Genetic imprints of therapeutic Ad26/MVA mosaic vaccine in rebound HIV-1 genome from acutely treated individuals

治疗性 Ad26/MVA 嵌合疫苗在急性治疗个体反弹的 HIV-1 基因组中的遗传印记

基本信息

  • 批准号:
    10175390
  • 负责人:
  • 金额:
    $ 20.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-07-08 至 2022-06-30
  • 项目状态:
    已结题

项目摘要

Summary Due to the persistent reservoir established soon after HIV-1 transmission, life-long ART is required to maintain viral load suppression in HIV-1 infected individuals. Development of strategies able to induce long-term, ART-free remission is a high public health priority. One important strategy is therapeutic HIV vaccine. Although to date, majority of therapeutic vaccines failed to show clinical benefit, some showed evidence of vaccine efficacy as a delayed time to rebound or decreased viral load set point. This provides the hope to achieve a long-term remission if optimized vaccine strategies can be developed. The proposed study leverages a highly unique opportunity to employ novel sequencing technologies to understand viral evolutionary patterns in response to therapeutic vaccination in a promising Ad26.Mos/MVA.Mos vaccine regimen amongst acutely treated individuals who underwent analytical treatment interruption (ATI) in the RV405 study. This will be the first HIV-1 genetic study in the setting of a randomized, placebo- controlled therapeutic vaccine trial. Preliminary analysis showed successfully elicited immune responses in all RV405 vaccine recipients and a slightly delayed time to viral load rebound in the vaccine arm. Our central hypothesis is that the immune responses elicited by Ad26/MVA vaccination will exert selection pressures on the replicating viruses during rebound, which will leave “genetic imprints” in the rebound viral genomes. Both the genetic background of the T/F virus and its evolutionary trajectory in response to vaccine-induced immune pressures will correlate with the vaccine outcomes. We propose the following specific aims: Aim 1: To compare the genetic compositions of pre-ART and rebound viral populations and to identify vaccine-related genetic imprints in rebound viral genomes. Aim 2: To identify viral genetic correlates of the vaccine outcomes in both the T/F and rebound viral genomes. Our long-term goal is to translate knowledge of HIV vulnerabilities into optimizing future vaccine strategies towards the goal of HIV remission and eradication.
总结 由于HIV-1传播后不久就建立了持久的储存库, 是维持HIV-1感染者病毒载量抑制所必需的。发展 因此,制定能够诱导长期、无抗逆转录病毒疗法缓解的战略是一项高度优先的公共卫生工作。 一个重要的战略是治疗性艾滋病毒疫苗。尽管到目前为止,大多数 治疗性疫苗未能显示临床益处,一些疫苗显示出疫苗的证据 有效性作为延迟的反弹时间或降低的病毒载量设定点。这提供了以下 如果能够开发出优化的疫苗策略,希望能够实现长期缓解。 这项拟议的研究利用了一个非常独特的机会, 技术来了解病毒的进化模式, 在有希望的Ad26.Mos/MVA.Mos疫苗方案中, 在RV 405中接受分析性治疗中断(ATI)的治疗个体 study.这将是第一个在随机、安慰剂背景下进行的HIV-1遗传研究, 对照治疗性疫苗试验初步分析显示成功地引出了 所有RV 405疫苗接种者的免疫应答和病毒感染时间的略微延迟 我们的中心假设是, 由Ad 26/MVA疫苗接种引起的免疫应答将对复制病毒施加选择压力 在反弹期间,这将在反弹病毒基因组中留下“遗传印记”。两 T/F病毒的遗传背景及其响应于 疫苗诱导的免疫压力将与疫苗结果相关。我们 提出以下具体目标: 目的1:比较ART前和反弹病毒群体的遗传组成 并鉴定反弹病毒基因组中与疫苗相关的遗传印记。 目的2:确定T/F和T/F中疫苗结果的病毒遗传相关性, 病毒基因组反弹 我们的长期目标是将艾滋病毒脆弱性的知识转化为优化未来 疫苗战略,以实现缓解和根除艾滋病毒的目标。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Immune escape mutations selected by neutralizing antibodies in natural HIV-1 infection can alter coreceptor usage repertoire of the transmitted/founder virus.
  • DOI:
    10.1016/j.virol.2022.01.010
  • 发表时间:
    2022-03
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Marichannegowda, Manukumar Honnayakanahalli;Song, Hongshuo
  • 通讯作者:
    Song, Hongshuo
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Hongshuo Song其他文献

Hongshuo Song的其他文献

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