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.

Keywords: adjuvant; delivery; dermabrasion; jet injector; microneedle; microparticles; nanoparticles; transfollicular.

Figure 1. Schematic representation of methods to enable or facilitate TCI: (A) transfollicular delivery, (B) mechanical dermabrasion, (C) jet injection of liquids or powders, (D) microneedles (Images are not drawn to scale).

Figure 2. Combinations of antigen and adjuvant in a particulate carrier: (A) adjuvants are co-administered with the encapsulated antigen, (B) antigen and adjuvant are encapsulated in separate particles, (C) antigen and adjuvant are co-encapsulated in the same particle, (D) the particle surface is decorated with the antigen and/or the adjuvant by physical or chemical association.