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.