Comparison of intradermal injection and epicutaneous laser microporation for antitumor vaccine delivery in a human skin explant model

Abstract

Human skin is a prime vaccination site containing multiple antigen presenting cells (APC), including Langerhans cells (LC) and dendritic cells (DC). APC deliver antigens to lymph nodes for induction of adaptive immunity through stimulating antigen specific T-and B-cells. Since intradermal (ID) injections require specific training, easy applicable delivery systems like laser microporation are emerging. In mice, combination of laser treatment and allergen injection showed enhanced T-cell responses and skewing of B-cell responses without adjuvants.However, it remains to be elucidated whether laser microporation can alter human skin DC phenotype and function without adjuvants. In an ex-vivo human skin explant model, we compared ID injection and laser microporation as anti-tumor vaccination strategy. A melanoma specific synthetic long peptide and multivalent dendrimer with gp100 antigen were used as vaccine formulation to measure APC phenotype, emigration and ability to stimulate gp100 specific CD8 + T-cells. We show that skin APC phenotype and emigration capacity was similar after laser microporation and ID injection. However, laser microporation reduced vaccine uptake by APC, resulting in decreased induction of gp100 specific CD8 + T-cell activation. To conclude, in our human skin model ID injection remains the most potent strategy to deliver antigens to skin APC for T-cell induction. Graphical Abstract

Palmitoylated antigens for the induction of anti-tumor CD8+ T cells and enhanced tumor recognition

“…To this end, gp100 C16:0 and unmodified gp100 peptides were injected into the dermis of human ex vivo skin explants with or without supplementation of the often used adjuvant combination granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-4. 27 Next crawl-out cells, which have a mixed phenotype, 28 were harvested 48 h after injection, stained for the presence of C16:0 peptide, or co-cultured with gp100-specific CD8 + T cells. Interestingly, in the context of the human skin tissue microenvironment, vaccination with C16:0 gp100 peptide led to uptake in multiple skin DC subsets ( Figure S2 ) and resulted in improved presentation to gp100-specific CD8 + T cells compared to unmodified gp100 peptides, as reflected by increased levels of IFNγ in the supernatant ( Figure 1 D).…”

Enhanced Immunogenicity of an Influenza Ectodomain Matrix-2 Protein Virus-like Particle (M2e VLP) Using Polymeric Microparticles for Vaccine Delivery

“…This robust immune response is likely linked to large populations of Langerhans cells and dermal dendritic cells in the skin that can take up, process, and present antigen to induce an immune response [33]. Additionally, skin immunization has previously been shown to be more potent and dose sparing compared to other immunization routes [34]. Therefore, exploring vaccination through the skin using antigen-and adjuvant-loaded polymeric microparticles will be beneficial to future vaccine development.…”