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[Preprint]. 2024 Jun 27:2023.07.16.549249. Originally published 2023 Jul 31. [Version 3] doi: 10.1101/2023.07.16.549249

Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Drive Distinct Immune Signatures and Potent Vaccine Responses

Ben S Ou, Julie Baillet, Maria V Filsinger Interrante, Julia Z Adamska, Xueting Zhou, Olivia M Saouaf, Jerry Yan, John H Klich, Carolyn K Jons, Emily L Meany, Adian S Valdez, Lauren Carter, Bali Pulendran, Neil P King, Eric A Appel
PMCID: PMC10418080  PMID: 37577608

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.

Teaser

Saponin-TLRa nanoadjuvants provide distinct immune signatures and drive potent, broad, durable COVID-19 and HIV vaccine responses.

Full Text Availability

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