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

Abstract

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.

Mutational escape from the polyclonal antibody response to SARS-CoV-2 infection is largely shaped by a single class of antibodies

“…These visualizations show that the arrangement of antibodies in the space of "viral escape" is indeed continuous, but that the class definitions based on structural analyses capture the high-level features of this arrangement since the structural footprint of an antibody largely determines which mutations most impact its binding. However, we suggest that in some cases, more Fortunately, no viral lineages currently combine these class 1 and 2 escape mutations with a class 3 escape mutation, although a moderate class 3 escape mutation (L452R) is present in the B.1.427/B.1.429 viral lineage that lacks other RBD escape mutations 3,49 . However, we suggest the appearance of a class 3 escape mutation on the background of a lineage that already has class 1 and 2 escape mutations such as K417N/T and E484K would be a worrying development, and should be monitored closely.…”

“…In this respect, it is noteworthy that two of the most prominent emerging viral lineages have also acquired a mutation (K417N/T) at the site that most potently escapes binding by class 1 antibodies. Fortunately, no viral lineages currently combine these class 1 and 2 escape mutations with a class 3 escape mutation, although a moderate class 3 escape mutation (L452R) is present in the B.1.427/B.1.429 viral lineage that lacks other RBD escape mutations 3, 49 . However, we suggest the appearance of a class 3 escape mutation on the background of a lineage that already has class 1 and 2 escape mutations such as K417N/T and E484K would be a worrying development, and should be monitored closely.…”

Rapid characterization of spike variants via mammalian cell surface display

“…The B.1.1.7, B.1.351, and B.1.1.248 lineages share a common N501Y RBD mutation that likely confers greater transmissibility (70-80%) 26,61,62 . The B.1.427/B.1.429 variant also exhibits improved transmissibility (18.6-24%) relative to the parental strain 29 . Compensatory mutations offset the de-stabilizing effects of NTD and RBD mutations that partially escape NTD- and RBD-binding nAbs.…”

“…SARS-CoV-2 strains have exploded across the globe, raising the specter of updated vaccine formulations and new therapeutic strategies. Improved genomic surveillance is also uncovering emerging variants, such as B.1.427/B.1.429 (California) and B.1.526 (New York) 24,29,60,61 . Using spike display, we screened variants B.1.1.7 (UK), B.1.351 (S. Africa), B.1.1.248 (Brazil), and B.1.427/B.1.429 (CA), and their individual mutations (Fig.…”

Research Methodology to Define the Introduction of the SARS-CoV-2 B.1.429 Variant in Hawaii

“…The L452R substitution originating in North America did so in Los Angeles (EPI_ISL_1303471), and is considered a substitution of two variants of concern (B.1.427 and B.1.429). 12 The CDC notes that these variants correlate to ~ 20% increased transmissibility of SARS-CoV-2, 13 and has reduced neutralization using convalescent sera, vaccinated sera, and sera from patients treated with therapeutics. 12 The D614G substitution, near ubiquitous among all SARS-CoV-2 sequences, is noted for increasing the tness of SARS-CoV-2.…”