Antigenic and virological traits of HIV-1 breakthrough infections in the VRC01 antibody-mediated prevention Phase 2b trial in sub-Saharan Africa

撒哈拉以南非洲 VRC01 抗体介导的预防 2b 期试验中 HIV-1 突破性感染的抗原和病毒学特征

基本信息

  • 批准号:
    10609096
  • 负责人:
  • 金额:
    $ 33.34万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-04-17 至 2025-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Whether through active or passive immunization, broadly neutralizing antibodies (bNAbs) will likely form a cornerstone of HIV prevention. This application proposes an ancillary study of the African component of the antibody-mediated prevention trial (AMP) (HVTN 703/HPTN 081). The AMP study is the first proof-of-concept trial to evaluate the safety and efficacy of a bNAb (VRC01) to block HIV acquisition. Our team is involved in the laboratory investigations to measure serum levels associated with protection, and through sieve analysis, to determine how predicted genotypic features correlate with prevention efficacy. The goal of this application is to provide a deeper understanding on how HIV-1 diversity affects the amount of antibody needed to prevent infection; and the clinical consequences of infection with VRC01-resistant viruses. The extreme diversity of circulating HIV strains, together with the flexibility of the Envelope protein (Env) in evading immune pressure, could threaten the effectiveness of immunization studies. Utilizing sequence data and functional env clones from AMP breakthrough infections, the first aim will provide an up-to-date bNAb sensitivity profile of circulating strains, providing data useful for future clinical trials. This analysis will be done using the standardized Env-pseudotyped assay, and a subset will also be evaluated using infectious env clones generated in PBMCs to verify these data. The parent protocol sieve analysis will predict genetic features that affect VRC01 neutralization susceptibility and resistance, and the second aim of this application will experimentally validate these predictions, as well as evaluate how the cognate Env of breakthrough infections influences the impact of these mutations. This will provide experimental data on how changes in envelope affect the amount of antibody needed for prevention of infection. Lastly, VRC01 escape mutations have been associated with reduced viral fitness and we will compare fitness of VRC01-resistant and sensitive viruses and determine how this affects key clinical markers such as HIV viral load and CD4 counts. The HVTN 703/HPTN 081 trial provides a unique opportunity to define the impact of diversity on bNAb efficacy in a sub-Saharan Africa setting where new prevention approaches are still urgently needed. This study will be led by investigators at the University of Cape Town and the Fred Hutchinson Cancer Research Center, in collaboration with the National Institute for Communicable Diseases, and includes a training partnership with North-West University in Mahikeng, South Africa. Information generated in this proposal will support the next phase of combination passive immunization trials and will provide seminal data to understand the prevention efficacy of VRC01.
项目总结

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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Peter B. Gilbert其他文献

Practice of Epidemiology Estimating the Efficacy of Preexposure Prophylaxis for HIV Prevention Among Participants With a Threshold Level of Drug Concentration
流行病学实践评估药物浓度阈值水平的参与者中暴露前预防对艾滋病毒预防的功效
  • DOI:
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    0
  • 作者:
    James Y. Dai;Peter B. Gilbert;James P. Hughes;Elizabeth R. Brown
  • 通讯作者:
    Elizabeth R. Brown
A comparative analysis of abandoned street children and formerly abandoned street children in La Paz, Bolivia
玻利维亚拉巴斯被遗弃街头儿童与曾经被遗弃街头儿童的比较分析
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    C;P. Barreda;V. Mendoza;L. Guzmán;Peter B. Gilbert
  • 通讯作者:
    Peter B. Gilbert
1 - Viral Kinetic Correlates of Cytomegalovirus Disease and Death after Hematopoietic Cell Transplant
  • DOI:
    10.1016/j.bbmt.2017.12.006
  • 发表时间:
    2018-03-01
  • 期刊:
  • 影响因子:
  • 作者:
    Elizabeth R. Duke;Peter B. Gilbert;Terry L. Stevens-Ayers;Jonathan L. Golob;Nicole Cossrow;Morgan A. Marks;Hong Wan;T. Christopher Mast;Meei-Li W. Huang;Keith R. Jerome;Lawrence Corey;Joshua T. Schiffer;Michael J. Boeckh
  • 通讯作者:
    Michael J. Boeckh
Efficient nonparametric estimation of the covariate-adjusted threshold-response function, a support-restricted stochastic intervention
协变量调整阈值响应函数的有效非参数估计,支持限制随机干预
  • DOI:
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    L. Laan;Wenbo Zhang;Peter B. Gilbert
  • 通讯作者:
    Peter B. Gilbert
Neutralizing antibody correlate of protection against severe-critical COVID-19 in the ENSEMBLE single-dose Ad26.COV2.S vaccine efficacy trial
在 ENSEMBLE 单剂量 Ad26.COV2.S 疫苗效力试验中与预防严重/危重 COVID-19 相关的中和抗体
  • DOI:
    10.1038/s41467-024-53727-y
  • 发表时间:
    2024-11-12
  • 期刊:
  • 影响因子:
    15.700
  • 作者:
    Lindsay N. Carpp;Ollivier Hyrien;Youyi Fong;David Benkeser;Sanne Roels;Daniel J. Stieh;Ilse Van Dromme;Griet A. Van Roey;Avi Kenny;Ying Huang;Marco Carone;Adrian B. McDermott;Christopher R. Houchens;Karen Martins;Lakshmi Jayashankar;Flora Castellino;Obrimpong Amoa-Awua;Manjula Basappa;Britta Flach;Bob C. Lin;Christopher Moore;Mursal Naisan;Muhammed Naqvi;Sandeep Narpala;Sarah O’Connell;Allen Mueller;Leo Serebryannyy;Mike Castro;Jennifer Wang;Christos J. Petropoulos;Alex Luedtke;Yiwen Lu;Chenchen Yu;Michal Juraska;Nima S. Hejazi;Daniel N. Wolfe;Jerald Sadoff;Glenda E. Gray;Beatriz Grinsztejn;Paul A. Goepfert;Linda-Gail Bekker;Aditya H. Gaur;Valdilea G. Veloso;April K. Randhawa;Michele P. Andrasik;Jenny Hendriks;Carla Truyers;An Vandebosch;Frank Struyf;Hanneke Schuitemaker;Macaya Douoguih;James G. Kublin;Lawrence Corey;Kathleen M. Neuzil;Dean Follmann;Richard A. Koup;Ruben O. Donis;Peter B. Gilbert
  • 通讯作者:
    Peter B. Gilbert

