Six-month follow-up of a booster dose of CoronaVac in two single-centre phase 2 clinical trials

Abstract

Determining the duration of immunity induced by booster doses of CoronaVac is crucial for informing recommendations for booster regimens and adjusting immunization strategies. In two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, immunogenicity and safety of four immunization regimens are assessed in adults aged 18 to 59 years and one immunization regimen in adults aged 60 years and older, respectively. Serious adverse events occurring within 6 months after booster doses are recorded as pre-specified secondary endpoints, geometric mean titres (GMTs) of neutralising antibodies one year after the 3-dose schedule immunization and 6 months after the booster doses are assessed as pre-specified exploratory endpoints, GMT fold-decreases in neutralization titres are assessed as post-hoc analyses. Neutralising antibody titres decline approximately 4-fold and 2.5-fold from day 28 to day 180 after third doses in adults aged 18-59 years of age and in adults aged 60 years and older, respectively. No safety concerns are identified during the follow-up period. There are increases in the magnitude and duration of humoral response with homologous booster doses of CoronaVac given 8 months after a primary two-dose immunization series, which could prolong protection and contribute to building our wall of population immunity. Trial number: NCT04352608 and NCT04383574.

Fig. 1. Neutralising antibody levels to ancestral SARS-CoV-2 in cohort 2b-28d-8m (adults aged 18–59 years old).

The number of participants for each group (placebo group, pink; 3 μg group, green; 6 μg group, blue) at each visit included in the analysis is provided below the bars. Dots are reciprocal neutralising antibody titres for individuals in the per-protocol population. Numbers above the bars are geometric mean titres (GMTs), and error bars indicate 95% CIs. GMTs and corresponding 95% CIs were calculated on the basis of standard normal distributions of log-transformed antibody titres. Numbers above the short horizontal lines are p values for comparisons between 3 μg group and 6 μg group using group t tests with log-transformation (two-sided). Titres lower than the limit of detection (1:4) are presented as half the limit of detection. The dotted horizontal line represents the protective threshold (1:33).

Fig. 2. Neutralising antibody levels to ancestral SARS-CoV-2 in cohort 3-28d-8m (adults aged 60 years and older).

The number of participants for each group (placebo group, pink; 1.5 μg group, yellow; 3 μg group, green; 6 μg group, blue) at each visit included in the analysis is provided below the bars. Dots are reciprocal neutralising antibody titres for individuals in the per-protocol population. Numbers above the bars are geometric mean titres (GMTs), and error bars indicate 95% CIs. GMTs and corresponding 95% CIs were calculated on the basis of standard normal distributions of log-transformed antibody titres. Numbers above the short horizontal lines are p values for comparisons between the 1.5 μg group, the 3 μg group and the 6 μg group using ANOVA models with log-transformation. Bonferroni correction done as a post hoc test if the variance was significant. Only P values indicating significant differences are marked. Titres lower than the limit of detection (1:4) are presented as half the limit of detection. The dotted horizontal line represents the protective threshold (1:33).

Fig. 3. Decline in neutralising antibodies to ancestral SARS-CoV-2 in 3 μg groups in cohort 2b-28d-8m and cohort 3-28d-8m.

The number of participants with paired samples for adults aged 18–59 (green) and adults aged 60 and over (blue) was 49 and 29, respectively. Numbers above the bars are geometric mean titres (GMTs), and error bars indicate the 95% CIs. The dotted horizontal line represents the protective threshold (1:33). Numbers above the short horizontal lines are pairwise fold-change values. GMTs and corresponding 95% CIs were calculated on the basis of standard normal distributions of log-transformed antibody titres. GMT fold decreases in neutralisation titre were calculated as ratios of paired sera at two visits. Comparisons between groups were conducted by group t tests with log-transformation (two-sided). P values of pairwise comparisons were P < 0.0001, P < 0.0001, P < 0.0001, P = 0.0187, from left to right, respectively.