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
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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