Background Two- and three-dose BNT162b2 vaccine effectiveness (VE) against SARS-CoV-2 infection, including Delta and Omicron variants, was assessed among adolescents in Canada where first and second doses were spaced longer than the manufacturer-specified 3-week interval. Methods Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection ≥14 days post-vaccination among 12-17-year-olds in Quebec and British Columbia, Canada between September 5, 2021-April 30, 2022 (epi-week 36-17). Delta-dominant and Omicron-dominant periods spanned epi-weeks 36-47 and 51-17, respectively. VE was explored by interval between first and second doses, time since second dose, and with a third dose. Results VE against Delta was ≥90% to at least 5 months post-second dose. VE against Omicron decreased from ∼65-75% at 2-3 weeks to ≤50% by the 3rd month post-vaccination, restored to ∼65% by a third dose. Although confidence intervals overlapped, VE against Omicron was ∼5-7% higher (absolute) when first and second doses were spaced ≥8 vs. 3-4 weeks apart. Conclusions In adolescents, two BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly-waning VE against Omicron. Longer interval between first and second doses and a third dose marginally improved Omicron protection. Updated vaccine antigens, increased doses and/or dosing-intervals may improve adolescent VE against immunological-escape variants.

Background and Objectives Two- and three-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccine effectiveness (VE) against SARS-CoV-2 infection, including Delta and Omicron variants, was assessed among adolescents in two Canadian provinces where first and second doses were spaced longer than the manufacturer-specified 3-week interval. Methods Test-negative design estimated VE against laboratory-confirmed SARS-CoV-2 infection among adolescents 12-17 years old in Quebec and British Columbia, Canada between September 5, 2021 (epi-week 36), and April 30, 2022 (epi-week 17). Delta-dominant and Omicron-dominant periods spanned epi-weeks 36-47 and 51-17, respectively. VE was assessed from 14 days and explored by interval between first and second doses, time since second dose, and with administration of a third dose. Results Median first-second dosing-interval was ~8 weeks and second-third dosing-interval was ~28-31 weeks. Median follow-up post-second-dose was ~10-11 weeks for Delta-dominant and ~21-22 weeks for Omicron-dominant periods, and ~3-9 weeks post-third dose. VE against Delta was ≥90% to at least the 5th month post-second dose. VE against Omicron declined from ~65-75% at 2-3 weeks to ≤50% by the 3rd month post-vaccination, restored to ~60-65% shortly following a third dose. VE exceeded 90% against Delta regardless of dosing-interval but appeared improved against Omicron with ≥8 weeks between first and second doses. Conclusion In adolescents, two BNT162b2 doses provided strong and sustained protection against Delta but reduced and rapidly-waning VE against Omicron. Longer interval between first and second doses and a third dose improved Omicron protection. Updated vaccine antigens, increased doses and/or dosing-intervals may be needed to improve adolescent VE against immunological-escape variants.