Evaluation of the potential of Boldoa saponins as vaccine adjuvants

Vaccines are one of the most effective health interventions ever developed and remain as one of the best shots to prevent epidemic diseases. Generally, traditional vaccines (live, but attenuated, or inactivated whole organisms) and new generation vaccines (e.g. recombinant proteins, purified antigen and DNA) are poorly immunogenic due to lack of effective immune stimulus. Therefore, adjuvants in vaccine formulations have become increasingly important ingredients to increase the immunological efficiency and improve vaccination schedules. Currently, over 100 potent adjuvants have been reported. However, most of them cannot be licensed for human use because of their undesired side effects. Even the most common chemical adjuvant(s) approved for use in licensed human vaccines (e.g. Alum; FDA approved, but neurotoxic) produce unwanted side effects including pain at injection site, inflammation, lymphadenopathy, granulomas and sterile abscess, among others. Due to toxicity issues, there is a critical need to develop or identify adjuvant molecules that initiate a potent immune response with less reactogenicity and less systemic toxicity. In this study, we propose to identify and investigate benchmarking candidate adjuvants based on saponins from Boldoa purpurascens which are safe and less toxic (preliminary results) than other adjuvant saponins (QS 21). The discovery of new saponin-adjuvant from this study would lead to more efficient vaccines aiming to elicit a specific, protective and long-lasting immunity after vaccination. The central research hypothesis of this study is that new saponins purified from Boldoa leaves and stems would exert the immune adjuvant activity without exhibiting systemic toxicity. To study this hypothesis, we will isolate the saponins and fully characterize their chemical structure. Their haemolytic and cytotoxic activity will be determined and the most promising saponin(s) and/or well characterised saponin fraction(s) will be evaluated in vitro on their potential as vaccin adjuvant.

Keywords:SAPONINS, STRUCTURE ELUCIDATION

Disciplines:Immunology, Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences