Developing Vertebrate-Specific Replication-Defective Dengue Virus as Novel Single-CycleDengue Vaccine Candidate

开发脊椎动物特异性复制缺陷型登革热病毒作为新型单周期登革热候选疫苗

基本信息

  • 批准号:
    10553634
  • 负责人:
  • 金额:
    $ 29.85万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-01-21 至 2024-12-31
  • 项目状态:
    已结题

项目摘要

Developing Vertebrate-Specific Replication-Defective Dengue Virus as a Novel Single-Cycle Dengue Vaccine Candidate Abstract With an estimated minimum of 390 million dengue virus (DENV) infections per year, the DENV epidemic was listed as one of the world's top 10 public health threats by WHO in 2019. At present, there is no specific treatment. A universal vaccine is urgently needed. DENV vaccine development's unique challenge is that a dengue vaccine must induce long-term protection against all four serotypes simultaneously. Historically, tetravalent live attenuated viral vaccines have shown that it is difficult to achieve balanced immunity to all four serotypes. Also, inactivated virus vaccines can't confer long-term immunity to prevent potential antibody-dependent enhancement (ADE). Mindful of these obstacles, we have investigated single-cycle, pseudoinfectious DENVs as vaccine candidates to induce balanced long-term immunity against all four serotypes. A significant impediment to this approach is that replicating pseudoinfecious DENVs usually require complicated and low-efficient packaging cells, making the scale-up production difficult and costly. Thus, towards the overall goal of developing a safe, effective, and affordable DENV vaccine, we converted dual-tropic DENVs into artificial insect-specific viruses to overcome the dependence on packaging cells to produce a single-cycle virus vaccine. These vertebrate-specific replication-defective DENVs (VSRD-DENV) were generated by optimizing the furin cleavage site in viral pre-membrane protein (prM). Preliminary animal experiments with VSRD-DENV1 and VSRD-DENV2 demonstrated that the VSRD-DENVs induced robust protective immunity with inherent high safety levels in mice. Based on these highly promising preliminary results and considering the urgent need for an effective dengue vaccine, Tengen Biomedical Co. and Howard University have teamed up to accelerate the evaluation of the VSRD-DENVs-based dengue vaccine. To achieve this goal, we propose to generate and characterize VSRD-DENV3 and VSRD-DENV4 vaccine candidate viruses. We will then perform a comprehensive analysis of the immunogenicity and protective efficacy of tetravalent VSRD-DENVs in a sensitive AG129 mouse model. Successful completion of these proposed studies will enable the dengue vaccine candidate into non-human primate testing and establish a platform for developing vaccines for other important flaviviruses.
发展脊椎动物特异性复制缺陷型登革病毒

项目成果

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XIAOWU PANG其他文献

XIAOWU PANG的其他文献

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{{ truncateString('XIAOWU PANG', 18)}}的其他基金

Developing Vertebrate-Specific Replication-Defective Dengue Virus as Novel Single-CycleDengue Vaccine Candidate
开发脊椎动物特异性复制缺陷型登革热病毒作为新型单周期登革热候选疫苗
  • 批准号:
    10384489
  • 财政年份:
    2022
  • 资助金额:
    $ 29.85万
  • 项目类别:
Development of Zika viral pseudoinfectious virus as Zika vaccine candidate
开发寨卡病毒假感染病毒作为寨卡候选疫苗
  • 批准号:
    10304384
  • 财政年份:
    2021
  • 资助金额:
    $ 29.85万
  • 项目类别:
Development of Zika viral pseudoinfectious virus as Zika vaccine candidate
开发寨卡病毒假感染病毒作为寨卡候选疫苗
  • 批准号:
    9536650
  • 财政年份:
    2017
  • 资助金额:
    $ 29.85万
  • 项目类别:
Development of a ZIKA viral pseudoinfectious virus as ZIKA vaccine candidate (STTR Phase II)
开发 ZIKA 病毒假感染病毒作为 ZIKA 候选疫苗(STTR II 期)
  • 批准号:
    10612753
  • 财政年份:
    2017
  • 资助金额:
    $ 29.85万
  • 项目类别:
Development of a ZIKA viral pseudoinfectious virus as ZIKA vaccine candidate (STTR Phase II)
开发 ZIKA 病毒假感染病毒作为 ZIKA 候选疫苗(STTR II 期)
  • 批准号:
    10397160
  • 财政年份:
    2017
  • 资助金额:
    $ 29.85万
  • 项目类别:
Development of a ZIKA viral pseudoinfectious virus as ZIKA vaccine candidate (STTR Phase II)
开发 ZIKA 病毒假感染病毒作为 ZIKA 候选疫苗(STTR II 期)
  • 批准号:
    10259140
  • 财政年份:
    2017
  • 资助金额:
    $ 29.85万
  • 项目类别:
1/2 Howard/Hopkins Intercenter Collaboration in HPV-Associated Cancer Studies
1/2 霍华德/霍普金斯大学 HPV 相关癌症研究的中心间合作
  • 批准号:
    8850130
  • 财政年份:
    2014
  • 资助金额:
    $ 29.85万
  • 项目类别:
1/2 Howard/Hopkins Intercenter Collaboration in HPV-Associated Cancer Studies
1/2 霍华德/霍普金斯大学 HPV 相关癌症研究的中心间合作
  • 批准号:
    9132724
  • 财政年份:
    2014
  • 资助金额:
    $ 29.85万
  • 项目类别:
Administration Core
行政核心
  • 批准号:
    8850131
  • 财政年份:
    2014
  • 资助金额:
    $ 29.85万
  • 项目类别:
Development of Pseudoinfectious VLP as Novel JEV Vaccine
新型乙脑疫苗假传染性VLP的研制
  • 批准号:
    7280433
  • 财政年份:
    2006
  • 资助金额:
    $ 29.85万
  • 项目类别:

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