Preclinical dose-ranging studies of a novel dry powder norovirus vaccine formulation

Vaccine. 2016 Mar 14;34(12):1452-8. doi: 10.1016/j.vaccine.2016.01.064. Epub 2016 Feb 10.


Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVac™) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose-dependent manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVac™ formulation, a total antigen dose of ≥ 15 μg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLPs based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimulatory adjuvant and provide a basis for the development of a GelVac™ bivalent GI/GII.4 norovirus VLP vaccine.

Keywords: Guinea Pigs; Intranasal; Norovirus; Vaccine; Virus-like Particles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • Dose-Response Relationship, Immunologic
  • Female
  • Guinea Pigs
  • Immunity, Mucosal*
  • Immunoglobulin G / blood
  • Neutralization Tests
  • Norovirus*
  • Powders*
  • Random Allocation
  • Vaccination / methods*
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / chemistry
  • Vaccines, Virus-Like Particle / immunology
  • Viral Vaccines / administration & dosage*
  • Viral Vaccines / chemistry*
  • Viral Vaccines / immunology


  • Antibodies, Viral
  • Immunoglobulin G
  • Powders
  • Vaccines, Virus-Like Particle
  • Viral Vaccines