Comparison of SARS-CoV-2 anti-spike receptor binding domain IgG antibody responses after CoronaVac, BNT162b2, ChAdOx1 COVID-19 vaccines, and a single booster dose: a prospective, longitudinal population-based study

Abstract

Background: Vaccination is an efficient strategy to control the COVID-19 pandemic. In north Cyprus, vaccine distribution started with CoronaVac followed by BNT162b2, and ChAdOx1 vaccines. An option to obtain a third booster dose with BNT162b2 or CoronaVac was later offered to people fully inoculated with CoronaVac. There are few simultaneous and comparative real-world antibody data for these three vaccines as well as boosters after CoronaVac vaccination. Our study was aimed at evaluating antibody responses after these vaccination schemes.

Methods: We did a prospective, longitudinal population-based study to measure SARS-CoV-2 anti-spike receptor binding domain (RBD) IgG concentrations, assessed by assaying blood samples collected, in participants in north Cyprus who had received the BNT162b2, ChAdOx1, or CoronaVac vaccine at 1 month and 3 months after the second dose. Participants were recruited when they voluntarily came to the laboratory for testing after vaccination, solicited from health-care access points, or from the general population. We also evaluated antibody responses 1 month after a booster dose of BNT162b2 or CoronaVac after primary CoronaVac regimen. Demographics, baseline characteristics, vaccination reactions, and percentage of antibody responders were collected by phone interviews or directly from the laboratory summarised by vaccine and age group. Antibody levels were compared between groups over time by parametric and non-parametric methods.

Findings: Recruitment, follow-up, and data collection was done between March 1 and Sept 30, 2021. BNT162b2 induced the highest seropositivity and anti-spike RBD IgG antibody titres, followed by ChAdOx1, and then by CoronaVac. In addition, the rate of decline of antibodies was fastest with CoronaVac, followed by ChAdOx1, and then by BNT162b2. For the older age group, the rate of seropositivity at 3 months after the second dose was 100% for BNT162b2, 90% for ChAdOx1, and 60% for CoronaVac. In the multivariate repeated measures model, lower antibody titres were also significantly associated with male sex, older age, and time since vaccination. Boosting a two-dose CoronaVac regimen at 6 months with a single BNT162b2 dose led to significantly increased titres of IgG compared with boosting with CoronaVac; for the 60 years and older age group, the geometric mean fold rise in antibody titre after the booster relative to 1 month post-baseline was 7·9 (95% CI 5·8-10·8) in the BNT162b2 boost group versus 2·8 (1·6-5·0) in the CoronaVac group.

Interpretation: These longitudinal data can help shape vaccination strategies. Given the low antibody titres and fast decline in the CoronaVac group in individuals 60 years or older, more potent vaccine options could be considered as the primary vaccination or booster dose in these high-risk populations to sustain antibody responses for longer.

Funding: Crowdfunded in north Cyprus.

Figure 1

Anti-spike RBD IgG titres by age group and vaccine type (A) Mean (standard error) anti-spike RBD IgG titres in individuals aged younger than 60 years at 1 and 3 months after the second vaccination dose of BNT162b2, ChAdOx1, or CoronaVac vaccines. (B) Mean (SE) anti-spike RBD IgG titres in individuals aged 60 years or older at 1 and 3 months after the second vaccination dose of BNT162b2, ChAdOx1, or CoronaVac vaccines. (C) Box-and-whisker plots overlaid with individual anti-spike RBD IgG titres in individuals younger than 60 years at 1 and 3 months after the second vaccination dose of BNT162b2, ChAdOx1, or CoronaVac vaccines. (D) Box-and-whisker plots overlaid with individual anti-spike RBD IgG titres in individuals 60 years or older at 1 and 3 months after the second vaccination dose of BNT162b2, ChAdOx1, or CoronaVac vaccines. RBD=receptor binding domain. *p<0·0001 for both overall antibody titre during the 3-month follow-up period and the rate of decline over time from the multivariate linear repeated measures model (table 3).

Figure 2

Anti-Spike RBD IgG titres by age group and vaccine plus booster (A) Mean (SE) anti-spike RBD IgG titres in individuals younger than 60 years (left) or 60 years or older (right) at 1 and 3 months after the second CoronaVac vaccination dose, followed by 1 month after a BNT162b2 or CoronaVac booster shot given at 6 months after the initial CoronaVac vaccination. For the 60 years and older age group, the geometric mean fold rise in antibody titres from 1 month after baseline to after the booster was approximately 8-fold in the BNT162b2 boost group versus approximately 3-fold in the CoronaVac group (7·9 [95% CI 5·8–10·8] in the BNT162b2 boost group vs 2·8 [95% CI 1·6–5·0] in the CoronaVac boost group). p values comparing the two groups in the right panel are from the Wilcoxon two-sample test. (B) Individual anti-spike RBD IgG titres over time in individuals younger than 60 years (left) or 60 years or older (right) at 1 and 3 months after the second CoronaVac vaccination dose, followed by 1 month after a single BNT162b2 booster shot given at 6 months after the initial CoronaVac vaccination. (C) Individual anti-spike RBD IgG titres in individuals younger than 60 years (left) or 60 years or older (right) at 1 and 3 months after the second CoronaVac vaccination dose, followed by 1 month after a single CoronaVac booster shot given at 6 months after the initial CoronaVac vaccination. Only one individual younger than 60 years of age received CoronaVac as a booster shot, and thus has been omitted from the mean plot in panel A. RBD=receptor binding domain.