Department of Medicine II (Gastroenterology, Hepatology, Endocrinology and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Faculty of Biology, University of Freiburg, Freiburg, Germany.
Nature. 2021 Sep;597(7875):268-273. doi: 10.1038/s41586-021-03841-4. Epub 2021 Jul 28.
SARS-CoV-2 spike mRNA vaccines mediate protection from severe disease as early as ten days after prime vaccination, when neutralizing antibodies are hardly detectable. Vaccine-induced CD8 T cells may therefore be the main mediators of protection at this early stage. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. Here we show on a single-epitope level that a stable and fully functional CD8 T cell response is vigorously mobilized one week after prime vaccination with bnt162b2, when circulating CD4 T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion that generated highly differentiated effector CD8 T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared with natural infection, vaccine-induced early memory T cells exhibited similar functional capacities but a different subset distribution. Our results indicate that CD8 T cells are important effector cells, are expanded in the early protection window after prime vaccination, precede maturation of other effector arms of vaccine-induced immunity and are stably maintained after boost vaccination.
SARS-CoV-2 刺突 mRNA 疫苗在初次接种后 10 天左右就可以介导对严重疾病的保护，此时几乎检测不到中和抗体。因此，疫苗诱导的 CD8 T 细胞可能是早期保护的主要介导者。然而，它们的诱导细节、与自然感染的比较以及与疫苗诱导免疫的其他方面的关联仍然不完全清楚。在这里，我们在单个表位水平上表明，在初次接种 bnt162b2 一周后，就会强烈动员出稳定且功能齐全的 CD8 T 细胞反应，而此时循环中的 CD4 T 细胞和中和抗体仍难以检测到。加强接种诱导了强烈的扩增，产生了高度分化的效应 CD8 T 细胞；然而，功能能力和记忆前体细胞池都没有受到影响。与自然感染相比，疫苗诱导的早期记忆 T 细胞表现出相似的功能能力，但亚群分布不同。我们的研究结果表明，CD8 T 细胞是重要的效应细胞，在初次接种后的早期保护窗内被扩增，先于疫苗诱导免疫的其他效应臂的成熟，并在加强接种后稳定维持。
