Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains
Abstract
Background: The degree of heterotypic immunity induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains is a major determinant of the spread of emerging variants and the success of vaccination campaigns, but remains incompletely understood.
Methods: We examined the immunogenicity of SARS-CoV-2 variant B.1.1.7 (Alpha) that arose in the United Kingdom and spread globally. We determined titres of spike glycoprotein-binding antibodies and authentic virus neutralising antibodies induced by B.1.1.7 infection to infer homotypic and heterotypic immunity.
Results: Antibodies elicited by B.1.1.7 infection exhibited significantly reduced recognition and neutralisation of parental strains or of the South Africa variant B.1.351 (Beta) than of the infecting variant. The drop in cross-reactivity was significantly more pronounced following B.1.1.7 than parental strain infection.
Conclusions: The results indicate that heterotypic immunity induced by SARS-CoV-2 variants is asymmetric.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Funding
Francis Crick Institute
- Nikhil Faulkner
- Kevin W Ng
- Mary Y Wu
- Ruth Harvey
- Saira Hussain
- Maria Greco
- William Bolland
- Scott Warchal
- Svend Kjaer
- Charles Swanton
- Sonia Gandhi
- Rupert Beale
- Steve j Gamblin
- John W McCauley
- Rodney Stuart Daniels
- Michael Howell
- David Bauer
- George Kassiotis
Max Planck Institute for Dynamics of Complex Technical Systems Magdeburg
- Alex Sigal
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Serum or plasma samples were obtained from University College London Hospitals (UCLH) (REC ref: 20/HRA/2505).
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Publication history
- Preprint posted: March 1, 2021 (view preprint)
- Received: April 11, 2021
- Accepted: July 26, 2021
- Accepted Manuscript published: July 29, 2021 (version 1)
- Version of Record published: August 9, 2021 (version 2)
Copyright
© 2021, Faulkner 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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Further reading
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- Epidemiology and Global Health
To curb the initial spread of SARS-CoV-2, many countries relied on nation-wide implementation of non-pharmaceutical intervention measures, resulting in substantial socio-economic impacts. Potentially, subnational implementations might have had less of a societal impact, but comparable epidemiological impact. Here, using the first COVID-19 wave in the Netherlands as a case in point, we address this issue by developing a high-resolution analysis framework that uses a demographically stratified population and a spatially explicit, dynamic, individual contact-pattern based epidemiology, calibrated to hospital admissions data and mobility trends extracted from mobile phone signals and Google. We demonstrate how a subnational approach could achieve similar level of epidemiological control in terms of hospital admissions, while some parts of the country could stay open for a longer period. Our framework is exportable to other countries and settings, and may be used to develop policies on subnational approach as a better strategic choice for controlling future epidemics.
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- Epidemiology and Global Health
- Immunology and Inflammation
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.