Robust priming of CD8⁺ T cells by viruses is considered to require infection and de novo expression of viral antigens. A corollary of this is that inactivated viruses are thought of as being inevitably poor vaccines for eliciting these responses. In contrast to this dogma, we found that some antigens present in vaccinia virus (VACV) virions prime strong CD8⁺ T cell responses when the virus was rendered noninfectious by heat. More surprisingly, in some cases these responses were similar in magnitude to those primed by infectious virus administered at an equivalent dose. Next, we tested whether this was a special property of particular antigens and their epitopes and found that foreign epitopes tagged onto three different VACV virion proteins were able to elicit CD8⁺ T cell responses irrespective of whether the virus was viable or heat killed. Further, the polyfunctionality and cytotoxic ability of the CD8⁺ T cells primed by these VACVs was equivalent irrespective of whether they were administered to mice as inactivated or live viruses. Finally, we used these VACVs in prime-boost combinations of inactivated and live virus and found that priming with dead virus before a live booster was the most immunogenic regime. We conclude that VACV virions can be efficient vectors for targeting antigens to dendritic cells for effective priming of CD8⁺ T cells, even when rendered noninfectious and speculate that this might also be the case for other viruses.

中文翻译：

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热灭活痘苗病毒病毒粒子对 CD8+ T 细胞的启动效果令人惊讶。

病毒对CD8 ⁺ T 细胞的强力启动被认为需要病毒抗原的感染和从头表达。由此推论，灭活病毒被认为是不可避免地无法引发这些反应的疫苗。与这一教条相反，我们发现，当痘苗病毒 (VACV) 病毒粒子中存在的一些抗原在病毒因加热而变得非传染性时引发强烈的 CD8 ^{+ T 细胞反应。}更令人惊讶的是，在某些情况下，这些反应的程度与以同等剂量施用传染性病毒引发的反应相似。接下来，我们测试了这是否是特定抗原及其表位的特殊性质，并发现标记在三种不同 VACV 病毒体蛋白上的外源表位能够引发 CD8 ⁺ T 细胞反应，无论病毒是否存活或热灭活。此外，由这些VACV引发的CD8 ⁺ T细胞的多功能性和细胞毒性能力是相同的，无论它们是作为灭活病毒还是活病毒施用于小鼠。最后，我们将这些 VACV 用于灭活病毒和活病毒的初免-加强组合，发现在活病毒加强之前先用死病毒进行初免是最具免疫原性的方案。我们得出的结论是，VACV 病毒颗粒可以成为将抗原靶向树突状细胞的有效载体，从而有效启动 CD8 ⁺ T 细胞，即使在变得非传染性时也是如此，并推测其他病毒也可能出现这种情况。