Prevailing Sydney like Norovirus GII.4 VLPs induce systemic and mucosal immune responses in mice

Mol Immunol. 2015 Dec;68(2 Pt A):367-72. doi: 10.1016/j.molimm.2015.09.006. Epub 2015 Sep 12.

Abstract

The newly emerged Norovirus (NoV) Sydney 2012 strain has been sweeping all over the world, causing acute non-bacterial gastroenteritis in adults and children. Due to a lack of cell culture system, virus like particles (VLPs) has been assembled and used as vaccine candidates in preclinical and clinical studies. Expression of the major capsid protein of NoVs using recombinant baculovirus expression system in Sf9 cells leads to formation of VLPs that are morphologically and antigenically similar to true virions. In this study, VLPs were successfully produced using the VP1 of Sydney-2012-like strain and its immunogenicity was evaluated by different routes and its capability in inducing mucosal immune responses in the presence and absence of adjuvants in BALB/c mice. Administration of NoV VLPs in the presence of Al(OH)3 or monophosphoryl lipid A (MPL-A) led to high titers of VLP-specific IgG antibodies. Administration of VLPs orally in the presence of cholera toxin subunit B (CTB) didn't enhance mucosal immune response as less fecal IgA positive mice were observed when compared with those given VLPs only. Our study represents the first immunogenicity study of VLPs derived from current pandemic Sydney 2012 strain and which might have implications in the development of NoVs vaccine in china.

Keywords: Adjuvants; Immune response; Norovirus; Sydney-2012-like strain.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Alum Compounds / administration & dosage
  • Animals
  • Antibodies, Viral / biosynthesis*
  • Baculoviridae / genetics
  • Caliciviridae Infections / immunology
  • Caliciviridae Infections / prevention & control*
  • Caliciviridae Infections / virology
  • Cholera Toxin / administration & dosage
  • Female
  • Gene Expression
  • Humans
  • Immunity, Mucosal / drug effects*
  • Immunization
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives
  • Mice
  • Mice, Inbred BALB C
  • Norovirus / genetics
  • Norovirus / immunology*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Sf9 Cells
  • Spodoptera
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / genetics
  • Viral Vaccines / immunology*
  • Virion / chemistry
  • Virion / genetics
  • Virion / immunology

Substances

  • Adjuvants, Immunologic
  • Alum Compounds
  • Antibodies, Viral
  • Lipid A
  • Recombinant Proteins
  • Vaccines, Virus-Like Particle
  • Viral Vaccines
  • aluminum sulfate
  • Cholera Toxin
  • monophosphoryl lipid A