Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant
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Abstract
We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0- to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.
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The Lambda variant is described as having mutations that increase infectivity and immune escape.
“The L452Q and F490S mutations reported in the RBD region have been shown to increase the viral infectivity, rendering the virus more infectious and able to escape immune response from specific monoclonal antibodies [51, 52] or disrupt the ability of vaccine-generated antibodies to recognize the variant [53].”
From Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe (2022) · cites this paper as [51]
The Results section (page unavailable) reports a twofold reduction in neutralization by vaccine-recipient plasma against B.1.429, supporting a limited claim about reduced vaccine-antibody activity. The study concerns a California variant with L452R, not the Lambda variant or its L452Q and F490S mutations; it does not establish that vaccine-generated antibodies cannot recognize Lambda. (LLM, conf=0.87)
Experimental — accuracy not yet measuredL452Q and F490S in RBD increase viral infectivity, making the virus more infectious and able to escape specific monoclonal antibodies or disrupt vaccine-generated antibody recognition.
“The L452Q and F490S mutations reported in the RBD region have been shown to increase the viral infectivity, rendering the virus more infectious and able to escape immune response from specific monoclonal antibodies [51, 52] or disrupt the ability of vaccine-generated antibodies to recognize the variant [53].”
From Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe (2022) · cites this paper as [51]
The Results section on antibody neutralization (page not available in our copy) reports a median twofold reduction in neutralization of the B.1.429 variant by plasma from vaccine recipients. But the paper studies L452R, not the cited L452Q and F490S mutations, and its Discussion describes vaccine-elicited neutralizing responses as robust despite the modest reduction. It therefore supports reduced neutralization of a different variant, not disrupted antibody recognition caused by the mutations named in the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredL452R has also been identified in B.1.427 and B.1.429, and T478K is found in B.1.1.519.
“L452R has also been identified in B.1.427 and B.1.429 (Deng et al., 2021), and T478K is found in B.1.1.519.”
From Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum (2021) · cites this paper as Deng et al., 2021
The Epsilon variant was estimated to be about 20% more transmissible than co-circulating lineages and to be associated with twofold higher upper-airway virus levels.
“It was estimated to be about 20% more transmissible than co-circulating lineages and to be associated with twofold higher upper-airway virus levels 123,192 .”
From The biological and clinical significance of emerging SARS-CoV-2 variants (2021) · cites this paper as [123]
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SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern
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Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail
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- Authors
- Deng, X., Garcia-Knight, M. A., Khalid, M. M., Servellita, V., Wang, C., Morris, M. K., Sotomayor-González, A., Glasner, D. R., Reyes, K. R., Gliwa, A. S., Reddy, N. P., Sanchez San Martin, C., Federman, S., Cheng, J., Balcerek, J., Taylor, J., Streithorst, J. A., Miller, S., Sreekumar, B., Chen, P.-Y., Schulze-Gahmen, U., Taha, T. Y., Hayashi, J. M., Simoneau, C. R., Kumar, G. R., McMahon, S., Lidsky, P. V., Xiao, Y., Hemarajata, P., Green, N. M., Espinosa, A., Kath, C., Haw, M., Bell, J., Hacker, J. K., Hanson, C., Wadford, D. A., Anaya, C., Ferguson, D., Frankino, P. A., Shivram, H., Lareau, L. F., Wyman, S. K., Ott, M., Andino, R., & Chiu, C. Y.
- Affiliations
- University of California, San Francisco (US)
- Gladstone Institutes (US)
- California Department of Public Health (US)
- Los Angeles County Department of Public Health (US)
- Monterey County Health Department (US)
- Innovative Genomics Institute (US)
- Corresponding author
- Andino, Raul
- Chiu, Charles Y.
- ORCID
- Deng, Xianding
- Garcia-Knight, Miguel A.
- Khalid, Mir M.
- Servellita, Venice
- Wang, Candace
- Morris, Mary Kate
- Sotomayor-González, Alicia
- Glasner, Dustin R.
- Reyes, Kevin R.
- Federman, Scot
- Cheng, Jing
- Balcerek, Joanna
- Taylor, Jordan
- Miller, Steve
- Sreekumar, Bharath
- Taha, Taha Y.
- Hayashi, Jennifer M.
- Simoneau, Camille R.
- Kumar, G. Renuka
- McMahon, Sarah
- Lidsky, Peter V.
- Xiao, Yinghong
- Hemarajata, Peera
- Green, Nicole M.
- Bell, John
- Hacker, Jill K.
- Hanson, Carl
- Wadford, Debra A.
- Frankino, Phillip A.
- Shivram, Haridha
- Lareau, Liana F.
- Wyman, Stacia K.
- Andino, Raul
- Chiu, Charles Y.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 184
- Issue
- 13
- Pages
- 3426-3437.e8
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC8057738
- OpenAlex
- W3155554970
- Cited by
- 651
- References
- 67
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 59 · 2023: 64 · 2022: 234 · 2021: 257
- FWCI
- 48.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 388 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- Roddenberry Foundation
- NIH
- Innovative Genomics Institute
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Physical Sciences › Mathematics › Modeling and Simulation › COVID-19 epidemiological studies
- Keywords
- SARS-CoV-2, L452R mutation, spike protein mutations, viral transmissibility, viral shedding, antibody neutralization, N501Y mutation, convalescent sera, COVID-19 vaccines, lung organoids, California
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.
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