Background: The COVID-19 pandemic catalysed rapid global vaccination efforts, with booster doses recommended to restores waning immunity. Optimising booster strategies is particularly important in low- and middle-income countries, where constrained supply and limited access to updated vaccines remain a barrier. Fractional booster dosing, using reduced vaccine volumes, has been proposed as a dose-sparing approach to extend supply and reduce costs without compromising safety or immunogenicity. 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, non-inferiority trial, adults in Mongolia who had been primed with ChAdOx1-S, BBIBP-CorV, or Gam-COVID-Vac were assigned (1:1) to 15 μg or 30 μg BNT162b2. Anti-spike IgG and surrogate virus neutralisation (sVNT) against Wuhan-Hu-1 and Omicron BA.1 were assessed to 24 months; a subset underwent IFN-γ release assays (Ag1/Ag2). Geometric mean ratios (GMRs; 15 μg/30 μg) were estimated using multivariable linear regression on log-transformed anti-spike IgG levels, adjusted for age group, priming strata, timing of blood draw, dosing intervals, and baseline levels. SARS-CoV-2 infections and serious adverse events (SAEs) were recorded. ClinicalTrials.gov: NCT05265065.
Findings: Of 601 enrolled participants (27 May–30 Sept 2022), 520 (86·5%) completed 24 months. IgG declined from six to 24 months but was similar between arms at 18 (GMR 1·08 [95% CI 0·97–1·22]) and 24 months (GMR 1·06 [95% CI 0·95–1·18]). IFN-γ peaked at 28 days and returned to baseline by 24 months (24-month GMRs: Ag1 1·17 [95% CI 0·82–1·66]; Ag2 1·06 [95% CI 0·73–1·54]). At 24 months, median sVNT inhibition remained high (Wuhan-Hu-1 88% (IQR 86–90) in both arms; Omicron BA.1 84% (IQR 71–88) with 30 μg and 85% (IQR 70–88) with 15 μg). Twenty-eight PCR-confirmed infections occurred; none required hospitalisation. Fifty-three SAEs occurred, balanced between arms, and none were vaccine related.
Interpretation: This trial provides comprehensive 24-month immunogenicity and safety data from a low-resource setting. 15 μg and 30 μg BNT162b2 boosters yielded equivalent neutralising and cellular responses, while binding IgG declined. Safety was favourable, and there were no COVID-19–related hospitalisations or deaths documented, supporting fractional dosing as a pragmatic, cost-saving option.
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