ABSTRACT
High effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported, but immune responses conferring this protection are not yet elucidated. In this analysis, our study (NCT04800133) aims to evaluate the humoral and cellular responses against wild-type and Omicron (BA.1, BA.2 and/or BA.5) SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents. At 6 months after 2 doses, S IgG, S IgG Fc receptor-binding, S-RBD IgG and neutralizing antibody responses waned significantly, yet neutralizing antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses. The antibody responses and S-specific IFN-γ+ and IL-2+ CD8+ T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2. Compared to adults, humoral responses for the third dose were non-inferior or superior in adolescents. The S-specific IFN-γ+ and IL-2+ CD4+ and CD8+ T cell responses in adolescents and adults were comparable. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, and PRNT50 against Omicron BA.2, as well as preserved cellular responses against BA.1 S. Sera from 100% and 96% of adolescents tested at 1 and 6 months after 2 doses could also neutralize BA.1. Based on PRNT50, we predict 92%, 89% and 68% effectiveness against COVID-19 with WT, BA.2 and BA.5 1 month after 3 doses. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after 3 doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.