Norovirus infection is the leading cause of acute nonbacterial gastroenteritis. Histoblood group antigens (HBGAs) are host susceptibility determinants for Norwalk virus (NV) infection. We hypothesized that antibodies that block NV-HBGA binding are associated with protection from clinical illness following NV exposure. We developed an HBGA blocking assay to examine the ability of human serum to block the interaction of NV viruslike particles with H type 1 and H type 3 glycans. Serum samples from persons who were experimentally challenged with NV were evaluated. There was a high correlation between the H type 1 and H type 3 synthetic glycan assays (r = 0.977; P < .001); the H type 1 assay had higher quantitative sensitivity (P < .001). Among 18 infected secretor-positive individuals, blocking titers peaked by day 28 after challenge and were higher for individuals who did not develop gastroenteritis than for those who developed gastroenteritis on days 0, 14, 28, and 180 (P < .05 for each). In addition, 6 of 6 subjects without gastroenteritis had measurable prechallenge blocking titers (>25), compared with 2 of 12 subjects with gastroenteritis (P = .002). Blocking antibodies correlate with protection against clinical NV gastroenteritis. This knowledge will help guide the evaluation of new vaccine strategies and the elucidation of the nature of immunity to the virus. Trial registration. ClinicalTrials.gov identifier: NCT00138476.
