title: Experimental human infection with Norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity.
abstract: The human noroviruses (NoVs) are genetically diverse, rapidly evolving RNA viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.
authors.affiliation: Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Czakó
authors.affiliation: Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas, USA Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Antone R
authors.initials: AR
authors.lastname: Opekun
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gilger
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
authors.affiliation: Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, Texas, USA Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA Department of Medicine, Baylor College of Medicine, Houston, Texas, USA mestes@bcm.edu.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D017250:Caliciviridae Infections / Q000276:immunology* / Q000821:virology; D015331:Cohort Studies; D003429:Cross Reactions; D005838:Genotype; D006801:Humans; D009663:Norwalk virus / Q000145:classification / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral