Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains

  1. Nikhil Faulkner
  2. Kevin W Ng
  3. Mary Y Wu
  4. Ruth Harvey
  5. Marios Margaritis
  6. Stavroula Paraskevopoulou
  7. Catherine Houlihan
  8. Saira Hussain
  9. Maria Greco
  10. William Bolland
  11. Scott Warchal
  12. Judith Heaney
  13. Hannah Rickman
  14. Moria Spyer
  15. Daniel Frampton
  16. Matthew Byott
  17. Tulio de Oliveira
  18. Alex Sigal
  19. Svend Kjaer
  20. Charles Swanton
  21. Sonia Gandhi
  22. Rupert Beale
  23. Steve j Gamblin
  24. John W McCauley
  25. Rodney Stuart Daniels
  26. Michael Howell
  27. David Bauer
  28. Eleni Nastouli
  29. SAFER Investigators
  30. George Kassiotis  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. University College London, United Kingdom
  3. University College London Hospital, United Kingdom
  4. University of KwaZulu-Natal,SA, South Africa
  5. Africa Health Research Institute, University of KwaZulu-Natal, South Africa
  6. The Francis Crick Insitute, United Kingdom

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

  1. Nikhil Faulkner

    Retroviral Immunology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Kevin W Ng

    Retroviral Immunology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1635-6768
  3. Mary Y Wu

    High Throughput Screening STP, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2074-6171
  4. Ruth Harvey

    Worldwide Influenza Centre, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Marios Margaritis

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Stavroula Paraskevopoulou

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Catherine Houlihan

    University College London Hospital, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Saira Hussain

    RNA Virus Replication Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Maria Greco

    RNA Virus Replication Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. William Bolland

    Retroviral Immunology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Scott Warchal

    High Throughput Screening STP, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. Judith Heaney

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Hannah Rickman

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Moria Spyer

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Daniel Frampton

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Matthew Byott

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Tulio de Oliveira

    School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal,SA, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  18. Alex Sigal

    School of Laboratory Medicine and Medical Sciences, Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8571-2004
  19. Svend Kjaer

    Structural Biology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9767-8683
  20. Charles Swanton

    Structural Biology, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  21. Sonia Gandhi

    Neurodegradation Biology Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  22. Rupert Beale

    Cell Biology of Infection Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6705-8560
  23. Steve j Gamblin

    Cell Biology of Infection Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  24. John W McCauley

    Worldwide Influenza Centre, The Francis Crick Insitute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4744-6347
  25. Rodney Stuart Daniels

    Worldwide Influenza Centre, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  26. Michael Howell

    High Throughput Screening, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  27. David Bauer

    RNA Virus Replication Laboratory, The Francis Crick Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  28. Eleni Nastouli

    Advanced Pathogen Diagnostics, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  29. SAFER Investigators

  30. George Kassiotis

    Retroviral Immunology, The Francis Crick Institute, London, United Kingdom
    For correspondence
    george.kassiotis@crick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8457-2633

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

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Preprint posted: March 1, 2021 (view preprint)
  2. Received: April 11, 2021
  3. Accepted: July 26, 2021
  4. Accepted Manuscript published: July 29, 2021 (version 1)
  5. 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.

Metrics

  • 2,656
    Page views
  • 244
    Downloads
  • 27
    Citations

Article citation count generated by polling the highest count across the following sources: PubMed Central, Crossref, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Nikhil Faulkner
  2. Kevin W Ng
  3. Mary Y Wu
  4. Ruth Harvey
  5. Marios Margaritis
  6. Stavroula Paraskevopoulou
  7. Catherine Houlihan
  8. Saira Hussain
  9. Maria Greco
  10. William Bolland
  11. Scott Warchal
  12. Judith Heaney
  13. Hannah Rickman
  14. Moria Spyer
  15. Daniel Frampton
  16. Matthew Byott
  17. Tulio de Oliveira
  18. Alex Sigal
  19. Svend Kjaer
  20. Charles Swanton
  21. Sonia Gandhi
  22. Rupert Beale
  23. Steve j Gamblin
  24. John W McCauley
  25. Rodney Stuart Daniels
  26. Michael Howell
  27. David Bauer
  28. Eleni Nastouli
  29. SAFER Investigators
  30. George Kassiotis
(2021)
Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains
eLife 10:e69317.
https://doi.org/10.7554/eLife.69317
  1. Further reading

Further reading

    1. Epidemiology and Global Health
    2. Evolutionary Biology
    Theo Sanderson
    Tools and Resources Updated

    The COVID-19 pandemic has resulted in a step change in the scale of sequencing data, with more genomes of SARS-CoV-2 having been sequenced than any other organism on earth. These sequences reveal key insights when represented as a phylogenetic tree, which captures the evolutionary history of the virus, and allows the identification of transmission events and the emergence of new variants. However, existing web-based tools for exploring phylogenies do not scale to the size of datasets now available for SARS-CoV-2. We have developed Taxonium, a new tool that uses WebGL to allow the exploration of trees with tens of millions of nodes in the browser for the first time. Taxonium links each node to associated metadata and supports mutation-annotated trees, which are able to capture all known genetic variation in a dataset. It can either be run entirely locally in the browser, from a server-based backend, or as a desktop application. We describe insights that analysing a tree of five million sequences can provide into SARS-CoV-2 evolution, and provide a tool at cov2tree.org for exploring a public tree of more than five million SARS-CoV-2 sequences. Taxonium can be applied to any tree, and is available at taxonium.org, with source code at github.com/theosanderson/taxonium.

    1. Epidemiology and Global Health
    2. Genetics and Genomics
    Amy L Roberts, Alessandro Morea ... Kerrin S Small
    Research Article

    Background:

    Ageing is a heterogenous process characterised by cellular and molecular hallmarks, including changes to haematopoietic stem cells and is a primary risk factor for chronic diseases. X chromosome inactivation (XCI) randomly transcriptionally silences either the maternal or paternal X in each cell of 46, XX females to balance the gene expression with 46, XY males. Age acquired XCI-skew describes the preferential selection of cells across a tissue resulting in an imbalance of XCI, which is particularly prevalent in blood tissues of ageing females, and yet its clinical consequences are unknown.

    Methods:

    We assayed XCI in 1575 females from the TwinsUK population cohort using DNA extracted from whole blood. We employed prospective, cross-sectional, and intra-twin study designs to characterise the relationship of XCI-skew with molecular and cellular measures of ageing, cardiovascular disease risk, and cancer diagnosis.

    Results:

    We demonstrate that XCI-skew is independent of traditional markers of biological ageing and is associated with a haematopoietic bias towards the myeloid lineage. Using an atherosclerotic cardiovascular disease risk score, which captures traditional risk factors, XCI-skew is associated with an increased cardiovascular disease risk both cross-sectionally and within XCI-skew discordant twin pairs. In a prospective 10 year follow-up study, XCI-skew is predictive of future cancer incidence.

    Conclusions:

    Our study demonstrates that age acquired XCI-skew captures changes to the haematopoietic stem cell population and has clinical potential as a unique biomarker of chronic disease risk.

    Funding:

    KSS acknowledges funding from the Medical Research Council [MR/M004422/1 and MR/R023131/1]. JTB acknowledges funding from the ESRC [ES/N000404/1]. MM acknowledges funding from the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, Chronic Disease Research Foundation (CDRF), Zoe Global Ltd and the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London.