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

SARS-CoV-2 刺突蛋白 L452R 变异株的传播、传染性和中和作用

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作者: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

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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