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Background: Children aged 6 months to 4 years have been recommended to receive three doses of BNT162b2, after COVID-19 infection, to immunize against SARS-CoV-2. Therefore, they might need fewer doses of vaccine compared with COVID-naïve children. Objective: To describe the immunogenicity of 2-dose BNT162b2 following COVID-19 in healthy young children previously infected with SARS-CoV-2. Materials and Methods: A prospective cohort study was conducted among children aged 6 months to 4 years who had SARS-CoV-2 infection during Delta-variant, which was July to November 2021, or Omicron-variant-predominant eras, which was February to August 2022. Participants received two doses of intramuscular BNT162b2 at an 8-week interval. Neutralizing antibodies against SARS-CoV-2 Omicron variant BA.4/5 were measured using pseudovirus neutralization tests (pVNT; ID50) at baseline and 28 days after the second dose. Results were compared with a parallel cohort of COVID-naïve children who received 3-doses of BNT162b2 at 0, 4 and 12 weeks. Results: Between November and December 2022, 80 children with a median age of 2.9 years (IQR 2.1 to 3.8) were enrolled. The median time from COVID-19 infection to the first dose was 13.8 months (IQR 13.8 to 16.2) in the Post-Delta Group, and 8.0 months (IQR 3.7 to 8.2) in the Post-Omicron Group. After 2-doses of BNT162b2, the geometric means (GMs) of pVNT increased from 105 (95% CI 48 to 231) to 863 (95% CI 638 to 1,168) in the Post-Delta Group and from 264 (95% CI 192 to 361) to 2,268 (95% CI 1,831 to 2,811) in the Post-Omicron Group. In comparison, the GM of pVNT was 59 (95% CI 31 to 114) in the parallel cohort of COVID-naïve children who received 3-doses of BNT162b2. Conclusion: Two doses of BNT162b2 were able to boost the immune response with high neutralizing antibodies against the circulating Omicron variant in children who were previously infected with SARS-CoV-2. [ABSTRACT FROM AUTHOR]