Communications Biology (Dec 2023)
SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode
- Jule Goike,
- Ching-Lin Hsieh,
- Andrew P. Horton,
- Elizabeth C. Gardner,
- Ling Zhou,
- Foteini Bartzoka,
- Nianshuang Wang,
- Kamyab Javanmardi,
- Andrew Herbert,
- Shawn Abbassi,
- Xuping Xie,
- Hongjie Xia,
- Pei-Yong Shi,
- Rebecca Renberg,
- Thomas H. Segall-Shapiro,
- Cynthia I. Terrace,
- Wesley Wu,
- Raghav Shroff,
- Michelle Byrom,
- Andrew D. Ellington,
- Edward M. Marcotte,
- James M. Musser,
- Suresh V. Kuchipudi,
- Vivek Kapur,
- George Georgiou,
- Scott C. Weaver,
- John M. Dye,
- Daniel R. Boutz,
- Jason S. McLellan,
- Jimmy D. Gollihar
Affiliations
- Jule Goike
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Ching-Lin Hsieh
- Department of Molecular Biosciences, The University of Texas at Austin
- Andrew P. Horton
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Elizabeth C. Gardner
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Ling Zhou
- Department of Molecular Biosciences, The University of Texas at Austin
- Foteini Bartzoka
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Nianshuang Wang
- Department of Molecular Biosciences, The University of Texas at Austin
- Kamyab Javanmardi
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Andrew Herbert
- U.S. Army Medical Research Institute of Infectious Diseases
- Shawn Abbassi
- U.S. Army Medical Research Institute of Infectious Diseases
- Xuping Xie
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch
- Hongjie Xia
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch
- Pei-Yong Shi
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch
- Rebecca Renberg
- DEVCOM Army Research Laboratory, Biotechnology Branch
- Thomas H. Segall-Shapiro
- Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital
- Cynthia I. Terrace
- DEVCOM Army Research Laboratory-South
- Wesley Wu
- Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital
- Raghav Shroff
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Michelle Byrom
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Andrew D. Ellington
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Edward M. Marcotte
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- James M. Musser
- Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital
- Suresh V. Kuchipudi
- Department of Veterinary and Biomedical Science and Animal Diagnostic Laboratory, The Pennsylvania State University
- Vivek Kapur
- Department of Animal Science and the Huck Institutes of the Life Sciences, The Pennsylvania State University
- George Georgiou
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Scott C. Weaver
- University of Texas Medical Branch, World Reference Center for Emerging Viruses and Arboviruses
- John M. Dye
- U.S. Army Medical Research Institute of Infectious Diseases
- Daniel R. Boutz
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- Jason S. McLellan
- Department of Molecular Biosciences, The University of Texas at Austin
- Jimmy D. Gollihar
- Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin
- DOI
- https://doi.org/10.1038/s42003-023-05649-6
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 13
Abstract
Abstract The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.
