Vaccination in Children with Paediatric Autoimmune and Autoinflammatory Rheumatic Diseases: Evidence on Safety, Immunogenicity and Effectiveness Across Live-Attenuated, mRNA and Recombinant Vaccines

Vaccination in children with paediatric autoimmune and autoinflammatory rheumatic diseases (pedAIIRDs) is clinically important but challenging. These children have an increased risk of infections due to both their underlying immune-mediated disease and the immunosuppressive therapies required for disease control. At the same time, immunosuppression may reduce vaccine-induced immune responses, while concerns about disease flares and the safety of live-attenuated vaccines may result in delayed or incomplete vaccination.

This thesis aimed to generate clinically applicable, real-world evidence on the safety, immunogenicity and effectiveness of vaccination in children with pedAIIRDs receiving immunosuppressive therapy. Five studies addressed three vaccine platforms: the live-attenuated measles-mumps-rubella (MMR) booster vaccine, COVID-19 mRNA vaccines and the recombinant zoster vaccine (RZV; Shingrix).

In a cohort of 186 children with juvenile idiopathic arthritis (JIA), MMR booster vaccination was not associated with increased disease activity, including in children receiving biological disease-modifying antirheumatic drugs, and no serious vaccine-related adverse events were observed. Long-term evaluation of 182 children with JIA showed that most patients maintained protective antibodies against measles, mumps and rubella. However, measles seroprotection five years after vaccination was significantly lower in patients receiving biologic therapy at vaccination than in those not receiving biologics, supporting a targeted approach to serological monitoring.

A systematic review and meta-analysis demonstrated that COVID-19 vaccination was associated with a marked reduction in the risk of multisystem inflammatory syndrome in children (MIS-C). In a prospective cohort of 157 children with paediatric rheumatic diseases, COVID-19 mRNA vaccination induced humoral responses in nearly all patients and adequate T-cell responses in most tested patients. Although antibody concentrations were lower in patients receiving biologic therapy, vaccine effectiveness against symptomatic COVID-19 was preserved. No increase in disease activity, myocarditis or serious adverse events was identified.

Finally, off-label use of RZV was evaluated in ten varicella-zoster-virus-naïve immunocompromised children for whom live-attenuated varicella vaccination was unsuitable. Nine of ten patients seroconverted following two doses. Two subsequently developed mild breakthrough varicella after household exposure and recovered without hospitalisation or antiviral treatment.

Together, these studies support a shift from broad vaccine avoidance towards individualised, treatment-specific vaccination strategies in immunocompromised children. The findings provide evidence for the safe use of selected live vaccines, targeted monitoring of long-term vaccine-induced immunity, effective use of mRNA vaccines and further evaluation of non-live vaccine alternatives. These results may contribute to future national and international vaccination recommendations for children with immune-mediated inflammatory diseases.