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

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
• nano-sized adjuvant
• S. aureus-mediated infections
• thermosetting polymeric solution
• in vivo immunisation
• nasal vaccination

Acknowledgements

We would like to thank Prof. M. Biggiogera, “Lazzaro Spallanzani” Department of Biology and Biotechnology, University of Pavia (Italy), for producing Transmission Electron Microscopy images.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

Additional information

Funding

This work was partially supported by Fondazione CARIPLO [Grant Vaccines 2009–3546] to prof. Pietro Speziale.