In vivo evaluation of new adjuvant systems based on combination of Salmonella Typhi porins with particulate systems: Liposomes versus polymeric particles

Int J Pharm. 2023 Dec 15:648:123568. doi: 10.1016/j.ijpharm.2023.123568. Epub 2023 Nov 2.

Abstract

Subunit vaccines that have weak immunogenic activity require adjuvant systems for enhancedcellular and long-acting humoral immune responses. Both lipid-based and polymeric-based particulate adjuvants have been widely investigated to induce the desired immune responses against the subunit vaccines. The adjuvant efficacy of these particulate adjuvants depends upon their physicochemical properties such as particle size, surface charge, shape and their composition. Previously, we showed in vitro effect of adjuvant systems based on combination of chitosan and Salmonella Typhi porins in microparticle or nanoparticle form, which were spherical with positive surface charge. In the present study, we have further developed an adjuvant system based on combination of porins with liposomes (cationic and neutral) and investigated the adjuvant effect of both the liposomal and polymeric systems in BALB/c mice using a model antigen, ovalbumin. Humoral immune responses were determined following priming and booster dose at 15-day intervals. In overall, IgM and IgG levels were induced in the presence of both the liposomal and polymeric adjuvant systems indicating the positive impact of combination with porins. The highest IgM levels were obtained on Day 8, and liposomal adjuvant systems were found to elicit significantly higher IgM levels compared to polymeric systems. IgG levels were increased significantly after booster, particularly more profound with the micro-sized polymeric system when compared to cationic liposomal system with nano-size. Our results demonstrated that the developed particulate systems are promising both as an adjuvant and delivery system, providing enhanced immune responses against subunit antigens, and have the potential for long-term protection.

Keywords: Chitosan; Liposomes; Microparticles; Nanoparticles; Porins; Vaccine adjuvant system.

MeSH terms

  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Pharmaceutic
  • Animals
  • Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Liposomes* / chemistry
  • Mice
  • Porins
  • Salmonella typhi*
  • Vaccines, Subunit

Substances

  • Liposomes
  • Porins
  • Adjuvants, Immunologic
  • Adjuvants, Pharmaceutic
  • Antigens
  • Vaccines, Subunit
  • Immunoglobulin G
  • Immunoglobulin M