Immune potentiator for increased safety and improved protection of vaccines by NF-kB modulation

Abstract

Many modern vaccines include adjuvants that activate the immune system and provide an enhanced humoral or cellular response. Current approved adjuvants are unable to provide desired responses against some pathogens (e.g. HIV or dengue). Many new adjuvants have been developed and demonstrate promising results, but side effects from the inflammatory response induced by these adjuvants have resulted in limited FDA approvals. No adjuvants yet possess the capability to independently modulate inflammation and protection. Here we demonstrate a method to limit inflammation and side effects associated with vaccination while retaining the protective responses using a variety of promising adjuvants. To accomplish this, we combined a selective NF-kB inhibitor with the immune adjuvant. The resulting vaccines reduce systemic inflammation and boost antibody responses. In an influenza challenge model, we demonstrate that this approach enhances protection. This method is generalizable across a broad range of adjuvants and antigens. We anticipate these studies will lead to a novel approach to vaccine formulation design that may prove general across a wide range of adjuvants, enabling their greater use in the public realm.