CNA-loaded PLGA nanoparticles improve humoral response againstS. aureus-mediated infections in a mouse model: subcutaneous vs. nasal administration strategy

J Microencapsul. 2016 Dec;33(8):750-762. doi: 10.1080/02652048.2016.1260661. Epub 2016 Dec 12.

Abstract

The aim of this work was the assessment of the "in vivo" immune response of a poly(lactide-co-glycolide)-based nanoparticulate adjuvant for a sub-unit vaccine, namely, a purified recombinant collagen-binding bacterial adhesion fragment (CNA19), against Staphylococcus aureus-mediated infections. "In vivo" immunogenicity studies were performed on mice: immunisation protocols encompassed subcutaneous and intranasal administration of CNA19 formulated as nanoparticles (NPs) and furthermore, CNA19-loaded NPs formulated in a set-up thermosetting chitosan-β-glycerolphosphate (chitosan-β-GP) solution for intranasal route in order to extend antigen exposure to nasal mucosa. CNA19 loaded NPs (mean size of about 195 nm, 9.04 ± 0.37μg/mg as CNA19 loading capacity) confirmed as suitable vaccine for subcutaneous administration with a more pronounced adjuvant effect (about 3-fold higher) with respect to aluminium, recognised as "reference" adjuvant. CNA19 loaded NPs formulated in an optimised thermogelling chitosan-β-GP solution showed promising results for eliciting an effective humoral response and a good chance as intranasal boosting dose.

Keywords: PLGA nanoparticles; S. aureus-mediated infections; in vivo immunisation; nano-sized adjuvant; nasal vaccination; thermosetting polymeric solution.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use
  • Administration, Intranasal
  • Animals
  • Drug Carriers / chemistry*
  • Female
  • Immunity, Humoral
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Staphylococcal Infections / immunology
  • Staphylococcal Infections / prevention & control*
  • Staphylococcal Vaccines / administration & dosage*
  • Staphylococcal Vaccines / pharmacology
  • Staphylococcal Vaccines / therapeutic use
  • Staphylococcus aureus / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / pharmacology
  • Vaccines, Synthetic / therapeutic use

Substances

  • Adjuvants, Immunologic
  • Drug Carriers
  • Staphylococcal Vaccines
  • Vaccines, Synthetic
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid