Enhancing immunogenicity and reducing dose of microparticulated synthetic vaccines: single intradermal administration

Our purpose was to evaluate the ability of a polymeric vehicle to release a model synthetic vaccine to the skin in order to reach a potent activation of the specific immune response. The peptide-loaded poly-D,L-lactide-co-glycolide acid (PLGA) microparticles were prepared by a double emulsion technique and administered to Balb/c mice. The immune response (antibody and T cell activation) obtained by the intradermal (i.d.) and the subcutaneous (s.c.) routes was tested. When similar doses of peptide-loaded microparticles were injected s.c. or i.d. in mice, the antipeptide IgG antibody immune response was found to be significantly higher after i.d. injection into the skin. We could also reduce the dose of antigen 10 times by the i.d. route and find a similar antibody response to that obtained by the s.c. immunization. At the lowest i.d. dose level, the IgG2a/IgG1 ratio was also incremented and the IgE production decreased. The i.d. microparticles induced, at both dose levels, a marked IFN-gamma secretion by peptide-stimulated splenocytes and lymph node cells and a significant T cell proliferation in spleen cell cultures. The results demonstrate that peptide-loaded microparticles were efficiently administered by the i.d. route because lower doses were required and powerful antibody and T cell responses were obtained compared to the conventional s.c. administration.