Particle based vaccine formulations for transcutaneous immunization

Abstract

Vaccine formulations on the basis of nano- (NP) or microparticles (MP) can solve issues with stabilization, controlled release, and poor immunogenicity of antigens. Likewise transcutaneous immunization (TCI) promises superior immunogenicity as well as the advantages of needle-free application compared with conventional intramuscular injections. Thus the combination of both strategies seems to be a very valuable approach. However, until now TCI using particle based vaccine formulations has made no impact on medical practice. One of the main difficulties is that NPs and MPs cannot penetrate the skin to an extent that would allow the application of the required dose of antigen. This is due to the formidable stratum corneum (SC) barrier, the limited amount of antigen in the formulation and often an insufficient immunogenicity. A multitude of strategies are currently under investigation to overcome these issues. We highlight selected methods presenting a spectrum of solutions ranging from transfollicular delivery, to devices disrupting the SC barrier and the combination of particle based vaccines with adjuvants discussing their advantages and shortcomings. Some of these are currently at an experimental state while others are already in clinical testing. All methods have been shown to be capable of transcutaneous antigen delivery.

Nanocarriers for optimizing the balance between interfollicular permeation and follicular uptake of topically applied clobetasol to minimize adverse effects

“…To elucidate this topic further, a larger range in particle size should be investigated in the future. As for the controls, the amount detected in the hair follicle of free CP in an ethanolic solution and free CP in HG, with and without the application of massage, was below the lower limit of quantification (LLOQ) for both experimental setups and thus negligible [19,29,39]. This confirms that by means of encapsulation a more targeted delivery to the hair follicle was achieved.…”

Inverse micellar sugar glass (IMSG) nanoparticles for transfollicular vaccination

“…Furthermore, antigen encapsulated in IMSG NPs turned out to be much more immunogenic (85 ± 5%) in comparison to our previously described antigen-loaded chitosan-PLGA NPs (65 ± 5%) when analyzed using ELISA [12]. Adjuvants play a vital role in vaccine development, as they increase immunogenicity of weak antigens as well as decrease the dose of the antigen required in vaccine formulations [3]. In this study we explored the possibility of improving the performance of the formulations by using c-di-AMP, since preliminary studies suggested that c-di-AMP was compatible with the nanoparticle-based platform.…”

“…by dispersing protein into an organic solution of surfactants and subsequently freeze drying them before introducing them into polymer solutions for tissue engineering. Administration of antigen solutions and particulate carriers by intradermal (ID) and intranasal (IN) routes has been widely studied [3,9]. However, recent attention focuses on non-invasive transcutaneous vaccination strategies.…”

Effect of vaccine administration modality on immunogenicity and efficacy

“…Transcutaneous immunization (TCI), another needle-free vaccination method, has been widely reviewed[144-147]. Transcutaneous delivery can lead to comparable or better efficacy than traditional injection, as seen with a trivalent inactivated influenza vaccine with heat-labile enterotoxin from Escherichia coli (LT) as an adjuvant in a dry patch[148].…”