Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial

J Infect Dis. 2016 Sep 15;214(6):845-53. doi: 10.1093/infdis/jiw259. Epub 2016 Jun 28.


Background: Noroviruses pose a significant public health risk, particularly in very young individuals, older adults, and individuals with underlying conditions. We assessed 2 bivalent norovirus virus-like particle (VLP) vaccine candidate formulations in healthy adults aged 18-49 years.

Methods: Enrolled subjects (n = 454) randomly assigned among 3 groups received intramuscular placebo (saline) or vaccines containing either 15 µg or 50 µg of GI.1 VLP and 50 µg GII.4 VLP (15/50 and 50/50 formulations) adjuvanted with monophosphoryl lipid A and Al(OH)3 We present safety and immunogenicity assessments up to 28 days after vaccination.

Results: No vaccine-related serious adverse events or adverse events of special interest were reported. Reactions were mainly mild to moderate, the most frequent being transient pain, in 8%, 64%, and 73% of placebo, 15/50, and 50/50 groups, respectively; transient myalgia, headache, and fatigue were the commonest systemic adverse events. Subjects assessed per protocol (n = 442) displayed rapid immune responses to vaccination, peaking by days 7-10 and persisting through day 28. GI.1 responses were highest with the 50/50 formulation, but GII.4 responses were higher with the 15/50 formulation.

Conclusions: Both candidate VLP vaccines were well tolerated and elicited robust immune responses by 7-10 days that persisted through day 28. The 15/50 formulation displayed the best balance of tolerability and immunogenicity.

Clinical trials registration: NCT02142504.

Keywords: immunogenicity; norovirus; safety; tolerability; vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Adolescent
  • Adult
  • Antibodies, Viral / blood
  • Caliciviridae Infections / prevention & control*
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Healthy Volunteers
  • Humans
  • Immunoglobulin A / blood
  • Injections, Intramuscular
  • Male
  • Middle Aged
  • Norovirus / immunology*
  • Placebos / administration & dosage
  • Time Factors
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / adverse effects
  • Vaccines, Virus-Like Particle / immunology*
  • Virion
  • Young Adult


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin A
  • Placebos
  • Vaccines, Virus-Like Particle

Associated data

  • ClinicalTrials.gov/NCT02142504