Humoral immune responses following inactivated COVID-19 vaccine with different booster intervals: a randomized interventional immunogenicity study.
TL;DR
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.
Abstract
Objectives
To evaluate the immunogenicity of booster doses at varying intervals after a two-dose primary series of inactivated COVID-19 vaccine.
Methods
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.
Results
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.
Conclusions
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.