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This is a PDF file of a peer-reviewed paper that has been accepted for publication.
Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and gures will undergo copyediting and a proof review before the paper is published in its nal form. Please note that during the production process errors may be discovered which could a ect the content, and all legal disclaimers apply.
Published online 28 July 2021
doi.org/10.1038/s41586-021-03841-4 (2021).
Valerie Oberhardt1,2,12, Hendrik Luxenburger1,3,12, Janine Kemming1,2,12, Isabel Schulien1,12, Kevin Ciminski4, Sebastian Giese4, Benedikt Csernalabics1, Julia Lang-Meli1,3, Iga Janowska5, Julian Staniek2,5, Katharina Wild1,6, Kristi Basho1, Mircea Stefan Marinescu1, Jonas Fuchs4, Fernando Topfstedt5, Ales Janda7, Oezlem Sogukpinar1, Hanna Hilger1, Katarina Stete1, Florian Emmerich8, Bertram Bengsch1,9, Cornelius F. Waller10, Siegbert Rieg1, Sagar1,
Tobias Boettler1,11, Katharina Zoldan1, Georg Kochs4, Martin Schwemmle4, Marta Rizzi5, Robert Thimme1,13✉, Christoph Neumann-Haefelin1,13✉ & Maike Hofmann1,13
Abstract
SARS-CoV-2 spike mRNA vaccines[SUP]1–3[/SUP] mediate protection from severe disease as early as 10 days post prime vaccination[SUP]3[/SUP], when neutralizing antibodies are hardly detectable[SUP]4–6[/SUP]. Vaccine-induced CD8+ T cells may thus be the main mediators of protection at this early stage[SUP]7,8[/SUP]. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. We show on a single epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after bnt162b2 prime vaccination when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion generating highly differentiated effector CD8+ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared to 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, 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.
https://www.nature.com/articles/s41586-021-03841-4_reference.pdf
Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and gures will undergo copyediting and a proof review before the paper is published in its nal form. Please note that during the production process errors may be discovered which could a ect the content, and all legal disclaimers apply.
Published online 28 July 2021
doi.org/10.1038/s41586-021-03841-4 (2021).
Valerie Oberhardt1,2,12, Hendrik Luxenburger1,3,12, Janine Kemming1,2,12, Isabel Schulien1,12, Kevin Ciminski4, Sebastian Giese4, Benedikt Csernalabics1, Julia Lang-Meli1,3, Iga Janowska5, Julian Staniek2,5, Katharina Wild1,6, Kristi Basho1, Mircea Stefan Marinescu1, Jonas Fuchs4, Fernando Topfstedt5, Ales Janda7, Oezlem Sogukpinar1, Hanna Hilger1, Katarina Stete1, Florian Emmerich8, Bertram Bengsch1,9, Cornelius F. Waller10, Siegbert Rieg1, Sagar1,
Tobias Boettler1,11, Katharina Zoldan1, Georg Kochs4, Martin Schwemmle4, Marta Rizzi5, Robert Thimme1,13✉, Christoph Neumann-Haefelin1,13✉ & Maike Hofmann1,13
Abstract
SARS-CoV-2 spike mRNA vaccines[SUP]1–3[/SUP] mediate protection from severe disease as early as 10 days post prime vaccination[SUP]3[/SUP], when neutralizing antibodies are hardly detectable[SUP]4–6[/SUP]. Vaccine-induced CD8+ T cells may thus be the main mediators of protection at this early stage[SUP]7,8[/SUP]. The details of their induction, comparison to natural infection, and association with other arms of vaccine-induced immunity remain, however, incompletely understood. We show on a single epitope level that a stable and fully functional CD8+ T cell response is vigorously mobilized one week after bnt162b2 prime vaccination when circulating CD4+ T cells and neutralizing antibodies are still weakly detectable. Boost vaccination induced a robust expansion generating highly differentiated effector CD8+ T cells; however, neither the functional capacity nor the memory precursor T cell pool was affected. Compared to 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, 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.
https://www.nature.com/articles/s41586-021-03841-4_reference.pdf