Alternative Serotype Adenovirus Vaccine Vectors Elicit Memory T Cells with Enhanced Anamnestic Capacity Compared to Ad5 Vectors
Alternative Serotype Adenovirus Vaccine Vectors Elicit Memory T Cells with Enhanced Anamnestic Capacity Compared to Ad5 Vectors
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DOI：
10.1128/jvi.02058-12
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发表时间：
2013-02-01
影响因子：
5.4
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
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作者：
Penaloza-MacMaster, Pablo;Provine, Nicholas M.;Barouch, Dan H.
在STEP研究中，基于腺病毒血清型5（Ad 5）载体的人类免疫缺陷病毒1型（HIV-1）疫苗的失败导致开发了衍生自替代血清型（如Ad 26、Ad 35和Ad 48）的腺病毒载体。我们最近已经证明，疫苗使用替代血清型广告载体赋予部分保护严格的猴免疫缺陷病毒（SIV）的挑战，恒河猴。然而，由Ad 5引起的T细胞应答与替代血清型Ad载体引起的T细胞应答之间的表型差异仍然未被探索。在这里，我们报告的幅度，表型，功能和记忆T细胞反应引起的小鼠的Ad 5，Ad 26，Ad 35，和Ad 48载体表达淋巴细胞脉络丛脑膜炎病毒（LCMV）糖蛋白（GP）的回忆能力。我们的数据表明，记忆T细胞引起的Ad 5载体是高的幅度，但表现出功能衰竭和减少回忆的潜力后，第二抗原的挑战相比，Ad 26，Ad 35，和Ad 48载体。这些数据表明，除了避免高基线Ad 5特异性中和抗体滴度之外，用替代血清型Ad载体接种疫苗提供了超过Ad 5载体的显著免疫学优势。
The failure of the adenovirus serotype 5 (Ad5) vector-based human immunodeficiency virus type 1 (HIV-1) vaccine in the STEP study has led to the development of adenovirus vectors derived from alternative serotypes, such as Ad26, Ad35, and Ad48. We have recently demonstrated that vaccines using alternative-serotype Ad vectors confer partial protection against stringent simian immunodeficiency virus (SIV) challenges in rhesus monkeys. However, phenotypic differences between the T cell responses elicited by Ad5 and those of alternative-serotype Ad vectors remain unexplored. Here, we report the magnitude, phenotype, functionality, and recall capacity of memory T cell responses elicited in mice by Ad5, Ad26, Ad35, and Ad48 vectors expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP). Our data demonstrate that memory T cells elicited by Ad5 vectors were high in magnitude but exhibited functional exhaustion and decreased anamnestic potential following secondary antigen challenge compared to Ad26, Ad35, and Ad48 vectors. These data suggest that vaccination with alternative-serotype Ad vectors offers substantial immunological advantages over Ad5 vectors, in addition to circumventing high baseline Ad5-specific neutralizing antibody titers.