Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

Abstract

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies, 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 5 months after 2 doses, S IgG, S IgG Fc receptor-binding, and neutralising antibody responses waned significantly, yet neutralising 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 or non-inferior. Interestingly, after 3 doses, adolescents had preserved S IgG, S IgG avidity, S IgG FcγRIIIa-binding, against Omicron BA.2, as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1, BA.2 and BA.5. Sera from 100 and 96% of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1. Our study found high antibody and T cell responses, including potent cross-variant reactivity, after three doses of BNT162b2 vaccine in adolescents in its current formulation, suggesting that current vaccines can be protective against symptomatic Omicron disease.

Superior antibody and membrane protein-specific T cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

“…Our recent publication on BNT162b2 by IM demonstrated consistent increases in S IgG avidity across time, while the concentrations of IgGs waned before dose 3 was administered as a booster vaccination to adolescents. 39 These findings support the notion that effective vaccination induces efficient immunity characterized by antibodies that have high avidity and increased effector functions against SARS-CoV-2 rather than large quantities of low-quality immunoglobulins. 40 In this regard, S IgG avidity maturation in our cohort appears to be markedly boosted by dose 3 of ID CoronaVac, and the kinetics of this antibody response is significantly different from IM.…”

“…CoronaVac in adolescents and children, as previously described. 14,16,39 The current pre- Procedures. Study doctors obtained informed assent from eligible participants and consent from their respective parents or legally acceptable representatives.…”

“…The SARS-CoV-2 S receptor-binding domain (S-RBD) IgG enzymelinked immunosorbent assay (ELISA) and PRNT have been validated in our previous publications. 14,16,39,47 The sVNT was carried out according to the manufacturer's instructions (GenScript Inc, Piscataway, USA) and our previous experiments, which have been validated. 14,16,39,47 Briefly, S-RBD IgG ELISA plates were coated overnight with 100 ng/well of purified recombinant S-RBD in PBS buffer, and then 100 µL Chonblock Blocking/Sample Dilution (CBSD) ELISA buffer (Chondrex Inc, Redmond, USA) were added.…”

“…14,16,39,47 The sVNT was carried out according to the manufacturer's instructions (GenScript Inc, Piscataway, USA) and our previous experiments, which have been validated. 14,16,39,47 Briefly, S-RBD IgG ELISA plates were coated overnight with 100 ng/well of purified recombinant S-RBD in PBS buffer, and then 100 µL Chonblock Blocking/Sample Dilution (CBSD) ELISA buffer (Chondrex Inc, Redmond, USA) were added. The incubation period of this mixture at room temperature (RT) was 2 hrs.…”

“…Values at or above an OD450 of 0.5 were considered positive, while values below were imputed as 0.25. 14,16,39 The sVNT was performed using 10 µL of each serum, positive and negative controls, which were diluted at 1:10 and mixed with an equal volume HRP conjugated to the wild type (WT) SARS-CoV-2 S-RBD (6 ng), and these were incubated for 30 mins at 37°C, then 100 μL of each sample was added to microtitre plate wells coated with angiotensin-converting enzyme-2 (ACE-2) receptor. 14,16,39 This plate was sealed for 15 mins at 37°C, washed with wash-solution, tapped dry, and then 100 μL of 3,3',5,5'-tetramethylbenzidine (TMB) was added.…”