaccinated animals. In contrast, seven of the eight control animals became infected with SIVsmE660 after these ten challenges. Additionally, the SIVsmE660-infected vaccinated animals controlled peak acute virus replication significantly better than the naive controls (Mann-Whitney test; p=0.038). Four of the five SIVsmE660 vaccinees rapidly brought virus replication under control by week 4 post-infection. Unfortunately, two of these four vaccinated animals lost control of virus replication during the chronic phase of infection. Bulk sequencing analysis of the circulating virus in these animals indicated that recombination had occurred between the vaccine and challenge strains and likely contributed to the increased virus replication in these animals. Overall, our results suggest that a well- designed HIV vaccine might both reduce the rate of acquisition and control viral replication. The research used WNPRC Virology & Immunology Services. PUBLICATION: Reynolds MR, Weiler AM, Piaskowski SM, Kolar HL, Hessell AJ, Weiker M, Weisgrau KL, Le¿n EJ, Rogers WE, Makowsky R, McDermott AB, Boyle R, Wilson NA, Allison DB, Burton DR, Koff WC, Watkins DI. Macaques vaccinated with simian immunodeficiency virus SIVmac239Delta nef delay acquisition and control replication after repeated low-dose heterologous SIV challenge. J Virol. 2010 Sep; 84(18):9190-9. Epub 2010 Jun 30. PMID: 20592091, PMCID: PMC2937616.