Robust genital gag-specific CD8+ T-cell responses in mice upon intramuscular immunization with simian adenoviral vectors expressing HIV-1-gag.

Most studies on E1-deleted adenovirus (Ad) vectors as vaccine carriers for antigens of HIV-1 have focused on induction of central immune responses although stimulation of mucosal immunity at the genital tract (GT), the primary port of entry of HIV-1, would also be highly desirable. In the present study, different immunization protocols using chimpanzee-derived adenoviral (AdC) vectors expressing gag of HIV-1 clade B given in heterologous prime-boost regimens were tested for induction of systemic and genital immune responses. Although i.n. immunization stimulated CD8+ T-cell responses that could be detected in the GT, this route only induced marginal cellular responses in systemic tissues and furthermore numbers of gag-specific CD8+ T-cells contracted sharply within a few weeks. In contrast, i.m. immunization induced higher and more sustained frequencies of vaccine-induced cells which could be detected in the GT as well as systemic compartments. Antigen-specific CD8+ T-cells could be detected 1 year after immunization in all compartments analyzed. Genital memory cells secreted IFN-γ, expressed high levels of CD103 and their phenotypes were consistent with a state of activation. Taken together, results presented here show that i.m. vaccination with AdC vectors is a suitable strategy to induce a long-lived genital CD8+ T-cell response.

大多数关于E1缺失的腺病毒（Ad）载体作为HIV - 1抗原疫苗载体的研究都集中在诱导中枢免疫反应上，尽管刺激HIV - 1主要入侵部位生殖道（GT）的黏膜免疫也是非常理想的。在本研究中，测试了使用表达HIV - 1 B亚型gag蛋白的黑猩猩来源腺病毒（AdC）载体以异源初免 - 加强方案进行的不同免疫程序对全身和生殖道免疫反应的诱导作用。尽管鼻内（i.n.）免疫刺激了在生殖道中可检测到的CD8 + T细胞反应，但这种途径仅在全身组织中诱导出微弱的细胞反应，而且gag特异性CD8 + T细胞数量在几周内急剧减少。相比之下，肌肉内（i.m.）免疫诱导了更高且更持久的疫苗诱导细胞频率，这些细胞在生殖道以及全身各部分均可检测到。在免疫1年后，在所有分析的部分都能检测到抗原特异性CD8 + T细胞。生殖道记忆细胞分泌干扰素 - γ，高水平表达CD103，其表型与激活状态一致。综上所述，此处呈现的结果表明，使用AdC载体进行肌肉内接种是诱导持久的生殖道CD8 + T细胞反应的合适策略。