A novel intramuscular bivalent norovirus virus-like particle vaccine candidate--reactogenicity, safety, and immunogenicity in a phase 1 trial in healthy adults

J Infect Dis. 2014 Dec 1;210(11):1763-71. doi: 10.1093/infdis/jiu337. Epub 2014 Jun 20.


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.

Keywords: gastroenteritis; norovirus; vaccine; virus-like particle.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing / blood
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Caliciviridae Infections / prevention & control*
  • Female
  • Follow-Up Studies
  • Gastroenteritis / prevention & control*
  • Humans
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Norovirus / immunology*
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / adverse effects
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / adverse effects
  • Viral Vaccines / immunology*
  • Young Adult


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Vaccines, Virus-Like Particle
  • Viral Vaccines

Associated data

  • ClinicalTrials.gov/NCT01168401