BNT162b2 effectiveness against Delta and Omicron variants of SARS-CoV-2 in adolescents aged 12-17 years, by dosing interval and duration

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.