mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralisation of P.1 Brazilian variant

  1. Helen Parry
  2. Gokhan Tut
  3. Rachel Bruton
  4. Sian Faustini
  5. Christine Stephens
  6. Philip Saunders
  7. Christopher Bentley
  8. Katherine Hilyard
  9. Kevin Brown
  10. Gayatri Amirthalingam
  11. Sue Charlton
  12. Stephanie Leung
  13. Emily Chiplin
  14. Naomi S Coombes
  15. Kevin R Bewley
  16. Elizabeth J Penn
  17. Cathy Rowe
  18. Ashley Otter
  19. Rosie Watts
  20. Silvia D'Arcangelo
  21. Bassam Hallis
  22. Andrew Makin
  23. Alex Richter
  24. Jianmin Zuo
  25. Paul Moss  Is a corresponding author
  1. University of Birmingham, United Kingdom
  2. Quinton and Harborne PCN, United Kingdom
  3. Vaccine Taskforce, United Kingdom
  4. National infection Service, United Kingdom
  5. National Infection Service, United Kingdom
  6. Oxford Immunotec Ltd, United Kingdom

Abstract

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80-96 years at 2 weeks after second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titres in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher respectively after dual vaccination. Post-vaccine sera mediated strong neutralisation of live Victoria infection and although neutralisation titres were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 Variant of Concern.

Data availability

All primary data are available at https://doi.org/10.5281/zenodo.4740081

Article and author information

Author details

  1. Helen Parry

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  2. Gokhan Tut

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  3. Rachel Bruton

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  4. Sian Faustini

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  5. Christine Stephens

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  6. Philip Saunders

    Quinton and Harborne PCN, Ridgacre House Surgery, Quinton, United Kingdom
    Competing interests
    No competing interests declared.
  7. Christopher Bentley

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  8. Katherine Hilyard

    Vaccine Taskforce, Department for Business, Energy and Industrial Strategy, London, United Kingdom
    Competing interests
    No competing interests declared.
  9. Kevin Brown

    National infection Service, Public Health England, Colindale, London NW9 5EQ, United Kingdom
    Competing interests
    No competing interests declared.
  10. Gayatri Amirthalingam

    National infection Service, Public Health England, Colindale, London NW9 5EQ, United Kingdom
    Competing interests
    No competing interests declared.
  11. Sue Charlton

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  12. Stephanie Leung

    Research, National Infection Service, Salisbury, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8880-2977
  13. Emily Chiplin

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  14. Naomi S Coombes

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  15. Kevin R Bewley

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  16. Elizabeth J Penn

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  17. Cathy Rowe

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  18. Ashley Otter

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  19. Rosie Watts

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  20. Silvia D'Arcangelo

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  21. Bassam Hallis

    National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, United Kingdom
    Competing interests
    No competing interests declared.
  22. Andrew Makin

    Oxford Immunotec Ltd, Abingdon, OX14 4SE, United Kingdom
    Competing interests
    Andrew Makin, is affiliated with Oxford Immunotec Ltd. The author has no financial interests to declare..
  23. Alex Richter

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  24. Jianmin Zuo

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    No competing interests declared.
  25. Paul Moss

    University of Birmingham, Birmingham, United Kingdom
    For correspondence
    p.moss@bham.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6895-1967

Funding

National Core Studies (Immunity programme)

  • Helen Parry
  • Gokhan Tut
  • Rachel Bruton
  • Sian Faustini
  • Christine Stephens
  • Paul Moss

UK Coronavirus Immunology Consortium (UKRI/DHSC)

  • Helen Parry
  • Gokhan Tut
  • Rachel Bruton
  • Sian Faustini
  • Christine Stephens
  • Paul Moss

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: Informed consent, and consent to publish, was obtained. The study was approved by UPH IRAS ethics 282164, Health Research Authority UK.

Copyright

© 2021, Parry 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

  • 1,745
    views
  • 128
    downloads
  • 18
    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. Helen Parry
  2. Gokhan Tut
  3. Rachel Bruton
  4. Sian Faustini
  5. Christine Stephens
  6. Philip Saunders
  7. Christopher Bentley
  8. Katherine Hilyard
  9. Kevin Brown
  10. Gayatri Amirthalingam
  11. Sue Charlton
  12. Stephanie Leung
  13. Emily Chiplin
  14. Naomi S Coombes
  15. Kevin R Bewley
  16. Elizabeth J Penn
  17. Cathy Rowe
  18. Ashley Otter
  19. Rosie Watts
  20. Silvia D'Arcangelo
  21. Bassam Hallis
  22. Andrew Makin
  23. Alex Richter
  24. Jianmin Zuo
  25. Paul Moss
(2021)
mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralisation of P.1 Brazilian variant
eLife 10:e69375.
https://doi.org/10.7554/eLife.69375

Share this article

https://doi.org/10.7554/eLife.69375

Further reading

    1. Microbiology and Infectious Disease
    Sromona D Mukherjee, Carlos Batagello ... Aaron W Miller
    Research Article

    Decades of research have made clear that host-associated microbiomes touch all facets of health. However, effective therapies that target the microbiome have been elusive given its inherent complexity. Here, we experimentally examined diet-microbe-host interactions through a complex systems framework, centered on dietary oxalate. Using multiple, independent molecular, rodent, and in vitro experimental models, we found that microbiome composition influenced multiple oxalate-microbe-host interfaces. Importantly, the administration of the oxalate-degrading specialist, Oxalobacter formigenes, was only effective against a poor oxalate-degrading microbiota background and gives critical new insights into why clinical intervention trials with this species exhibit variable outcomes. Data suggest that, while heterogeneity in the microbiome impacts multiple diet-host-microbe interfaces, metabolic redundancy among diverse microorganisms in specific diet-microbe axes is a critical variable that may impact the efficacy of bacteriotherapies, which can help guide patient and probiotic selection criteria in probiotic clinical trials.

    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease
    Saugat Poudel, Jason Hyun ... Bernhard O Palsson
    Research Article

    The Staphylococcus aureus clonal complex 8 (CC8) is made up of several subtypes with varying levels of clinical burden; from community-associated methicillin-resistant S. aureus USA300 strains to hospital-associated (HA-MRSA) USA500 strains and ancestral methicillin-susceptible (MSSA) strains. This phenotypic distribution within a single clonal complex makes CC8 an ideal clade to study the emergence of mutations important for antibiotic resistance and community spread. Gene-level analysis comparing USA300 against MSSA and HA-MRSA strains have revealed key horizontally acquired genes important for its rapid spread in the community. However, efforts to define the contributions of point mutations and indels have been confounded by strong linkage disequilibrium resulting from clonal propagation. To break down this confounding effect, we combined genetic association testing with a model of the transcriptional regulatory network (TRN) to find candidate mutations that may have led to changes in gene regulation. First, we used a De Bruijn graph genome-wide association study to enrich mutations unique to the USA300 lineages within CC8. Next, we reconstructed the TRN by using independent component analysis on 670 RNA-sequencing samples from USA300 and non-USA300 CC8 strains which predicted several genes with strain-specific altered expression patterns. Examination of the regulatory region of one of the genes enriched by both approaches, isdH, revealed a 38-bp deletion containing a Fur-binding site and a conserved single-nucleotide polymorphism which likely led to the altered expression levels in USA300 strains. Taken together, our results demonstrate the utility of reconstructed TRNs to address the limits of genetic approaches when studying emerging pathogenic strains.