Role of Adjuvants for Vaccines Delivered via Skin: A comprehensive analysis

Skin is body’s largest organ and serves as a protective barrier from physical, thermal, and mechanical challenges from the environment. Alongside, skin hosts key players of the immune system, such as the professional antigen-presenting cells (APCs) like the Langerhans cells in the epidermis, and circulating macrophages in the blood. Further, the literature supports that the APCs can be activated by antigen or vaccine delivery via multiple routes of administration through the skin. Once activated, the stimulated APCs drain to the associated lymph nodes and gain access to the lymphatic system. This further allows the APCs to engage with the adaptive immune system and activate cellular and humoral immune response. Thus, vaccine delivery via skin offers advantages such as high-capacity delivery , superior immunogenicity, convenient delivery, improved patient acceptance, elimination of the hazards, and limitations of other routes of administration such as oral and intramuscular. Several preclinical and clinical studies have demonstrated the significance of vaccine delivery using various routes of administration via skin.. However, such vaccines often employ the use of adjuvant/(s), along with the antigen of interest. Adjuvants augment the overall immune response to a vaccine antigen and improve the therapeutic efficacy. Due to these reasons, adjuvants have been successfully used with infectious disease vaccines, cancer immunotherapy, and immune-mediated diseases . To capture these developments, this review will summarize preclinical and clinical study results of vaccine delivery via skin in the presence of adjuvants. A focused discussion regarding the FDA-approved adjuvants will address the experiences of using such adjuvant containing vaccines. In addition, the challenges and regulatory concerns with these adjuvants will be discussed. Finally, the review will share the future prospects of adjuvant containing vaccines delivered via skin