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

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• SARS-CoV-2 entry relies on the spike (S) glycoprotein, with the receptor-binding domain (RBD) and N-terminal domain (NTD) as key antibody targets.
• The CAL.20C (B.1.427/B.1.429) variant, with mutations S13I, W152C, and L452R, poses a threat to existing immune responses.
• The impact of these mutations on neutralizing antibodies from infection or vaccination remains unclear.

Approach:

• Assessed neutralizing antibody responses using pseudoviruses expressing wildtype or B.1.427/B.1.429 spike proteins.
• Evaluated plasma from individuals with natural SARS-CoV-2 infection or mRNA vaccination.
• Tested the activity of RBD-specific and NTD-specific monoclonal antibodies (mAbs) against the variant.

Key Points:

• Neutralizing titers were reduced 3-6 fold against the B.1.427/B.1.429 variant compared to wildtype.
• The L452R mutation in the RBD impaired or abolished the activity of 14/35 RBD-specific mAbs.
• NTD-targeting mAbs lost neutralization activity due to structural rearrangements in the NTD antigenic supersite, influenced by the S13I mutation.

Conclusions:

• The CAL.20C variant exhibits significant immune evasion capabilities due to mutations in its spike protein.
• Antibody responses generated by natural infection or mRNA vaccination are less effective against this variant.
• Monitoring signal peptide variants is crucial for understanding SARS-CoV-2 evolution and immune escape mechanisms.