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Sci Adv. 2018 Sep 19;4(9):eaat7459. doi: 10.1126/sciadv.aat7459. eCollection 2018 Sep.

Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10.

Author information

1
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, School of Public Health, Xiamen University, Xiamen 361102, P.R. China.
2
California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
3
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Chemistry and Biochemistry and Division of Biological Sciences, University of California, San Diego, San Diego, CA 92093-0378, USA.

Abstract

Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has made therapeutic antibody identification a public health priority. By targeting a local isolate, CVA10-FJ-01, we obtained a potent antibody, 2G8, against all three capsid forms of CVA10. We show that 2G8 exhibited both 100% preventive and 100% therapeutic efficacy against CVA10 infection in mice. Comparisons of the near-atomic cryo-electron microscopy structures of the three forms of CVA10 capsid and their complexes with 2G8 Fab reveal that a single Fab binds a border region across the three capsid proteins (VP1 to VP3) and explain 2G8's remarkable cross-reactivities against all three capsid forms. The atomic structures of this first neutralizing antibody of CVA10 should inform strategies for designing vaccines and therapeutics against CVA10 infections.

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