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


Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
03 Dec 2021
Historique:
entrez: 3 12 2021
pubmed: 4 12 2021
medline: 9 3 2022
Statut: ppublish

Résumé

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 AS01

Identifiants

pubmed: 34860581
doi: 10.1126/sciimmunol.abf1152
pmc: PMC8763571
mid: NIHMS1767963
doi:

Substances chimiques

Adjuvants, Immunologic 0
Saponins 0
Toll-Like Receptors 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabf1152

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI153098
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI144462
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007386
Pays : United States
Organisme : NIAID NIH HHS
ID : R61 AI161818
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014051
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI048240
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214913
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI104715
Pays : United States
Organisme : NIH HHS
ID : U42 OD011023
Pays : United States
Organisme : NIAID NIH HHS
ID : R61 AI161297
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137057
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI125068
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI125068
Pays : United States
Organisme : NIH HHS
ID : P51 OD011133
Pays : United States
Organisme : NIH HHS
ID : S10 OD021831
Pays : United States

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Auteurs

Murillo Silva (M)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.

Yu Kato (Y)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Mariane B Melo (MB)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

Ivy Phung (I)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Brian L Freeman (BL)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Zhongming Li (Z)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Kangsan Roh (K)

Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.

Jan W Van Wijnbergen (JW)

Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.

Hannah Watkins (H)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Chiamaka A Enemuo (CA)

Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

Brittany L Hartwell (BL)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Jason Y H Chang (JYH)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Shuhao Xiao (S)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Kristen A Rodrigues (KA)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Kimberly M Cirelli (KM)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Na Li (N)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Sonya Haupt (S)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Aereas Aung (A)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Benjamin Cossette (B)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Wuhbet Abraham (W)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Swati Kataria (S)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Raiza Bastidas (R)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.

Jinal Bhiman (J)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.

Caitlyn Linde (C)

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

Nathaniel I Bloom (NI)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.

Bettina Groschel (B)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.

Erik Georgeson (E)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.

Nicole Phelps (N)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.

Ayush Thomas (A)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Julia Bals (J)

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

Diane G Carnathan (DG)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

Daniel Lingwood (D)

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

Dennis R Burton (DR)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.

Galit Alter (G)

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.

Timothy P Padera (TP)

Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.

Angela M Belcher (AM)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

William R Schief (WR)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.

Guido Silvestri (G)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.

Ruth M Ruprecht (RM)

Texas Biomedical Research Institute, San Antonio, TX 78227, USA.

Shane Crotty (S)

Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.

Darrell J Irvine (DJ)

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

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