Repurposed, small molecule kinase inhibitors, such as epidermal growth factor receptor (EGFR) inhibitors, as topical vaccine adjuvants.
In order to create long lasting protection from infection, many vaccines require the use of an adjuvant. Adjuvants for vaccines work to enhance the immune response particularly in cases where the vaccine alone is incapable of eliciting a sufficient response. Currently, there is growing interest in creating vaccines with higher efficacy, stronger safety profiles, and which provide longer-lasting protection. Adjuvants offer an avenue for improving these qualities in existing or new vaccines. One area where such adjuvants are of particular interest is influenza vaccines. Because clinical effectiveness in high-risk populations including the very young and the elderly is considerably lower (approximately 40%), there is a distinct need to improve the effectiveness of flu vaccines in these populations.
Adjuvants are often combined with a vaccine when the vaccine is unable to provide a sufficient immunological response in order to limit the required dose of the vaccine material while maintaining a similar response or to increase the response so that only a single vaccine is required rather than multiples. Emory researchers have found a new uses for topical kinase inhibitors such as those that are currently used systemically (by oral administration) in the treatment of cancer; specifically applying these compounds topically leads to increased production of cytokines and chemokines by skin cells and as a result increases the recruitment of immune cells such as antigen-presenting cells into the skin. As a result, this recruitment leads to an enhanced immune response to vaccination. Therefore these inhibitors may have untapped therapeutic value when used topically to increase protective immune responses to vaccination and in likely in other settings where enhanced local skin immunity is desired.
Proof of concept animal experiments completed using an influenza model. HA neutralizing antibody titers and protection against infection increased after topical application at the site of vaccination as compared to control.
Publication: Pollack BP. 2012. Oncoimmunology. 1: 71-74.
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