VACCINES ADJUVANT DEVELOPMENT PROGRAM IN INFECTIOUS AND IMMUNE MEDIATED DISEASES

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Vaccination is a key biomedical intervention to reduce infection, cancer, and other diseases, but responses to vaccines may be inadequate in breadth, magnitude and/or durability. Agents that activate innate immune signaling via selective activation of pattern recognition receptors (PRRs) can serve as adjuvants to enhance vaccine-induced immune responses and protection. High throughput screening on primary human cells in culture (in vitro) identified a novel imidazopyrimidine adjuvant, Precision Vaccines Program (PVP)-037, which demonstrated broad innate immune activation via the PRR Toll-like receptor-7 (TLR7), including cytokine induction from human leukocytes in vitro as well as enhancement of influenza antigen-specific humoral responses in mice in vivo. As Contractor, the Precision Vaccine Program (PVP) at Boston Children’s Hospital (BCH) will supervise, coordinate, and undertake research activities aimed at developing a novel small molecule imidazopyridine TLR7 agonist analog, optimizing adjuvant formulation and stability as well as adjuvanticity in combination with licensed HA protein-based influenza vaccine towards human leukocytes in vitro and in animal models in vivo. The production of adjuvant formulation will be completed under good laboratory practice (GLP), to support Investigational New Drug application (IND)-enabling activities in preparedness for chemistry, manufacturing, and control (CMC) process-development and pre-current Good Manufacturing Practice (cGMP) production-grade formulation scaled up.