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Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants.
Science. 2021 Aug 13; 373(6556)Sci

Abstract

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC50) 0.3 to 11.1 nanograms per milliliter; IC80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.

Authors+Show Affiliations

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa. SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Department of Epidemiology, UNC Chapel Hill School of Public Health, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. njsull@mail.nih.gov.Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34210892

Citation

Wang, Lingshu, et al. "Ultrapotent Antibodies Against Diverse and Highly Transmissible SARS-CoV-2 Variants." Science (New York, N.Y.), vol. 373, no. 6556, 2021.
Wang L, Zhou T, Zhang Y, et al. Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science. 2021;373(6556).
Wang, L., Zhou, T., Zhang, Y., Yang, E. S., Schramm, C. A., Shi, W., Pegu, A., Oloniniyi, O. K., Henry, A. R., Darko, S., Narpala, S. R., Hatcher, C., Martinez, D. R., Tsybovsky, Y., Phung, E., Abiona, O. M., Antia, A., Cale, E. M., Chang, L. A., ... Misasi, J. (2021). Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. Science (New York, N.Y.), 373(6556). https://doi.org/10.1126/science.abh1766
Wang L, et al. Ultrapotent Antibodies Against Diverse and Highly Transmissible SARS-CoV-2 Variants. Science. 2021 Aug 13;373(6556) PubMed PMID: 34210892.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants. AU - Wang,Lingshu, AU - Zhou,Tongqing, AU - Zhang,Yi, AU - Yang,Eun Sung, AU - Schramm,Chaim A, AU - Shi,Wei, AU - Pegu,Amarendra, AU - Oloniniyi,Olamide K, AU - Henry,Amy R, AU - Darko,Samuel, AU - Narpala,Sandeep R, AU - Hatcher,Christian, AU - Martinez,David R, AU - Tsybovsky,Yaroslav, AU - Phung,Emily, AU - Abiona,Olubukola M, AU - Antia,Avan, AU - Cale,Evan M, AU - Chang,Lauren A, AU - Choe,Misook, AU - Corbett,Kizzmekia S, AU - Davis,Rachel L, AU - DiPiazza,Anthony T, AU - Gordon,Ingelise J, AU - Hait,Sabrina Helmold, AU - Hermanus,Tandile, AU - Kgagudi,Prudence, AU - Laboune,Farida, AU - Leung,Kwanyee, AU - Liu,Tracy, AU - Mason,Rosemarie D, AU - Nazzari,Alexandra F, AU - Novik,Laura, AU - O'Connell,Sarah, AU - O'Dell,Sijy, AU - Olia,Adam S, AU - Schmidt,Stephen D, AU - Stephens,Tyler, AU - Stringham,Christopher D, AU - Talana,Chloe Adrienna, AU - Teng,I-Ting, AU - Wagner,Danielle A, AU - Widge,Alicia T, AU - Zhang,Baoshan, AU - Roederer,Mario, AU - Ledgerwood,Julie E, AU - Ruckwardt,Tracy J, AU - Gaudinski,Martin R, AU - Moore,Penny L, AU - Doria-Rose,Nicole A, AU - Baric,Ralph S, AU - Graham,Barney S, AU - McDermott,Adrian B, AU - Douek,Daniel C, AU - Kwong,Peter D, AU - Mascola,John R, AU - Sullivan,Nancy J, AU - Misasi,John, Y1 - 2021/07/01/ PY - 2021/02/20/received PY - 2021/06/28/accepted PY - 2021/7/3/pubmed PY - 2021/8/21/medline PY - 2021/7/2/entrez JF - Science (New York, N.Y.) JO - Science VL - 373 IS - 6556 N2 - The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC50) 0.3 to 11.1 nanograms per milliliter; IC80 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development. SN - 1095-9203 UR - https://www.unboundmedicine.com/medline/citation/34210892/Ultrapotent_antibodies_against_diverse_and_highly_transmissible_SARS-CoV-2_variants. L2 - https://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=34210892 DB - PRIME DP - Unbound Medicine ER -