Adjuvants for Skin Vaccination

Vaccines delivered through the skin have produced superior immune responses when compared with conventional intramuscular vaccinations for over two centuries. Skin vaccinations provide improved immunity to pathogens, which can be further enhanced by adding an adjuvant. Adjuvants are added to vaccines to increase the potency and longevity of the immune response, enhance the breadth of immunity, and reduce disease occurrence. Currently, the few available adjuvants used for inactivated vaccines are not approved for skin immunization because of possible local or systemic adverse reactions such as inflammation, edema, or delayed-type hypersensitivity. Hence, there is a critical need for the discovery and development of immune potentiators compatible with skin delivery of vaccines. In this review, we describe adjuvants that are under investigation for use with skin vaccination, namely, bacterial toxins, pathogen recognition receptor agonists, and chemical adjuvants. We also discuss the impact of mechanical injury on immunity and the adjuvant role of apoptosis or pyroptosis. The safety, reactogenicity, and long-term effects of these adjuvants with antigens will need to be addressed for their application in humans.