OPTIMIZE THE IMMUNOGENICITY OF MVA-BASED AIDS VACCINES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 该项目的总体目标是确定可以显著增强基于改良安卡拉牛痘(MVA)病毒载体的艾滋病疫苗免疫原性的策略。 在本报告期间，我们确定，从基于MVA的艾滋病疫苗载体的骨架中组合缺失几个内源性痘病毒免疫逃避基因可以增强这些载体在MHC不同的猕猴种群中诱导HIV特异性CD8和CD4T细胞和抗体反应的能力。在Mamu-A*01阳性恒河猴中，也研究了表达SIV Angtigen的工程MVA载体诱导系统和粘膜细胞免疫以及保护病原性SIV攻击的能力。从5型腺病毒以外的平台开发高免疫原性的艾滋病疫苗载体仍然是该领域和未来对艾滋病疫苗T细胞假说的临床评估的高度优先事项。

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.