TY - JOUR
T1 - mRNA-1273 vaccinated inflammatory bowel disease patients receiving TNF inhibitors develop broad and robust SARS-CoV-2-specific CD8+ T cell responses
AU - van den Dijssel, Jet
AU - Duurland, Mariël C.
AU - Konijn, Veronique A. L.
AU - Kummer, Laura Y. L.
AU - Hagen, Ruth R.
AU - Kuijper, Lisan H.
AU - Wieske, Luuk
AU - van Dam, Koos P. J.
AU - Stalman, Eileen W.
AU - Steenhuis, Maurice
AU - Geerdes, Dionne M.
AU - Mok, Juk Yee
AU - Kragten, Angela H. M.
AU - Menage, Charlotte
AU - Koets, Lianne
AU - Veldhuisen, Barbera
AU - Verstegen, Niels J. M.
AU - van der Schoot, C. Ellen
AU - van Esch, Wim J. E.
AU - D'Haens, Geert R. AM.
AU - Löwenberg, Mark
AU - Volkers, Adriaan G.
AU - Rispens, Theo
AU - Kuijpers, Taco W.
AU - Eftimov, Filip
AU - van Gisbergen, Klaas P. JM.
AU - van Ham, S. Marieke
AU - ten Brinke, Anja
AU - van de Sandt, Carolien E.
AU - T2B! immunity against SARS-CoV-2 study group
AU - van Allaart, Renée C. F.
AU - Baars, Adája E.
AU - Bekkenk, Marcel W.
AU - Bemelman, Frederike J.
AU - Bos, Amélie V.
AU - Bosma, Angela L.
AU - van Gils, Marit J.
AU - Hilhorst, Marc L.
AU - Musters, Annelie H.
AU - van Kempen, Zoé L. E.
AU - Kreher, Christine
AU - van der Kooi, Anneke J.
AU - Parra Sanchez, Agner R.
AU - Post, Nicoline F.
AU - Ruiter, Annabel M.
AU - Spuls, Phyllis I.
AU - Takkenberg, R. Bart
AU - Tas, Sander W.
AU - Vegting, Yosta
AU - Wolbink, Gerrit J.
AU - Zwinderman, Koos A. H.
AU - Boekel, Laura
AU - Broens, Bo
AU - Brusse, Esther
AU - Elias, George
AU - Mirfazeli, Elham S.
AU - Killestein, Joep
AU - Rutgers, Abraham
AU - Voskuyl, Alexandre E.
N1 - Publisher Copyright: © 2024 The Authors
PY - 2024/4/1
Y1 - 2024/4/1
N2 - 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.
AB - 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.
KW - Adalimumab
KW - CD8 T cells
KW - Inflammatory bowel disease
KW - Infliximab
KW - SARS-CoV-2 vaccination
KW - TNF inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85186085937&partnerID=8YFLogxK
U2 - 10.1016/j.jaut.2024.103175
DO - 10.1016/j.jaut.2024.103175
M3 - Article
C2 - 38387105
SN - 0896-8411
VL - 144
JO - Journal of autoimmunity
JF - Journal of autoimmunity
M1 - 103175
ER -