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Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity

Author

Listed:
  • Carolina Lucas

    (Yale University School of Medicine)

  • Chantal B. F. Vogels

    (Yale School of Public Health)

  • Inci Yildirim

    (Yale University School of Medicine
    Yale University)

  • Jessica E. Rothman

    (Yale School of Public Health)

  • Peiwen Lu

    (Yale University School of Medicine)

  • Valter Monteiro

    (Yale University School of Medicine)

  • Jeff R. Gehlhausen

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Melissa Campbell

    (Yale University School of Medicine)

  • Julio Silva

    (Yale University School of Medicine)

  • Alexandra Tabachnikova

    (Yale University School of Medicine)

  • Mario A. Peña-Hernandez

    (Yale University School of Medicine)

  • M. Catherine Muenker

    (Yale School of Public Health)

  • Mallery I. Breban

    (Yale School of Public Health)

  • Joseph R. Fauver

    (Yale School of Public Health)

  • Subhasis Mohanty

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Jiefang Huang

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Albert C. Shaw

    (Yale University School of Medicine
    Yale University School of Medicine)

  • Albert I. Ko

    (Yale School of Public Health
    Yale University School of Medicine)

  • Saad B. Omer

    (Yale School of Public Health
    Yale University
    Yale University School of Medicine)

  • Nathan D. Grubaugh

    (Yale School of Public Health
    Yale University)

  • Akiko Iwasaki

    (Yale University School of Medicine
    Howard Hughes Medical Institute)

Abstract

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination1–6. Here we analysed the development of anti-SARS-CoV-2 antibody and T cell responses in individuals who were previously infected (recovered) or uninfected (naive) and received mRNA vaccines to SARS-CoV-2. While individuals who were previously infected sustained higher antibody titres than individuals who were uninfected post-vaccination, the latter reached comparable levels of neutralization responses to the ancestral strain after the second vaccine dose. T cell activation markers measured upon spike or nucleocapsid peptide in vitro stimulation showed a progressive increase after vaccination. Comprehensive analysis of plasma neutralization using 16 authentic isolates of distinct locally circulating SARS-CoV-2 variants revealed a range of reduction in the neutralization capacity associated with specific mutations in the spike gene: lineages with E484K and N501Y/T (for example, B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (for example, B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from individuals who were previously infected and vaccinated displayed overall better neutralization capacity than plasma from individuals who were uninfected and also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the effect of emerging variants on antibody neutralizing activity.

Suggested Citation

  • Carolina Lucas & Chantal B. F. Vogels & Inci Yildirim & Jessica E. Rothman & Peiwen Lu & Valter Monteiro & Jeff R. Gehlhausen & Melissa Campbell & Julio Silva & Alexandra Tabachnikova & Mario A. Peña-, 2021. "Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity," Nature, Nature, vol. 600(7889), pages 523-529, December.
  • Handle: RePEc:nat:nature:v:600:y:2021:i:7889:d:10.1038_s41586-021-04085-y
    DOI: 10.1038/s41586-021-04085-y
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    Citations

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    Cited by:

    1. Zhenhao Fang & Lei Peng & Renata Filler & Kazushi Suzuki & Andrew McNamara & Qianqian Lin & Paul A. Renauer & Luojia Yang & Bridget Menasche & Angie Sanchez & Ping Ren & Qiancheng Xiong & Madison Stri, 2022. "Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Jillian R. Jaycox & Carolina Lucas & Inci Yildirim & Yile Dai & Eric Y. Wang & Valter Monteiro & Sandra Lord & Jeffrey Carlin & Mariko Kita & Jane H. Buckner & Shuangge Ma & Melissa Campbell & Albert , 2023. "SARS-CoV-2 mRNA vaccines decouple anti-viral immunity from humoral autoimmunity," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    3. 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.
    4. Milja Belik & Pinja Jalkanen & Rickard Lundberg & Arttu Reinholm & Larissa Laine & Elina Väisänen & Marika Skön & Paula A. Tähtinen & Lauri Ivaska & Sari H. Pakkanen & Hanni K. Häkkinen & Eeva Ortamo , 2022. "Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Grace Kenny & Sophie O’Reilly & Neil Wrigley Kelly & Riya Negi & Colette Gaillard & Dana Alalwan & Gurvin Saini & Tamara Alrawahneh & Nathan Francois & Matthew Angeliadis & Alejandro Abner Garcia Leon, 2023. "Distinct receptor binding domain IgG thresholds predict protective host immunity across SARS-CoV-2 variants and time," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. 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.

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