Grant: Project Grant - PA: Pandemic and Health Emergencies Research

Vaccination is our most effective method of defending against disease-causing microbes. Effective vaccination requires multiple injections to achieve strong and lasting protection. Vaccine strategies that require fewer injections will serve personal health, population-wide health, and reduce health-delivery burdens. Vaccines are typically mixtures of immune activators called adjuvants and microbial products (called antigens) injected into muscle. The adjuvant prepares the immune system to respond and the antigen, typically a fragment or extract of the relevant pathogen, triggers the specific immune response. We have found in a mouse model, that vaccination efficacy can be enhanced if the adjuvant is applied before exposure to antigen to the most superficial skin layers, conditioning the skin before injection of the vaccine. The skin is a complex multi-layered structure that serves as a barrier to harmful material in the environment, and is well-equipped for sensing infection. In the most superficial skin layer, the epidermis, cells forming the barrier (skin cells) may have an active role in responding to adjuvant, and thus preparing the immune system for response. We will study how skin cells respond to adjuvant and how other specialized immune cells in superficial layers of skin contribute to the improved vaccination efficacy we observe. We will also develop a novel application system than does not rely on needles or damaging the skin to apply large molecules such as adjuvant into the skin. We will compare the efficacy of our system (topical adjuvant and standard vaccine for hepatitis B) to a vaccine that is commercially available (HeplisavB) and has a similar adjuvant co-injected. Ultimately we hope to develop a product that can be applied to the skin before vaccination and that will improve the efficacy of all vaccines.