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Toll-Like Receptor-2 Vaccine Adjuvants

Small molecule compounds that act as vaccine adjuvants by specifically binding to Toll-Like Receptor-2 (TLR2).

Toll-like receptors (TLRs) are pattern recognition receptors that recognize microbial components and endogenous ligands. TLRs initiate rapid intracellular signaling pathways involving activation of transcription factors, MAP kinases and interferon regulatory factors, which result in innate immune activation, including production of pro-inflammatory cytokines, chemokines, interferons and immunoglobulins and co-stimulatory molecules. Among TLRs, TLR2 recognizes the broadest range of microbial derived agonists, including lipopolysaccharides from different bacterial strains, lipopeptides, lipoproteins and glycoproteins, zymosan and peptidoglycan. TLR2 is also known to involve in virus or viral proteins induced signaling pathway and cytokine production, including Epstein-Barr virus, measles virus, hepatitis B and C virus, and herpes simplex virus among others.

As a result of their involvement in regulating an inflammatory response, TLRs have been shown to play a role in the pathogenesis of many diseases, including autoimmunity, infectious disease and inflammation. Compositions for modulation of TLR activity are of interest for a variety of purposes, including use as an adjuvant.


Compounds for use as adjuvants that selectively bind TLR2 causing an immune response that would otherwise be caused by molecular recognition of highly conserved microbial molecules found on a given pathogen.


The compounds bind the receptor causing a cascading immune response similar to the response that would occur as if the pathogen itself was bound. The current invention has the ability to be administered in a number of forms including subcutaneous inoculation.


The compounds have excellent safety profiles in animal models and human subjects, are devoid of significant pro-inflammatory activity in ex vivo human blood models, and yet potently adjuvantic.


This lead adjuvant compound is highly potent (EC50 = 0.25 nM), chemically stable, highly water-soluble (>10 mg/mL), human TLR2- specific agonist, which was found to have an excellent safety profile and displayed prominent adjuvantic activities in rabbit models.

Additional Details


University of Kansas

Intellectual Property Protection

Pending Patent

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