Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
J Virol. 2013 Feb;87(3):1359-72. doi: 10.1128/JVI.02055-12. Epub 2012 Nov 21.
Adenovirus (Ad) vectors are widely used as experimental vaccines against several infectious diseases, but the magnitude, phenotype, and functionality of CD8(+) T cell responses induced by different adenovirus serotypes have not been compared. To address this question, we have analyzed simian immunodeficiency virus Gag-specific CD8(+) T cell responses in mice following vaccination with Ad5, Ad26, and Ad35. Our results show that although Ad5 is more immunogenic than Ad26 and Ad35, the phenotype, function, and recall potential of memory CD8(+) T cells elicited by these vectors are substantially different. Ad26 and Ad35 vectors generated CD8(+) T cells that display the phenotype and function of long-lived memory T cells, whereas Ad5 vector-elicited CD8(+) T cells are of a more terminally differentiated phenotype. In addition, hepatic memory CD8(+) T cells elicited by Ad26 and Ad35 mounted more robust recall proliferation following secondary challenge than those induced by Ad5. Furthermore, the boosting potential was higher following priming with alternative-serotype Ad vectors than with Ad5 vectors in heterologous prime-boost regimens. Anamnestic CD8(+) T cell responses were further enhanced when the duration between priming and boosting was extended from 30 to 60 days. Our results demonstrate that heterologous prime-boost vaccine regimens with alternative-serotype Ad vectors elicited more functional memory CD8(+) T cells than any of the regimens containing Ad5. In summary, these results suggest that alternative-serotype Ad vectors will prove useful as candidates for vaccine development against human immunodeficiency virus type 1 and other pathogens and also emphasize the importance of a longer rest period between prime and boost for generating optimal CD8(+) T cell immunity.
腺病毒（Ad）载体被广泛用作针对多种传染病的实验性疫苗，但不同血清型腺病毒诱导的 CD8(+)T 细胞反应的幅度、表型和功能尚未进行比较。为了解决这个问题，我们分析了用 Ad5、Ad26 和 Ad35 疫苗接种后，小鼠中针对猿猴免疫缺陷病毒 Gag 的特异性 CD8(+)T 细胞反应。我们的结果表明，尽管 Ad5 比 Ad26 和 Ad35 更具免疫原性，但这些载体诱导的记忆 CD8(+)T 细胞的表型、功能和回忆潜能有很大不同。Ad26 和 Ad35 载体产生的 CD8(+)T 细胞表现出长寿命记忆 T 细胞的表型和功能，而 Ad5 载体诱导的 CD8(+)T 细胞则表现出更终末分化的表型。此外，与 Ad5 诱导的记忆 CD8(+)T 细胞相比，Ad26 和 Ad35 诱导的肝记忆 CD8(+)T 细胞在二次挑战后引发更强烈的回忆性增殖。此外，在异源初免-加强免疫方案中，用替代血清型 Ad 载体进行初免比用 Ad5 载体进行初免的增强潜力更高。在从 30 天延长至 60 天的时间间隔内进行初免和加强免疫后，记忆性 CD8(+)T 细胞反应进一步增强。我们的结果表明，用替代血清型 Ad 载体进行的异源初免-加强免疫方案比任何包含 Ad5 的方案都能诱导更多功能的记忆 CD8(+)T 细胞。总之，这些结果表明，替代血清型 Ad 载体将作为针对人类免疫缺陷病毒 1 和其他病原体的疫苗候选物证明是有用的，并且还强调了在初免和加强免疫之间延长休息期对于产生最佳 CD8(+)T 细胞免疫的重要性。
