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).

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

  • 2,861
    views
  • 273
    downloads
  • 39
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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

Share this article

https://doi.org/10.7554/eLife.69317

Further reading

    1. Epidemiology and Global Health
    2. Evolutionary Biology
    Renan Maestri, Benoît Perez-Lamarque ... Hélène Morlon
    Research Article

    Several coronaviruses infect humans, with three, including the SARS-CoV2, causing diseases. While coronaviruses are especially prone to induce pandemics, we know little about their evolutionary history, host-to-host transmissions, and biogeography. One of the difficulties lies in dating the origination of the family, a particularly challenging task for RNA viruses in general. Previous cophylogenetic tests of virus-host associations, including in the Coronaviridae family, have suggested a virus-host codiversification history stretching many millions of years. Here, we establish a framework for robustly testing scenarios of ancient origination and codiversification versus recent origination and diversification by host switches. Applied to coronaviruses and their mammalian hosts, our results support a scenario of recent origination of coronaviruses in bats and diversification by host switches, with preferential host switches within mammalian orders. Hotspots of coronavirus diversity, concentrated in East Asia and Europe, are consistent with this scenario of relatively recent origination and localized host switches. Spillovers from bats to other species are rare, but have the highest probability to be towards humans than to any other mammal species, implicating humans as the evolutionary intermediate host. The high host-switching rates within orders, as well as between humans, domesticated mammals, and non-flying wild mammals, indicates the potential for rapid additional spreading of coronaviruses across the world. Our results suggest that the evolutionary history of extant mammalian coronaviruses is recent, and that cases of long-term virus–host codiversification have been largely over-estimated.

    1. Cancer Biology
    2. Epidemiology and Global Health
    Chelsea L Hansen, Cécile Viboud, Lone Simonsen
    Research Article

    Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer’s. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2–7%) than cancers with a poor survival rate (lung and pancreatic, 0–1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19.