mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses

Jet van den Dijssel, Mariël C. Duurland, Veronique AL Konijn, Laura YL Kummer, Ruth R. Hagen, Lisan H. Kuijper, Luuk Wieske, Koos PJ van Dam, Eileen W. Stalman, Maurice Steenhuis, Dionne M. Geerdes, Juk Yee Mok, Angela HM Kragten, Charlotte Menage, Lianne Koets, Barbera Veldhuisen, Niels JM Verstegen, C. Ellen van der Schoot, Wim JE van Esch, Geert RAM D'HaensMark Löwenberg, Adriaan G. Volkers, Theo Rispens, Taco W. Kuijpers, Filip Eftimov, Klaas PJM van Gisbergen, S. Marieke van Ham, Anja ten Brinke, Carolien E. van de Sandt*, the T2B! Immunity against SARS-CoV-2 study group, Esther Brusse

*Corresponding author for this work

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SARS-CoV-2-specific CD8+ T cells recognize conserved viral peptides and in the absence of cross-reactive antibodies form an important line of protection against emerging viral variants as they ameliorate disease severity. SARS-CoV-2 mRNA vaccines induce robust spike-specific antibody and T cell responses in healthy individuals, but their effectiveness in patients with chronic immune-mediated inflammatory disorders (IMIDs) is less well defined. These patients are often treated with systemic immunosuppressants, which may negatively affect vaccine-induced immunity. Indeed, TNF inhibitor (TNFi)-treated inflammatory bowel disease (IBD) patients display reduced ability to maintain SARS-CoV-2 antibody responses post-vaccination, yet the effects on CD8+ T cells remain unclear. Here, we analyzed the impact of IBD and TNFi treatment on mRNA-1273 vaccine-induced CD8+ T cell responses compared to healthy controls in SARS-CoV-2 experienced and inexperienced patients. CD8+ T cells were analyzed for their ability to recognize 32 SARS-CoV-2-specific epitopes, restricted by 10 common HLA class I allotypes using heterotetramer combinatorial coding. This strategy allowed in-depth ex vivo profiling of the vaccine-induced CD8+ T cell responses using phenotypic and activation markers. mRNA vaccination of TNFi-treated and untreated IBD patients induced robust spike-specific CD8+ T cell responses with a predominant central memory and activated phenotype, comparable to those in healthy controls. Prominent non-spike-specific CD8+ T cell responses were observed in SARS-CoV-2 experienced donors prior to vaccination. Non-spike-specific CD8+ T cells persisted and spike-specific CD8+ T cells notably expanded after vaccination in these patient cohorts. Our data demonstrate that regardless of TNFi treatment or prior SARS-CoV-2 infection, IBD patients benefit from vaccination by inducing a robust spike-specific CD8+ T cell response.

Original languageEnglish
Article number103175
JournalJournal of Autoimmunity
Publication statusPublished - Apr 2024

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