A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity

Murillo Silva, Yu Kato, Mariane B. Melo, Ivy Phung, Brian L. Freeman, Zhongming Li, Kangsan Roh, Jan W. Van Wijnbergen, Hannah Watkins, Chiamaka A. Enemuo, Brittany L. Hartwell, Jason Y.H. Chang, Shuhao Xiao, Kristen A. Rodrigues, Kimberly M. Cirelli, Na Li, Sonya Haupt, Aereas Aung, Benjamin Cossette, Wuhbet AbrahamSwati Kataria, Raiza Bastidas, Jinal Bhiman, Caitlyn Linde, Nathaniel I. Bloom, Bettina Groschel, Erik Georgeson, Nicole Phelps, Ayush Thomas, Julia Bals, Diane G. Carnathan, Daniel Lingwood, Dennis R. Burton, Galit Alter, Timothy P. Padera, Angela M. Belcher, William R. Schief, Guido Silvestri, Ruth M. Ruprecht, Shane Crotty, Darrell J. Irvine

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP). Saponin-containing adjuvants exhibited distinctive mechanisms of action, altering lymph flow in a mast cell-dependent manner and promoting antigen entry into draining lymph nodes. SMNP was particularly effective, exhibiting even greater potency than the compositionally related adjuvant AS01B in mice, and primed robust germinal center B cell, TFH, and HIV tier 2 neutralizing antibodies in nonhuman primates. Together, these findings shed new light on mechanisms by which saponin adjuvants act to promote the immune response and suggest that SMNP may be a promising adjuvant in the setting of HIV, SARS-CoV-2, and other pathogens.

Original languageEnglish (US)
Article numbereabf1152
JournalScience Immunology
Issue number66
StatePublished - Dec 24 2021
Externally publishedYes

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