title: Rapid Responses to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: A Randomized Controlled Trial.
abstract: 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.
  
  
  BACKGROUND
  NCT02142504.
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.affiliation: Takeda Pharmaceuticals International, Zurich, Switzerland.
authors.forename: Frank
authors.initials: F
authors.lastname: Baehner
authors.affiliation: Takeda Pharmaceuticals International, Zurich, Switzerland.
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Cramer
authors.affiliation: Takeda Vaccines, Deerfield, Illinois.
authors.forename: Eric
authors.initials: E
authors.lastname: Song
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: Paul M
authors.initials: PM
authors.lastname: Mendelman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D017250:Caliciviridae Infections / Q000517:prevention & control*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D029322:Norovirus / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D013997:Time Factors; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014771:Virion; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007070:Immunoglobulin A; D010919:Placebos; D058425:Vaccines, Virus-Like Particle
keywords: immunogenicity; norovirus; safety; tolerability; vaccine