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A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.
Silva, Murillo; Kato, Yu; Melo, Mariane B; Phung, Ivy; Freeman, Brian L; Li, Zhongming; Roh, Kangsan; Van Wijnbergen, Jan W; Watkins, Hannah; Enemuo, Chiamaka A; Hartwell, Brittany L; Chang, Jason Y H; Xiao, Shuhao; Rodrigues, Kristen A; Cirelli, Kimberly M; Li, Na; Haupt, Sonya; Aung, Aereas; Cossette, Benjamin; Abraham, Wuhbet; Kataria, Swati; Bastidas, Raiza; Bhiman, Jinal; Linde, Caitlyn; Bloom, Nathaniel I; Groschel, Bettina; Georgeson, Erik; Phelps, Nicole; Thomas, Ayush; Bals, Julia; Carnathan, Diane G; Lingwood, Daniel; Burton, Dennis R; Alter, Galit; Padera, Timothy P; Belcher, Angela M; Schief, William R; Silvestri, Guido; Ruprecht, Ruth M; Crotty, Shane; Irvine, Darrell J.
  • Silva M; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Kato Y; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Melo MB; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Phung I; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Freeman BL; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Li Z; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Roh K; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
  • Van Wijnbergen JW; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Watkins H; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Enemuo CA; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.
  • Hartwell BL; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Chang JYH; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Xiao S; Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Rodrigues KA; Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, MGH Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Cirelli KM; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Li N; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Haupt S; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Aung A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Cossette B; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Abraham W; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Kataria S; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Bastidas R; Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Bhiman J; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Linde C; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Bloom NI; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Groschel B; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Georgeson E; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego (UCSD), La Jolla, CA 92093, USA.
  • Phelps N; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Thomas A; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Bals J; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Carnathan DG; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Lingwood D; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Burton DR; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Alter G; Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Padera TP; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Belcher AM; Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Schief WR; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
  • Silvestri G; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
  • Ruprecht RM; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Crotty S; Department of Immunology and Microbiology, Scripps Research Institute, La Jolla, CA 92037, USA.
  • Irvine DJ; IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
Sci Immunol ; 6(66): eabf1152, 2021 Dec 03.
Article in English | MEDLINE | ID: covidwho-1583226
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 cell­dependent 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Saponins / Adjuvants, Immunologic / Toll-Like Receptors / Adaptive Immunity / Lymph Topics: Vaccines Limits: Animals Language: English Journal: Sci Immunol Year: 2021 Document Type: Article Affiliation country: Sciimmunol.abf1152

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Saponins / Adjuvants, Immunologic / Toll-Like Receptors / Adaptive Immunity / Lymph Topics: Vaccines Limits: Animals Language: English Journal: Sci Immunol Year: 2021 Document Type: Article Affiliation country: Sciimmunol.abf1152