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

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 modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) such as TLR1/2a, TLR4a, TLR7/8a, or a mixture of TLR4a and TLR7/8a adjuvants and denoted them as TLR1/2a-SNP, TLR4a-SNP, TLR7/8a-SNP, and TLR4a-TLR7/8a-SNP respectively. These TLRa-SNPs greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of this newly designed adjuvant technology to a range of different antigens. More importantly, in addition to their potency, different formulations of TLRa-SNPs induced unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could have a major impact on modern vaccine indications.