Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Xianding Deng; Miguel A. Garcia-Knight; Mir M. Khalid; Venice Servellita; Candace Wang; Mary Kate Morris; Alicia Sotomayor-González; Dustin R. Glasner; Kevin R. Reyes; Amelia S. Gliwa; Nikitha P. Reddy; Claudia Sanchez San Martin; Scot Federman; Jing Cheng; Joanna Balcerek; Jordan Taylor; Jessica A. Streithorst; Steve Miller; Bharath Sreekumar; Pei-Yi Chen; Ursula Schulze-Gahmen; Taha Y. Taha; Jennifer M. Hayashi; Camille R. Simoneau; G. Renuka Kumar; Sarah McMahon; Peter V. Lidsky; Yinghong Xiao; Peera Hemarajata; Nicole M. Green; Alex Espinosa; Chantha Kath; Monica Haw; John Bell; Jill K. Hacker; Carl Hanson; Debra A. Wadford; Carlos Anaya; Donna Ferguson; Phillip A. Frankino; Haridha Shivram; Liana F. Lareau; Stacia K. Wyman; Melanie Ott; Raul Andino; Charles Y. Chiu

doi:10.1016/j.cell.2021.04.025

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Xianding Deng, Miguel A. Garcia-Knight, Mir M. Khalid, Venice Servellita, Candace Wang, Mary Kate Morris, Alicia Sotomayor-González, Dustin R. Glasner, Kevin R. Reyes, Amelia S. Gliwa, Nikitha P. Reddy, Claudia Sanchez San Martin, Scot Federman, Jing Cheng, Joanna Balcerek, Jordan Taylor, Jessica A. Streithorst, Steve Miller, Bharath Sreekumar, Pei-Yi ChenUrsula Schulze-Gahmen, Taha Y. Taha, Jennifer M. Hayashi, Camille R. Simoneau, G. Renuka Kumar, Sarah McMahon, Peter V. Lidsky, Yinghong Xiao, Peera Hemarajata, Nicole M. Green, Alex Espinosa, Chantha Kath, Monica Haw, John Bell, Jill K. Hacker, Carl Hanson, Debra A. Wadford, Carlos Anaya, Donna Ferguson, Phillip A. Frankino, Haridha Shivram, Liana F. Lareau, Stacia K. Wyman, Melanie Ott^*, Raul Andino^*, Charles Y. Chiu^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

347 Citations (Scopus)

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. © 2021 Elsevier Inc.

Original language	English
Article number	e8
Pages (from-to)	3426-3437
Journal	Cell
Volume	184
Issue number	13
Online published	20 Apr 2021
DOIs	https://doi.org/10.1016/j.cell.2021.04.025
Publication status	Published - 24 Jun 2021
Externally published	Yes

Research Keywords

20C/L452R
antibody neutralization
B.1.427/B.1.429
COVID-19
genomic epidemiology
L452R mutation
molecular dating
pseudovirus infectivity studies
SARS-CoV-2
spike protein
variant of concern
viral whole-genome sequencing

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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., ... Chiu, C. Y. (2021). Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant. Cell, 184(13), 3426-3437. Article e8. https://doi.org/10.1016/j.cell.2021.04.025

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title = "Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant",

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. {\textcopyright} 2021 Elsevier Inc.",

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author = "Xianding Deng and Garcia-Knight, {Miguel A.} and Khalid, {Mir M.} and Venice Servellita and Candace Wang and Morris, {Mary Kate} and Alicia Sotomayor-Gonz{\'a}lez and Glasner, {Dustin R.} and Reyes, {Kevin R.} and Gliwa, {Amelia S.} and Reddy, {Nikitha P.} and {Sanchez San Martin}, Claudia and Scot Federman and Jing Cheng and Joanna Balcerek and Jordan Taylor and Streithorst, {Jessica A.} and Steve Miller and Bharath Sreekumar and Pei-Yi Chen and Ursula Schulze-Gahmen and Taha, {Taha Y.} and Hayashi, {Jennifer M.} and Simoneau, {Camille R.} and Kumar, {G. Renuka} and Sarah McMahon and Lidsky, {Peter V.} and Yinghong Xiao and Peera Hemarajata and Green, {Nicole M.} and Alex Espinosa and Chantha Kath and Monica Haw and John Bell and Hacker, {Jill K.} and Carl Hanson and Wadford, {Debra A.} and Carlos Anaya and Donna Ferguson and Frankino, {Phillip A.} and Haridha Shivram and Lareau, {Liana F.} and Wyman, {Stacia K.} and Melanie Ott and Raul Andino and Chiu, {Charles Y.}",

