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

Abstract

The emergence of SARS-CoV-2 variants with mutations in major neutralizing antibody-binding sites can affect humoral immunity induced by infection or vaccination^1–6. We analysed the development of anti-SARS-CoV-2 antibody and T cell responses in previously infected (recovered) or uninfected (naive) individuals that received mRNA vaccines to SARS-CoV-2. While previously infected individuals sustained higher antibody titres than uninfected individuals 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 (e.g., B.1.351 and P.1) had the greatest reduction, followed by lineages with L452R (e.g., B.1.617.2). While both groups retained neutralization capacity against all variants, plasma from previously infected vaccinated individuals displayed overall better neutralization capacity when compared to plasma from uninfected individuals that also received two vaccine doses, pointing to vaccine boosters as a relevant future strategy to alleviate the impact of emerging variants on antibody neutralizing activity.

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Author notes

1. These authors contributed equally: Carolina Lucas, Chantal B.F. Vogels, Inci Yildirim

2. These authors jointly supervised this work: Saad B. Omer, Nathan D. Grubaugh and Akiko Iwasaki

Affiliations

1. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA

   Carolina Lucas, Peiwen Lu, Valter Monteiro, Jeff R. Gelhausen, Julio Silva, Alexandra Tabachikova, Mario A. Peña-Hernandez, Subhasis Mohanty, Jiefang Huang, Albert C. Shaw & Akiko Iwasaki

2. Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA

   Chantal B. F. Vogels, Jessica E. Rothman, M. Catherine Muenker, Mallery I. Breban, Joseph R. Fauver, Mary Petrone, Isabel Ott, Anne Watkins, Chaney Kalinich, Tara Alpert, Anderson Brito, Rebecca Earnest, Albert I. Ko, Saad B. Omer & Nathan D. Grubaugh

3. Department of Pediatric, Section of Infectious Diseases and Global Health, Yale University School of Medicine, New Haven, CT, USA

   Inci Yildirim

4. Yale Institute for Global Health, Yale University, New Haven, CT, USA

   Inci Yildirim & Saad B. Omer

5. Department of Dermatology, Yale University School of Medicine, New Haven, CT, USA

   Jeff R. Gelhausen

6. Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA

   Melissa Campbell, Subhasis Mohanty, Jiefang Huang, Albert C. Shaw, Albert I. Ko & Saad B. Omer

7. Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT, USA

   Nathan D. Grubaugh

8. Howard Hughes Medical Institute, Chevy Chase, MD, USA

   Akiko Iwasaki

9. Connecticut State Department of Public Health, Rocky Hill, CT, USA

   Claire Pearson, Anthony Muyombwe, Randy Downing & Jafar Razeq

10. Murphy Medical Associates, Greenwich, CT, USA

    Steven Murphy, Caleb Neal, Eva Laszlo & Ahmad Altajar

11. Yale Center for Genome Analysis, Yale University, New Haven, CT, USA

    Irina Tikhonova, Christopher Castaldi, Shrikant Mane & Kaya Bilguvar

12. Department of Laboratory Medicine, Yale New Haven Hospital, New Haven, CT, USA

    Nicholas Kerantzas

13. Center for Outcomes Research and Evaluation, Yale New Haven Hospital, New Haven, CT, USA

    David Ferguson & Wade Schulz

14. Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, USA

    Wade Schulz

15. Departments of Laboratory Medicine and Medicine, Yale University School of Medicine, New Haven, CT, USA

    Marie Landry & David Peaper

Authors

1. Carolina Lucas
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2. Chantal B. F. Vogels
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3. Inci Yildirim
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4. Jessica E. Rothman
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5. Peiwen Lu
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6. Valter Monteiro
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7. Jeff R. Gelhausen
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8. Melissa Campbell
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9. Julio Silva
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10. Alexandra Tabachikova
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11. Mario A. Peña-Hernandez
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12. M. Catherine Muenker
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13. Mallery I. Breban
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14. Joseph R. Fauver
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15. Subhasis Mohanty
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16. Jiefang Huang
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17. Albert C. Shaw
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18. Albert I. Ko
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19. Saad B. Omer
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20. Nathan D. Grubaugh
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21. Akiko Iwasaki
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Consortia

Yale SARS-CoV-2 Genomic Surveillance Initiative

• Claire Pearson
• , Anthony Muyombwe
• , Randy Downing
• , Jafar Razeq
• , Mary Petrone
• , Isabel Ott
• , Anne Watkins
• , Chaney Kalinich
• , Tara Alpert
• , Anderson Brito
• , Rebecca Earnest
• , Steven Murphy
• , Caleb Neal
• , Eva Laszlo
• , Ahmad Altajar
• , Irina Tikhonova
• , Christopher Castaldi
• , Shrikant Mane
• , Kaya Bilguvar
• , Nicholas Kerantzas
• , David Ferguson
• , Wade Schulz
• , Marie Landry
•  & David Peaper

Corresponding author

Correspondence to Akiko Iwasaki.

Supplementary information

Supplementary Data 1

Detailed clinical and immunological data for each patient. Clinical information, demographics and exact counts for immunological data.

Reporting Summary

Peer Review File

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Cite this article

Lucas, C., Vogels, C.B.F., Yildirim, I. et al. Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity. Nature (2021). https://ift.tt/3as31ng

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• Received: 10 July 2021

• Accepted: 30 September 2021

• Published: 11 October 2021

• DOI: https://doi.org/10.1038/s41586-021-04085-y

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