Evaluation of antibody kinetics and durability in health individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): a cross-sectional and cohort study in Zhejiang, China
- Zhejiang Provincial Center for Disease Control and Prevention, China
- Ningbo University, China
- Xihu District Center for Disease Control and Prevention, China
- Shangyu District Center for Disease Control and Prevention, China
- Kaihua District Center for Disease Control and Prevention, China
- Yuecheng District Center for Disease Control and Prevention, China
- Jiaxing Center for Disease Control and Prevention, China
- Longyou District Center for Disease Control and Prevention, China
- Xiamen University, China
Abstract
Background: 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) to 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.
Data availability
All data generated or analysed during this study are included in this published article and its supplementary information files, or are available in database Dryad (https://datadryad.org/).
Article and author information
Author details
Funding
Key Research and Development Program of Zhejiang Province, 2021C03200
- Hangjie Zhang
- Nani Nani Xu
- Bo Chen
- Yuting Liao
- Juan Yang
- Jianmin Jiang
- Huakun Lv
Key Program of Health Commission of Zhejiang Province/ Science Foundation of National Health Commission, WKJ-ZJ-2221
- Jianmin Jiang
- Huakun Lv
Major program of Zhejiang Municipal Natural Science Foundation, LD22H190001
- Hangjie Zhang
Explorer Program of Zhejiang Municipal Natural Science Foundation, LQ23H00001
- Hangjie Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Alex Sigal, Africa Health Research Institute, South Africa
Ethics
Human subjects: We state that we conformed with the Helsinki Declaration of 1975 (as revised in 2008) concerning Human and Animal Rights, and that we followed out the policy concerning Informed Consent as shown on Springer.com. The study protocol and informed consent form were approved by the Medical Ethics Committee of The Zhejiang Center for Disease Control and Prevention (2021-044-01). Written informed consent was obtained from all study participants.
Version history
- Received: October 9, 2022
- Preprint posted: November 4, 2022 (view preprint)
- Accepted: February 20, 2023
- Accepted Manuscript published: March 16, 2023 (version 1)
- Version of Record published: April 17, 2023 (version 2)
Copyright
© 2023, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evaluation of antibody kinetics and durability in health individuals vaccinated with inactivated COVID-19 vaccine (CoronaVac): a cross-sectional and cohort study in Zhejiang, China
eLife 12:e84056.
https://doi.org/10.7554/eLife.84056
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Background:
Few national-level studies have evaluated the impact of ‘hybrid’ immunity (vaccination coupled with recovery from infection) from the Omicron variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Methods:
From May 2020 to December 2022, we conducted serial assessments (each of ~4000–9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots (DBSs) to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results:
Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than 6 months earlier, spike levels fell notably and continuously for the 9-month post-vaccination. In contrast, among adults infected within 6 months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than 6 months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% confidence interval 11–14%) before omicron to 78% (76–80%) by December 2022, equating to 25 million infected adults cumulatively. However, the coronavirus disease 2019 (COVID-19) weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions:
Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected DBSs are a practicable biological surveillance platform.
Funding:
Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael’s Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
