Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity
Open accessPublished version of a preprint
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. 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Vaccination of convalescent individuals improved cross-reactivity to variants.
“and improved cross-reactivity to variants.27, 28, 29, 30”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [30]
Vaccination of convalescent individuals led to 2-10-fold higher neutralisation titres than naive individuals after primary vaccination.
“Aggregating these studies, we found that vaccination of convalescent individuals led to 2–10-fold higher neutralisation titres than that seen in naive individuals after primary vaccination (figure 3 ; appendix p 19)26, 27, 28, 29, 30, 31”
From Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis (2022) · cites this paper as [30]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 39 · Cited by 226
Research works printed but not linked: 1
- [8]Walsh EE Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N. Engl. J. Med 383, 2439– 2450 (2020). 33053279 PMC7583697
- Authors
- Lucas, C., Vogels, C. B. F., Yildirim, I., Rothman, J. E., Lu, P., Monteiro, V., Gehlhausen, J. R., Campbell, M., Silva, J., Tabachnikova, A., Peña-Hernandez, M. A., Muenker, M. C., Breban, M. I., Fauver, J. R., Mohanty, S., Huang, J., Initiative, Y. S.-C.-2. G. S., Pearson, C., Muyombwe, A., Downing, R., Razeq, J., Petrone, M., Ott, I., Watkins, A., Kalinich, C., Alpert, T., Brito, A., Earnest, R., Murphy, S., Neal, C., Laszlo, E., Altajar, A., Tikhonova, I., Castaldi, C., Mane, S., Bilguvar, K., Kerantzas, N., Ferguson, D., Schulz, W., Landry, M., Peaper, D., Shaw, A. C., Ko, A. I., Omer, S. B., Grubaugh, N. D., & Iwasaki, A.
- Affiliations
- Yale University (US)
- Connecticut Department of Public Health (US)
- Greenwich Public Schools (US)
- Yale New Haven Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Iwasaki, Akiko
- ORCID
- Lucas, Carolina
- Vogels, Chantal B. F.
- Yildirim, Inci
- Rothman, Jessica E.
- Lu, Peiwen
- Monteiro, Valter
- Gehlhausen, Jeff R.
- Campbell, Melissa
- Silva, Julio
- Tabachnikova, Alexandra
- Muenker, M. Catherine
- Breban, Mallery I.
- Fauver, Joseph R.
- Mohanty, Subhasis
- Huang, Jiefang
- Petrone, Mary
- Ott, Isabel
- Watkins, Anne
- Kalinich, Chaney
- Alpert, Tara
- Brito, Anderson
- Earnest, Rebecca
- Neal, Caleb
- Tikhonova, Irina
- Castaldi, Christopher
- Mane, Shrikant
- Ferguson, David
- Schulz, Wade
- Landry, Marie
- Peaper, David
- Shaw, Albert C.
- Ko, Albert I.
- Omer, Saad B.
- Grubaugh, Nathan D.
- Iwasaki, Akiko
- Venue
- Nature
- Published
- 2021-10-11
- Volume
- 600
- Issue
- 7889
- Pages
- 523-529
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9348899
- OpenAlex
- W3206303627
- Cited by
- 226
- References
- 39
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 17 · 2023: 49 · 2022: 118 · 2021: 23
- FWCI
- 16.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- medRxiv (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Pfizer
- Yale University
- Ludwig Family Foundation
- Moderna
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (Rubicon 019.181EN.004, 019.181EN.004)
- National Institute of Allergy and Infectious Diseases (T32AI007019)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32AR007016)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- SARS-CoV-2 variants, mRNA vaccines, neutralizing antibodies, T cell response, prior SARS-CoV-2 infection, booster vaccination, spike protein mutations, E484K, N501Y, L452R, Beta variant, P.1, Delta variant, humoral immunity
- MeSH terms
- COVID-19, SARS-CoV-2, mRNA Vaccines, BNT162 Vaccine, 2019-nCoV Vaccine mRNA-1273, Adult, Aged, Antibodies, Viral, Female, Health Personnel, Humans, Male, Middle Aged, Mutation, Retrospective Studies, T-Lymphocytes, Vaccines, Synthetic, Immunity, Humoral, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
