Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation

Ou, B. S.; Baillet, J.; Filsinger Interrante, M. V.; Adamska, J. Z.; Zhou, X.; Saouaf, O.; Yan, J.; Klich, J.; Jons, C. K.; Meany, E.; Valdez, A. S.; Carter, L.; Pulendran, B.; King, N. P.; Appel, E.

doi:10.1101/2023.07.16.549249

bioRxiv · 10.1101/2023.07.16.549249

Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation

Ou, B. S.·Baillet, J.·Filsinger Interrante, M. V.·Adamska, J. Z.·Zhou, X.·Saouaf, O.·Yan, J.·Klich, J.·Jons, C. K.·Meany, E.·Valdez, A. S.·Carter, L.·Pulendran, B.·King, N. P.·Appel, E.

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Abstract

Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, SARS-CoV-2, and HIV. Herein, we developed a highly modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, TLR7/8a adjuvants and their mixtures. These various TLRa-SNP adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could improve the design of vaccines for and dramatically impact modern vaccine development. TeaserSaponin-TLRa nanoadjuvants provide distinct immune signatures and drive potent, broad, durable COVID-19 and HIV vaccine responses.

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Ou, B. S., Baillet, J., Filsinger Interrante, M. V., Adamska, J. Z., Zhou, X., Saouaf, O., Yan, J., Klich, J., Jons, C. K., Meany, E., Valdez, A. S., Carter, L., Pulendran, B., King, N. P., Appel, E.. 2023-07-31. Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation. https://doi.org/10.1101/2023.07.16.549249

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