Biodistribution and Adjuvant Effect of an Intranasal Vaccine Based on Chitosan Nanoparticles against Paracoccidioidomycosis.

ABSTRACT

Paracoccidioidomycosis (PCM) is a fungal infection caused by the thermodimorphic Paracoccidioides sp. PCM mainly affects the lungs, but, if it is not contained by the immune response, the disease can spread systemically. An immune response derived predominantly from Th1 and Th17 T cell subsets facilitates the elimination of Paracoccidioides cells. In the present work, we evaluated the biodistribution of a prototype vaccine based on the immunodominant and protective P. brasiliensis P10 peptide within chitosan nanoparticles in BALB/c mice infected with P. brasiliensis strain 18 (Pb18). The generated fluorescent (FITC or Cy5.5) or non-fluorescent chitosan nanoparticles ranged in diameter from 230 to 350 nm, and both displayed a Z potential of +20 mV. Most chitosan nanoparticles were found in the upper airway, with smaller amounts localized in the trachea and lungs. The nanoparticles complexed or associated with the P10 peptide were able to reduce the fungal load, and the use of the chitosan nanoparticles reduced the necessary number of doses to achieve fungal reduction. Both vaccines were able to induce a Th1 and Th17 immune response. These data demonstrates that the chitosan P10 nanoparticles are an excellent candidate vaccine for the treatment of PCM.