Therapeutic use of an enhanced form of CD4-Ig
增强型 CD4-Ig 的治疗用途
基本信息
- 批准号:10851165
- 负责人:
- 金额:$ 20.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-12-04 至 2025-11-30
- 项目状态:未结题
- 来源:
- 关键词:AntibodiesAntibody ResponseAwardCollaborationsDependovirusFc domainHIV-1HumanInfectionInstructionLaboratoriesMacaca mulattaMediatingPropertyResidual stateRoleSIVSerumTechnologyTherapeutic UsesTransgenesViralViral reservoirVirus Replicationadeno-associated viral vectorantiretroviral therapyimmune clearanceimmunogenicityimprovedinhibitorpeptidomimeticspreventreceptorsimian human immunodeficiency virustyrosine O-sulfate
项目摘要
eCD4-Ig is a potent and exceptionally broad fusion of the first two domains of CD4 to an antibody Fc
domain and a short tyrosine-sulfated coreceptor-mimetic peptide. In rhesus macaques, adeno-associated
virus (AAV)-expressed eCD4-Ig mediates consistent and very effective long-term protection against SHIV-
AD8 and SIVmac239. eCD4-Ig also has properties that make it especially useful for establishing a
functional cure in rhesus macaques and perhaps in humans. These include its potency, breadth, difficulty-
of-escape, low immunogenicity when expressed by AAV, consistent expression by AAV, potent intrinsic
ADCC activity, and collaboration with serum antibodies to mediate ADCC. These properties allow eCD4-
Ig to circumvent two major problems associated with using AAV-expressed antibodies to establish
functional cures, namely immune clearance and viral escape.
In the forthcoming award period, we will improve the technologies allowing AAV-mediated delivery of
eCD4-Ig by optimizing its expression as an AAV transgene, by eliminating residual antibody responses to
AAV-delivered eCD4-Ig, and by assessing the role of the eCD4-Ig Fc domain in anti-eCD4-Ig antibody
responses and in control an established SIVmac239 infection. These efforts will develop technologies that
can be applied to the ongoing efforts by many laboratories to prevent new infections, to provide long-
acting alternatives to combined antiretroviral therapies, and to reduce the scale of the viral reservoir.
RELEVANCE (See instructions):
eCD4-Ig is a potent and exceptionally broad HIV-1 and SIV entry inhibitor that, when delivered by an
AAV vector, provides rhesus macaques robust long-term protection from new infections, and by itself
suppresses viral replication in the absence of anti-retroviral therapies. Here we seek to optimize and
better understand these properties of AAV-delivered eCD4-Ig.
eCD4-Ig是CD4的前两个结构域与抗体Fc的有效且异常广泛的融合
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 }}
Michael R. Farzan其他文献
Michael R. Farzan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('Michael R. Farzan', 18)}}的其他基金
eCD4-mediated control of SIV infection in the brain
eCD4 介导的脑部 SIV 感染控制
- 批准号:
10698442 - 财政年份:2023
- 资助金额:
$ 20.01万 - 项目类别:
Safe, CRISPR/Cas-free B cell editing for therapeutic applications
用于治疗应用的安全、无 CRISPR/Cas 的 B 细胞编辑
- 批准号:
10725412 - 财政年份:2023
- 资助金额:
$ 20.01万 - 项目类别:
Improving mRNA vaccines with extracellular vesicle-associated immunogens
使用细胞外囊泡相关免疫原改进 mRNA 疫苗
- 批准号:
10573644 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Improving mRNA vaccines with extracellular vesicle-associated immunogens
使用细胞外囊泡相关免疫原改进 mRNA 疫苗
- 批准号:
10850617 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Engineering CAR-B cells for an HIV-1 functional cure
改造 CAR-B 细胞以实现 HIV-1 功能性治愈
- 批准号:
10514882 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Engineering CAR-B cells for an HIV-1 functional cure
改造 CAR-B 细胞以实现 HIV-1 功能性治愈
- 批准号:
10844837 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Therapeutic Use of an Enhanced Form of CD4-Ig
增强形式的 CD4-Ig 的治疗用途
- 批准号:
9970576 - 财政年份:2020
- 资助金额:
$ 20.01万 - 项目类别:
Eliciting tyrosine-sulfated neutralizing antibodies recognizing the Env apex
引发识别 Env 顶点的酪氨酸硫酸化中和抗体
- 批准号:
10013483 - 财政年份:2020
- 资助金额:
$ 20.01万 - 项目类别:
相似海外基金
Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study
描述 SARS-CoV-2 抗体反应及其与患者因素的关联:参与 GENCOV 研究的参与者的血清学分析
- 批准号:
495256 - 财政年份:2023
- 资助金额:
$ 20.01万 - 项目类别:
Understanding the human antibody response to a malaria transmission-blocking vaccine
了解人类抗体对疟疾传播阻断疫苗的反应
- 批准号:
MR/X009491/1 - 财政年份:2023
- 资助金额:
$ 20.01万 - 项目类别:
Research Grant
Probing the role of peptidoglycan modification in the antibody response to Staphylococcus aureus
探讨肽聚糖修饰在金黄色葡萄球菌抗体反应中的作用
- 批准号:
10549646 - 财政年份:2023
- 资助金额:
$ 20.01万 - 项目类别:
Identification of the antigenic targets of the clonal antibody response to Clostridioides difficile infection
鉴定针对艰难梭菌感染的克隆抗体反应的抗原靶点
- 批准号:
10742376 - 财政年份:2023
- 资助金额:
$ 20.01万 - 项目类别:
Genetic, structural and functional profiling of the human antibody response to arenavirus infection
人类抗体对沙粒病毒感染反应的遗传、结构和功能分析
- 批准号:
10688292 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Molecular dissection of IgA antibody response by developing monoclonal IgA antibodies from nasal mucosa of mice
通过从小鼠鼻粘膜中开发单克隆 IgA 抗体对 IgA 抗体反应进行分子剖析
- 批准号:
22H02875 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
绘制布氏锥虫变异表面糖蛋白的抗体反应
- 批准号:
10634694 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Genetic, structural and functional profiling of the human antibody response to arenavirus infection
人类抗体对沙粒病毒感染反应的遗传、结构和功能分析
- 批准号:
10514498 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
绘制布氏锥虫变异表面糖蛋白的抗体反应
- 批准号:
10527979 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Factors related to antibody response of COVID-19 vaccines: with focusing on metabolomics
与 COVID-19 疫苗抗体反应相关的因素:重点关注代谢组学
- 批准号:
22H03334 - 财政年份:2022
- 资助金额:
$ 20.01万 - 项目类别:
Grant-in-Aid for Scientific Research (B)