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

Valerie Oberhardt,Florian Emmerich,Kevin Ciminski,Christiane Waller ,Iga Janowska,Marta Rizzi,Georg Kochs,Oezlem Sogukpinar,Aleš Janda ,Isabel Schulien,Robert Thimme,Jonas Fuchs,Julia Lang‐Meli ,Fernando Topfstedt,Mircea Stefan Marinescu,Benedikt Csernalabics,Sebastian Giese,Julian Staniek,Katharina Wild,Sagar Sagar,Katharina Zoldan,Janine Kemming,Siegbert Rieg,Hanna Hilger,Hendrik Luxenburger,Martin Schwemmle,Katarina Stete,Kristi Basho,Christoph Neumann‐Haefelin ,Tobias Böettler ,Bertram Bengsch,Maike Hofmann

doi:10.1038/s41586-021-03841-4

Valerie Oberhardt, Florian Emmerich + Show 30 more

Open Access

https://doi.org/10.1038/s41586-021-03841-4

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Abstract

SARS-CoV-2 spike mRNA vaccines1–3 mediate protection from severe disease as early as ten days after prime vaccination3, when neutralizing antibodies are hardly detectable4–6. Vaccine-induced CD8+ T cells may therefore be the main mediators of protection at this early stage7,8. 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.

Highlights

By this approach, the strength, dynamics and functional capacity are underestimated or even blurred in contrast to analyses performed at the single epitope level[5]
CD38, T-BET, TOX and BCL-2 are plotted on the diffusion map. d, e, Calculated ex vivo frequencies of non-naive spike-specific CD8+ T cells expressing CD127 or TCF-1 for spike-specific CD8+ T cells
We assessed the induction of spike-specific memory precursor CD8+ T cells that are characterized by CD127, BCL-2 and TCF-1 expression and are relevant for maintaining the CD8+ T cell response[13,14]

Summary

Discussion

A robust, stable and fully functional spike-specific CD8+ T cell response is elicited already after prime vaccination at a time point when neutralizing antibodies were hardly detectable and coincides with the protective effect observed for mRNA vaccines that starts at [10,11,12] dpp[2,3]. Functional vaccine-elicited early memory CD8+ T cells patrol the periphery for SARS-CoV-2 at least within the first months. The functional capacity of spike-specific early memory CD8+ T cells is similar after vaccination and natural infection up to [3,4] months after boost or symptom onset. 4. Sahin, U. et al COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. M. et al Rapid induction of antigen-specific CD4+ T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccination. R. et al Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. S. et al SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. K. et al SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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