DEVELOPMENT OF UM-1098: A NOVEL SYNTHETIC TH17 INDUCING ADJUVANT AND DELIVERY SYSTEM

The development and clinical evaluation of safe and effective Th17 inducing adjuvants is urgently needed for the advancement of vaccines to combat the ongoing threat of bacterial and fungal pathogens including Mycobacterium tuberculosis (Mtb), Bordetella pertussis, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia, Candida albicans, Aspergillus fumigatus and others. Vaccination against TB and other bacterial and fungal pathogens has been hampered by the lack of appropriate adjuvants for inducing Th17 immunity. Thus, the next generation of vaccine adjuvants capable of inducing broadly protective immune responses against emerging bacterial and fungal pathogens represents a critical unmet need. This Adjuvant Development Contract will advance one such adjuvant – UM-1098: a Th17 inducing synthetic Mincle ligand– towards human clinical trials. UM-1098 was identified through the NIAID Adjuvant Discovery Program via a comprehensive and iterative structure-activity relationship (SAR) investigations to identify a novel synthetic diaryl trehalose Mincle receptor ligand paired with a novel nanoparticle delivery system. This adjuvant and delivery system has a well-established safety and efficacy profile in mice, pigs and non-human primates (NHPs) across multiple highly relevant antigen/pathogen platforms including TB and Bordetella pertussis. The advantages of UM-1098 over previously developed Mincle adjuvants includes improved formulation physiochemical properties, thermostability, robust safety profile, and most importantly, superior antigen-specific Th17, Th1, and humoral immunity across rodents, pigs and NHPs. When co-administered with an antigen, UM-1098 adjuvant induces durable cell-mediated and humoral immunity with demonstrated protection against Mtb and Bordetella pertussis challenge.