IMMUNOGENICITY AND PROTECTION OF LIVE ATTENUATED SIV239 DELTA NEF IN RHESUS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 目的：利用SIV减毒活疫苗作为研究的独特机会 有效的抗免疫缺陷病毒免疫反应。 进度： 我们用活的SIV减毒株给8只恒河猴接种疫苗。 SIVmac239nef在2009年春天。我们监测了SIV特异性病毒的发展 在这个队列中使用各种检测方法进行免疫反应。接种疫苗的动物， 与8名幼稚的对照组一起，接受直肠内挑战(I.R.)带着重复的、低的 2009年秋天，未克隆的“蜂群”病毒SIVsmE660的剂量。我们检测到一种 与NAVE控制相比，SIVsmE660的采购量显著减少(日志- 等级检验；p=0.023)。在十次粘膜挑战后，我们检测到 在8只接种疫苗的动物中，只有5只出现了挑战菌株。相比之下，有七个 在这10次挑战后，8只对照动物感染了SIVsmE660。 此外，感染SIVsmE660疫苗的动物控制了急性病毒的高峰 复制显著好于幼稚对照(Mann-Whitney检验；p=0.038)。 五名SIVsmE660疫苗接种者中有四人迅速控制了病毒复制 感染后4周。不幸的是，这四只接种疫苗的动物中有两只丢失了 在慢性感染阶段控制病毒复制。批量测序 对这些动物体内传播病毒的分析表明，重组已经 在疫苗和挑战毒株之间发生，并可能导致 这些动物体内的病毒复制增加。总体而言，我们的结果表明- 设计的艾滋病毒疫苗可能既能降低获得率，又能控制病毒 复制。 这项研究使用了WNPRC病毒学和免疫学服务。 出版物： 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容 勒恩·EJ，罗杰斯·韦，马科斯基·R，麦克德莫特·AB，博伊尔·R，威尔逊·纳，艾莉森·DB， 伯顿博士，科夫·WC，沃特金斯DI。接种猴免疫缺陷疫苗的猕猴 病毒SIVmac239 Delta nef重复后延迟获取和控制复制 低剂量异源SIV挑战。J·维罗尔。2010年9月；84(18)：9190-9。EPub 2010年6月30日PMID：20592091，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.