Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation

Xianding Deng(University of California, San Francisco), Miguel Garcia-Knight(University of California, San Francisco), Mir M. Khalid(Gladstone Institutes), Venice Servellita(University of California, San Francisco), Candace Wang(University of California, San Francisco), Mary Kate Morris(California Department of Public Health), Alicia Sotomayor-González(University of California, San Francisco), Dustin R. Glasner(University of California, San Francisco), Kevin Reyes(University of California, San Francisco), Amelia S. Gliwa(University of California, San Francisco), Nikitha P. Reddy(University of California, San Francisco), Claudia Sanchez San Martin(University of California, San Francisco), Scot Federman(University of California, San Francisco), Jing Cheng(University of California, San Francisco), Joanna Balcerek(University of California, San Francisco), Jordan E. Taylor(University of California, San Francisco), Jessica Streithorst(University of California, San Francisco), Steve Miller(University of California, San Francisco), G. Renuka Kumar(Gladstone Institutes), Bharath Sreekumar(Gladstone Institutes), Peiyi Chen(Gladstone Institutes), Ursula Schulze‐Gahmen(Gladstone Institutes), Taha Y. Taha(Gladstone Institutes), Jennifer M. Hayashi(Gladstone Institutes), Camille R. Simoneau(Gladstone Institutes), Sarah McMahon(Gladstone Institutes), Peter V. Lidsky(University of California, San Francisco), Yinghong Xiao(University of California, San Francisco), Peera Hemarajata(Los Angeles County Department of Public Health), Nicole M. Green(Los Angeles County Department of Public Health), Alex Espinosa(California Department of Public Health), Chantha Kath(California Department of Public Health), Monica Haw(California Department of Public Health), John Bell(California Department of Public Health), Jill K. Hacker(California Department of Public Health), Carl V. Hanson(California Department of Public Health), Debra A. Wadford(California Department of Public Health), Carlos Anaya(Monterey County Health Department), Donna Ferguson(Monterey County Health Department), Liana F. Lareau(Innovative Genomics Institute), Phillip A. Frankino(Innovative Genomics Institute), Haridha Shivram(Innovative Genomics Institute), Stacia K. Wyman(Innovative Genomics Institute), Mélanie Ott(Gladstone Institutes), Raul Andino(University of California, San Francisco), Charles Y. Chiu(University of California, San Francisco)
medRxiv
March 9, 2021
10.1101/2021.03.07.21252647
Cited by 247Open Access
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Abstract

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 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 found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 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 associated with decreased antibody neutralization warrants further investigation.

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