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

Xianding Deng, M. Garcia-Knight, M. Khalid, V. Servellita, Candace Wang, M. Morris, Alicia Sotomayor-González, Dustin R. Glasner, Kevin R Reyes, Amelia S. Gliwa, N. P. Reddy, Claudia Sanchez San Martin, S. Federman, Jing Cheng, J. Balcerek, Jordan Taylor, Jessica A. Streithorst, Steve Miller, G. R. Kumar, B. Sreekumar, Pei-Yi Chen, U. Schulze-Gahmen, Taha Y. Taha, Jennifer M. Hayashi, C. Simoneau, Sarah McMahon, Peter V. Lidsky, Yinghong Xiao, P. Hemarajata, N. Green, A. Espinosa, Chantha Kath, M. Haw, J. Bell, J. Hacker, C. Hanson, D. Wadford, C. Anaya, D. Ferguson, L. F. Lareau, Phillip A. Frankino, Haridha Shivram, S. Wyman, M. Ott, R. Andino, C. Chiu

medRxiv, 2021

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 remnant nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 or 20C/L452R, 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 estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. This variant is characterized by three mutations in the spike protein, including a L452R substitution in the receptor-binding domain. 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 SARS-CoV-2 variants of concern (B.1.1.7, B.1.351, and P.1 lineages). 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.

Cited by 78 publications.

Field of study: Medicine

10.1101/2021.03.07.21252647