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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Author

Listed:
  • Zijun Wang

    (The Rockefeller University)

  • Fabian Schmidt

    (The Rockefeller University)

  • Yiska Weisblum

    (The Rockefeller University)

  • Frauke Muecksch

    (The Rockefeller University)

  • Christopher O. Barnes

    (California Institute of Technology)

  • Shlomo Finkin

    (The Rockefeller University)

  • Dennis Schaefer-Babajew

    (The Rockefeller University)

  • Melissa Cipolla

    (The Rockefeller University)

  • Christian Gaebler

    (The Rockefeller University)

  • Jenna A. Lieberman

    (National Institutes of Health)

  • Thiago Y. Oliveira

    (The Rockefeller University)

  • Zhi Yang

    (California Institute of Technology)

  • Morgan E. Abernathy

    (California Institute of Technology)

  • Kathryn E. Huey-Tubman

    (California Institute of Technology)

  • Arlene Hurley

    (The Rockefeller University)

  • Martina Turroja

    (The Rockefeller University)

  • Kamille A. West

    (National Institutes of Health Clinical Center)

  • Kristie Gordon

    (The Rockefeller University)

  • Katrina G. Millard

    (The Rockefeller University)

  • Victor Ramos

    (The Rockefeller University)

  • Justin Silva

    (The Rockefeller University)

  • Jianliang Xu

    (National Institutes of Health)

  • Robert A. Colbert

    (National Institutes of Health)

  • Roshni Patel

    (The Rockefeller University)

  • Juan Dizon

    (The Rockefeller University)

  • Cecille Unson-O’Brien

    (The Rockefeller University)

  • Irina Shimeliovich

    (The Rockefeller University)

  • Anna Gazumyan

    (The Rockefeller University)

  • Marina Caskey

    (The Rockefeller University)

  • Pamela J. Bjorkman

    (California Institute of Technology)

  • Rafael Casellas

    (National Institutes of Health
    National Institutes of Health)

  • Theodora Hatziioannou

    (The Rockefeller University)

  • Paul D. Bieniasz

    (The Rockefeller University
    The Rockefeller University)

  • Michel C. Nussenzweig

    (The Rockefeller University
    The Rockefeller University)

Abstract

Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccine against SARS-CoV-21–4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small—but significant—margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5–8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid a potential loss of clinical efficacy.

Suggested Citation

  • Zijun Wang & Fabian Schmidt & Yiska Weisblum & Frauke Muecksch & Christopher O. Barnes & Shlomo Finkin & Dennis Schaefer-Babajew & Melissa Cipolla & Christian Gaebler & Jenna A. Lieberman & Thiago Y. , 2021. "mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants," Nature, Nature, vol. 592(7855), pages 616-622, April.
  • Handle: RePEc:nat:nature:v:592:y:2021:i:7855:d:10.1038_s41586-021-03324-6
    DOI: 10.1038/s41586-021-03324-6
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    Cited by:

    1. X. Tong & R. P. McNamara & M. J. Avendaño & E. F. Serrano & T. García-Salum & C. Pardo-Roa & H. L. Bertera & T. M. Chicz & J. Levican & E. Poblete & E. Salinas & A. Muñoz & A. Riquelme & G. Alter & R., 2023. "Waning and boosting of antibody Fc-effector functions upon SARS-CoV-2 vaccination," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Davida S. Smyth & Monica Trujillo & Devon A. Gregory & Kristen Cheung & Anna Gao & Maddie Graham & Yue Guan & Caitlyn Guldenpfennig & Irene Hoxie & Sherin Kannoly & Nanami Kubota & Terri D. Lyddon & M, 2022. "Tracking cryptic SARS-CoV-2 lineages detected in NYC wastewater," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
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    6. Sissy Therese Sonnleitner & Martina Prelog & Stefanie Sonnleitner & Eva Hinterbichler & Hannah Halbfurter & Dominik B. C. Kopecky & Giovanni Almanzar & Stephan Koblmüller & Christian Sturmbauer & Leon, 2022. "Cumulative SARS-CoV-2 mutations and corresponding changes in immunity in an immunocompromised patient indicate viral evolution within the host," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    7. 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.
    8. João Faro-Viana & Marie-Louise Bergman & Lígia A. Gonçalves & Nádia Duarte & Teresa P. Coutinho & Patrícia C. Borges & Christian Diwo & Rute Castro & Paula Matoso & Vanessa Malheiro & Ana Brennand & L, 2022. "Population homogeneity for the antibody response to COVID-19 BNT162b2/Comirnaty vaccine is only reached after the second dose across all adult age ranges," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    9. 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.
    10. 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.
    11. Ma’ayan Israeli & Yaara Finkel & Yfat Yahalom-Ronen & Nir Paran & Theodor Chitlaru & Ofir Israeli & Inbar Cohen-Gihon & Moshe Aftalion & Reut Falach & Shahar Rotem & Uri Elia & Ital Nemet & Limor Klik, 2022. "Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Robert M. Cox & Carolin M. Lieber & Josef D. Wolf & Amirhossein Karimi & Nicole A. P. Lieberman & Zachary M. Sticher & Pavitra Roychoudhury & Meghan K. Andrews & Rebecca E. Krueger & Michael G. Natchu, 2023. "Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Andrew P. Hederman & Harini Natarajan & Leo Heyndrickx & Kevin K. Ariën & Joshua A. Wiener & Peter F. Wright & Evan M. Bloch & Aaron A. R. Tobian & Andrew D. Redd & Joel N. Blankson & Amihai Rottenstr, 2023. "SARS-CoV-2 vaccination elicits broad and potent antibody effector functions to variants of concern in vulnerable populations," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    14. Silva Guljaš & Zvonimir Bosnić & Tamer Salha & Monika Berecki & Zdravka Krivdić Dupan & Stjepan Rudan & Ljiljana Majnarić Trtica, 2021. "Lack of Informations about COVID-19 Vaccine: From Implications to Intervention for Supporting Public Health Communications in COVID-19 Pandemic," IJERPH, MDPI, vol. 18(11), pages 1-15, June.
    15. 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.
    16. 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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