The Norwalk, Snow Mountain (SMA), and Hawaii agents are etiologically associated with separate outbreaks of acute viral gastroenteritis. Previous cross-challenge of volunteers, immune electron microscopy, and/or enzyme-immunoassay analysis suggested that these agents are antigenically distinct. We examined paired sera from human volunteers challenged with these agents for the presence of homologous and heterologous serum antibody titer rises to the agents. Two-way cross-reactions occurred between Hawaii agent and SMA. A one-way cross-reaction occurred between Norwalk agent and SMA, as volunteers challenged with Norwalk agent had heterologous serum antibody titer rises to SMA, but the reverse did not occur. The Norwalk and Hawaii agents had minimal cross-reaction, with only one volunteer challenged with Hawaii agents having a heterologous rise to Norwalk agent. These observations indicate varying degrees of antigenic relatedness among these agents.
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