Safety and immunogenicity of a reduced, homologous booster dose of the BNT162b2 mRNA COVID-19 vaccine: a single blind, randomized, non-inferiority follow-up trial.

BACKGROUND

Reduced-dose primo-vaccination against COVID-19 demonstrated safety and immunogenicity, as evidenced by us and others. Fractional booster dosing may similarly maintain strong immunogenicity and protection while reducing reactogenicity, improving acceptability, and conserving supplies.

OBJECTIVE

To evaluate the safety and humoral immunogenicity of a reduced-dose (10 μg) versus full-dose (30 μg) BNT162b2 booster in healthy adults.

METHODS

In this single-blind, randomized, non-inferiority follow-up trial in Belgium, 132 adults ≥18 years were enrolled, including participants from the REDU-VAC cohort primed with two doses of either 20 μg or 30 μg BNT162b2. Randomized participants received a 10 μg or 30 μg booster. Blood samples were collected at baseline (D0), day 28 (D28), and month 6 (M6). The primary outcome was SARS-CoV-2 anti-RBD IgG geometric mean titers (GMT) at D28. Secondary outcomes included safety, reactogenicity, anti-RBD IgG titers, neutralizing antibody titers (Wuhan, Omicron BA.1), avidity, and incidence of breakthrough infections (BTI) post D28. Mixed-effects linear models were used to assess the impacts, and a non-inferiority analysis was conducted at D28.

RESULTS

No life-threatening adverse events were reported. Reactogenicity was significantly lower in the reduced-dose group (41% vs. 78%, P < 0.0001). Baseline titers were unaffected by priming dose concentration, while previously infected participants exhibited higher titers. At D28, the reduced-dose booster did not meet non-inferiority criteria for humoral immune responses. By M6, antibody titers declined across both groups, with no significant differences between reduced- and full-dose recipients. BTI incidence (69% vs. 62%, P = 0.56) and symptomatology were comparable between groups.

CONCLUSIONS

The reduced-dose booster elicited moderately lower short-term humoral responses compared to the full dose, but these differences disappeared by six months and had no detectable impact on BTI rates. Combined with a significantly lower reactogenicity profile, reduced-dose regimens represent a cost-effective strategy to sustain immunity and reduce public health burdens. The study was registered at Clinicaltrials.gov (NCT04852861).