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Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost

Author

Listed:
  • Frauke Muecksch

    (The Rockefeller University)

  • Zijun Wang

    (The Rockefeller University)

  • Alice Cho

    (The Rockefeller University)

  • Christian Gaebler

    (The Rockefeller University)

  • Tarek Tanfous

    (The Rockefeller University)

  • Justin DaSilva

    (The Rockefeller University)

  • Eva Bednarski

    (The Rockefeller University)

  • Victor Ramos

    (The Rockefeller University)

  • Shuai Zong

    (The Rockefeller University)

  • Brianna Johnson

    (The Rockefeller University)

  • Raphael Raspe

    (The Rockefeller University)

  • Dennis Schaefer-Babajew

    (The Rockefeller University)

  • Irina Shimeliovich

    (The Rockefeller University)

  • Mridushi Daga

    (The Rockefeller University)

  • Kai-Hui Yao

    (The Rockefeller University)

  • Fabian Schmidt

    (The Rockefeller University)

  • Katrina G. Millard

    (The Rockefeller University)

  • Martina Turroja

    (The Rockefeller University)

  • Mila Jankovic

    (The Rockefeller University)

  • Thiago Y. Oliveira

    (The Rockefeller University)

  • Anna Gazumyan

    (The Rockefeller University)

  • Marina Caskey

    (The Rockefeller University)

  • Theodora Hatziioannou

    (The Rockefeller University)

  • Paul D. Bieniasz

    (The Rockefeller University
    The Rockefeller University)

  • Michel C. Nussenzweig

    (The Rockefeller University
    The Rockefeller University)

Abstract

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1–3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

Suggested Citation

  • Frauke Muecksch & Zijun Wang & Alice Cho & Christian Gaebler & Tarek Tanfous & Justin DaSilva & Eva Bednarski & Victor Ramos & Shuai Zong & Brianna Johnson & Raphael Raspe & Dennis Schaefer-Babajew & , 2022. "Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost," Nature, Nature, vol. 607(7917), pages 128-134, July.
  • Handle: RePEc:nat:nature:v:607:y:2022:i:7917:d:10.1038_s41586-022-04778-y
    DOI: 10.1038/s41586-022-04778-y
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    Cited by:

    1. Mark Chernyshev & Mrunal Sakharkar & Ruth I. Connor & Haley L. Dugan & Daniel J. Sheward & C. G. Rappazzo & Aron Stålmarck & Mattias N. E. Forsell & Peter F. Wright & Martin Corcoran & Ben Murrell & L, 2023. "Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Chengzi I. Kaku & Tyler N. Starr & Panpan Zhou & Haley L. Dugan & Paul Khalifé & Ge Song & Elizabeth R. Champney & Daniel W. Mielcarz & James C. Geoghegan & Dennis R. Burton & Raiees Andrabi & Jesse D, 2023. "Evolution of antibody immunity following Omicron BA.1 breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. 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.
    4. Mingxi Li & Yifei Ren & Zhen Qin Aw & Bo Chen & Ziqing Yang & Yuqing Lei & Lin Cheng & Qingtai Liang & Junxian Hong & Yiling Yang & Jing Chen & Yi Hao Wong & Jing Wei & Sisi Shan & Senyan Zhang & Jiwa, 2022. "Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    5. Leander Witte & Viren A. Baharani & Fabian Schmidt & Zijun Wang & Alice Cho & Raphael Raspe & Camila Guzman-Cardozo & Frauke Muecksch & Marie Canis & Debby J. Park & Christian Gaebler & Marina Caskey , 2023. "Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. 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.
    7. Dapeng Li & David R. Martinez & Alexandra Schäfer & Haiyan Chen & Maggie Barr & Laura L. Sutherland & Esther Lee & Robert Parks & Dieter Mielke & Whitney Edwards & Amanda Newman & Kevin W. Bock & Mahn, 2022. "Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    8. Kuan-Ying A. Huang & Xiaorui Chen & Arpita Mohapatra & Hong Thuy Vy Nguyen & Lisa Schimanski & Tiong Kit Tan & Pramila Rijal & Susan K. Vester & Rory A. Hills & Mark Howarth & Jennifer R. Keeffe & Ale, 2023. "Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. 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.
    10. Yubin Liu & Ziyi Wang & Xinyu Zhuang & Shengnan Zhang & Zhicheng Chen & Yan Zou & Jie Sheng & Tianpeng Li & Wanbo Tai & Jinfang Yu & Yanqun Wang & Zhaoyong Zhang & Yunfeng Chen & Liangqin Tong & Xi Yu, 2023. "Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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