Oral Presentation 15th Lorne Infection and Immunity 2025

Impaired humoral immune memory formation after COVID-19 vaccination in patients with inflammatory bowel disease receiving anti-TNF treatment (#23)

Paul Gill 1 , Lachlan Bradbury 1 , Alina Wang 1 , Kathryn Demase 2 , Jo McKenzie 2 , Julie Hogg 2 , Holly Fryer 1 , Daryl Geers 3 , Mark Hogarth 4 , Rory de Vries 3 , Robyn O'Hehir 1 5 , Miles Sparrow 2 6 , Menno van Zelm 1 5 7
  1. Immunology, Monash University, Melbourne
  2. Gastroenterology, Alfred Health, Melbourne
  3. Viroscience, Erasmus MC, Rotterdam, The Netherlands
  4. Burnet Institute, Melbourne
  5. Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne
  6. Gastroenterology, Monash University, Melbourne
  7. Immunology, Erasmus MC, Rotterdam, The Netherlands

Background: Yearly booster vaccinations are recommended to improve protection against severe COVID-19, particularly in immunocompromised people. Vaccines may be poorly immunogenic in these people, but this is mainly based on what is known about antibody responses; the formation of memory B cells (Bmem) is not well defined. Here, we evaluated antibody and Bmem responses in patients with inflammatory bowel disease (IBD) receiving anti-TNF treatment after COVID-19 booster vaccination.

 

Methodology: Blood was sampled before, and 1 and 6 months after mono- or bivalent booster vaccination from 21 healthy controls and 23 IBD patients receiving intravenous Infliximab. SARS-CoV-2 recombinant spike receptor binding domain (RBD) proteins from ancestral, Omicron BA.1, BA.5, XBB.1.5 and JN.1 variants were produced for ELISA-based serology to quantify RBD-specific serum IgG and tetramerised for immunophenotyping of Bmem using flow cytometry.

 

Results: Ancestral and variant-specific serum IgG in IBD patients significantly increased from pre to 1-month post, but were significantly lower than in controls. Similarly, ancestral and BA.5-specific Bmem numbers in patients increased after vaccination but were still significantly lower than controls. Within RBD-specific Bmem, patients had increased frequencies of recently-activated CD71+ and CD21lo cells, and reduced mature CD27+ Bmem after vaccination than controls. While in controls, the IgG4+ Bmem proportion increased, patients showed higher frequencies of IgG3+ Bmem following vaccination. Although absolute numbers of variant specific Bmem were lower in patients, the capacity of patient Bmem to bind BA.1 and XBB.1.5 was significantly increased 1-month post vaccination compared to healthy controls.

 

Conclusion: Infliximab-treated IBD patients have reduced capacity to generate serum IgG and Bmem in response to COVID-19 booster vaccination compared to healthy controls. Together this suggests that overall immunogenicity is reduced in patients. Phenotyping of Bmem at 6-months post vaccination is ongoing to assess durability of the response to inform on the need and frequency of booster vaccinations.