Low CD8 T-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination
Low CD8 T-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination
复制标题
DOI：
10.1128/jvi.79.14.8960-8968.2005
复制
发表时间：
2005-07-01
影响因子：
5.4
通讯作者：
Ahmed, R
中科院分区：
文献类型：
--
作者：
Wherry, EJ;Blattman, JN;Ahmed, R
治疗性疫苗接种有可能在慢性感染期间增强免疫反应和加强病毒控制。然而，许多治疗性疫苗接种方法都没有达到预期的效果，并且并不总是观察到有效增强抗病毒t细胞反应。为了研究这些问题，我们使用慢性感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）的小鼠模型研究了治疗性疫苗接种的影响。我们的研究结果表明，使用表达LCMV GP33 CD8 t细胞表位的重组痘苗病毒进行治疗性疫苗接种可以有效地加速病毒控制。然而，疫苗接种时病毒载量较低的小鼠对治疗性疫苗的反应优于病毒载量较高的小鼠。此外，来自慢性感染小鼠的gp33特异性CD8 T细胞的增殖潜力大大低于来自对LCMV免疫的小鼠的gp33特异性记忆CD8 T细胞，这表明T细胞扩增不良可能是治疗性疫苗反应不理想的重要原因。因此，我们的研究结果强调了治疗性疫苗在慢性感染期间对病毒控制的潜在积极作用，但也提供了证据表明，疫苗接种时的高病毒载量和应答T细胞的低增殖潜力可能限制了治疗性疫苗接种的有效性。
Therapeutic vaccination has the potential to boost immune responses and enhance viral control during chronic infections. However, many therapeutic vaccination approaches have fallen short of expectations, and effective boosting of antiviral T-cell responses is not always observed. To examine these issues, we studied the impact of therapeutic vaccination, using a murine model of chronic infection with lymphocytic choriomeningitis virus (LCMV). Our results demonstrate that therapeutic vaccination using a recombinant vaccinia virus expressing the LCMV GP33 CD8 T-cell epitope can be effective at accelerating viral control. However, mice with lower viral loads at the time of vaccination responded better to therapeutic vaccination than did those with high viral loads. Also, the proliferative potential of GP33-specific CD8 T cells from chronically infected mice was substantially lower than that of GP33-specific memory CD8 T cells from mice with immunity to LCMV, suggesting that poor T-cell expansion may be an important reason for suboptimal responses to therapeutic vaccination. Thus, our results highlight the potential positive effects of therapeutic vaccination on viral control during chronic infection but also provide evidence that a high viral load at the time of vaccination and the low proliferative potential of responding T cells are likely to limit the effectiveness of therapeutic vaccination.