Targeting glycoprotein (G) domain-III for pan-lyssavirus nanobody therapeutics

靶向糖蛋白 (G) 结构域 III 用于泛狂犬病病毒纳米抗体治疗

基本信息

  • 批准号:
    10667756
  • 负责人:
  • 金额:
    $ 22.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-03-07 至 2023-11-01
  • 项目状态:
    已结题

项目摘要

Abstract The lethal rabies encephalitis diseases are caused by members of the zoonotic lyssavirus genus. The high genetic diversity separates lyssavirus members into three phylogroups, while cross-phylogroup (especially to phylogroups 2 and 3) protection has not been established by current post-exposure prophylaxis (PEP) or antibody therapeutics. To achieve more broadly effective countermeasures to rabies disease worldwide and to prepare for the emergence of new lyssaviruses, effective therapeutic agents against all phylogroups are necessary. Lyssavirus G glycoprotein is the sole antibody target on the virion surface, which adopt distinct conformations between pre- and post- fusion states as other class-III viral fusion machineries. Domain-III of lyssavirus G glycoprotein encompasses a large neutralizing antibody-accessible surface in the native state. Sequence analysis on domain-III revealed several conserved patches across all phylogroups, which could potentially serve as target epitopes for pan-lyssavirus neutralizers. Antigen-specific nanobodies have been considered as promising therapeutic agents against various infectious diseases and non-infectious diseases, which have the advantage in binding compact and hidden epitopes that are out of reach for conventional antibodies. We hypothesized that by focusing immune recognition on the lyssavirus G domain-III conserved epitopes, we can identify pan-lyssavirus neutralizing nanobodies for immunotherapeutics. In this study, we propose two specific aims: (1) to use a structure-based and antibody-guided approach to design and characterize the antigenicity of lyssavirus glycoprotein domain-III, a site of viral vulnerability targeted by several broadly neutralizing antibodies, for revelation of the antibody neutralization mechanism; (2) to identify and characterize pan-lyssavirus neutralizing nanobodies for therapeutics by focusing immune recognition on lyssavirus G domain III conserved epitopes.
摘要

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Kai Xu其他文献

Kai Xu的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Kai Xu', 18)}}的其他基金

Structure, function, and antigenicity of emerging henipavirus surface glycoproteins
新兴亨尼帕病毒表面糖蛋白的结构、功能和抗原性
  • 批准号:
    10567931
  • 财政年份:
    2023
  • 资助金额:
    $ 22.82万
  • 项目类别:

相似海外基金

How novices write code: discovering best practices and how they can be adopted
新手如何编写代码:发现最佳实践以及如何采用它们
  • 批准号:
    2315783
  • 财政年份:
    2023
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Standard Grant
One or Several Mothers: The Adopted Child as Critical and Clinical Subject
一位或多位母亲:收养的孩子作为关键和临床对象
  • 批准号:
    2719534
  • 财政年份:
    2022
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633211
  • 财政年份:
    2020
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Studentship
A material investigation of the ceramic shards excavated from the Omuro Ninsei kiln site: Production techniques adopted by Nonomura Ninsei.
对大室仁清窑遗址出土的陶瓷碎片进行材质调查:野野村仁清采用的生产技术。
  • 批准号:
    20K01113
  • 财政年份:
    2020
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2436895
  • 财政年份:
    2020
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Studentship
A comparative study of disabled children and their adopted maternal figures in French and English Romantic Literature
英法浪漫主义文学中残疾儿童及其收养母亲形象的比较研究
  • 批准号:
    2633207
  • 财政年份:
    2020
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Studentship
The limits of development: State structural policy, comparing systems adopted in two European mountain regions (1945-1989)
发展的限制:国家结构政策,比较欧洲两个山区采用的制度(1945-1989)
  • 批准号:
    426559561
  • 财政年份:
    2019
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Research Grants
Securing a Sense of Safety for Adopted Children in Middle Childhood
确保被收养儿童的中期安全感
  • 批准号:
    2236701
  • 财政年份:
    2019
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Studentship
A Study on Mutual Funds Adopted for Individual Defined Contribution Pension Plans
个人设定缴存养老金计划采用共同基金的研究
  • 批准号:
    19K01745
  • 财政年份:
    2019
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Structural and functional analyses of a bacterial protein translocation domain that has adopted diverse pathogenic effector functions within host cells
对宿主细胞内采用多种致病效应功能的细菌蛋白易位结构域进行结构和功能分析
  • 批准号:
    415543446
  • 财政年份:
    2019
  • 资助金额:
    $ 22.82万
  • 项目类别:
    Research Fellowships
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了