Peter B. Gilbert的其他文献

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{{ truncateString('Peter B. Gilbert', 18)}}的其他基金

CoVPN Cross-Protocol Analyses
CoVPN 跨协议分析
  • 批准号:
    10570780
  • 财政年份:
    2022
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN 5001 - A prospective study of acute immune responses to SARS-CoV-2 infection
CoVPN 5001 - 对 SARS-CoV-2 感染的急性免疫反应的前瞻性研究
  • 批准号:
    10581432
  • 财政年份:
    2022
  • 资助金额:
    $ 33.34万
  • 项目类别:
HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals
HVTN 405/HPTN 1901 表征恢复期个体的 SARS-CoV-2 特异性免疫力
  • 批准号:
    10570787
  • 财政年份:
    2022
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN 3006: A randomized controlled study to assess SARS-CoV-2 infection, viral shedding, and subsequent potential transmission in university students immunized with Moderna COVID-19 Vaccine
CoVPN 3006:一项随机对照研究,旨在评估接种 Moderna COVID-19 疫苗的大学生中的 SARS-CoV-2 感染、病毒脱落以及随后的潜在传播
  • 批准号:
    10375264
  • 财政年份:
    2021
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN Cross-Protocol Analyses
CoVPN 跨协议分析
  • 批准号:
    10322571
  • 财政年份:
    2021
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN 5001 A prospective study of acute immune responses to SARS-CoV-2 infection SDMC
CoVPN 5001 对 SARS-CoV-2 感染的急性免疫反应的前瞻性研究 SDMC
  • 批准号:
    10319288
  • 财政年份:
    2021
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN 3003 A Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older SDMC
CoVPN 3003 评估 Ad26.COV2.S 在 18 岁及以上成人中预防 SARS-CoV-2 介导的 COVID-19 的功效和安全性的 3 期研究 SDMC
  • 批准号:
    10320660
  • 财政年份:
    2020
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN Cross-Protocol Analyses
CoVPN 跨协议分析
  • 批准号:
    10247368
  • 财政年份:
    2020
  • 资助金额:
    $ 33.34万
  • 项目类别:
CoVPN 3001 A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine SDMC
CoVPN 3001 评估 mRNA-1273 SARS-CoV-2 疫苗 SDMC 的功效、安全性和免疫原性的 3 期、随机、分层、观察者盲法、安慰剂对照研究
  • 批准号:
    10217912
  • 财政年份:
    2020
  • 资助金额:
    $ 33.34万
  • 项目类别:
HVTN 405/HPTN 1901 Characterizing SARS-CoV-2-specific immunity in convalescent individuals
HVTN 405/HPTN 1901 表征恢复期个体的 SARS-CoV-2 特异性免疫力
  • 批准号:
    10166307
  • 财政年份:
    2020
  • 资助金额:
    $ 33.34万
  • 项目类别:

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Active immunization mouse model by cN1A peptides
cN1A肽主动免疫小鼠模型
  • 批准号:
    18K15370
  • 财政年份:
    2018
  • 资助金额:
    $ 33.34万
  • 项目类别:
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Development of an efficient oocyte collection method using active immunization against inhibin in cynomolgus monkeys.
使用食蟹猴主动免疫抑制素开发有效的卵母细胞收集方法。
  • 批准号:
    17H06766
  • 财政年份:
    2017
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肺孢子虫的被动和主动免疫
  • 批准号:
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Active Immunization for Treating Methamphetamine Abuse
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  • 批准号:
    8136035
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Can passive or active immunization alter the course of infection with circoviral DNA?
被动或主动免疫可以改变圆环病毒 DNA 的感染过程吗?
  • 批准号:
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治疗甲基苯丙胺滥用的主动免疫
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针对儿童艾滋病的被动-主动免疫策略
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    7065729
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    2006
  • 资助金额:
    $ 33.34万
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