OPTIMIZE THE IMMUNOGENICITY OF MVA-BASED AIDS VACCINES
优化基于 MVA 的艾滋病疫苗的免疫原性
基本信息
- 批准号:8357426
- 负责人:
- 金额:$ 7.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-08-01 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:AIDS VaccinesAcuteAgonistAnatomic SitesAnatomyAntibodiesAntibody FormationAppearanceCD4 Positive T LymphocytesCD8B1 geneConsensusEngineeringEscape MutantFundingGenesGoalsGrantHIVHIV AntigensHIV vaccineImmuneImmunizationInfectionLymphoidMacacaMacaca mulattaMucous MembraneNational Center for Research ResourcesPeripheral Blood Mononuclear CellPhasePopulationPoxviridaePrimatesPrincipal InvestigatorRegimenResearchResearch InfrastructureResourcesSIVSourceT cell responseTissuesUnited States National Institutes of HealthVaccine AdjuvantVaccinesVariantViral VectorVirusVirus Replicationbasecostenv Gene Productsgag Gene Productsimmunogenicitylymph nodespressurerectal
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
The overall goal of this project is to identify strategies by which the immunogenicity of AIDS vaccines derived from MVA-based viral vectors can be significantly augmented. We previously developed and characterized an MVA-based HIV vaccine (from which four endogenous poxvirus immune-evasion genes have been deleted) that expresses consensus HIV subtype C Gag and Env antigens (MVA4-HIV). In MHC-disparate populations of rhesus macaques, this genetically engineered vaccine was shown to elicit significantly higher levels of HIV-specific CD8 and CD4 T cell responses and up to 25-fold higher titers of HIV envelope-specific antibodies, as compared to the unmodified parental control vaccine. Recently, we completed a study, in rhesus macaques, which demonstrated that the HIV-specific antibody responses elicited by the MVA4-HIV vaccine may be further augmented through an immunization regimen that includes co-administration of a TLR-9 agonist, but not a TLR-7/8 agonist, as a vaccine adjuvant.
In another study of macaques immunized with MVA-based vaccines expressing SIV, rather than HIV, antigens, we took a deep pyrosequencing approach to characterize the appearance, dynamics and anatomic dissemination of CTL escape mutant viruses in lymphoid versus mucosal tissues following SIVmac239 infection. Our results indicate that lymph nodes, rather than peripheral blood mononuclear cells or rectal mucosa, represent the primary source of CTL escape mutants during the acute phase of SIV infection, suggesting that lymph nodes are the main anatomic sites of virus replication and/or the tissues in which CTL pressure is most effective in selecting SIV escape variants.
这个子项目是利用资源的许多研究子项目之一。
由NIH/NCRR资助的中心拨款提供。对子项目的主要支持
子项目的首席调查员可能是由其他来源提供的,
包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能
表示该子项目使用的中心基础设施的估计数量,
不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。
该项目的总体目标是确定能够显著增强基于MVA的病毒载体的艾滋病疫苗的免疫原性的策略。我们之前开发并鉴定了一种基于MVA的HIV疫苗(其中四个内源性痘病毒免疫逃避基因已被删除),该疫苗表达一致的HIV C亚型Gag和环境抗原(MVA4-HIV)。在MHC不同的猕猴种群中,这种基因工程疫苗被证明与未经修改的父母对照疫苗相比,诱导了显著更高的HIV特异性CD8和CD4T细胞反应水平,以及高达25倍的HIV包膜特异性抗体效价。最近,我们在恒河猴身上完成了一项研究,该研究表明,MVA4-HIV疫苗引起的HIV特异性抗体反应可以通过一种免疫方案进一步增强,该免疫方案包括联合给予TLR-9激动剂,而不是TLR-7/8激动剂作为疫苗佐剂。
在另一项对表达SIV而不是HIV抗原的MVA疫苗免疫的猕猴的研究中,我们采用深度焦磷酸测序的方法来表征SIVmac239感染后CTL逃逸突变病毒在淋巴组织和粘膜组织中的外观、动态和解剖扩散。我们的结果表明,在SIV感染急性期,CTL逃逸突变体的主要来源是淋巴结,而不是外周血单个核细胞或直肠粘膜,这表明淋巴是病毒复制的主要解剖部位和/或CTL压力在选择SIV逃逸突变体时最有效的组织。
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 }}
DAVID A GARBER其他文献
DAVID A GARBER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('DAVID A GARBER', 18)}}的其他基金
OPTIMIZE THE IMMUNOGENICITY OF MVA-BASED AIDS VACCINES
优化基于 MVA 的艾滋病疫苗的免疫原性
- 批准号:
8172361 - 财政年份:2010
- 资助金额:
$ 7.43万 - 项目类别:
相似海外基金
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
21K17323 - 财政年份:2021
- 资助金额:
$ 7.43万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of acute poisoning mechanism due to abuse of CB1 receptor agonist.
阐明滥用 CB1 受体激动剂引起的急性中毒机制。
- 批准号:
19K19485 - 财政年份:2019
- 资助金额:
$ 7.43万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Tissue repair effect in acute myocardial infarction through mobilization of endogenous Muse cells by sphingosine-1-phosphate receptor 2 agonist
1-磷酸鞘氨醇受体2激动剂动员内源性Muse细胞对急性心肌梗死的组织修复作用
- 批准号:
18K15843 - 财政年份:2018
- 资助金额:
$ 7.43万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6115624 - 财政年份:1998
- 资助金额:
$ 7.43万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6219539 - 财政年份:1998
- 资助金额:
$ 7.43万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6276858 - 财政年份:1997
- 资助金额:
$ 7.43万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6250152 - 财政年份:1997
- 资助金额:
$ 7.43万 - 项目类别:
ACUTE CHRONIC HORMONAL CHANGES WITH LHRH-AGONIST THERAPY
LHRH 激动剂治疗引起的急性慢性荷尔蒙变化
- 批准号:
6279945 - 财政年份:1997
- 资助金额:
$ 7.43万 - 项目类别:
EFFECT OF ACUTE E PROSTAGLANDIN AGONIST N BAL EICO
急性 E 型前列腺素激动剂 N BAL EICO 的作用
- 批准号:
6246787 - 财政年份:1997
- 资助金额:
$ 7.43万 - 项目类别:
PSYCHOPHARMACOLOGY OF DA AGONIST CNS EFFECTS: ACUTE AND CHRONIC STUDIES
DA 激动剂中枢神经系统影响的精神药理学:急性和慢性研究
- 批准号:
3891471 - 财政年份:
- 资助金额:
$ 7.43万 - 项目类别: