SARS-CoV-2 B.1.617 Mutations L452R and E484Q Are Not Synergistic for Antibody Evasion
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The SARS-CoV-2 B.1.617 variant emerged in the Indian state of Maharashtra in late 2020. There have been fears that 2 key mutations seen in the receptor-binding domain, L452R and E484Q, would have additive effects on evasion of neutralizing antibodies. We report that spike bearing L452R and E484Q confers modestly reduced sensitivity to BNT162b2 mRNA vaccine-elicited antibodies following either first or second dose. The effect is similar in magnitude to the loss of sensitivity conferred by L452R or E484Q alone. These data demonstrate reduced sensitivity to vaccine-elicited neutralizing antibodies by L452R and E484Q but lack of synergistic loss of sensitivity.
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L452R has resulted in 3-fold to 10-fold reduced susceptibility to about one third of convalescent and vaccinee plasma samples.
“L452R has resulted in 3-fold to 10-fold reduced susceptibility to about one third of convalescent and vaccinee plasma samples”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [165]
Even though E484Q is more likely than T478K to evade antibody neutralization, only the Delta variant has demonstrated increased transmissibility, spreading to 54 countries and rapidly replacing the Alpha variant in the UK and the USA.
“Even though E484Q is more likely than T478K to evade antibody neutralization 48,100,165 , only the Delta variant has demonstrated increased transmissibility, spreading to 54 countries and rapidly replacing the Alpha variant in the UK 32,35 and the USA 33 .”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [165]
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- Authors
- Ferreira, I. A. T. M., Kemp, S. A., Datir, R., Saito, A., Meng, B., Rakshit, P., Takaori-Kondo, A., Kosugi, Y., Uriu, K., Kimura, I., Shirakawa, K., Abdullahi, A., Agarwal, A., Ozono, S., Tokunaga, K., Sato, K., Gupta, R. K., CITIID-NIHR BioResource COVID-19 Collaboration, I. S.-C.-2. G. C., & The Genotype to Phenotype Japan (G2P-Japan) Consortium
- Affiliations
- University of Cambridge (GB)
- University of Miyazaki (JP)
- National Center for Disease Control (IN)
- Department of Hematology and Oncology, Kyoto University, Kyoto,Japan
- Institute of Medical Science, The University of Tokyo (JP)
- Kyoto University (JP)
- Institute of Genomics and Integrative Biology (IN)
- National Institute of Infectious Diseases (JP)
- Japan Science and Technology Agency (JP)
- Corresponding author
- Gupta, Ravindra K
- ORCID
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-09-09
- Volume
- 224
- Issue
- 6
- Pages
- 989-994
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC8420622
- OpenAlex
- W3180925673
- Cited by
- 151
- References
- 16
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 18 · 2023: 31 · 2022: 73 · 2021: 16
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Infectious Diseases (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Apollo
- Greater South Information System
- Funders
- Wellcome Trust (WT108082AIA)
- AMED (20fk0108413)
- COVID-19 Genomics UK
- Medical Research Council UK Research and Innovation
- National Institute of Health Research
- Genome Research Ltd
- Cambridge NIHRB
- Biomedical Research Centre
- Bill and Melinda Gates Foundation (OPP1175094)
- Rosetrees Trust
- 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, L452R mutation, receptor binding domain, antibody escape, neutralizing antibodies, BNT162b2 mRNA vaccine, vaccine-elicited antibodies, spike protein mutations
- MeSH terms
- Angiotensin-Converting Enzyme 2, COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Animals, Antibodies, Viral, Chlorocebus aethiops, Humans, India, Mutation, Protein Binding, Serine Endopeptidases, Vero Cells, Immune Evasion, Antibodies, Neutralizing, HEK293 Cells, Spike Glycoprotein, Coronavirus
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