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Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants

Author

Listed:
  • Emanuele Andreano

    (Fondazione Toscana Life Sciences)

  • Ida Paciello

    (Fondazione Toscana Life Sciences)

  • Giulia Piccini

    (VisMederi S.r.l)

  • Noemi Manganaro

    (Fondazione Toscana Life Sciences)

  • Piero Pileri

    (Fondazione Toscana Life Sciences)

  • Inesa Hyseni

    (VisMederi S.r.l
    VisMederi Research S.r.l.)

  • Margherita Leonardi

    (VisMederi S.r.l
    VisMederi Research S.r.l.)

  • Elisa Pantano

    (Fondazione Toscana Life Sciences)

  • Valentina Abbiento

    (Fondazione Toscana Life Sciences)

  • Linda Benincasa

    (VisMederi Research S.r.l.)

  • Ginevra Giglioli

    (VisMederi Research S.r.l.)

  • Concetta De Santi

    (Fondazione Toscana Life Sciences)

  • Massimiliano Fabbiani

    (Siena University Hospital)

  • Ilaria Rancan

    (Siena University Hospital
    University of Siena)

  • Mario Tumbarello

    (Siena University Hospital
    University of Siena)

  • Francesca Montagnani

    (Siena University Hospital
    University of Siena)

  • Claudia Sala

    (Fondazione Toscana Life Sciences)

  • Emanuele Montomoli

    (VisMederi S.r.l
    VisMederi Research S.r.l.
    University of Siena)

  • Rino Rappuoli

    (Fondazione Toscana Life Sciences
    University of Siena)

Abstract

The emergence of SARS-CoV-2 variants is jeopardizing the effectiveness of current vaccines and limiting the application of monoclonal antibody-based therapy for COVID-19 (refs. 1,2). Here we analysed the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to investigate the nature of the B cell and antibody response at the single-cell level. Almost 6,000 cells were sorted, over 3,000 cells produced monoclonal antibodies against the spike protein and more than 400 cells neutralized the original SARS-CoV-2 virus first identified in Wuhan, China. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants escaped almost 70% of these antibodies, while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part, this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in people who were convalescent and generated potent and broadly neutralizing antibodies. Our data suggest that people who are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control emerging SARS-CoV-2 variants.

Suggested Citation

  • Emanuele Andreano & Ida Paciello & Giulia Piccini & Noemi Manganaro & Piero Pileri & Inesa Hyseni & Margherita Leonardi & Elisa Pantano & Valentina Abbiento & Linda Benincasa & Ginevra Giglioli & Conc, 2021. "Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants," Nature, Nature, vol. 600(7889), pages 530-535, December.
    • Handle: RePEc:nat:nature:v:600:y:2021:i:7889:d:10.1038_s41586-021-04117-7
    DOI: 10.1038/s41586-021-04117-7
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    Citations

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    Cited by:

    1. Simone Lanini & Stefano Milleri & Emanuele Andreano & Sarah Nosari & Ida Paciello & Giulia Piccini & Alessandra Gentili & Adhuna Phogat & Inesa Hyseni & Margherita Leonardi & Alessandro Torelli & Eman, 2022. "Safety and serum distribution of anti-SARS-CoV-2 monoclonal antibody MAD0004J08 after intramuscular injection," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    2. Jernej Pušnik & Werner O. Monzon-Posadas & Jasmin Zorn & Kathrin Peters & Maximilian Baum & Hannah Proksch & Celina Beta Schlüter & Galit Alter & Tanja Menting & Hendrik Streeck, 2023. "SARS-CoV-2 humoral and cellular immunity following different combinations of vaccination and breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Tiago Gräf & Alexander A. Martinez & Gonzalo Bello & Simon Dellicour & Philippe Lemey & Vittoria Colizza & Mattia Mazzoli & Chiara Poletto & Vanessa Leiko Oikawa Cardoso & Alexandre Freitas Silva & Fe, 2024. "Dispersion patterns of SARS-CoV-2 variants Gamma, Lambda and Mu in Latin America and the Caribbean," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Emanuele Andreano & Ida Paciello & Giulio Pierleoni & Giuseppe Maccari & Giada Antonelli & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevra Giglioli & Giulia Piccini & Concetta De Santi &, 2023. "mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    5. Emanuele Andreano & Ida Paciello & Giulio Pierleoni & Giulia Piccini & Valentina Abbiento & Giada Antonelli & Piero Pileri & Noemi Manganaro & Elisa Pantano & Giuseppe Maccari & Silvia Marchese & Lore, 2023. "B cell analyses after SARS-CoV-2 mRNA third vaccination reveals a hybrid immunity like antibody response," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    6. Emanuele Andreano & Ida Paciello & Silvia Marchese & Lorena Donnici & Giulio Pierleoni & Giulia Piccini & Noemi Manganaro & Elisa Pantano & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevr, 2022. "Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    7. Ighor Arantes & Gonzalo Bello & Valdinete Nascimento & Victor Souza & Arlesson Silva & Dejanane Silva & Fernanda Nascimento & Matilde Mejía & Maria Júlia Brandão & Luciana Gonçalves & George Silva & C, 2023. "Comparative epidemic expansion of SARS-CoV-2 variants Delta and Omicron in the Brazilian State of Amazonas," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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