BNT162b2 mRNA vaccine elicits robust virus-specific antibodies but poor cross-protective CD8⁺ memory T cell responses in adolescents with type 1 diabetes

Background: COVID-19 mRNA vaccines have demonstrated 95 % efficacy in the general population. However, their immunogenicity in adolescents with Type 1 Diabetes (T1D), who exhibit weaken immune responses, remains insufficiently explored. Methods: Longitudinal analysis of innate immune responses following PRR-agonists and BNT162b2 vaccine stimulations, along with S-specific antibody responses, memory T cell recall responses, and RNA-sequencing were assessed in eight T1D adolescents and 16 healthy controls at six different timepoints. Results: After BNT162b2 vaccination, T1D adolescents produced SARS-CoV-2-specific binding and neutralizing antibodies (Nabs) comparable to healthy controls. Lower pre-vaccination blood HbA1c level correlated with higher antibody responses among T1D adolescents. However, they exhibited impaired TLR9-induced B cells and the first vaccine-induced monocyte activation. These differences were supported by transcriptomic analysis, which revealed the impairment in innate immune-related signatures both before and after vaccination. One year post-second vaccination, T1D adolescents demonstrated compromised cross-protection of T cell against BA.1 compared to healthy controls, which correlated with impaired innate immune responses identified in this study. Conclusion: This study reveals that while T1D adolescents vaccinated with the BNT162b2 vaccine develop robust S-specific antibodies, their cross-protective T cell responses are suboptimal.