Gene

Coronavirus

Molecular biology

Spike (software development)

Biology

Signal peptide

Spike Protein

Peptide

Virology

Receptor

Glycoprotein

Immunity

Mutation

Titer

Economics

Biochemistry

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Coronavirus disease 2019 (COVID-19)

Immunology

Genetics

Monoclonal antibody

Immune system

Management

Antigen

Evasion (ethics)

Infectious disease (medical specialty)

Medicine

Chemistry

Virus

Peptide sequence

Disease

Antibody

Neutralization

Pathology

Science

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or from convalescent individuals exhibited neutralizing titers that were reduced 2- to 3.5-fold against the B.1.427/B.1.429 variant relative to wild-type pseudoviruses. The L452R mutation reduced neutralizing activity in 14 of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 of 10 NTD-specific mAbs because the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and the formation of a new disulfide bond, as revealed by mass spectrometry and structural studies.

SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern