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
- 来源:
- 关键词:AcuteAdherenceAntibody ResponseAntigensAttentionCellsClinicalDevelopmentDisease remissionDouble-Blind MethodDrug resistanceEpitopesExhibitsFutureGeneticGenetic DeterminismGenetic studyGenomeGenomic ImprintingGoalsHIVHIV GenomeHIV InfectionsHIV vaccineHIV-1HumanImmuneImmune responseIndividualInfectionInterruptionKnowledgeLifeModelingMosaicismMutationNatureOutcomeParticipantPatternPhasePlacebosPopulationProbabilityRNA-Directed DNA PolymeraseRandomizedRegimenSamplingTherapeuticTimeTranslatingVaccinationVaccine AntigenVaccine TherapyVaccinesVial deviceViralViral GenomeViral Load resultVirusantiretroviral therapyarmcostfitnessimmunogenicityimprovedin vivononhuman primatenovel sequencing technologyplacebo controlled studypressurepublic health prioritiesresponsesafety studyside effectsocial stigmatherapeutic vaccinetransmission processvaccine efficacyvaccine trialviral reboundvirologyvirus genetics
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)
Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study.
- DOI:10.1016/j.ebiom.2023.104867
- 发表时间:2023-12
- 期刊:
- 影响因子:11.1
- 作者:
- 通讯作者:
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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