Rapid and stable mobilization of CD8+ T cells by SARS-CoV-2 mRNA vaccine

被引:242
|
作者
Oberhardt, Valerie [1 ,2 ]
Luxenburger, Hendrik [1 ,3 ]
Kemming, Janine [1 ,2 ]
Schulien, Isabel [1 ]
Ciminski, Kevin [4 ]
Giese, Sebastian [4 ]
Csernalabics, Benedikt [1 ]
Lang-Meli, Julia [1 ,3 ]
Janowska, Iga [5 ]
Staniek, Julian [2 ,5 ]
Wild, Katharina [1 ,6 ]
Basho, Kristi [1 ]
Marinescu, Mircea Stefan [1 ]
Fuchs, Jonas [4 ]
Topfstedt, Fernando [5 ]
Janda, Ales [7 ]
Sogukpinar, Oezlem [1 ]
Hilger, Hanna [1 ]
Stete, Katarina [1 ]
Emmerich, Florian [8 ]
Bengsch, Bertram [1 ,9 ,10 ]
Waller, Cornelius F. [11 ]
Rieg, Siegbert [1 ]
Sagar [1 ]
Boettler, Tobias [1 ,12 ]
Zoldan, Katharina [1 ]
Kochs, Georg [4 ]
Schwemmle, Martin [4 ]
Rizzi, Marta [5 ]
Thimme, Robert [1 ]
Neumann-Haefelin, Christoph [1 ]
Hofmann, Maike [1 ]
机构
[1] Univ Freiburg, Dept Med 2, Gastroenterol Hepatol Endocrinol & Infect Dis, Fac Med,Freiburg Univ Med Ctr, Freiburg, Germany
[2] Univ Freiburg, Fac Biol, Freiburg, Germany
[3] Univ Freiburg, IMM PACT, Fac Med, Freiburg, Germany
[4] Univ Freiburg, Freiburg Univ Med Ctr, Inst Virol, Fac Med, Freiburg, Germany
[5] Univ Freiburg, Freiburg Univ Med Ctr, Dept Rheumatol & Clin Immunol, Fac Med, Freiburg, Germany
[6] Univ Freiburg, Fac Chem & Pharm, Freiburg, Germany
[7] Ulm Univ Med Ctr, Dept Pediat & Adolescent Med, Ulm, Germany
[8] Univ Freiburg, Inst Transfus Med & Gene Therapy, Fac Med, Freiburg Univ Med Ctr, Freiburg, Germany
[9] Univ Freiburg, Signalling Res Ctr BIOSS, Freiburg, Germany
[10] Univ Freiburg, Signalling Res Ctr CIBSS, Freiburg, Germany
[11] Univ Freiburg, Dept Haematol, Oncol Stem Cell Transplantat, Fac Med,Freiburg Univ Med Ctr, Freiburg, Germany
[12] Univ Freiburg, Berta Ottenstein Programme, Fac Med, Freiburg, Germany
关键词
EFFECTOR; DIFFERENTIATION; PRECURSOR; RESPONSES;
D O I
10.1038/s41586-021-03841-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
SARS-CoV-2 spike mRNA vaccines(1-3) mediate protection from severe disease as early as ten days after prime vaccination(3), when neutralizing antibodies are hardly detectable(4-6). Vaccine-induced CD8(+) T cells may therefore be the main mediators of protection at this early stage(7,8). 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.
引用
收藏
页码:268 / +
页数:27
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