title: Frequent Use of the IgA Isotype in Human B Cells Encoding Potent Norovirus-Specific Monoclonal Antibodies That Block HBGA Binding.
abstract: Noroviruses (NoV) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. Despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. Recent studies have shown an association of protection with NoV-specific serum histo-blood group antigen-blocking antibody and with serum IgA in patients vaccinated with NoV VLPs. Here, we describe the isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors.
authors.affiliation: Department of Pediatrics, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.|Vanderbilt Vaccine Center, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Gopal
authors.initials: G
authors.lastname: Sapparapu
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Rita
authors.initials: R
authors.lastname: Czakó
authors.affiliation: Department of Pathology, Microbiology and Immunology, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Alvarado
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Sreejesh
authors.initials: S
authors.lastname: Shanker
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.|Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: B V Venkataram
authors.initials: BV
authors.lastname: Prasad
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.|Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.|Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.affiliation: Department of Pediatrics, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.|Vanderbilt Vaccine Center, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.|Department of Pathology, Microbiology and Immunology, Vanderbilt Medical Center, Nashville, Tennessee, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001789:Blood Group Antigens / Q000276:immunology*; D015153:Blotting, Western; D017250:Caliciviridae Infections / Q000276:immunology*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D005759:Gastroenteritis / Q000276:immunology; D006801:Humans; D006825:Hybridomas; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D009663:Norwalk virus / Q000276:immunology; D016133:Polymerase Chain Reaction
chemical_list: D000911:Antibodies, Monoclonal; D001789:Blood Group Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G