The synergy of dmLT and saponin: Evaluating adjuvant combinations in oral vaccines 9323

Abstract Description The adjuvant effects of saponins, derived from the South American tree Quilaja Saponaria, are currently included in several injected vaccines. LT(R192G/L211A), or dmLT has been developed based on over 35 years of research on the use of bacterial ADP-ribosylating enterotoxins as adjuvants, including injected and oral delivery in Phase 1 and 2 clinical trials. While both adjuvants have been pursued independently, they have not been pursued together. Here, we explored combinations of saponin and dmLT adjuvant (SDA) for oral and sublingual delivery. First, we tested SDA combinations in a monocyte cell line (THP-1) to identify specific ratios with optimal activation of antigen presentation by upregulation of surface markers (MHC-II, CD86, CD40) and cytokine secretion (IL-1 beta, IFN-gamma). Next, we explored dosing combinations for evidence of vesicle structures by cyro-electron microscopy. Lastly, we identified that sublingual vaccination with SDA and protein antigen achieved equivalent or better antibody responses than an intramuscular injection. This is the first combination adjuvant designed for oral delivery to achieve all the benefits of mucosal, needle-free vaccination without issues of poor systemic immunity Funding Sources Supported by NIH/NIAID contract # 75N93023C00045 and R01AI166682-01 Topic Categories Vaccines and Immunotherapy (VAC)