Saponin nanoparticle adjuvants incorporating Toll-like receptor agonists drive distinct immune signatures and potent vaccine responses-Reference-Cited by-同舟云学术

Saponin nanoparticle adjuvants incorporating Toll-like receptor agonists drive distinct immune signatures and potent vaccine responses

Published:2024-08-09 Issue:32 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Ou Ben S.¹^ORCID,Baillet Julie²^ORCID,Filsinger Interrante Maria V.³⁴⁵^ORCID,Adamska Julia Z.⁶^ORCID,Zhou Xueting¹^ORCID,Saouaf Olivia M.²^ORCID,Yan Jerry¹^ORCID,Klich John H.¹^ORCID,Jons Carolyn K.²^ORCID,Meany Emily L.¹^ORCID,Valdez Adian S.⁷⁸^ORCID,Carter Lauren⁷⁸^ORCID,Pulendran Bali⁶⁹¹⁰^ORCID,King Neil P.⁷⁸^ORCID,Appel Eric A.¹²³⁶¹¹^ORCID

Affiliation:

1. Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

2. Department of Materials Science & Engineering, Stanford University, Stanford, CA 94305, USA.

3. Stanford ChEM-H, Stanford University, Stanford, CA 94305, USA.

4. Stanford Biophysics Program, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.

5. Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.

6. Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.

7. Department of Biochemistry, University of Washington, Seattle, WA 98109, USA.

8. Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.

9. Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.

10. Department of Pathology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.

11. Department of Pediatrics-Endocrinology, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.

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, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and human immunodeficiency virus (HIV). Herein, we developed a highly modular saponin-based nanoparticle platform incorporating Toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, and TLR7/8a adjuvants and their mixtures. These various TLRa–saponin nanoparticle adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific T helper 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 that could improve the design of vaccines and affect modern vaccine development.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adn7187

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