Abstract

Background. Vaccines against norovirus, the leading cause of acute gastroenteritis, should protect against medically significant illness and reduce transmission. Methods. In this randomized, double-blind, placebo-controlled trial, 18- to 50-year-olds received 2 injections of placebo or norovirus GI.1/GII.4 bivalent vaccine-like particle (VLP) vaccine with 3-O-desacyl-4′-monophosphoryl lipid A (MPL) and alum. Participants were challenged as inpatients with GII.4 virus (4400 reverse transcription polymerase chain reaction [RT-PCR] units), and monitored for illness and infection. Results. Per protocol, 27 of 50 (54.0%) vaccinees and 30 of 48 (62.5%) controls were infected. Using predefined illness and infection definitions, vaccination did not meet the primary endpoint, but self-reported cases of severe (0% vaccinees vs 8.3% controls; P = .054), moderate or greater (6.0% vs 18.8%; P = .068), and mild or greater severity of vomiting and/or diarrhea (20.0% vs 37.5%; P = .074) were less frequent. Vaccination also reduced the modified Vesikari score from 7.3 to 4.5 (P = .002). Difficulties encountered were low norovirus disease rate, and inability to define illness by quantitative RT-PCR or further antibody rise in vaccinees due to high vaccine-induced titers. By day 10, 11 of 49 (22.4%) vaccinees were shedding virus compared with 17 of 47 (36.2%) placebo recipients (P = .179). Conclusions. Bivalent norovirus VLP vaccine reduced norovirus-related vomiting and/or diarrhea; field efficacy studies are planned. Clinical Trials Registration. NCT01609257.