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SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern.
Science. 2021 08 06; 373(6555):648-654.Sci

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Vir Biotechnology, San Francisco, CA 94158, USA.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Vir Biotechnology, San Francisco, CA 94158, USA.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Vir Biotechnology, San Francisco, CA 94158, USA.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.Independent physician, 6828 Balerna, Switzerland.Clinical Research Unit, Clinica Luganese Moncucco, 6900 Lugano, Switzerland.Clinical Research Unit, Clinica Luganese Moncucco, 6900 Lugano, Switzerland.Clinic of Internal Medicine and Infectious Diseases, Clinica Luganese Moncucco, 6900 Lugano, Switzerland.Center for Emerging and Re-emerging Infectious Diseases, Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.Vir Biotechnology, San Francisco, CA 94158, USA.Vir Biotechnology, San Francisco, CA 94158, USA.Vir Biotechnology, San Francisco, CA 94158, USA.Vir Biotechnology, San Francisco, CA 94158, USA.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland. lpiccoli@vir.bio dcorti@vir.bio dveesler@uw.edu.Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland. lpiccoli@vir.bio dcorti@vir.bio dveesler@uw.edu.Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. lpiccoli@vir.bio dcorti@vir.bio dveesler@uw.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34210893

Citation

McCallum, Matthew, et al. "SARS-CoV-2 Immune Evasion By the B.1.427/B.1.429 Variant of Concern." Science (New York, N.Y.), vol. 373, no. 6555, 2021, pp. 648-654.
McCallum M, Bassi J, De Marco A, et al. SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science. 2021;373(6555):648-654.
McCallum, M., Bassi, J., De Marco, A., Chen, A., Walls, A. C., Di Iulio, J., Tortorici, M. A., Navarro, M. J., Silacci-Fregni, C., Saliba, C., Sprouse, K. R., Agostini, M., Pinto, D., Culap, K., Bianchi, S., Jaconi, S., Cameroni, E., Bowen, J. E., Tilles, S. W., ... Veesler, D. (2021). SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. Science (New York, N.Y.), 373(6555), 648-654. https://doi.org/10.1126/science.abi7994
McCallum M, et al. SARS-CoV-2 Immune Evasion By the B.1.427/B.1.429 Variant of Concern. Science. 2021 08 6;373(6555):648-654. PubMed PMID: 34210893.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern. AU - McCallum,Matthew, AU - Bassi,Jessica, AU - De Marco,Anna, AU - Chen,Alex, AU - Walls,Alexandra C, AU - Di Iulio,Julia, AU - Tortorici,M Alejandra, AU - Navarro,Mary-Jane, AU - Silacci-Fregni,Chiara, AU - Saliba,Christian, AU - Sprouse,Kaitlin R, AU - Agostini,Maria, AU - Pinto,Dora, AU - Culap,Katja, AU - Bianchi,Siro, AU - Jaconi,Stefano, AU - Cameroni,Elisabetta, AU - Bowen,John E, AU - Tilles,Sasha W, AU - Pizzuto,Matteo Samuele, AU - Guastalla,Sonja Bernasconi, AU - Bona,Giovanni, AU - Pellanda,Alessandra Franzetti, AU - Garzoni,Christian, AU - Van Voorhis,Wesley C, AU - Rosen,Laura E, AU - Snell,Gyorgy, AU - Telenti,Amalio, AU - Virgin,Herbert W, AU - Piccoli,Luca, AU - Corti,Davide, AU - Veesler,David, Y1 - 2021/07/01/ PY - 2021/03/31/received PY - 2021/06/25/accepted PY - 2021/7/3/pubmed PY - 2021/8/14/medline PY - 2021/7/2/entrez SP - 648 EP - 654 JF - Science (New York, N.Y.) JO - Science VL - 373 IS - 6555 N2 - 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. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/34210893/SARS-CoV-2_immune_evasion_by_the_B.1.427/B.1.429_variant_of_concern. L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=34210893 DB - PRIME DP - Unbound Medicine ER -