Inflammatory Cutaneous Reactions with Systemic CD8+ T-Cell Responses upon Photochemical Internalization of Antigens in Mice

Vaccination can prevent infections and modulate immune-related diseases. While conventional vaccines primarily stimulate CD4 + T cells and antibody production, effective anti-tumor immunity requires activation of CD8 + T cells. Photochemical internalization (PCI) is a promising technology that can facilitate cytosolic antigen delivery, promoting CD8 + T-cell responses. Here, we studied early immune and cutaneous reactions following PCI-based vaccination with the photosensitizer disulphonated tetraphenyl chlorine (TPCS2a). Mice were vaccinated intradermally with ovalbumin antigen and TPCS2a, followed by light treatment. We assessed cutaneous inflammatory reactions through histology, immunohistochemistry, fluorescence microscopy, and real-time PCR. Systemic inflammatory and immune reactions were analyzed in blood, lymph nodes, and in spleen by flow cytometry, clinical chemistry and ELISA. TPCS2a was retained in cutaneous structures, accumulated in draining lymph nodes, and light activation triggered dose- and time-dependent cutaneous inflammatory reactions including infiltration of innate myeloid CD11b + and GR1 + macrophages, cross-presenting dendritic cells and neutrophils, alongside enhanced local and systemic production of pro-inflammatory cytokines. High TPCS2a doses triggered severe cutaneous and systemic reactions, but PCI-treated skin showed a high degree of plasticity and healing. These mechanistic insights into local and systemic effects of PCI-based vaccination may contribute to translating PCI into clinical practice and wider application.