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Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2

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Listed:
  • Dami A. Collier

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge
    University College London)

  • Isabella A. T. M. Ferreira

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • Prasanti Kotagiri

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • Rawlings P. Datir

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge
    University College London)

  • Eleanor Y. Lim

    (University of Cambridge)

  • Emma Touizer

    (University College London)

  • Bo Meng

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • Adam Abdullahi

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID))

  • Anne Elmer

    (NIHR Bioresource
    University of Cambridge, Cambridge Biomedical Campus)

  • Nathalie Kingston

    (NIHR Bioresource
    University of Cambridge, Cambridge Biomedical Campus)

  • Barbara Graves

    (NIHR Bioresource)

  • Emma Gresley

    (NIHR Bioresource
    University of Cambridge, Cambridge Biomedical Campus)

  • Daniela Caputo

    (NIHR Bioresource
    University of Cambridge, Cambridge Biomedical Campus)

  • Laura Bergamaschi

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID))

  • Kenneth G. C. Smith

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • John R. Bradley

    (University of Cambridge
    NIHR Bioresource)

  • Lourdes Ceron-Gutierrez

    (Addenbrookes Hospital)

  • Paulina Cortes-Acevedo

    (Laboratorio de Inmunología, FES-Cuautitlán, UNAM)

  • Gabriela Barcenas-Morales

    (Laboratorio de Inmunología, FES-Cuautitlán, UNAM)

  • Michelle A. Linterman

    (Immunology Programme, Babraham Institute)

  • Laura E. McCoy

    (University College London)

  • Chris Davis

    (University of Glasgow)

  • Emma Thomson

    (University of Glasgow)

  • Paul A. Lyons

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • Eoin McKinney

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • Rainer Doffinger

    (University of Cambridge, Cambridge Biomedical Campus)

  • Mark Wills

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

  • Ravindra K. Gupta

    (Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID)
    University of Cambridge)

Abstract

Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.

Suggested Citation

  • Dami A. Collier & Isabella A. T. M. Ferreira & Prasanti Kotagiri & Rawlings P. Datir & Eleanor Y. Lim & Emma Touizer & Bo Meng & Adam Abdullahi & Anne Elmer & Nathalie Kingston & Barbara Graves & Emma, 2021. "Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2," Nature, Nature, vol. 596(7872), pages 417-422, August.
  • Handle: RePEc:nat:nature:v:596:y:2021:i:7872:d:10.1038_s41586-021-03739-1
    DOI: 10.1038/s41586-021-03739-1
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    Cited by:

    1. Juan Carlos Yam-Puc & Zhaleh Hosseini & Emily C. Horner & Pehuén Pereyra Gerber & Nonantzin Beristain-Covarrubias & Robert Hughes & Aleksei Lulla & Maria Rust & Rebecca Boston & Magda Ali & Katrin Fis, 2023. "Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Matt D. T. Hitchings & Otavio T. Ranzani & Murilo Dorion & Tatiana Lang D’Agostini & Regiane Cardoso de Paula & Olivia Ferreira Pereira de Paula & Edlaine Faria de Moura Villela & Mario Sergio Scaramu, 2021. "Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    3. Daan K. J. Pieren & Sebastián G. Kuguel & Joel Rosado & Alba G. Robles & Joan Rey-Cano & Cristina Mancebo & Juliana Esperalba & Vicenç Falcó & María J. Buzón & Meritxell Genescà, 2023. "Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Jae Sung Lim & Eun Jae Jeon & Hye Sun Go & Hyung-Jin Kim & Kye Young Kim & Thi Quynh Trang Nguyen & Da Young Lee & Kyu Suk Kim & Federico Pietrocola & Seol Hee Hong & Shee Eun Lee & Kyoung-Shim Kim & , 2024. "Mucosal TLR5 activation controls healthspan and longevity," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. Gayatri Amirthalingam & Jamie Lopez Bernal & Nick J. Andrews & Heather Whitaker & Charlotte Gower & Julia Stowe & Elise Tessier & Sathyavani Subbarao & Georgina Ireland & Frances Baawuah & Ezra Linley, 2021. "Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    6. Laurent Renia & Yun Shan Goh & Angeline Rouers & Nina Bert & Wan Ni Chia & Jean-Marc Chavatte & Siew‐Wai Fong & Zi Wei Chang & Nicole Ziyi Zhuo & Matthew Zirui Tay & Yi-Hao Chan & Chee Wah Tan & Nicho, 2022. "Lower vaccine-acquired immunity in the elderly population following two-dose BNT162b2 vaccination is alleviated by a third vaccine dose," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Helen Ward & Matthew Whitaker & Barnaby Flower & Sonja N. Tang & Christina Atchison & Ara Darzi & Christl A. Donnelly & Alexandra Cann & Peter J. Diggle & Deborah Ashby & Steven Riley & Wendy S. Barcl, 2022. "Population antibody responses following COVID-19 vaccination in 212,102 individuals," Nature Communications, Nature, vol. 13(1), pages 1-6, December.
    8. Adam Abdullahi & David Oladele & Michael Owusu & Steven A. Kemp & James Ayorinde & Abideen Salako & Douglas Fink & Fehintola Ige & Isabella A. T. M. Ferreira & Bo Meng & Augustina Angelina Sylverken &, 2022. "SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    9. Eva Stadler & Martin T. Burgess & Timothy E. Schlub & Shanchita R. Khan & Khai Li Chai & Zoe K. McQuilten & Erica M. Wood & Mark N. Polizzotto & Stephen J. Kent & Deborah Cromer & Miles P. Davenport &, 2023. "Monoclonal antibody levels and protection from COVID-19," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    10. Kevin J. Kramer & Erin M. Wilfong & Kelsey Voss & Sierra M. Barone & Andrea R. Shiakolas & Nagarajan Raju & Caroline E. Roe & Naveenchandra Suryadevara & Lauren M. Walker & Steven C. Wall & Ariana Pau, 2022. "Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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