Fractional BNT162b2 boosters induce durable immune responses after non-mRNA priming in Mongolia: a randomised controlled trial

Introduction: COVID-19 boosters restore waning immunity. After demonstrating non-inferiority of 15 μg versus 30 μg BNT162b2 at 28 days in Mongolian adults, we assessed 24-month immunogenicity and safety. Methods: In this randomised, controlled trial, adults primed with ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac were assigned (1:1) to 15 μg or 30 μg BNT162b2. Anti-spike IgG, surrogate virus neutralisation (sVNT) against Wuhan-Hu-1 and Omicron BA.1, and interferon-gamma (IFN-γ) release assays (Ag1/Ag2) were assessed to 24 months. SARS-CoV-2 infections and serious adverse events (SAEs) were recorded. ClinicalTrials.gov: NCT05265065. Results: Of 601 participants, 520 (86.5%) completed follow-up. IgG and IFN-γ responses were comparable between arms at 24 months (IgG geometric mean ratio (GMR) 1.06 [95% CI 0.95-1.18]; Ag1 GMR 1.17 [95% CI 0.82-1.66]; Ag2 GMR 1.06 [95% CI 0.73-1.54]). Median sVNT inhibition remained high (Wuhan-Hu-1 88% [interquartile range (IQR) 86-90]; Omicron BA.1 85% [IQR 70-88]). Twenty-eight SARS-CoV-2 infections occurred. Fifty-three SAEs were balanced by study arm, and none were vaccine related. Discussion: Equivalent immunity and safety from 15 μg and 30 μg BNT162b2 boosters support fractional dosing as a cost-saving strategy. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05265065, identifier NCT05265065.