Correlates of protective immunity to HCV and rational vaccine design: Project 3

HCV 保护性免疫与合理疫苗设计的相关性:项目 3

基本信息

  • 批准号:
    10608113
  • 负责人:
  • 金额:
    $ 95.72万
  • 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

Hepatitis C virus (HCV) continues to infect ~71 million people worldwide with an estimated 1.5 to 2 million new infections each year. A complete eradication of HCV infection warrants development of an effective vaccine that can rapidly induce a durable anti-viral immunity and prevent infection. Evidence from spontaneous controllers suggests that a broad and durable HCV-specific CD4 and CD8 T cell responses are critical for effective control of HCV infection. In addition, a protective role for neutralizing antibody against viral glycoproteins E1&E2 has also been implicated. Furthermore, it is critical generate anti-viral immunity in the liver (the primary site of virus replication). Thus, the primary goal of this proposal is to develop a vaccination strategy using DNA, modified vaccinia Ankara (MVA), and protein-based vaccines that will generate a robust and broad HCV specific T and B cell responses in blood and liver against multiple HCV proteins. We hypothesize that induction of a strong, broad, and persistent T cell response against HCV antigens in the blood and liver combined with induction of strong neutralizing antibody response will provide protection against HCV infection and different combinations of DNA/MVA/protein vaccination can be harnessed to achieve the desired protective immunity. We propose to achieve these objectives using 3 specific aims. In Aim 1 we will construct and characterize DNA and MVA vaccines expressing HCV core, NS3-NS5 and E1E2 proteins. In Aim 2 we will optimize the DNA/MVA vaccine modality for inducing strong T cell and antibody responses. The optimizations will include testing the E1E2 in two forms either presented on the virus-like particle (VLP) or secreted. In addition, we will test the influence of CD40L adjuvant on cellular and humoral immunity. In Aim 3 we will optimize E1E2 protein boosts for DNA/MVA vaccine for further enhancing the antibody responses. By completion of these studies we hope generate an optimal vaccine against HCV that induces strong T cell and neutralizing antibody responses.
丙型肝炎病毒(HCV)继续感染全球约7100万人,估计新增150万至200万人

项目成果

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专利数量(0)

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Rama Rao Amara其他文献

Rama Rao Amara的其他文献

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{{ truncateString('Rama Rao Amara', 18)}}的其他基金

B and T Cell Biology of Protection from and Eradication of SIV/SHIV Infection
预防和根除 SIV/SHIV 感染的 B 和 T 细胞生物学
  • 批准号:
    10462362
  • 财政年份:
    2022
  • 资助金额:
    $ 95.72万
  • 项目类别:
B and T Cell Biology of Protection from and Eradication of SIV/SHIV Infection
预防和根除 SIV/SHIV 感染的 B 和 T 细胞生物学
  • 批准号:
    10618319
  • 财政年份:
    2022
  • 资助金额:
    $ 95.72万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 3
HCV 保护性免疫与合理疫苗设计的相关性:项目 3
  • 批准号:
    10393619
  • 财政年份:
    2021
  • 资助金额:
    $ 95.72万
  • 项目类别:
Correlates of protective immunity to HCV and rational vaccine design: Project 3
HCV 保护性免疫与合理疫苗设计的相关性:项目 3
  • 批准号:
    10205769
  • 财政年份:
    2021
  • 资助金额:
    $ 95.72万
  • 项目类别:
MVA based SARS-CoV-2 vaccines
基于 MVA 的 SARS-CoV-2 疫苗
  • 批准号:
    10221340
  • 财政年份:
    2020
  • 资助金额:
    $ 95.72万
  • 项目类别:
Combined cytokine therapy for sustained HIV remission
联合细胞因子疗法可持续缓解艾滋病毒
  • 批准号:
    10348184
  • 财政年份:
    2020
  • 资助金额:
    $ 95.72万
  • 项目类别:
Combined cytokine therapy for sustained HIV remission
联合细胞因子疗法可持续缓解艾滋病毒
  • 批准号:
    10573329
  • 财政年份:
    2020
  • 资助金额:
    $ 95.72万
  • 项目类别:
Targeting PD-1 Pathway for Functional Cure of AIDS
靶向 PD-1 通路实现艾滋病功能性治愈
  • 批准号:
    10349439
  • 财政年份:
    2019
  • 资助金额:
    $ 95.72万
  • 项目类别:
MVA Prime/Novel Trimeric Cyclically Permuted Envelope Protein Boost Vaccines for HIV
MVA Prime/新型三聚体循环排列包膜蛋白增强 HIV 疫苗
  • 批准号:
    10449340
  • 财政年份:
    2019
  • 资助金额:
    $ 95.72万
  • 项目类别:
MVA based SARS-CoV-2 vaccines
基于 MVA 的 SARS-CoV-2 疫苗
  • 批准号:
    10265756
  • 财政年份:
    2019
  • 资助金额:
    $ 95.72万
  • 项目类别:

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地方性落叶型天疱疮中 IgE 抗体对 Dsg1 和环境抗原的反应
  • 批准号:
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    8965123
  • 财政年份:
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  • 批准号:
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