Long-term persistence of antibodies after diphtheria/tetanus vaccination in immunosuppressed patients with inflammatory rheumatic diseases and healthy controls

Vaccine. 2022 Aug 5;40(33):4897-4904. doi: 10.1016/j.vaccine.2022.06.013. Epub 2022 Jul 7.


Many vaccines demonstrate high effectiveness for years. This prospective multicentre study was conducted in Switzerland to assess the long-term persistence of antibodies to the diphtheria/tetanus (dT)-vaccine in adult patients with rheumatic diseases (PRDs). 163 PRDs and 169 controls were included in the study. The median age of all participants was 50 years (range: 18-83 years) and 56% were female. After a median time interval of 16 years after vaccination, the median anti-vaccine antibody concentrations were lower in PRDs than in controls for tetanus (1.68 vs 2.01; p = 0.049) and diphtheria (0.05 vs 0.22; p = 0.002). Based on the currently accepted seroprotection threshold (antibody concentration ≥ 0.1 IU/ml), PRDs had lower proportions of short-term tetanus and diphtheria protection as demonstrated by crude odds ratios (OR) of 0.30 (p = 0.017) and OR: 0.52 (p = 0.004), respectively. After adjusting for 'age' and 'time since last dT vaccination', the strength of associations became weaker; for tetanus, borderline evidence remained for a true difference between PRDs and controls (OR: 0.36 [p = 0.098]), however, not for diphtheria (OR: 0.86 [p = 0.58]). We hypothesize that in the presence of rheumatic diseases and its immunosuppressive treatment, vaccine-specific long-lived plasma cells (LLPCs) may be diminished or competitively displaced by rheumatism-specific LLPCs, a process which may decrease the persistence of vaccine-specific antibodies. Novel studies should be designed by incorporating methodologies allowing to determine the attributable fraction of immunosuppressive/immunomodulatory medications and rheumatic disease itself on long-lasting vaccine-specific antibody persistence, as well as, further study the role of LLPCs.

Keywords: Diphtheria; Long-term immunogenicity; Rheumatism; Tetanus; Vaccination; Vaccine.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial
  • Diphtheria* / prevention & control
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine
  • Female
  • Humans
  • Immunization, Secondary / methods
  • Male
  • Middle Aged
  • Prospective Studies
  • Rheumatic Diseases*
  • Tetanus* / prevention & control
  • Vaccination / methods
  • Whooping Cough* / prevention & control
  • Young Adult


  • Antibodies, Bacterial
  • Diphtheria-Tetanus Vaccine
  • Diphtheria-Tetanus-Pertussis Vaccine