Vaccination Alters the Balance between Protective Immunity, Exhaustion, Escape, and Death in Chronic Infections
Vaccination Alters the Balance between Protective Immunity, Exhaustion, Escape, and Death in Chronic Infections
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DOI：
10.1128/jvi.00166-11
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发表时间：
2011-06-01
影响因子：
5.4
通讯作者：
Antia, Rustom
中科院分区：
文献类型：
--
作者：
Johnson, Philip L. F.;Kochin, Beth F.;Antia, Rustom
虽然基于T细胞的疫苗有可能提供针对慢性病毒感染的保护，但它们也有可能在随后的病毒感染后产生免疫病理学。我们开发了一个数学模型来研究T细胞导致保护与不良病理的条件。该模型说明了当疫苗接种产生中等数量的特异性CD8 T细胞时，病毒清除和免疫耗竭之间的平衡可能会被破坏。令人惊讶的是，我们的模型表明，疫苗接种的这种不利影响在很大程度上不受逃避T细胞识别的突变病毒的产生的影响，并且不能通过简单地增加T细胞应答的质量（亲和力）或多样性来避免。在开发针对持续性感染的疫苗时应考虑这些发现。
While T cell-based vaccines have the potential to provide protection against chronic virus infections, they also have the potential to generate immunopathology following subsequent virus infection. We develop a mathematical model to investigate the conditions under which T cells lead to protection versus adverse pathology. The model illustrates how the balance between virus clearance and immune exhaustion may be disrupted when vaccination generates intermediate numbers of specific CD8 T cells. Surprisingly, our model suggests that this adverse effect of vaccination is largely unaffected by the generation of mutant viruses that evade T cell recognition and cannot be avoided by simply increasing the quality (affinity) or diversity of the T cell response. These findings should be taken into account when developing vaccines against persistent infections.