LAUSR

The long‐term protective efficacy of neutralizing antibodies (Nabs) against Omicron subvariants after inactivated booster vaccines remains elusive. During the follow‐up study, 54 healthy volunteers aged 20–31 years received inactivated CoronaVac booster vaccinations and were monitored for 221 days. The dynamic efficacy and durability of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.2, and BA4/5 were assessed using a pseudotyped virus neutralization assay at up to nine time points post immunization. The antibody response against Omicron subvariants was substantially weaker than D614G, with BA.4/5 being the least responsive. The geometric mean titer (GMT) of Nab against Omicron subvariants BA.1, BA.2, BA.2.12.1, and BA.4/5 was 2.2‐, 1.7‐, 1.8‐, and 2.2‐fold lower than that against D614G (ps < 0.0001). The gap in Nab response between Omicron subvariants was pronounced during the 2 weeks–2 months following booster vaccination (ps < 0.05). Seven months post booster, the antibody potency against D614G was maintained at 100% (50% for Nab titers ≥ 100 50% inhibitory dilution [EC50]), whereas at 77.3% for BA.1, 90.9% for BA.2, 86.4% for BA.2.12.1, and 86.4% for BA.4/5 (almost 20% for Nab titers ≥ 100 EC50). Despite the inevitable immune escape, Omicron subvariants maintained sustained and measurable antibody potency post‐booster vaccination during long‐term monitoring, which could help optimize immunization strategies.