Small molecule adjuvants that act as vaccine adjuvants by specifically binding to Toll-Like Receptor-8 (TLR8).
The lead adjuvants are novel compounds that selectively bind to TLR8. Once bound to TLR8, the compounds elicit an immune response that is similar to a response that would result from molecular recognition of a pathogen.
The infectious agent recognized by TLR8 is typically a segment of single stranded RNA. Upon recognition of the RNA, a proinflammatory cytokine profile is induced. This profile protects neonates and infants against infection.
The invention provides a potent TLR8 agonist that effectively elicits a response in neonatal antigen presenting cells (APCs). This makes the compounds ideal for use as a neonatal vaccine adjuvant.
The adjuvants bind to the TLR8 receptor site causing an immune response similar to the response elicited upon binding of the single stranded RNA to the TLR8 receptor. This response has been verified using ex vivo human blood.
Most adjuvants of TLR8 also induce a response in TLR7 as well. Activation of TLR7 is not desirable because it does not result in the induction of a cytokine profile that is protective of neonates and infants. Both QSAR studies as well as in ex vivo blood, these adjuvants only cause TLR8 induction.
The lead adjuvants are highly potent (0.2 micro molar), chemically stable, easily amendable, TLR8 specific agonists. This has been verified by both QASR and ex vivo human blood studies. Furthermore, because they are specific for TLR8, risk of side effects would be minimal.