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

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.
这个子项目是利用这些资源的众多研究子项目之一

项目成果

期刊论文数量(0)
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DAVID A GARBER其他文献

DAVID A GARBER的其他文献

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{{ 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:
MOLECULAR BASIS OF ANTIVENIC VARIATION ON MALARIA
疟疾抗药变异的分子基础
  • 批准号:
    6971070
  • 财政年份:
    2004
  • 资助金额:
    $ 7.43万
  • 项目类别:
Homeostasis of T cells in primates
灵长类动物 T 细胞的稳态
  • 批准号:
    6804620
  • 财政年份:
    2003
  • 资助金额:
    $ 7.43万
  • 项目类别:
MOLECULAR BASIS OF ANTIGENIC VARIATION ON MALARIA
疟疾抗原变异的分子基础
  • 批准号:
    6939973
  • 财政年份:
    2003
  • 资助金额:
    $ 7.43万
  • 项目类别:

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阐明滥用 CB1 受体激动剂引起的急性中毒机制。
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