Oregon National Primate Research Center, Oregon Health & Sciences University, Beaverton, Oregon, USA.
J Virol. 2012 Dec;86(24):13735-44. doi: 10.1128/JVI.02178-12. Epub 2012 Oct 10.
CD8(+) T cells play an important role in protection against both acute and persistent viral infections, and new vaccines that induce CD8(+) T cell immunity are currently needed. Here, we show that lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cells can be generated in response to a nonreplicating H(2)O(2)-inactivated whole-virus vaccine (H(2)O(2)-LCMV). Vaccine-induced CD8(+) T cell responses exhibited an increased ability to produce multiple cytokines at early time points following immunization compared to infection-induced responses. Vaccination with H(2)O(2)-LCMV induced the expansion of a narrow subset of the antigen-specific CD8(+) T cells induced by LCMV strain Arm infection, resulting in a distinct immunodominance hierarchy. Acute LCMV infection stimulated immunodominance patterns that shifted over time or after secondary infection, whereas vaccine-generated immunodominance profiles remained remarkably stable even following subsequent viral infection. Vaccine-induced CD8(+) T cell populations expanded sharply in response to challenge and were then maintained at high levels, with responses to individual epitopes occupying up to 40% of the CD8(+) T cell compartment at 35 days after challenge. H(2)O(2)-LCMV vaccination protected animals against challenge with chronic LCMV clone 13, and protection was mediated by CD8(+) T cells. These results indicate that vaccination with an H(2)O(2)-inactivated whole-virus vaccine induces LCMV-specific CD8(+) T cells with unique functional characteristics and provides a useful model for studying CD8(+) T cells elicited in the absence of active viral infection.
CD8(+) T 细胞在抵抗急性和持续性病毒感染中发挥着重要作用，目前需要开发能够诱导 CD8(+) T 细胞免疫的新型疫苗。在这里，我们表明针对淋巴细胞性脉络丛脑膜炎病毒（LCMV）的特异性 CD8(+) T 细胞可以针对非复制性 H2O2 灭活全病毒疫苗（H2O2-LCMV）产生。与感染诱导的反应相比，疫苗诱导的 CD8(+) T 细胞反应在免疫后早期具有更高的产生多种细胞因子的能力。用 H2O2-LCMV 疫苗接种诱导了由 LCMV 菌株 Arm 感染诱导的抗原特异性 CD8(+) T 细胞的一个狭窄亚群的扩增，导致了独特的免疫优势层次。急性 LCMV 感染刺激的免疫优势模式随着时间的推移或二次感染而改变，而疫苗产生的免疫优势谱即使在随后的病毒感染后仍然保持显著稳定。疫苗诱导的 CD8(+) T 细胞群体对挑战迅速扩张，然后维持在高水平，对个体表位的反应在挑战后 35 天占据了高达 40%的 CD8(+) T 细胞区室。H2O2-LCMV 疫苗接种可保护动物免受慢性 LCMV 克隆 13 的挑战，保护作用由 CD8(+) T 细胞介导。这些结果表明，用 H2O2 灭活的全病毒疫苗接种可诱导具有独特功能特征的 LCMV 特异性 CD8(+) T 细胞，并为研究在无活性病毒感染情况下诱导的 CD8(+) T 细胞提供了有用的模型。
