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Particle-based drug delivery systems target active compounds to the hair follicle and may result in a better penetration and higher efficiency of compound uptake by skin resident cells. As previously proposed, such delivery systems could be important tools for vaccine delivery. In this study, we investigated the penetration of solid fluorescent 40 or 200 nm polystyrene nanoparticles (NPs) as well as virus particles in murine skin to further investigate the efficacy of transcutaneously (TC) applied particulate vaccine delivery route. We demonstrated that 40 and 200 nm NPs and modified vaccinia Ankara (MVA) expressing the green-fluorescent protein penetrated deeply into hair follicles and were internalized by perifollicular antigen-presenting cells (APCs). Fibered-based confocal microscopy analyses allowed visualizing in vivo particle penetration along the follicular duct, diffusion into the surrounding tissue, uptake by APCs and transport to the draining lymph nodes. The application of small particles, such as ovalbumin coding DNA or MVA, induced both humoral and cellular immune responses. Furthermore, TC applied MVA induced protection against vaccinia virus challenge. Our results strengthen the concept of TC targeting of cutaneous APCs by hair follicles and will contribute to the development of advanced vaccination protocols using NPs or viral vectors.

Different primings with DNA and fowlpox virus (FP) recombinants or FP alone were used in a pre-clinical trial to evaluate and compare immunogenicity and efficacy against HIV/SHIV. Three immunization regimens were tested in three groups of mice in which the SIV gag/pol and HIV-1 env transgenes were separately expressed by DNA and FP vectors, followed by VLP(SHIV) boosting. All of the protocols were effective in eliciting homologous neutralizing antibodies, although the mice immunized with DNA followed by FP recombinants or DNA+FP recombinants showed both high titres of neutralizing antibodies and high frequencies of env-specific IFNgamma-producing T lymphocytes. Vaccine efficacy, as demonstrated by growth control of env-expressing tumours, was obtained in both of these two groups of mice. These results establish a preliminary profile for the combined use of these recombinant vectors in protocols to be tested in the SHIV-macaque model of HIV-1 infection.