Development of Glycyrrhizinic Acid-Based Lipid Nanoparticle (LNP-GA) as An Adjuvant That Improves the Immune Response to Porcine Epidemic Diarrhea Virus Spike Recombinant Protein

Viruses. 2024 Mar 11;16(3):431. doi: 10.3390/v16030431.

Abstract

Porcine epidemic diarrhea virus (PEDV) has affected the pork industry worldwide and during outbreaks the mortality of piglets has reached 100%. Lipid nanocarriers are commonly used in the development of immunostimulatory particles due to their biocompatibility and slow-release delivery properties. In this study, we developed a lipid nanoparticle (LNP) complex based on glycyrrhizinic acid (GA) and tested its efficacy as an adjuvant in mice immunized with the recombinant N-terminal domain (NTD) of porcine epidemic diarrhea virus (PEDV) spike (S) protein (rNTD-S). The dispersion stability analysis (Z-potential -27.6 mV) confirmed the size and charge stability of the LNP-GA, demonstrating that the particles were homogeneously dispersed and strongly anionic, which favors nanoparticles binding with the rNTD-S protein, which showed a slightly positive charge (2.11 mV) by in silico analysis. TEM image of LNP-GA revealed nanostructures with a spherical-bilayer lipid vesicle (~100 nm). The immunogenicity of the LNP-GA-rNTD-S complex induced an efficient humoral response 14 days after the first immunization (p < 0.05) as well as an influence on the cellular immune response by decreasing serum TNF-α and IL-1β concentrations, which was associated with an anti-inflammatory effect.

Keywords: immune response; lipid nanoparticle; porcine epidemic diarrhea virus; recombinant protein.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Viral
  • Coronavirus Infections*
  • Glycyrrhizic Acid / pharmacology
  • Immunity
  • Lipids
  • Liposomes*
  • Mice
  • Nanoparticles*
  • Porcine epidemic diarrhea virus* / genetics
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Swine
  • Swine Diseases*
  • Viral Vaccines*

Substances

  • Antibodies, Viral
  • Lipid Nanoparticles
  • Glycyrrhizic Acid
  • Spike Glycoprotein, Coronavirus
  • Adjuvants, Immunologic
  • Recombinant Proteins
  • Lipids
  • Viral Vaccines
  • Liposomes