Impact of the TLR4 agonist BECC438 on a novel vaccine formulation against Shigella spp.

• DOI: 10.3389/fimmu.2023.1194912
• Publication Date: 2023-09-06T19:18:53Z
• Authors: Ti Lu; Sayan Das; Debaki R. Howlader; Akshay Jain; Gang Hu; Zackary K. Dietz; Qi Zheng; Siva Sai Kumar Ra...; Sean K. Whittier; David J. Varisco; Robert K. Ernst; William D. Picking; Wendy L. Picking
• Keywords: Shigellosis

Shigellosis (bacillary dysentery) is a severe gastrointestinal infection with global incidence of 90 million cases annually. Despite the severity this disease, there currently no licensed vaccine against shigellosis. Shigella ’s primary virulence factor its type III secretion system (T3SS), which specialized nanomachine used to manipulate host cells. A fusion T3SS injectisome needle tip protein IpaD and translocator IpaB, termed DBF, when admixed mucosal adjuvant double-mutant labile toxin (dmLT) from enterotoxigenic E. coli was protective using murine pulmonary model. To facilitate production platform, recombinant that consisted LTA-1, active moiety dmLT, DBF were genetically fused, resulting in L-DBF, showed improved protection challenge. extrapolate mice humans, we modified formulation provide for multivalent presentation addition an approved use human vaccines. Here, show L-DBF formulated (admix) newly developed TLR4 agonist called BECC438 (a detoxified lipid analog identified as Bacterial Enzymatic Combinatorial Chemistry candidate #438), oil-in-water emulsion, has very high efficacy at low antigen doses lethal challenge our mouse Optimal observed introduced site (intranasally). When then evaluated immune response it elicits, appeared correlate IFN-γ IL-17 lymphocytes.