Animal Models & Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD, USA.
J Virol. 2013 Mar;87(6):3526-37. doi: 10.1128/JVI.02686-12. Epub 2013 Jan 16.
We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. All macaques were primed with DNA plasmids expressing SIV gag, pol, env, and Retanef genes and were boosted with recombinant modified vaccinia Ankara virus (MVA) expressing the same genes, either once (1 × MVA) or twice (2 × MVA), or were boosted once with MVA followed by a single boost with replication-competent adenovirus (Ad) type 5 host range mutant (Ad5 h) expressing SIV gag and nef genes but not Retanef or env (1 × MVA/Ad5). While two of the vaccine regimens (1 × MVA and 1 × MVA/Ad5) protected from high levels of SIV replication only during the acute phase of infection, the 2 × MVA regimen, with the highest anti-SIV gp120 titers, protected during the acute phase and transiently during the chronic phase of infection. Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses.
我们比较了三种疫苗方案对猿猴免疫缺陷病毒（SIV）挑战的相对疗效，这三种疫苗方案引起了类似频率的 SIV 特异性 CD4(+)和 CD8(+)T 细胞反应，但对 gp120 包膜蛋白的抗体反应水平不同。所有的猴子都用表达 SIV gag、pol、env 和 Retanef 基因的 DNA 质粒进行了初免，并用表达相同基因的重组改良安卡拉痘苗病毒（MVA）进行了加强免疫，加强免疫方案分别为一次（1×MVA）、两次（2×MVA），或先用 MVA 加强一次，再用复制型腺病毒（Ad）5 型宿主范围突变体（Ad5 h）加强一次，Ad5 h 表达 SIV gag 和 nef 基因，但不表达 Retanef 或 env（1×MVA/Ad5）。虽然两种疫苗方案（1×MVA 和 1×MVA/Ad5）在感染急性期仅能防止高水平的 SIV 复制，但 2×MVA 方案由于具有最高的抗 SIV gp120 滴度，不仅在感染急性期，而且在感染慢性期的短暂时间内也能起到保护作用。这第三组的 Mamu-A*01 猴子表现出持续存在的 Gag CD8(+)CM9(+)效应记忆 T 细胞，这些细胞表面程序性死亡受体 1（PD-1）的表达水平较低，与主要组织相容性复合体 I（MHC-I）和 MHC-II 抗原相关的基因表达水平较高。控制 SIV 复制的事实与 SIV 包膜蛋白的高抗体滴度和持久的效应 SIV 特异性 CD8(+)T 细胞有关，这表明，在挑战时存在抗体可能通过增强抗原摄取来增加固有免疫募集活性，并可能导致次级 SIV 特异性 CD8(+)T 细胞反应的质量和效力提高。
