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: 7958169
• 负责人: John David Altman
• 金额: $ 5.67万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958169
• 关键词: AIDS Vaccines; Acquired Immunodeficiency Syndrome; Adenoviruses; Antibody Formation; CD4 Positive T Lymphocytes; CD8B1 gene; Cellular Immunity; Clinical assessments; Computer Retrieval of Information on Scientific Projects Database; Development; Engineering; Funding; Future; Genes; Goals; Grant; Immune; Institution; Macaca mulatta; Modified Vaccinia Virus Ankara; Population; Poxviridae; Primates; Reporting; Research; Research Personnel; Resources; SIV; Serotyping; Source; T-Lymphocyte; United States National Institutes of Health; Vertebral column; Viral Vector; base; combinatorial; immunogenic; immunogenicity; vector

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overall goal of this project has been to identify strategies by which the immunogenicity of AIDS vaccines that are derived from Modified Vaccinia Ankara (MVA)-based viral vectors can be significantly augmented. In this reporting period, we determined that combinatorial deletion of several endogenous poxvirus immune-evasion genes from the backbone of MVA-based AIDS vaccine vectors confers an enhanced ability upon such vectors to elicit HIV-specific CD8 and CD4 T cell and antibody responses in MHC-disparate populations of rhesus macaques. The capacity of engineered MVA vectors that express SIV angtigens to elicit systemic and mucosal cellular immunity and to protect against pathogenic SIV challenge has also been investigated in Mamu-A*01-positive rhesus macaques. The development of highly immunogenic AIDS vaccine vectors from platforms other than adenovirus serotype-5 remains a high priority for the field and for future clinical assessments of the T cell hypothesis of AIDS vaccines.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 该项目的总体目标是确定策略，通过该策略，可以显着增强来自基于改良安卡拉牛痘（MVA）的病毒载体的艾滋病疫苗的免疫原性。 在本报告期内，我们确定，从MVA为基础的艾滋病疫苗载体的骨架中组合删除几个内源性痘病毒免疫逃避基因，赋予这些载体在恒河猴的MHC不同群体中引发HIV特异性CD 8和CD 4 T细胞和抗体应答的能力增强。 表达SIV抗原的工程化MVA载体引发全身和粘膜细胞免疫并保护免受致病性SIV攻击的能力也已经在Mamu-A*01阳性恒河猴中进行了研究。 从腺病毒血清型5以外的平台开发高免疫原性AIDS疫苗载体仍然是该领域和AIDS疫苗的T细胞假说的未来临床评估的高度优先事项。