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

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-Hernandez, M. Catherine Muenker, Mallery I. Breban, Joseph R. Fauver, Subhasis Mohanty, Jiefang Huang, Albert C. Shaw, Albert I. Ko, Saad B. Omer, Nathan D. Grubaugh and Akiko Iwasaki ()
Additional contact information
Carolina Lucas: Yale University School of Medicine
Chantal B. F. Vogels: Yale School of Public Health
Inci Yildirim: Yale University School of Medicine
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
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
Jiefang Huang: Yale University School of Medicine
Albert C. Shaw: Yale University School of Medicine
Albert I. Ko: Yale School of Public Health
Saad B. Omer: Yale School of Public Health
Nathan D. Grubaugh: Yale School of Public Health
Akiko Iwasaki: Yale University School of Medicine

Nature, 2021, vol. 600, issue 7889, 523-529

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-04085-y

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