Glucan Particles Are a Powerful Adjuvant for the HBsAg, Favoring Antiviral Immunity

Mol Pharm. 2019 May 6;16(5):1971-1981. doi: 10.1021/acs.molpharmaceut.8b01322. Epub 2019 Apr 23.

Abstract

The lack of vaccine adjuvants that are able to induce robust T cell responses fosters the search for more powerful options. Pathogen-like particles are a promising approach. The adjuvant activity of pathogen-like particles is highly influenced by size and surface composition. This study aimed to evaluate the adjuvant potential of two different β-glucan-based particles, blend chitosan/β-glucan particles (ChiGluPs), which are positively charged and have mean size of 1276 nm, and neutral yeast-derived glucan particles (GPs), with a mean size of 3 μm. Additionally, chitosan particles (ChiPs) were used to understand the effect of β-glucan addition (ChiGluPs). Mouse spleen cells responded through the production of either TNF-α or RANTES, following in vitro stimulation with particles containing either β-glucan (ChiGluPs and GPs) or chitosan (ChiGluPs and ChiPs). Human monocytes responded to all particles through TNF-α secretion. Subcutaneous vaccination of mice with the hepatitis B surface antigen (HBsAg) showed increased serum IgG for all particles compared to HBsAg alone (435-, 4500-, or 2500-fold increase for either ChiPs, ChiGluPs, or GPs). Interestingly, only GPs elicited the secretion of HBsAg-specific Th1, Th2, Th9, Th17, Th22, and Treg-related cytokines. This study demonstrates, for the first time, that GPs can have a significant role against the hepatitis B virus by favoring antiviral immunity.

Keywords: chitosan; hepatitis B antigen; polymeric particles; vaccine adjuvants; β-glucan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Adjuvants, Pharmaceutic / chemistry
  • Adjuvants, Pharmaceutic / pharmacology*
  • Animals
  • Cell Survival
  • Chitosan / chemistry
  • Chitosan / pharmacology*
  • Cytokines / metabolism
  • Female
  • Healthy Volunteers
  • Hepatitis B / prevention & control
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / pharmacology*
  • Hepatitis B Vaccines / chemistry
  • Hepatitis B Vaccines / pharmacology*
  • Humans
  • Immunity, Cellular / immunology*
  • Immunoglobulin G / blood
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / metabolism
  • Particle Size
  • Saccharomyces cerevisiae / chemistry
  • Spleen / cytology
  • Spleen / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccination
  • beta-Glucans / chemistry
  • beta-Glucans / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Adjuvants, Pharmaceutic
  • Cytokines
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Immunoglobulin G
  • Tumor Necrosis Factor-alpha
  • beta-Glucans
  • Chitosan