Comparison of safety and immunogenicity of CoronaVac and ChAdOx1 against the SARS-CoV-2 circulating variants of concern (Alpha, Delta, Beta) in Thai healthcare workers

Abstract

Background: Inactivated vaccine (CoronaVac) and chimpanzee adenovirus-vector vaccine (ChAdOx1) have been widely used in resource-limited settings. However, the information on the reactogenicity and immunogenicity of these two vaccines in the same setting are limited.

Methods: Healthy health care workers (HCWs) aged 18 years or older were randomly assigned to receive either two doses of CoronaVac at 4 weeks interval or two doses of ChAdOx1 at 10 weeks interval. Self-reported adverse events (AEs) were collected for 7 days following each vaccination. Immunogenicity was determined by IgG antibodies levels against receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S1 subunit) and the 50% plaque reduction neutralization titers against various strains.

Results: Of the 360 HCWs, 180 in each vaccine group, the median (interquartile range: IQR) age was 35 (29-44) years old and 84.2% were female. Participants who received ChAdOx1 reported higher frequency of AEs than those received CoronaVac after both the first dose (84.4% vs. 66.1%, P < 0.001) and second dose (75.6% vs. 60.6%, P = 0.002), with more AEs in those younger than 30 years of age for both vaccines. The seroconversion rates were 75.6% and 100% following the first dose of CoronaVac and ChAdOx1, respectively. All participants were seropositive at 2 weeks after the second dose. The anti-SARS-CoV-2 RBD IgG levels induced by CoronaVac was lower than ChAdOX1 with geometric means of 164.4 and 278.5 BAU/mL, respectively (P = 0.0066). Both vaccines induced similar levels of neutralizing antibodies against the Wuhan strain, with the titers of 337.4 and 331.2; however, CoronaVac induced significantly lower GMT against Alpha (23.1 vs. 92.5), Delta (21.2 vs. 69.7), and Beta (10.2 vs. 43.6) variants, respectively.

Conclusion: CoronaVac induces lower measurable antibodies against circulating variants but with lower frequency of AEs than ChAdOx1. An earlier boosting to prevent breakthrough infections may be needed.

Keywords: ChAdOx1; CoronVac; Heath care workers; Immunogenicity; Thailand; Variant of concern.

Fig. 1

Flow diagram of enrollment and vaccination of healthcare worker participants.

Fig. 2

Adverse events following CoronaVac or ChAdOx1 vaccination. The stacked bars showed the percentage of participants who had indicated mild and moderate adverse events after the first and second dose of CoronaVac (A) and ChAdOx1 (B). The stacked bars showed the percentage of participants aged lower (light color bar) or above thirty years old (dark color bar), who had indicated adverse events after the first and second dose of CoronaVac (C) and ChAdOx1 (D). Chi-square was used for statistical analyses and the p values were shown on the graphs.

Fig. 3

Anti-SARS-CoV-2 RBD IgG levels following CoronaVac or ChAdOx1 vaccination. (A) Anti-SARS-CoV-2 RBD IgG levels in the plasma of study subjects before and various time points after vaccination with CoronaVac (blue) or ChAdOx1 (red). Convalescent sera at 4 weeks and 12 weeks after illness from the patients who recovered from the COVID-19 during Dec 2020 and early 2021 were included as reference level (orange). (B) Anti-SARS-CoV-2 RBD IgG levels in the plasma of study subjects among different age groups at 4 weeks after the second dose vaccination of CoronaVac (blue) or ChAdOx1 (red). The numbers in the graph represent geometric mean and the error bars represent 95% confidence interval. The number of tested samples were indicated below each time point. Two-tailed unpair t test was used to compared the IgG level between two conditions with indicated p value. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

Plaque reduction neutralization test (PRNT₅₀) titers for different SARS-CoV-2 strains. (A) Dot plots demonstrates PRNT₅₀ titer against Wuhan (red), Alpha (teal), Delta (orange) and Beta (purple) strains in the plasma of study subjects at 2 weeks after two doses of CoronaVac or ChAdOx1. (B) Scatter dot plots demonstrates PRNT₅₀ titer against Delta strain at 2 weeks after 2-dose vaccination with CoronaVac (blue) and ChAdOx1 (red) compared with the convalescent sera at 2 weeks after illness of the patients infected with B.1.36.16 strain (green) and Delta strain (orange). The PRNT₅₀ titer of 1:5 was used for all that were below the detectable level (<1:10). The geometric mean titer (GMT) and lower and upper 95% confidence interval (CI) are indicated. (C) Correlation between the level of anti-SARS-CoV-2 RBD IgG and plaque reduction neutralization test (PRNT₅₀) titers for wildtype and VOC. Dot plots shows the correlation between the level of anti-SARS-CoV-2 RBD IgG and PRNT50 titer against Wuhan (red), Alpha (teal), Delta (orange) and Beta (purple) strains in the plasma of study subjects at 2 weeks after two doses of CoronaVac (n = 50) or (D) ChAdOx1 (n = 30). The PRNT₅₀ titer of 1:5 was used for all that were below the detectable level (<1:10). Pearson’s correlation coefficient (r) with p value for each strain was indicated. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Supplementary figure 1