{
  "abstract": "Background Plasmablast-derived HBV surface antigen (HBsAg)-specific monoclonal antibody (mAb) and structural basis for binding to native HBsAg are poorly known.Objective We aimed to identify plasmablast-derived HBsAg-specific mAbs, evaluate their antiviral activities and resolve their structure for binding to native HBsAg.Design A previously vaccinated volunteer was enrolled in this study, who was boosted with a dose of recombinant hepatitis B vaccine and donated the blood sample. Activated plasmablasts were sorted from fresh peripheral blood mononuclear cells and mAbs were expressed. Their gene features, cross-genotypic binding activities and antiviral functions in vitro and in vivo were comprehensively analysed. The cryo-electron microscopy (cryo-EM) was used to determine the structure of representative mAb bound to the native HBsAg.Results In this study, we cloned a series of HBsAg-specific mAbs directly from clonally expanded plasmablasts from a vaccinated individual. Most of the mAbs displayed cross-reactivities of binding to different genotype HBsAg proteins and antiviral functions such as neutralisation and antibody-dependent cellular phagocytosis. These human anti-HBsAg mAbs, especially SY-4-class and SY-23-class, could be good candidates for antibody drugs. The cryo-EM structure of SY-23 bound to the dimeric HBsAg was determined, revealing its binding mechanism and unprecedented structural detail of the major antigenic loop (AGL) of HBsAg.Conclusion Overall, our work has uncovered the diverse gene features and varied anti-HBV activities of plasmablast-derived mAbs, providing a series of antibody drug candidates and the long-sought-after atomic model of AGL has paved the way for a wholistic characterisation of the AGL’s dynamic conformation during HBV infection and immune response.",
  "authors": [
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China",
        "Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong, China"
      ],
      "name": "Bin Ju"
    },
    {
      "affiliations": [
        "Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Zhouqing Liu"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Hu Yan"
    },
    {
      "affiliations": [
        "Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Yong Liu"
    },
    {
      "affiliations": [
        "State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, Hubei, China"
      ],
      "name": "Lu Zhang"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Xiangyang Ge"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Xin Wang"
    },
    {
      "affiliations": [
        "Cryo-EM Center, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Zhu Si"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Bing Zhou"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Qing Fan"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Miao Wang"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Yuxiao Li"
    },
    {
      "affiliations": [
        "Shenzhen Kangtai Biological Products, Shenzhen, Guangdong, China"
      ],
      "name": "Wenlong Lai"
    },
    {
      "affiliations": [
        "Shenzhen Kangtai Biological Products, Shenzhen, Guangdong, China"
      ],
      "name": "Jianhui Gan"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Haiyan Wang"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Juanjuan Zhao"
    },
    {
      "affiliations": [
        "State Key Laboratory of Virology and Biosafety, Hubei Provincial Research Center for Basic Biological Sciences, Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Center for Life and Medical Sciences, TaiKang Medical School, Wuhan University, Wuhan, Hubei, China"
      ],
      "name": "Yuchen Xia"
    },
    {
      "affiliations": [
        "Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China",
        "Institute for Biological Electron Microscopy, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Maofu Liao"
    },
    {
      "affiliations": [
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Department of Biochemistry, the Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China",
        "Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong, China",
        "Shenzhen Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Shenzhen, Guangdong, China"
      ],
      "name": "Zheng Zhang"
    }
  ],
  "title": "Characterisation of plasmablast-derived HBsAg-specific antibody and its structural basis for binding to native HBsAg dimer",
  "uid": "0638fa62-8e3f-5e9c-8ad7-5235be7fda1a"
}