Humoral immune responses following inactivated COVID-19 vaccine with different booster intervals: a randomized...

To evaluate the immunogenicity of booster doses at varying intervals after a two-dose primary series of inactivated COVID-19 vaccine.

This randomized, open-label interventional study in Zhejiang, China, allocated 431 participants via stratified block randomization to a control group (primary series only) or booster groups at 1, 4, 6, or 11 months after the primary series. Laboratory staff and statisticians were blinded. Immunogenicity endpoints included anti-RBD IgG, live-virus microneutralization, and pseudovirus neutralization against wild-type, Delta, and Omicron BA.1.

At 1 month post-booster, live wild-type neutralizing antibody GMT (Geometric mean titer) increased with longer intervals, from 42.96 (1-Month group) to 149.93 (11-Month group). Anti-RBD and anti-S1+N IgG concentrations were significantly higher in the 4-, 6-, and 11-Month group. Pseudovirus neutralization inhibition percentages decreased progressively across variants: wild-type (72.81%-86.70%), Delta (24.32%-35.82%), Omicron BA.1 (0.26%-2.97%). GMT declined substantially by 6 months post-booster (12.08 and 17.95 in the 1- and 4-Month group), and age was significantly negatively associated with humoral responses only in the 6-Month group.

All booster regimens elicited greater binding and neutralizing responses than the two-dose primary series, with peak responses at 1 month post-booster increasing progressively as the interval lengthened (up to 11 months). However, neutralizing activity against Omicron BA.1 was negligible across regimens, and antibody levels declined substantially by 6 months post-booster.