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 Abraham; Swati 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

doi:10.1126/SCIIMMUNOL.ABF1152

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 journal › Article › peer-review

21 Scopus citations

Abstract

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 language	English (US)
Article number	eabf1152
Journal	Science Immunology
Volume	6
Issue number	66
DOIs	https://doi.org/10.1126/SCIIMMUNOL.ABF1152
State	Published - Dec 24 2021
Externally published	Yes

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© 2021 American Association for the Advancement of Science. All rights reserved.

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Silva, M., Kato, Y., Melo, M. B., Phung, I., Freeman, B. L., Li, Z., Roh, K., Van Wijnbergen, J. W., Watkins, H., Enemuo, C. A., Hartwell, B. L., Chang, J. Y. H., Xiao, S., Rodrigues, K. A., Cirelli, K. M., Li, N., Haupt, S., Aung, A., Cossette, B., ... Irvine, D. J. (2021). A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity. Science Immunology, 6(66), [eabf1152]. https://doi.org/10.1126/SCIIMMUNOL.ABF1152

Silva, M, Kato, Y, Melo, MB, Phung, I, Freeman, BL, Li, Z, Roh, K, Van Wijnbergen, JW, Watkins, H, Enemuo, CA, Hartwell, BL, Chang, JYH, Xiao, S, Rodrigues, KA, Cirelli, KM, Li, N, Haupt, S, Aung, A, Cossette, B, Abraham, W, Kataria, S, Bastidas, R, Bhiman, J, Linde, C, Bloom, NI, Groschel, B, Georgeson, E, Phelps, N, Thomas, A, Bals, J, Carnathan, DG, Lingwood, D, Burton, DR, Alter, G, Padera, TP, Belcher, AM, Schief, WR, Silvestri, G, Ruprecht, RM, Crotty, S & Irvine, DJ 2021, 'A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity', Science Immunology, vol. 6, no. 66, eabf1152. https://doi.org/10.1126/SCIIMMUNOL.ABF1152

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title = "A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity",

abstract = "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.",

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

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doi = "10.1126/SCIIMMUNOL.ABF1152",

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T1 - A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity

AU - Silva, Murillo

AU - Kato, Yu

AU - Melo, Mariane B.

AU - Phung, Ivy

AU - Freeman, Brian L.

AU - Li, Zhongming

AU - Roh, Kangsan

AU - Van Wijnbergen, Jan W.

AU - Watkins, Hannah

AU - Enemuo, Chiamaka A.

AU - Hartwell, Brittany L.

AU - Chang, Jason Y.H.

AU - Xiao, Shuhao

AU - Rodrigues, Kristen A.

AU - Cirelli, Kimberly M.

AU - Li, Na

AU - Haupt, Sonya

AU - Aung, Aereas

AU - Cossette, Benjamin

AU - Abraham, Wuhbet

AU - Kataria, Swati

AU - Bastidas, Raiza

AU - Bhiman, Jinal

AU - Linde, Caitlyn

AU - Bloom, Nathaniel I.

AU - Groschel, Bettina

AU - Georgeson, Erik

AU - Phelps, Nicole

AU - Thomas, Ayush

AU - Bals, Julia

AU - Carnathan, Diane G.

AU - Lingwood, Daniel

AU - Burton, Dennis R.

AU - Alter, Galit

AU - Padera, Timothy P.

AU - Belcher, Angela M.

AU - Schief, William R.

AU - Silvestri, Guido

AU - Ruprecht, Ruth M.

AU - Crotty, Shane

AU - Irvine, Darrell J.

PY - 2021/12/24

Y1 - 2021/12/24

N2 - 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.

AB - 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.

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

Abstract

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