Dominant induction of vaccine antigen-specific cytotoxic T lymphocyte responses after simian immunodeficiency virus challenge.
Dominant induction of vaccine antigen-specific cytotoxic T lymphocyte responses after simian immunodeficiency virus challenge.
复制标题
猿猴免疫缺陷病毒攻击后，显着诱导疫苗抗原特异性细胞毒性 T 淋巴细胞反应。
DOI：
10.1016/j.bbrc.2011.04.071
复制
发表时间：
2011
影响因子：
3.1
通讯作者：
Y.
中科院分区：
文献类型：
--
作者：
Takahara;Y.
细胞毒性 T 淋巴细胞 (CTL) 反应对于控制人类和猿类免疫缺陷病毒（HIV 和 SIV）复制至关重要。一种有前途的艾滋病疫苗策略是诱导 CTL 记忆，从而与自然 HIV 感染相比，在病毒暴露后产生更有效的 CTL 反应。我们之前开发了一种 CTL 诱导疫苗，并在一些接种疫苗的恒河猴中显示出对 SIV 的控制。这些基于疫苗的 SIV 控制剂主要在攻击后的急性期引发疫苗抗原特异性 CTL 反应。在这里，我们检查了那些未能控制 SIV 复制的接种疫苗的动物在攻击后的 CTL 反应。具有主要组织相容性复合物 I 类单倍型 90-088-Ij 的未接种疫苗的恒河猴在 SIV 攻击后显着引发 SIV 非 Gag 抗原特异性 CTL 反应，而那些通过预防性疫苗接种诱导出 Gag 特异性 CTL 记忆的恒河猴未能在急性期以显性 Gag 特异性 CTL 反应控制 SIV 复制，表明显性 即使在非对照者中，攻击后也会诱导疫苗抗原特异性 CTL 反应。进一步分析表明，预防性疫苗接种会导致病毒暴露后显着诱导疫苗抗原特异性 CTL 反应，但会延迟 SIV 非疫苗抗原特异性 CTL 反应。这些结果意味着预防性疫苗接种对病毒暴露后的 CTL 免疫优势有显着影响，为开发 CTL 诱导艾滋病疫苗的抗原设计提供了见解。
Cytotoxic T lymphocyte (CTL) responses are crucial for the control of human and simian immunodeficiency virus (HIV and SIV) replication. A promising AIDS vaccine strategy is to induce CTL memory resulting in more effective CTL responses post-viral exposure compared to those in natural HIV infections. We previously developed a CTL-inducing vaccine and showed SIV control in some vaccinated rhesus macaques. These vaccine-based SIV controllers elicited vaccine antigen-specific CTL responses dominantly in the acute phase post-challenge. Here, we examined CTL responses post-challenge in those vaccinated animals that failed to control SIV replication. Unvaccinated rhesus macaques possessing the major histocompatibility complex class I haplotype90-088-Ijdominantly elicited SIV non-Gag antigen-specific CTL responses after SIV challenge, while those induced with Gag-specific CTL memory by prophylactic vaccination failed to control SIV replication with dominant Gag-specific CTL responses in the acute phase, indicating dominant induction of vaccine antigen-specific CTL responses post-challenge even in non-controllers. Further analysis suggested that prophylactic vaccination results in dominant induction of vaccine antigen-specific CTL responses post-viral exposure but delays SIV non-vaccine antigen-specific CTL responses. These results imply a significant influence of prophylactic vaccination on CTL immunodominance post-viral exposure, providing insights into antigen design in development of a CTL-inducing AIDS vaccine.