BASE AWARD

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For effective next-generation vaccines, the identification of high-quality target antigens combined with effective adjuvants will be critical. Immunoadjuvants are key components in vaccine formulations since they enhance and shape immune responses to vaccines in both immunocompetent and immunosenescent individuals. Bacterial Enzymatic Combinatorial Chemistry (BECC) technology allows for the efficient production of rationally designed lipid A agonists which signal through the host innate immune system via toll-like receptor 4 (TLR4). BECC-based adjuvants generate a balanced Th1/Th2 response yielding antigen and dose sparing, increased T-cell mediated effector immunity, enhanced proliferation of T follicular helper (Tfh) cells, and the establishment of a longer-lasting humoral immunity in adult and aged populations. BECC470s is a rationally designed synthetic TLR4-based ligand from this process. The objective of this proposal is to develop the adjuvant potential of BECC470s and evaluate it for preclinical testing with three established immunogenic vaccine antigens: 1) Influenza A HA protein, 2) Staphylococcus aureus detoxified α-hemolysin, and 3) Pseudomonas spp. T3SS fusion protein (L-PaF). BECC470s will be evaluated for biophysical properties, safety, immune stimulatory potential, and antigen sparing when developed as independent vaccine formulations that include Antigen System (AS) biosimilars (AS01, AS03, and AS04 biosimilars, and micellular) in both adult and elderly populations. These studies will allow for IND-enabling development of BECC470s through immunological characterization studies, as well as compound optimization for three separate and unique component vaccines.