Defining the protective efficacy of antibodies against the EBV gH/gL glycoprotein complex

定义针对 EBV gH/gL 糖蛋白复合物的抗体的保护功效

基本信息

  • 批准号:
    10199986
  • 负责人:
  • 金额:
    $ 43.28万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2019
  • 资助国家:
    美国
  • 起止时间:
    2019-08-09 至 2022-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Epstein-Barr virus (EBV) is a nearly ubiquitous orally-transmitted pathogen for which there is no vaccine. Following primary infection, most individuals carry the virus asymptomatically; however, unchecked infection in immunocompromised individuals, such as those living with HIV-1/AIDS, can lead to the development of lymphomas. These include Non-Hodgkin's Lymphomas such as plasmablastic lymphoma, primary central nervous system lymphoma, primary effusion lymphoma and diffuse large B-cell lymphoma, as well as classic Hodgkin's lymphoma. Overall, HIV-infected individuals have a 60–200-fold higher relative risk to develop Non- Hodgkin's Lymphomas and an 8–10-fold higher relative risk to develop Hodgkin's Lymphoma compared to uninfected individuals. Thus, a safe and effective vaccine that prevents EBV infection and/or eliminates the EBV- associated component of risk could have a significant clinical benefit, particularly in resource-poor areas where HIV-1 is endemic. Successful vaccines are usually protective because they elicit neutralizing antibodies. At present it is not currently known whether pre-existing neutralizing antibodies can block EBV transmission. Since both B cells and epithelial cells are present in the nasopharynx, a preventative EBV vaccine would likely need to elicit antibodies that can block infection of both cell types. To date, subunit vaccine efforts focused on the gp350 glycoprotein which binds to complement receptors 1 and 2 and promotes attachment and internalization of virions by B cells without mediating membrane fusion. A phase II trial of a gp350 vaccine reduced the incidence of infectious mononucleosis but failed to protect against infection. Antibodies against gp350 can inhibit EBV infection of B cells, but most epithelial cells do not express complement receptors. Thus, the inability of gp350 vaccines to protect against EBV infection may be due to their inability to elicit antibodies that neutralize EBV infection of epithelial cells. We recently isolated a monoclonal antibody, AMMO1 that binds to the EBV gH/gL glycoprotein complex, which is an important regulator of fusion between the host cell and viral membranes. AMMO1 binds to gH/gL in a manner that disrupts membrane fusion and neutralizes EBV infection of both B and epithelial cells demonstrating, in principle, that vaccine elicited gH/gL antibodies could be more efficacious than those against gp350. The goal of this proposal is to define the protective capacity of AMMO1 and other anti-EBV monoclonal antibodies against EBV infection in complementary animal models: humanized mice that harbor human B cells and in infant rhesus macaques, which can be orally infected with the rhesus ortholog of EBV. We will also evaluate the ability of several gH/gL-based vaccines to elicit neutralizing antibodies and compare these gp350-based vaccines in relevant animal challenge models. These studies will delineate the role that antibodies play in preventing EBV infection and inform vaccine development. Moreover, the proposed challenge studies in infant macaques are highly relevant to the target-population in Sub-Sharan Africa where EBV infection normally occurs in the first 3 years of life.
项目总结/文摘

项目成果

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Andrew McGuire其他文献

Andrew McGuire的其他文献

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{{ truncateString('Andrew McGuire', 18)}}的其他基金

Development of an anti-idiotype based vaccine for respiratory syncytial virus
呼吸道合胞病毒抗独特型疫苗的研制
  • 批准号:
    10593361
  • 财政年份:
    2021
  • 资助金额:
    $ 43.28万
  • 项目类别:
Development of an anti-idiotype based vaccine for respiratory syncytial virus
呼吸道合胞病毒抗独特型疫苗的研制
  • 批准号:
    10414112
  • 财政年份:
    2021
  • 资助金额:
    $ 43.28万
  • 项目类别:
Development of an anti-idiotype based vaccine for respiratory syncytial virus
呼吸道合胞病毒抗独特型疫苗的研制
  • 批准号:
    10302873
  • 财政年份:
    2021
  • 资助金额:
    $ 43.28万
  • 项目类别:
Defining the protective efficacy of antibodies against the EBV gH/gL glycoprotein complex
定义针对 EBV gH/gL 糖蛋白复合物的抗体的保护功效
  • 批准号:
    10593368
  • 财政年份:
    2019
  • 资助金额:
    $ 43.28万
  • 项目类别:
Defining the protective efficacy of antibodies against the EBV gH/gL glycoprotein complex
定义针对 EBV gH/gL 糖蛋白复合物的抗体的保护功效
  • 批准号:
    10455109
  • 财政年份:
    2019
  • 资助金额:
    $ 43.28万
  • 项目类别:
Defining the protective efficacy of antibodies against the EBV gH/gL glycoprotein complex
定义针对 EBV gH/gL 糖蛋白复合物的抗体的保护功效
  • 批准号:
    10669738
  • 财政年份:
    2019
  • 资助金额:
    $ 43.28万
  • 项目类别:
Evaluating anti-idiotypic antibodies as novel vaccine candidates against HIV-1
评估抗独特型抗体作为针对 HIV-1 的新型候选疫苗
  • 批准号:
    10062817
  • 财政年份:
    2018
  • 资助金额:
    $ 43.28万
  • 项目类别:
Evaluating anti-idiotypic antibodies as novel vaccine candidates against HIV-1
评估抗独特型抗体作为针对 HIV-1 的新型候选疫苗
  • 批准号:
    10300442
  • 财政年份:
    2018
  • 资助金额:
    $ 43.28万
  • 项目类别:
Evaluating anti-idiotypic antibodies as novel vaccine candidates against HIV-1
评估抗独特型抗体作为针对 HIV-1 的新型候选疫苗
  • 批准号:
    10540731
  • 财政年份:
    2018
  • 资助金额:
    $ 43.28万
  • 项目类别:
Evaluating anti-idiotypic antibodies as novel vaccine candidates against HIV-1
评估抗独特型抗体作为针对 HIV-1 的新型候选疫苗
  • 批准号:
    10593447
  • 财政年份:
    2018
  • 资助金额:
    $ 43.28万
  • 项目类别:

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