Evaluation of antibody kinetics and durability in healthy individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): A cross-sectional and cohort study in Zhejiang, China
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Curated by eLife
eLife assessment
This study presents important evidence that boosting with the Sinovac Coronavac inactivated vaccine would provide considerable protection from ancestral SARS-CoV-2 in terms of elicited neutralizing antibodies but would offer minimal protection against Omicron subvariants. The evidence supporting the claims of the authors is solid, although using a dilution series instead of one plasma dilution for Omicron neutralization would have strengthened the study. The work will be of very wide interest to the biomedical community and beyond, since it points to the need for a better booster vaccine in China.
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- Immunology and Inflammation (eLife)
Abstract
Although inactivated COVID-19 vaccines are proven to be safe and effective in the general population, the dynamic response and duration of antibodies after vaccination in the real world should be further assessed.
Methods:
We enrolled 1067 volunteers who had been vaccinated with one or two doses of CoronaVac in Zhejiang Province, China. Another 90 healthy adults without previous vaccinations were recruited and vaccinated with three doses of CoronaVac, 28 days and 6 months apart. Serum samples were collected from multiple timepoints and analyzed for specific IgM/IgG and neutralizing antibodies (NAbs) for immunogenicity evaluation. Antibody responses to the Delta and Omicron variants were measured by pseudovirus-based neutralization tests.
Results:
Our results revealed that binding antibody IgM peaked 14–28 days after one dose of CoronaVac, while IgG and NAbs peaked approximately 1 month after the second dose then declined slightly over time. Antibody responses had waned by month 6 after vaccination and became undetectable in the majority of individuals at 12 months. Levels of NAbs to live SARS-CoV-2 were correlated with anti-SARS-CoV-2 IgG and NAbs to pseudovirus, but not IgM. Homologous booster around 6 months after primary vaccination activated anamnestic immunity and raised NAbs 25.5-fold. The neutralized fraction subsequently rose to 36.0% for Delta (p=0.03) and 4.3% for Omicron (p=0.004), and the response rate for Omicron rose from 7.9% (7/89)–17.8% (16/90).
Conclusions:
Two doses of CoronaVac vaccine resulted in limited protection over a short duration. The inactivated vaccine booster can reverse the decrease of antibody levels to prime strain, but it does not elicit potent neutralization against Omicron; therefore, the optimization of booster procedures is vital.
Funding:
Key Research and Development Program of Zhejiang Province; Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission; Major Program of Zhejiang Municipal Natural Science Foundation; Explorer Program of Zhejiang Municipal Natural Science Foundation.
Article activity feed
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eLife assessment
This study presents important evidence that boosting with the Sinovac Coronavac inactivated vaccine would provide considerable protection from ancestral SARS-CoV-2 in terms of elicited neutralizing antibodies but would offer minimal protection against Omicron subvariants. The evidence supporting the claims of the authors is solid, although using a dilution series instead of one plasma dilution for Omicron neutralization would have strengthened the study. The work will be of very wide interest to the biomedical community and beyond, since it points to the need for a better booster vaccine in China.
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Reviewer #1 (Public Review):
In this work, Zhang et al. test neutralizing antibody immunity elicited by a primary vaccination series and homologous boosting with the Sinovac-inactivated COVID-19 vaccine CoronaVac.
While the interpretation of the data is complicated by how some of the experiments were done, it seems that boosting with CoronaVac has only a marginal effect on Omicron (BA.1 subvariant) neutralization.
After primary vaccination comprising two doses, SARS-CoV-2 neutralization, as assessed by a live virus neutralization assay and pseudovirus neutralization assay, are low in absolute terms at peak response 1-month post-second dose (~GMT ~20), then wane. Boosting with a third dose of CoronaVac results in neutralization levels about an order of magnitude higher relative to 1-month post-primary vaccination. However, neutralizing …
Reviewer #1 (Public Review):
In this work, Zhang et al. test neutralizing antibody immunity elicited by a primary vaccination series and homologous boosting with the Sinovac-inactivated COVID-19 vaccine CoronaVac.
While the interpretation of the data is complicated by how some of the experiments were done, it seems that boosting with CoronaVac has only a marginal effect on Omicron (BA.1 subvariant) neutralization.
After primary vaccination comprising two doses, SARS-CoV-2 neutralization, as assessed by a live virus neutralization assay and pseudovirus neutralization assay, are low in absolute terms at peak response 1-month post-second dose (~GMT ~20), then wane. Boosting with a third dose of CoronaVac results in neutralization levels about an order of magnitude higher relative to 1-month post-primary vaccination. However, neutralizing capacity against Omicron (subvariant BA.1) is very limited even at the peak response from the boost, and the great majority of participant samples neutralize less than 50% of Omicron infection with relatively concentrated plasma (1:50).
Form an immunogenicity perspective, puts the utility of homologous boosting with CoronaVac into question given the current Omicron circulating subvariants.
While the strength of this study lies in the implications of the results, a weakness is how the pseudovirus results were done, and these are key to interpreting the data. For these, the authors did not fit a dose-response curve to a dilution series but rather used one plasma concentration (1:50 dilution) and measured percent inhibition. Not doing the measurement with multiple dilutions make the results less accurate and conclusions weaker.
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Reviewer #2 (Public Review):
This manuscript shows that two doses of the live attenuated Coronavac vaccine induce neutralising antibodies in the majority of individuals, though neutralisation is modest for Omicron BA.1 even after 1 month post-dose two, and substantial waning at 12 months is noted. Boosting achieves higher neutralisation than for prior doses.
Strengths of the work are the significant sample size in the cross-sectional part and a smaller prospective part which adds value to the study as a whole.
The assays used are appropriate, with PV bearing Wu-hu-1, Delta, and Omicron spike proteins.
Weakness includes the fact that the cross-sectional aspect recruits at different sites at different time points, introducing the fact that observed differences in vaccine response may be related to the underlying population differences.
In …
Reviewer #2 (Public Review):
This manuscript shows that two doses of the live attenuated Coronavac vaccine induce neutralising antibodies in the majority of individuals, though neutralisation is modest for Omicron BA.1 even after 1 month post-dose two, and substantial waning at 12 months is noted. Boosting achieves higher neutralisation than for prior doses.
Strengths of the work are the significant sample size in the cross-sectional part and a smaller prospective part which adds value to the study as a whole.
The assays used are appropriate, with PV bearing Wu-hu-1, Delta, and Omicron spike proteins.
Weakness includes the fact that the cross-sectional aspect recruits at different sites at different time points, introducing the fact that observed differences in vaccine response may be related to the underlying population differences.
In addition, the data on third-dose boosting do not appear to include VOC. This is important because data from other vaccines suggest broadening of neutralisation with the third dose.
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