Epidermal micro-perforation potentiates the efficacy of epicutaneous vaccination

Abstract The skin is an immune organ comprised of a large network of antigen-presenting cells such as dendritic cells, making it an attractive target for the development of new vaccines and immunotherapies. Recently, we developed a new innovative and non-invasive vaccination method without adjuvant based on epicutaneous vaccine patches on which antigen forms a dry deposit. Here we describe in mice a method for potentiating the efficacy of our epicutaneous vaccination approach using a minimally invasive and epidermis-limited skin preparation based on laser-induced micro-perforation. Our results showed that epidermal micro-perforation increased trans-epidermal water loss, resulting in an enhancement of antigen solubilization from the surface of the patch, and increased the quantity of antigen delivered to the epidermis. Importantly, this was not associated with an increase in systemic passage of the antigen. Skin micro-perforation slightly activated keratinocytes without inducing an excessive level of local inflammation. Moreover, epidermal micro-perforation improved antigen capture by epidermal dendritic cells and specifically increased the level of Langerhans cells activation. Finally, we observed that epidermal micro-perforation significantly increased the level of the specific antibody response induced by our epicutaneous Pertussis vaccine candidate containing non-adsorbed recombinant Pertussis Toxin and reduced the amount of antigen dose required. Overall, these data confirm the benefit of a minimal and controlled epidermal preparation for improving the effectiveness of an epicutaneous patch-based vaccine, without adversely affecting the safety of the method.