BASE AWARD

对于有效的下一代疫苗，鉴别高质量的靶抗原和有效的佐剂将是至关重要的。免疫佐剂是疫苗配方中的关键成分，因为它们增强和塑造免疫正常和免疫衰老个体对疫苗的免疫反应。细菌酶组合化学（BECC）技术允许高效生产合理设计的脂质A激动剂，通过toll样受体4 （TLR4）通过宿主先天免疫系统发出信号。基于becc的佐剂产生平衡的Th1/Th2应答，产生抗原和剂量节约，增加T细胞介导的效应免疫，增强T滤泡辅助（Tfh）细胞的增殖，并在成人和老年人群体中建立更持久的体液免疫。becc470就是通过这一过程合理设计的基于tlr4的合成配体。

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.