T cell immunity to SARS-CoV-2 vaccination in inflammatory bowel disease patients treated with anti-cytokine biologics.

Anti-TNF and anti-IL-12/IL-23 are commonly used therapies for immune-mediated inflammatory diseases (IMIDs), including inflammatory bowel disease (IBD). Although several studies have shown intact T cell responses following 2 to 3 doses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in biologics treated IMID patients, our group previously reported increased waning of T cell responses at 3-4 mos following the second vaccine dose in IMID patients compared to healthy controls, raising the possibility that a suboptimal initial T cell response could impact long term immunity. Here, to reduce patient heterogeneity, we focused only on IBD patients and further investigated T cell responses in vaccinated, untreated and biologics treated IBD patients compared to healthy controls. Following 1 vaccine dose, we observed a decreased frequency of Spike-reactive Th1 polarized cells and an increased frequency of Th2 cells in the IBD patients in general, relative to healthy controls. Additionally, IBD patients exhibited increased waning of Spike-specific cytokine T cell responses after 2 doses of vaccine. We also observed IBD-treatment specific effects. Spike-specific IL-2 secretion from anti-TNF or anti-IL-12/IL-23-treated patients' T cells was lower than from untreated patients following 1 dose of vaccine. However, single-cell RNA-sequencing of Spike-responsive T cells from anti-TNF and anti-IL-12/IL-23 treated IBD patients and healthy controls 2-4 wk after 2 or 3 vaccine doses revealed no major differences in T cell subsets, transcriptomes or TCR diversity. Thus, despite some evidence of impaired primary T cell responses, Spike-reactive T cells in patients treated with anti-TNF or anti-IL-12/IL-23 appear indistinguishable from healthy controls following a full vaccine course.