year = "2021",

month = jun,

day = "24",

doi = "10.1016/j.cell.2021.04.025",

language = "English",

volume = "184",

pages = "3426--3437",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "13",

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Deng, X, Garcia-Knight, MA, Khalid, MM, Servellita, V, Wang, C, Morris, MK, Sotomayor-González, A, Glasner, DR, Reyes, KR, Gliwa, AS, Reddy, NP, Sanchez San Martin, C, Federman, S, Cheng, J, Balcerek, J, Taylor, J, Streithorst, JA, Miller, S, Sreekumar, B, Chen, P-Y, Schulze-Gahmen, U, Taha, TY, Hayashi, JM, Simoneau, CR, Kumar, GR, McMahon, S, Lidsky, PV, Xiao, Y, Hemarajata, P, Green, NM, Espinosa, A, Kath, C, Haw, M, Bell, J, Hacker, JK, Hanson, C, Wadford, DA, Anaya, C, Ferguson, D, Frankino, PA, Shivram, H, Lareau, LF, Wyman, SK, Ott, M, Andino, R & Chiu, CY 2021, 'Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant', Cell, vol. 184, no. 13, e8, pp. 3426-3437. https://doi.org/10.1016/j.cell.2021.04.025

TY - JOUR

T1 - Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

AU - Deng, Xianding

AU - Garcia-Knight, Miguel A.

AU - Khalid, Mir M.

AU - Servellita, Venice

AU - Wang, Candace

AU - Morris, Mary Kate

AU - Sotomayor-González, Alicia

AU - Glasner, Dustin R.

AU - Reyes, Kevin R.

AU - Gliwa, Amelia S.

AU - Reddy, Nikitha P.

AU - Sanchez San Martin, Claudia

AU - Federman, Scot

AU - Cheng, Jing

AU - Balcerek, Joanna

AU - Taylor, Jordan

AU - Streithorst, Jessica A.

AU - Miller, Steve

AU - Sreekumar, Bharath

AU - Chen, Pei-Yi

AU - Schulze-Gahmen, Ursula

AU - Taha, Taha Y.

AU - Hayashi, Jennifer M.

AU - Simoneau, Camille R.

AU - Kumar, G. Renuka

AU - McMahon, Sarah

AU - Lidsky, Peter V.

AU - Xiao, Yinghong

AU - Hemarajata, Peera

AU - Green, Nicole M.

AU - Espinosa, Alex

AU - Kath, Chantha

AU - Haw, Monica

AU - Bell, John

AU - Hacker, Jill K.

AU - Hanson, Carl

AU - Wadford, Debra A.

AU - Anaya, Carlos

AU - Ferguson, Donna

AU - Frankino, Phillip A.

AU - Shivram, Haridha

AU - Lareau, Liana F.

AU - Wyman, Stacia K.

AU - Ott, Melanie

AU - Andino, Raul

AU - Chiu, Charles Y.

PY - 2021/6/24

Y1 - 2021/6/24

N2 - 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. © 2021 Elsevier Inc.

AB - 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. © 2021 Elsevier Inc.

KW - 20C/L452R

KW - antibody neutralization

KW - B.1.427/B.1.429

KW - COVID-19

KW - genomic epidemiology

KW - L452R mutation

KW - molecular dating

KW - pseudovirus infectivity studies

KW - SARS-CoV-2

KW - spike protein

KW - variant of concern

KW - viral whole-genome sequencing

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85105784011&origin=recordpage

U2 - 10.1016/j.cell.2021.04.025

DO - 10.1016/j.cell.2021.04.025

M3 - RGC 21 - Publication in refereed journal

C2 - 33991487

SN - 0092-8674

VL - 184

SP - 3426

EP - 3437

JO - Cell

JF - Cell

IS - 13

M1 - e8

ER -

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Abstract

Research Keywords

UN SDGs

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