title: Serum Immunoglobulin A Cross-Strain Blockade of Human Noroviruses.
abstract: Background.  Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods.  Immunoglobulin (Ig)A was purified from sera collected from GI.1-infected participants, and potential neutralization activity was measured using a surrogate neutralization assay based on antibody blockade of ligand binding. Human and mouse monoclonal antibodies (mAbs) were produced to multiple GI VLPs to characterize GI epitopes. Results.  Immunoglobulin A purified from day 14 post-GI.1 challenge sera blocked binding of GI.1, GI.3, and GI.4 to carbohydrate ligands. In some subjects, purified IgA preferentially blocked binding of other GI VLPs compared with GI.1, supporting observations that the immune response to GI.1 infection may be influenced by pre-exposure history. For other subjects, IgA equivalently blocked multiple GI VLPs. Only strain-specific mAbs recognized blockade epitopes, whereas strain cross-reactive mAbs recognized nonblockade epitopes. Conclusions.  These studies are the first to describe a functional role for serum IgA in norovirus immunity and the first to characterize human monoclonal antibodies to GI strains, expanding our understanding of norovirus immunobiology.
authors.affiliation: Department of Epidemiology , University of North Carolina , Chapel Hill.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Lindesmith
authors.affiliation: Institute for Research in Biomedicine , Bellinzona , Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Beltramello
authors.affiliation: Department of Epidemiology , University of North Carolina , Chapel Hill.
authors.forename: Jesica
authors.initials: J
authors.lastname: Swanstrom
authors.affiliation: Department of Epidemiology , University of North Carolina , Chapel Hill.
authors.forename: Taylor A
authors.initials: TA
authors.lastname: Jones
authors.affiliation: Institute for Research in Biomedicine , Bellinzona , Switzerland ; Humabs BioMed SA , Bellinzona , Switzerland.
authors.forename: Davide
authors.initials: D
authors.lastname: Corti
authors.affiliation: Institute for Research in Biomedicine , Bellinzona , Switzerland ; Institute of Microbiology , ETH Zurich , Switzerland.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzavecchia
authors.affiliation: Department of Epidemiology , University of North Carolina , Chapel Hill.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
keywords: BOB assay; IgA; Norwalk virus; blockade antibody; monoclonal antibody; neutralization; norovirus