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

doi:10.1126/sciadv.adn7187

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

Sci Adv. 2024 Aug 9;10(32):eadn7187. doi: 10.1126/sciadv.adn7187. Epub 2024 Aug 7.

Authors

Ben S Ou¹, Julie Baillet², Maria V Filsinger Interrante^{3

4

5}, Julia Z Adamska⁶, Xueting Zhou¹, Olivia M Saouaf², Jerry Yan¹, John H Klich¹, Carolyn K Jons², Emily L Meany¹, Adian S Valdez^{7

8}, Lauren Carter^{7

8}, Bali Pulendran^{6

9

10}, Neil P King^{7

8}, Eric A Appel^{1

2

3

6

11

12}

Affiliations

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.
¹² Woods Institute for the Environment, 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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

AIDS Vaccines / immunology
Adjuvants, Immunologic* / pharmacology
Adjuvants, Vaccine / chemistry
Animals
COVID-19 / immunology
COVID-19 / prevention & control
COVID-19 / virology
COVID-19 Vaccines* / immunology
Cytokines / metabolism
Humans
Mice
Nanoparticles* / chemistry
SARS-CoV-2* / immunology
Saponins* / chemistry
Saponins* / immunology
Saponins* / pharmacology
Toll-Like Receptor Agonists*

Substances

Adjuvants, Immunologic
Adjuvants, Vaccine
AIDS Vaccines
COVID-19 Vaccines
Cytokines
Saponins
Toll-Like Receptor Agonists

Abstract

Publication types

MeSH terms

Substances

Grants and funding