Poster Presentation Second Round 16th Lorne Infection and Immunity 2026

Low antibody responses after monovalent XBB.1.5 or JN.1 COVID-19 booster vaccination in people with interstitial lung disease (#140)

Paul A Gill 1 , Arwel W Jones 2 , Alina Wang 1 , Irene Boo 3 , Daryl Geers 4 , Luca Zaeck 4 , Rathika Dharmalingam 2 , Heiman Cheung 2 , Phillip M Hogarth 3 , Robyn O'Hehir 1 5 , Heidi Drummer 3 , Rory D de Vries 4 , Anne E Holland 2 5 6 , Menno C van Zelm 1 5 7
  1. Department of Immunology, Monash University, Melbourne
  2. Respiratory Research@Alfred, Monash University, Melbourne, VIC, Australia
  3. Burnet Institute, Melbourne
  4. Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands
  5. Department of Respiratory Medicine, Alfred Hospital, Melbourne, VIC
  6. Department of Physiotherapy, Alfred Hospital, Melbourne, VIC
  7. Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands

Background: People with interstitial lung disease (ILD) are at risk for developing severe COVID-19 due to underlying disease, particularly those on immunosuppressive treatment. Yearly booster vaccinations are recommended; however, it is unclear how vaccine immunogenicity compares to controls. Here, we evaluated the antibody response in patients with ILD after COVID-19 booster vaccination.

 

Methodology: Blood was sampled before, and 1 and 6-months after monovalent XBB.1.5 or JN.1 mRNA-based booster vaccination of 22 controls (median age: 56) and 26 people with ILD (median age: 64). SARS-CoV-2 recombinant spike receptor binding domain proteins from ancestral, Omicron BA.1, BA.5, XBB.1.5 and JN.1 variants were produced for ELISA-based serology. Neutralising antibodies were assessed using an infectious virus plaque reduction neutralisation test.

 

Results: ILD patients had a median duration of 5 years since diagnosis and 58% on systemic immunosuppressive therapy. Booster vaccination induced a significant increase of ancestral, XBB.1.5 and JN.1 variant-specific serum IgG in people with ILD, but antibody levels were significantly lower than in controls. Neutralising antibody responses to ancestral and XBB.1.5 variants at 1M and 6M post-vaccination were also significantly lower in people with ILD than in controls. Additionally, neutralising antibodies were less durable and more patients had undetectable at 6M post-vaccination (35 vs 5%). Variant-binding capacity of serum IgG was comparable between patients and controls after vaccination, highlighting that patient antibody responses were directed toward the viral variant in the vaccine despite the magnitude of response being lower.

 

Conclusion: Based on serum IgG responses, COVID-19 booster vaccinations are less immunogenic in people with ILD compared to controls; however, the response is still directed to the omicron subvariant contained in the booster vaccine. Phenotyping of SARS-CoV-2 specific memory B cells to assess if people with ILD can mount durable immune memory to respond to breakthrough infection is ongoing.