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

Authors:

• van den Dijssel, Jet
• Duurland, Mariël C.
• Konijn, Veronique AL.
• Kummer, Laura YL.
• Hagen, Ruth R.
• Kuijper, Lisan H.
• Wieske, Luuk
• van Dam, Koos PJ.
• Stalman, Eileen W.
• Steenhuis, Maurice
• Geerdes, Dionne M.
• Mok, Juk Yee
• Kragten, Angela HM.
• Menage, Charlotte
• Koets, Lianne
• Veldhuisen, Barbera
• Verstegen, Niels JM.
• van der Schoot, C Ellen
• van Esch, Wim JE.
• D'Haens, Geert RAM.
• Löwenberg, Mark
• Volkers, Adriaan G.
• Rispens, Theo
• Kuijpers, Taco W.
• Eftimov, Filip
• van Gisbergen, Klaas PJM.
• van Ham, S Marieke
• ten Brinke, Anja
• van de Sandt, Carolien E.
• van Allaart, Renée CF.
• Baars, Adája E.
• Bekkenk, Marcel W.
• Bemelman, Frederike J.
• Boekel, Laura
• Bos, Amélie V.
• Bosma, Angela L.
• Broens, Bo
• Brusse, Esther
• Busch, Matthias H.
• Cristianawati, Olvi
• van Doorn, Pieter A.
• Elias, George
• van Els, Cécile ACM.
• van Gils, Marit J.
• Goedee, H Stephan
• Hijnen, Dirk Jan
• Hilhorst, Marc L.
• Horváth, Barbara
• Jallah, Papay BP.
• de Jongh, Rivka
• Mirfazeli, Elham S.
• Musters, Annelie H.
• Keijser, Jim BD.
• van Kempen, Zoé LE.
• Killestein, Joep
• Kreher, Christine
• de Leeuw, Karina
• van der Kooi, Anneke J.
• van Ouwerkerk, Lotte
• van Paassen, Pieter
• Cabeza, Virginia Palomares
• Parra Sanchez, Agner R.
• Ludo van der Pol, W.
• Post, Nicoline F.
• Raaphorst, Joop
• Ruiter, Annabel M.
• Rutgers, Abraham
• Schreurs, Corine RG.
• Spuls, Phyllis I.
• Takkenberg, R Bart
• Tas, Sander W.
• Teng, YK Onno
• Vegting, Yosta
• Verschuuren, Jan JGM.
• Voskuyl, Alexandre E.
• de Wit, Jelle
• Wolbink, Gerrit J.
• van der Woude, Diane
• Zwinderman, Koos AH.

Details:

Journal of Autoimmunity, Volume 144, 2024-04-30

Article Link: Click here

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.