权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
Hongshuo Song
金额：
$ 20.96万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
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：
https://reporter.nih.gov/project-details/10175390
关键词：
Acute Adherence Antibody Response Antigens Attention Cells Clinical Development Disease remission Double-Blind Method Drug resistance Epitopes Exhibits Future Genetic Genetic Determinism Genetic study Genome Genomic Imprinting Goals HIV HIV Genome HIV Infections HIV vaccine HIV-1 Human Immune Immune response Individual Infection Interruption Knowledge Life Modeling Mosaicism Mutation Nature Outcome Participant Pattern Phase Placebos Population Probability RNA-Directed DNA Polymerase Randomized Regimen Sampling Therapeutic Time Translating Vaccination Vaccine Antigen Vaccine Therapy Vaccines Vial device Viral Viral Genome Viral Load result Virus antiretroviral therapy arm cost fitness immunogenicity improved in vivo nonhuman primate novel sequencing technology placebo controlled study pressure public health priorities response safety study side effect social stigma therapeutic vaccine transmission process vaccine efficacy vaccine trial viral rebound virology virus 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