Adaptive immunity in acute HIV infection

急性艾滋病毒感染中的适应性免疫

• 批准号: 8574935
• 负责人: Bruce D Walker
• 金额: $ 36.12万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8574935
• 关键词: AIDS Vaccines; Acute; Alleles; Animal Model; Antigens; Biological Assay; CD8B1 gene; Cells; Containment; Data; Development; Disease; Disease Progression; Epitopes; Event; Failure; Funding; Generations; Goals; HIV; HIV Infections; Human; Immune; Immunity; Individual; Infection; Interferons; Outcome; Persons; Phase; Production; Relative (related person); Staging; T cell response; T-Lymphocyte; Vaccine Design; Vaccines; Variant; Viral; Viral Load result; Work; adaptive immunity; antigen processing; base; response

Although development of an effective AIDS vaccine to provide sterilizing immunity remains an elusive goal, vaccine protection from disease progression has been achieved in animal models, supporting this approach as a realistic goal for first generation vaccines for humans. Expanding evidence indicates that events in the acute stage of infection determine long-term outcome, and that HIV-specific CD8 T cells are critical for containment of viral replication. Major challenges persist, including the tremendous HIV diversity among strains, and that the relative contributions of individual responses to immune containment in acute infection and over the course of disease are not known. This is now an even more critical issue given the failure of a recent phase lib study of a CTL based vaccine, which was recently shown to be ineffective in influencing viral set point after infection, despite the induction of strong CDS T cell responses by IFN-y Elispot. During the past funding period, we have worked closely with each of the other PLs on this PO1 to generate preliminary data indicating that only a subset of HLA alleles and epitopes participate in the acute phase CD8 T cell response; that antigen processing contributes to immunodominance by favoring the production of certain epitopes over others; that some anti-HIV responses contribute to immune containment, whereas others act as

尽管开发有效的辅助疫苗以提供消毒免疫仍然是一个难以捉摸的目标，但 在动物模型中已经实现了免受疾病进展的疫苗保护，支持这种方法 作为人类第一代疫苗的现实目标。扩大证据表明 急性感染阶段决定了长期结局，HIV特异性CD8 T细胞对于 病毒复制的控制。主要挑战持续存在，包括巨大的艾滋病毒多样性 菌株，以及急性感染中个人对免疫遏制的相对贡献 在整个疾病过程中，尚不清楚。鉴于失败，这现在是一个更关键的问题 最近对基于CTL的疫苗的LIB阶段研究，该研究最近被证明是无效的 影响感染后的病毒设定点，尽管通过 ifn-y Elispot。在过去的资金期间，我们已经与其他PLS紧密合作 PO1生成初步数据，表明只有HLA等位基因和表位的子集参与 急性CD8 T细胞反应；这种抗原加工通过偏爱 生产某些表位的人；某些抗HIV反应有助于免疫遏制， 而其他人则是