title: A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults.
abstract: BACKGROUND
  Noroviruses are the most important viral causes of gastroenteritis-related morbidity and mortality. A randomized, double-blind, placebo-controlled study evaluated an adjuvanted bivalent intramuscular norovirus virus-like particle (VLP) vaccine.
  
  
  METHODS
  Forty-eight adults aged 18-49 years received either 2 doses containing genotype GI.1 VLP and a consensus GII.4 VLP or 2 doses of placebo. Doses (5 µg, 15 µg, 50 µg, or 150 µg of each VLP) were administered 4 weeks apart in the first stage. Subsequently, 54 adults, aged 18-49 (n=16), 50-64 (n=19), and 65-85 (n=19) years, received 2 doses of vaccine containing 50 µg of each VLP. Total and class-specific antibody responses, as well as histoblood group antigen (HBGA) blocking antibody responses, were measured before and after each dose.
  
  
  RESULTS
  Local reactions were mainly injection site pain/tenderness, with no reported fever or vaccine-related serious adverse events. One dose of vaccine containing 50 µg of each VLP increased GI.1 geometric mean titers (GMTs) by 118-fold, 83-fold, and 24-fold and increased GII.4 GMTs by 49-fold, 25-fold, and 9-fold in subjects aged 18-49, 50-64, and 65-83 years, respectively. Serum antibody responses peaked at day 7 after the first dose, with no evidence of boosting following a second dose. Most subjects achieved HBGA-blocking antibody titers of ≥200.
  
  
  CONCLUSIONS
  The vaccine was well tolerated and immunogenic. Rapid immune response to a single dose may be particularly useful in military personnel and travelers and in the control of outbreaks. Clinical Trials Registration. NCT01168401.
authors.affiliation: University of Rochester Medical Center, New York.
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Saint Louis University, School of Medicine, St. Louis, Missouri.
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.affiliation: Naval Medical Research Center, Silver Springs.
authors.forename: Robert
authors.initials: R
authors.lastname: Gormley
authors.affiliation: University of Maryland School of Medicine, Baltimore.
authors.forename: Wilbur H
authors.initials: WH
authors.lastname: Chen
authors.affiliation: EMMES, Rockville, Maryland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ferreira
authors.affiliation: Takeda Vaccines, Bozeman, Montana.
authors.forename: Robert
authors.initials: R
authors.lastname: Goodwin
authors.affiliation: Takeda Vaccines, Zurich, Switzerland.
authors.forename: Astrid
authors.initials: A
authors.lastname: Borkowski
authors.affiliation: Takeda Vaccines, Zurich, Switzerland.
authors.forename: Ralf
authors.initials: R
authors.lastname: Clemens
authors.affiliation: Takeda Vaccines, Bozeman, Montana.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mendelman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D017250:Caliciviridae Infections / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D005759:Gastroenteritis / Q000517:prevention & control*; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines
keywords: gastroenteritis; norovirus; vaccine; virus-like particle