Correlates of protective immunity to HCV and rational vaccine design

HCV 保护性免疫与合理疫苗设计的相关性

基本信息

  • 批准号:
    10608105
  • 负责人:
  • 金额:
    $ 205.42万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-15 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

Abstract Prevention of HCV infection remains an important public health objective even with the recent adoption of highly effective antiviral therapies. Importantly, treatment with direct acting antivirals (DAAs) does not prevent reinfection in those who have successfully been treated. A vaccine to prevent HCV persistence is needed to stem an emerging epidemic of infection in adolescents and young adults who inject drugs that have limited access to screening and treatment. Only twenty five percent of acute HCV infections resolve spontaneously. Resolution does, however, sharply reduce the risk of persistent infection upon re-exposure to the virus. Memory CD4+ T helper and CD8+ cytotoxic T cell responses contribute to accelerated clearance of a second infection. However, the role of neutralizing antibodies during reinfection is less clear. Importantly, vaccines to generate an equivalent T cell response failed to thwart off the rate of persistence in naïve recipients. Here, we will test the central hypothesis that memory CD4+ T cells contribute significantly to HCV reinfection outcome by promoting expansion of HCV-specific B cells and production of broadly neutralizing antibodies that contribute to viral clearance. Unique features of this proposal are (i) the use of longitudinal samples from the Montreal cohort of high- risk people who inject drugs. Participants are monitored prior to, during, and after HCV infection and then subsequently followed again when they have been re-exposed to HCV a second time after resolving their primary infection. (ii) We have assembled a team of investigators in Cairo, Egypt who will assist us with recruiting and treating subjects undergoing DAA treatment. Egypt has the highest prevalence of HCV infection in the world. In 2014, Egypt's government has made DAA treatment affordable and 2.5 million subjects have started treatment. Understanding the immune responses in these two cohorts will provide us with valuable information to develop an efficacious vaccine regimen that would emulate the successful responses generated during a natural challenge with HCV. Three highly interactive Projects are proposed. Project 1 (N. Shoukry, PI) will compare the frequency, breadth, function, and phenotype of CD4+ T cells in HCV reinfections that either resolve or become persistent. Project 2 (A. Grakoui, PI) will use new state of the art technology to isolate and characterize antigen-specific B cells during HCV reinfection and post DAA treatment. Project 3 (R. Amara, PI) will develop vaccine modalities to induce both a CD4+ T helper response and a robust antigen-specific antibody response in blood and liver using DNA, modified vaccinia Ankara (MVA) and protein-based vaccines against HCV proteins in non-human primates.
摘要

项目成果

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Arash Grakoui其他文献

Arash Grakoui的其他文献

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{{ truncateString('Arash Grakoui', 18)}}的其他基金

Correlates of protective immunity to HCV and rational vaccine design
HCV 保护性免疫与合理疫苗设计的相关性
  • 批准号:
    10393614
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Admin Core
HCV 保护性免疫与合理疫苗设计的相关性:Admin Core
  • 批准号:
    10393615
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design
HCV 保护性免疫与合理疫苗设计的相关性
  • 批准号:
    10205764
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 2
HCV 保护性免疫与合理疫苗设计的相关性:项目 2
  • 批准号:
    10205768
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 2
HCV 保护性免疫与合理疫苗设计的相关性:项目 2
  • 批准号:
    10393618
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 2
HCV 保护性免疫与合理疫苗设计的相关性:项目 2
  • 批准号:
    10608110
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Admin Core
HCV 保护性免疫与合理疫苗设计的相关性:Admin Core
  • 批准号:
    10205765
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Admin Core
HCV 保护性免疫与合理疫苗设计的相关性:Admin Core
  • 批准号:
    10608106
  • 财政年份:
    2021
  • 资助金额:
    $ 205.42万
  • 项目类别:
Dynamics of antigen specific B and Tfh responses during acute and chronic HCV
急性和慢性 HCV 期间抗原特异性 B 和 Tfh 反应的动态
  • 批准号:
    10063938
  • 财政年份:
    2017
  • 资助金额:
    $ 205.42万
  • 项目类别:
Dynamics of antigen specific B and Tfh responses during acute and chronic HCV
急性和慢性 HCV 期间抗原特异性 B 和 Tfh 反应的动态
  • 批准号:
    10305612
  • 财政年份:
    2017
  • 资助金额:
    $ 205.42万
  • 项目类别:

相似海外基金

Biomarkers of spontaneous acute hepatitis C virus resolution
自发性急性丙型肝炎病毒消退的生物标志物
  • 批准号:
    8262303
  • 财政年份:
    2012
  • 资助金额:
    $ 205.42万
  • 项目类别:
Biomarkers of spontaneous acute hepatitis C virus resolution
自发性急性丙型肝炎病毒消退的生物标志物
  • 批准号:
    8458955
  • 财政年份:
    2012
  • 资助金额:
    $ 205.42万
  • 项目类别:
Baltimore Acute Hepatitis C Cooperative Center
巴尔的摩急性丙型肝炎合作中心
  • 批准号:
    8625266
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Mechanisms of repeated control of acute hepatitis C infection in humans
反复控制人类急性丙型肝炎感染的机制
  • 批准号:
    9900734
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Baltimore Acute Hepatitis C Cooperative Center
巴尔的摩急性丙型肝炎合作中心
  • 批准号:
    8445240
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Baltimore Acute Hepatitis C Cooperative Center
巴尔的摩急性丙型肝炎合作中心
  • 批准号:
    8240544
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Baltimore Acute Hepatitis C Cooperative Center
巴尔的摩急性丙型肝炎合作中心
  • 批准号:
    8054921
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Mechanisms of repeated control of acute hepatitis C infection in humans
反复控制人类急性丙型肝炎感染的机制
  • 批准号:
    9246424
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Baltimore Acute Hepatitis C Cooperative Center
巴尔的摩急性丙型肝炎合作中心
  • 批准号:
    7912185
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
Mechanisms of repeated control of acute hepatitis C infection in humans
反复控制人类急性丙型肝炎感染的机制
  • 批准号:
    9098149
  • 财政年份:
    2010
  • 资助金额:
    $ 205.42万
  • 项目类别:
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