Journal
SCIENCE
Volume 373, Issue 6555, Pages 648-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abi7994
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Funding
- National Institute of Allergy and Infectious Diseases [DP1AI158186, HHSN272201700059C, U01 AI151698-01]
- Pew Biomedical Scholars Award
- Burroughs Wellcome Fund
- Fast Grants
- Natural Sciences and Engineering Research Council of Canada
- Pasteur Institute
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The novel CAL.20C (B.1.427/B.1.429) variant carries spike protein mutations, resulting in reduced neutralizing titers in vaccinated individuals and convalescent individuals. The L452R mutation reduces neutralizing activity in RBD-specific monoclonal antibodies, while the S13I and W152C mutations lead to the total loss of neutralization in NTD-specific antibodies due to antigenic supersite remodeling.
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.
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