Rationally Designed Human TLR8-selective Agonists
Novel compounds for activation of toll-like receptor-8 (TLR8) for use as adjuvants
Background
The rising prevalence of diseases such as autoimmune disorders, cancers, and increased incidences of zoonotic diseases has increased the demand for improved vaccine immunizations. Incorporating an adjuvant into a vaccine formulation can result in a robust and long-lasting immune response. Newer adjuvants have been developed to target specific components of the body’s immune response so that protection against disease is stronger and lasts longer. Although the body’s innate immunity is a specific immune response component that acts as the body’s first line of immune defense, adjuvants that target the innate immune pathway have been under-developed.
Toll-like receptors (TLRs) are a family of proteins whose primary function is to activate innate immune responses while facilitating adaptive immune responses. Of the 10 known TLRs, each differs in their expression in various target cells and exerts distinct functions by activating varied immune cascades. Stimulation of TLR8 activates conventional dendritic cell (cDC) and specifically enhanced T follicular cell responses. These novel TLR8 agonists are specific for TLR8 and are particularly potent in inducing the T helper type 1 (Th1) cell-biasing cytokines IFN-γ and IL-12 to invoke a specific immune response in the body.
Technology Overview
These novel compounds selectively activate TLR8 and potentially act as potent adjuvants for cell-mediated immune responses by activating the body’s innate immune responses.
TLR8 agonists in general have a better clinical safety profile compared to other TLRspecific agonists such as TLR4, 7, TLR7/8 dual, and TLR9. This can potentially allow for vaccine formulations suitable for systemic administration.
Benefits
Most adjuvants in current use generate a broad immune response. Because the novel TLR8 agonists only activate cells that express TLR8, which are generally expressed on different immune cells from other TLRs, a vaccine can be designed for a specific, desired immune cell response which can ultimately lead to a more robust immune response.
Applications
- Vaccine adjuvants
- Anticancer therapies
- Immunomodulating agents