Reduced vaccine-induced germinal center outputs in inflammatory bowel disease patients treated with anti-TNF biologics

Tumor necrosis factor (TNF) blocking agents are widely used to treat patients with immune-mediated inflammatory diseases. The complete absence of TNF in mice impairs germinal center responses. Less is known about the impact of anti-TNF therapy on specific immune responses in humans. The widespread vaccination against SARS-CoV-2 offered an unprecedented opportunity to investigate the effects of biological therapies on the response to a specific immunization. Previous work demonstrated that inflammatory bowel disease (IBD) patients treated with anti-TNF agents exhibit decreased Spike (S)-specific antibody responses compared to IBD patients treated with anti-IL-12/23 or healthy controls, even after four doses of mRNA vaccine. Here, we performed immune profiling of S-specific memory B cells (MBCs) isolated from anti-TNF treated- or anti-IL-12/23- treated IBD patients and healthy controls via 5' single cell RNA-sequencing, CITE-sequencing, and BCR-sequencing, to examine the transcriptome of and breadth of memory B cell responses to SARS-CoV-2 mRNA vaccination. This study provided in vivo evidence that anti-TNF, but not anti-IL-12/23, therapy impairs the quantity of and quality of antigen-specific germinal center outputs in humans. CITE-seq and BCR-seq: From the PBMCs of healthy controls (n=3), anti-TNF treated IBD patients (n=5) and anti-IL-12/23 treated IBD patients (n=4) isolated 3-4 months post vaccine dose 2 (Timepoint 4) and vaccine dose 3 (Timepoint 6), we tagged each individual with an unique TotalSeqC hastag antibody (HTOs) and sorted for Spike-specific memory B cells, which were then analyzed using CITE-seq and BCR-seq. Patients were matched between timepoints, with the exception of one anti-TNF treated IBD patient (TotalSeq-C hashtag #12) that was only sampled at Timepoint 4.