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

虽然开发一种有效的艾滋病疫苗来提供绝育免疫仍然是一个难以捉摸的目标， 在动物模型中已经实现了疫苗对疾病进展的保护，支持了这种方法 作为第一代人类疫苗的现实目标。越来越多的证据表明， 感染的急性期决定长期结果，HIV特异性CD 8 T细胞对于 遏制病毒复制重大挑战依然存在，包括艾滋病毒在不同国家的多样性 菌株，以及急性感染中个体对免疫遏制反应的相对贡献 以及在疾病过程中的变化尚不清楚。这是一个更加关键的问题， 最近的一项基于CTL的疫苗的IIb期研究，最近显示该疫苗在免疫缺陷病毒中无效。 影响感染后的病毒设定点，尽管通过诱导强烈的CDS T细胞应答， IFN-γ Elispot。在过去的拨款期内，我们与其他参与计划的公司紧密合作， PO 1产生初步数据，表明只有HLA等位基因和表位的一个子集参与免疫应答。 急性期CD 8 T细胞应答;抗原加工通过促进免疫优势， 某些表位的产生超过其他表位;一些抗HIV反应有助于免疫遏制， 而另一些则充当