Abstract 2030 Uncovering Vaccine Adjuvants from Toll-like Receptor 4 Agonist

Vaccines serve an essential role in the prevention of infectious diseases. Recombinant subunit vaccines frequently necessitate the incorporation of adjuvants due to the limited immunogenicity of the chosen antigen. The use of appropriate adjuvants decreases the amount of costly antigen and the number of vaccine doses required to achieve protection. Toll-like receptor 4 agonist have demonstrated their capacity to enhance immunogenicity as exemplified by the clinically accepted vaccine adjuvant, monophosphoryl lipid A (MPL). Yet, MPL does not serve as a universal adjuvant. The development of new adjuvants heavily depends on undertaking structural modifications and complex chemical syntheses, often resulting in hyperactivation of the MyD88 pathway and compromising the potential to elicit robust protective immunity through the TRIF pathway. In our pursuit of novel adjuvants, we explored the promising realm of immune-boosting herbal medicines known for their safety and efficacy. Lipopolysaccharide (LPS) is known to contribute to the immune-boosting activity of herbal medicines (1). Since LPS is an endotoxin, there must be a mechanism in which the proinflammatory response is regulated. Hypothesis/Central Question. Anti-inflammatory phytochemicals (AIPs) in herbal medicines selectively attenuate the pro-inflammatory effect without compromising protective immunity. To test this hypothesis, AIPs were mixed with LPS and subjected to in vitro MyD88 cell assay (2) and in vivo viral challenge. Results. Screening LPS-AIP mixtures revealed different activation of MyD88 and TRIF pathways. Two LPS-AIP mixtures showed attenuation of the pro-inflammatory response while promoting protective immunity. Conclusion. LPS-AIP mixtures have the potential to serve as vaccine adjuvants. By leveraging this approach, we aim to facilitate the advancement of new adjuvant candidates, bolstering the development of more potent and successful vaccines. Research conducted in this study is supported by the National Institutes of Health under award number SC3GM130409.