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.
Highlights
Norwalk virus, the prototype of human noroviruses (NoVs), was the first virus identified in 1972 as a causative agent for acute gastroenteritis [1]
We sought to isolate blocking monoclonal IgA antibodies (mAbs) to the NoV capsid protein from volunteers challenged with Norwalk virus (NV)
peripheral blood mononuclear cell (PBMC) isolated from two NV-immune donors were transformed with EBV, and the lymphoblastoid cell lines (LCLs) supernatants were screened for binding to NV virus-like particles (VLP) and separately for blocking of binding to H3-PAA glycan
Summary
The prototype of human noroviruses (NoVs), was the first virus identified in 1972 as a causative agent for acute gastroenteritis [1]. VP1 is a major capsid ~60 kDa protein and can self-assemble into virus-like particles (VLP) that resemble native virions both morphologically and antigenically [4]. Human susceptibility to NoVs depends on the expression of histo-blood group antigens (HBGAs) on the intestinal epithelial cells [6,7,8]. These blood group carbohydrates are thought to play a role as receptors or co-receptors based on recent studies of correlations between susceptibility, HBGA profile and secretor status (expression of secretor enzyme α1,2 fucosyltransferase) [2,9,10]
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