Impaired memory B-cell formation after mRNA-based COVID-19 booster vaccination in patients with inflammatory bowel disease receiving anti-TNF treatment

Background

Patients receiving anti-TNF treatment for chronic inflammatory disease display impaired antibody responses, but it remains unclear how immune memory formation is affected. We evaluated antibody responses and memory B cells (Bmem) after COVID-19 booster vaccination in inflammatory bowel disease (IBD) patients receiving anti-TNF treatment.

Methodology

Blood was sampled at baseline, 1, and 6 months after WH1/BA.5 bivalent or XBB.1.5 monovalent vaccination from 27 IBD patients receiving intravenous anti-TNF and 44 controls. Neutralizing antibodies were measured using an infectious virus assay. SARS-CoV-2 spike receptor binding domain (RBD)-specific serum IgG was quantified by ELISA, and RBD-specific Bmem were immunophenotyped by flow cytometry using recombinant proteins from ancestral, Omicron BA.1, BA.5, XBB.1.5, and JN.1 variants.

Results

Serum IgG to vaccine RBD and neutralizing antibodies in patients increased pre to 1 month post-vaccination, but were lower than controls. Ancestral-, BA.5- and XBB.1.5-specific Bmem increased after vaccination but were significantly lower in patients than controls. Within RBD-specific Bmem, frequencies of recently activated CD21 ^lo cells were increased after vaccination, and were higher in patients than controls. Fewer antigen-specific Bmem in patients expressed IgG4, and more expressed IgG3 or IgD following vaccination. Following vaccination, more RBD-specific Bmem recognized multiple viral variants. However, patients had fewer Bmem that could bind to subvariants than controls.

Conclusion

Antibody and Bmem responses to COVID-19 booster vaccination in anti-TNF-treated IBD patients displayed reduced capacity, durability and cross-reactivity, suggesting impaired immune memory for protection against breakthrough infection. This supports the recommendation for annual booster vaccination to prevent severe disease and viral spread.

Highlights

• IBD patients on anti-TNF biologics mount antibody responses and form vaccine-specific memory B cells following WH1/BA.5 bivalent or XBB.1.5 monovalent mRNA COVID-19 booster vaccination.

• Vaccine-specific antibody responses and memory B cell formation in patients are significantly lower than in controls at 1- and 6 months after vaccination, indicative of poorer peak response and durability.

• Despite multiple vaccinations, vaccine-specific memory B cells from patients display phenotypic alterations and reduced recognition of multiple SARS-CoV-2 Omicron subvariants, potentially a consequence of impaired germinal center responses in patients.