A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.

针对梅毒螺旋体外膜蛋白的全球梅毒疫苗。

基本信息

项目摘要

The scientific premise of this CRC proposal rests upon our three decades of work defining the molecular architecture of the outer membrane (OM) of Treponema pallidum subsp. pallidum (TPA), coupled with our recent successes combining bioinformatics, biophysical techniques, and localization methods with live TPA to topologically characterize TPA outer membrane proteins (OMPs) and define the syphilis spirochete's `OMPeome'--its repertoire of OMPs. Its central hypothesis is that the principal targets for a syphilis vaccine reside within TPA's repertoire of rare outer membrane proteins (OMPs). The projects in the proposal employ three different, but closely integrated, strategies to exploit this novel application of reverse vaccinology to develop a syphilis vaccine with global efficacy. Project 1 is `immune-agnostic', selecting leading vaccine candidates based on genomic sequences, bioinformatics, biophysical analysis, and structural modeling. Project 2 takes its cue from the human immune system: since the large majority of untreated individuals do eventually control TPA infection, it stands to reason that OMPs targeted by opsonic antibodies6-9 should be excellent vaccine candidates. Project 3 borrows a page from the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) `book', using state-of-the art recombinant B cell and phage technology to generate broadly reactive, opsonic monoclonal antibodies directed against surface-exposed loops of TPA OMPs. The extraordinary deep sequencing capabilities of the Genetics and Genomics core will provide the data needed to tailor these approaches for efficacy on a global scale. This CRC, led by two senior investigators, established collaborators with complementary clinical and research backgrounds, pulls together (a) the unique capabilities of the Spirochete Research Laboratories at UConn Health; (b) the world-class B cell technology and vaccine research infrastructure of the Duke Human Vaccine Institute (DHVI); (c) the international health infrastructure and expertise of the University of North Carolina Institute for Global Health and Infectious Diseases; and (d) the unparalleled knowledge of TPA genomics at Masaryk University to achieve our long-term objective. The Administrative Core will provide the managerial oversight needed to integrate these capabilities and resources to strengthen existing collaborations and foster new ones within the Center and with other CRCs. The ultimate strength of this CRC is the diversity and complementarity of approaches, technologies, resources, and expertise it marshals to interrogate the TPA OMPeome to achieve our long-term goals. An effective syphilis vaccine would represent a triumph of biomedical research over an ailment that for more than five centuries has exacted a heavy toll on humanity4,5 and that has defied conventional public health strategies for containment. If successful, the scientific and public health impact of our approach to reverse vaccinology will extend well beyond syphilis, establishing a paradigm applicable to other recalcitrant organisms.
这项CRC提案的科学前提是基于我们三十年来定义分子的工作

项目成果

期刊论文数量(0)
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Michael Anthony Moody其他文献

Michael Anthony Moody的其他文献

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{{ truncateString('Michael Anthony Moody', 18)}}的其他基金

Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC)
新发传染病研究中心协调中心 (EIDRC CC)
  • 批准号:
    10879862
  • 财政年份:
    2020
  • 资助金额:
    $ 221.92万
  • 项目类别:
Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC)
新发传染病研究中心协调中心 (EIDRC CC)
  • 批准号:
    10396064
  • 财政年份:
    2020
  • 资助金额:
    $ 221.92万
  • 项目类别:
Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC)
新发传染病研究中心协调中心 (EIDRC CC)
  • 批准号:
    10891936
  • 财政年份:
    2020
  • 资助金额:
    $ 221.92万
  • 项目类别:
Emerging Infectious Diseases Research Centers Coordination Center (EIDRC CC)
新发传染病研究中心协调中心 (EIDRC CC)
  • 批准号:
    10616668
  • 财政年份:
    2020
  • 资助金额:
    $ 221.92万
  • 项目类别:
A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.
针对梅毒螺旋体外膜蛋白的全球梅毒疫苗。
  • 批准号:
    10618184
  • 财政年份:
    2019
  • 资助金额:
    $ 221.92万
  • 项目类别:
Prevalence of syphilis and other sexually transmitted infections in men and transgender women who have sex with men in Cali, Colombia
哥伦比亚卡利男男性行为者和跨性别女性梅毒和其他性传播感染的患病率
  • 批准号:
    10559087
  • 财政年份:
    2019
  • 资助金额:
    $ 221.92万
  • 项目类别:
Monoclonal antibodies against surface epitopes of Treponema pallidum outer membrane proteins
抗梅毒螺旋体外膜蛋白表面表位的单克隆抗体
  • 批准号:
    10618194
  • 财政年份:
    2019
  • 资助金额:
    $ 221.92万
  • 项目类别:
A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.
针对梅毒螺旋体外膜蛋白的全球梅毒疫苗。
  • 批准号:
    10765594
  • 财政年份:
    2019
  • 资助金额:
    $ 221.92万
  • 项目类别:
A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.
针对梅毒螺旋体外膜蛋白的全球梅毒疫苗。
  • 批准号:
    10806303
  • 财政年份:
    2019
  • 资助金额:
    $ 221.92万
  • 项目类别:
A Global Syphilis Vaccine Targeting Outer Membrane Proteins of Treponema pallidum.
针对梅毒螺旋体外膜蛋白的全球梅毒疫苗。
  • 批准号:
    10399442
  • 财政年份:
    2019
  • 资助金额:
    $ 221.92万
  • 项目类别:

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