title: Norovirus vaccine against experimental human GII.4 virus illness: a challenge study in healthy adults.
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.
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio.
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.affiliation: Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: G Marshall
authors.initials: GM
authors.lastname: Lyon
authors.affiliation: University of Rochester Medical Center, New York.
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.affiliation: University of Maryland School of Medicine, Baltimore.
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio.
authors.forename: Xi
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Centers for Disease Control and Prevention.
authors.forename: Jan
authors.initials: J
authors.lastname: Vinjé
authors.affiliation: Centers for Disease Control and Prevention.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gregoricus
authors.affiliation: Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Ohio.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Frenck
authors.affiliation: Emory University Rollins School of Public Health, Atlanta, Georgia.
authors.forename: Christine L
authors.initials: CL
authors.lastname: Moe
authors.affiliation: Shin Nippon Biomedical Laboratories, Baltimore.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Al-Ibrahim
authors.affiliation: The EMMES Corp, Rockville, Maryland.
authors.forename: Jill
authors.initials: J
authors.lastname: Barrett
authors.affiliation: The EMMES Corp, Rockville, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.affiliation: Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas.
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
authors.affiliation: Takeda Vaccines Inc, Deerfield, Illinois.
authors.forename: Robert
authors.initials: R
authors.lastname: Goodwin
authors.affiliation: Takeda Pharmaceuticals International, Zurich, Switzerland.
authors.forename: Astrid
authors.initials: A
authors.lastname: Borkowski
authors.affiliation: Takeda Pharmaceuticals International, Zurich, Switzerland.
authors.forename: Ralf
authors.initials: R
authors.lastname: Clemens
authors.affiliation: Takeda Vaccines Inc, Deerfield, Illinois.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mendelman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D017250:Caliciviridae Infections / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005759:Gastroenteritis / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000276:immunology*; D014611:Vaccination; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D008050:Lipid A; D014765:Viral Vaccines; C048436:monophosphoryl lipid A
keywords: acute gastroenteritis; challenge; norovirus; vaccine