title: Norovirus vaccine against experimental human Norwalk Virus illness.
abstract: BACKGROUND
  Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled, multicenter trial to assess the safety, immunogenicity, and efficacy of an investigational, intranasally delivered norovirus viruslike particle (VLP) vaccine (with chitosan and monophosphoryl lipid A as adjuvants) to prevent acute viral gastroenteritis after challenge with a homologous viral strain, Norwalk virus (genotype GI.1). Healthy adults 18 to 50 years of age received two doses of either vaccine or placebo and were subsequently inoculated with Norwalk virus and monitored for infection and gastroenteritis symptoms.
  
  
  RESULTS
  Ninety-eight persons were enrolled and randomly assigned to receive vaccine (50 participants) or placebo (48 participants), and 90 received both doses (47 participants in the vaccine group and 43 in the placebo group). The most commonly reported symptoms after vaccination were nasal stuffiness, nasal discharge, and sneezing. Adverse events occurred with similar frequency among vaccine and placebo recipients. A Norwalk virus-specific IgA seroresponse (defined as an increase by a factor of 4 in serum antibody levels) was detected in 70% of vaccine recipients. Seventy-seven of 84 participants inoculated with Norwalk virus were included in the per-protocol analysis. Vaccination significantly reduced the frequencies of Norwalk virus gastroenteritis (occurring in 69% of placebo recipients vs. 37% of vaccine recipients, P=0.006) and Norwalk virus infection (82% of placebo recipients vs. 61% of vaccine recipients, P=0.05).
  
  
  CONCLUSIONS
  This norovirus VLP vaccine provides protection against illness and infection after challenge with a homologous virus. (Funded by LigoCyte Pharmaceuticals and the National Institutes of Health; ClinicalTrials.gov number, NCT00973284.).
authors.affiliation: Baylor College of Medicine, Houston, TX 77030, USA. ratmar@bcm.edu
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.forename: David I
authors.initials: DI
authors.lastname: Bernstein
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Harro
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Al-Ibrahim
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ferreira
authors.forename: Mary K
authors.initials: MK
authors.lastname: Estes
authors.forename: David Y
authors.initials: DY
authors.lastname: Graham
authors.forename: Antone R
authors.initials: AR
authors.lastname: Opekun
authors.forename: Charles
authors.initials: C
authors.lastname: Richardson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mendelman
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D017250:Caliciviridae Infections / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005759:Gastroenteritis; D006801:Humans; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D014765:Viral Vaccines