BNT162b2 mRNA Vaccine Demonstrates Strong Immunogenicity and Favorable Safety Profile in Adolescents with Juvenile Immune-Mediated Inflammatory Disease
Key Insights
The BNT162b2 mRNA vaccine induced robust seroconversion rates of 97–100% in adolescents with juvenile IMID, comparable to adults with IMID, regardless of immunosuppression degree.
Safety analysis showed predominantly mild local adverse events, with juvenile patients experiencing less joint pain and shorter fatigue duration than adults.
Disease activity in patients with juvenile SLE and JIA remained stable throughout the vaccination series, with no significant post-vaccination flares observed.
The BNT162b2 (Pfizer–BioNTech (search)) mRNA COVID-19 vaccine generates strong humoral immune responses and demonstrates a favorable safety profile in adolescents with juvenile immune-mediated inflammatory disease (search) (IMID), according to findings from the Brazilian SAFER study published in Pediatric Research. The multicenter, observational, longitudinal real-world study provides critical evidence for a population that has been largely underrepresented in COVID-19 vaccine clinical trials, addressing persistent gaps in knowledge about vaccine performance in pediatric patients with immune dysregulation and immunosuppressive treatment.
The study, conducted across seven Brazilian university centers, enrolled 86 adolescents aged 12–17 years with confirmed juvenile IMID, including juvenile idiopathic arthritis (search) (JIA, 41.8%), juvenile systemic lupus erythematosus (search) (jSLE, 38.4%), and other inflammatory conditions. A control group of 37 adults with IMID aged 18–40 years who received the same BNT162b2 vaccine was used for comparison. Both groups were predominantly female (75% juvenile, 86% adult) and had comparable degrees of immunosuppression, with high-grade immunosuppression present in 60% and 62% of patients, respectively.
Robust Immunogenicity Across All Patient Groups
Immunogenicity was assessed by measuring IgG antibodies against the SARS-CoV-2 spike receptor-binding domain via chemiluminescence at four time points: before the first dose, before the second dose, four weeks after the second dose, and after the third dose. Seropositivity was defined as titers ≥7 binding antibody units (BAU).
The seroconversion rate after the second dose reached 97% in the overall group and 100% among patients who were seronegative at baseline. Following the third dose, seroconversion reached 100% across all groups. There was a significant increase in IgG-S levels after both the first and second doses in both the juvenile and adult cohorts (p < 0.001).
Analysis of normalized IgG titers over time revealed a median IgG log titer of 0.76 at baseline, rising to 5.64 after the first dose, 8.24 after the second dose, and 7.80 after the third dose. Statistically significant increases were observed when comparing baseline to post-first dose (p < 0.001), baseline to post-second dose (p < 0.001), baseline to post-third dose (p < 0.001), and first to second dose (p = 0.015). Notably, no significant difference was found between second and third dose titers (p = 1), suggesting a trend toward stabilization rather than further boosting.
Multivariate linear regression found no association between IgG levels after the third dose and age (β = −0.004; 95% CI: −0.850 to 0.842; p = 0.992), reactive serology at inclusion (β = −0.318; 95% CI: −1.200 to 0.565; p = 0.472), or degree of immunosuppression (low degree: β = 0.594; 95% CI: −0.671 to 1.858; p = 0.349; high degree: β = −0.048; 95% CI: −1.024 to 0.929; p = 0.922).
Favorable Safety Profile with Milder Reactions in Adolescents
Safety was assessed through diaries recording symptoms during the 28 days after each dose and active surveillance via scheduled telephone contacts and medical visits. The most common adverse events in the juvenile group were local reactions at the injection site, occurring in 77% after the first dose, 44% after the second dose, and 25% after the third dose.
When compared with the adult cohort, adolescents experienced significantly less joint pain after both the first dose (15% vs. 41%, p = 0.003) and second dose (24% vs. 0%, p = 0.003). The duration of tiredness or lack of energy was also significantly shorter in the juvenile cohort (3.00 days [IQR 2.00–4.00] vs. 5 days [IQR 2.00–17.00], p = 0.034). No serious or life-threatening adverse events were reported, and no differences in adverse event incidence were observed between groups after the third dose.
Stable Disease Activity Throughout Vaccination
Disease activity monitoring in patients with jSLE using the SLEDAI-2K score showed no significant worsening after vaccination. At inclusion, 19.2% of jSLE patients were in remission, 46.2% had low disease activity, and 34.6% had high disease activity. After the third dose, 72.7% were in remission, with 9.09% and 18.2% having low and high disease activity, respectively. No statistically significant differences in disease activity were observed at any post-vaccination time point.
For JIA patients, the median Physician Global Assessment (PGA) score was 1.00 at inclusion, 0.0 after the first dose, 0.50 after the second dose, and 0.00 after the third dose, indicating stable or improved disease control throughout the immunization series.
Real-World Context and Limitations
The frequency of previous natural SARS-CoV-2 exposure was lower in the juvenile cohort (8.14%) compared with adults (30.6%, p < 0.001), a finding the authors hypothesize may be related to delayed school reopening in Brazil compared with other countries. The median time between the second and third dose was 148 days, and the median time between the third dose and post-third-dose serology collection was 155 days.
The authors acknowledge several limitations, including the observational real-life design, the limited number of participants available at reference centers, and loss of adherence after the third dose, which may have contributed to nonsignificant results in some analyses. The study was approved by the National Research Ethics Committee (CONEP) under protocol CAAE 43479221.0.1001.5505 and conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.
This study represents the first investigation conducted in Brazilian reference centers to present long-term real-life data on the safety and immunogenicity of the SARS-CoV-2 vaccine in adolescents with juvenile IMID treated with a variety of immunosuppressive agents, helping to close a critical evidence gap in pediatric vaccine research.