Elucidating the Mechanisms of Action of Saponin-Derived Adjuvants. 2018

Dante J Marciani
Qantu Therapeutics, Inc., 612 East Main Street, Lewisville, TX 75057, USA. Electronic address: dmarciani@earthlink.net.

Numerous triterpenoid saponins are adjuvants that modify the activities of T cells and antigen-presenting cells, like dendritic cells (DCs). Saponins can induce either proinflammatory Th1/Th2 or sole anti-inflammatory Th2 immunities. Structure-activity relationships (SARs) have shown that imine-forming carbonyl groups are needed for T cell activation leading to induction of Th1/Th2 immunities. While saponins having different triterpenoid aglycons and oligosaccharide chains can activate DCs to induce Th1/Th2 immunoresponses, fucopyranosyl residues from their oligosaccharides by binding to the DC-SIGN receptor can bias DCs toward a sole Th2 immunity. Here we discuss the mechanisms of action of these saponins in view of new information, which may serve as a basis to design improved adjuvants and related drugs.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000938 Antigen-Presenting Cells A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors. Accessory Cells, Immunologic,Antigen-Presenting Cell,Immunologic Accessory Cells,Accessory Cell, Immunologic,Cell, Immunologic Accessory,Cells, Immunologic Accessory,Immunologic Accessory Cell,Antigen Presenting Cell,Antigen Presenting Cells,Cell, Antigen-Presenting,Cells, Antigen-Presenting
D012503 Saponins A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycone moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Saponin
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D018417 Th1 Cells A subset of helper-inducer T-lymphocytes which synthesize and secrete INTERLEUKIN-2; INTERFERON-GAMMA; and INTERLEUKIN-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions. T Helper 1 Cells,TH-1 Cells,Type 1 Helper T Cells,Cell, TH-1,Cell, Th1,Cells, TH-1,Cells, Th1,TH 1 Cells,TH-1 Cell,Th1 Cell
D018418 Th2 Cells A subset of helper-inducer T-lymphocytes which synthesize and secrete the INTERLEUKINS IL-4; IL-5; IL-6; and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses. T Helper 2 Cell,T Helper2 Cell,TH-2 Cell,Th2 Cell,Type-2 Helper T Cell,T Helper 2 Cells,T Helper2 Cells,TH-2 Cells,Type-2 Helper T Cells,Cell, T Helper2,Cell, TH-2,Cell, Th2,Cells, T Helper2,Cells, TH-2,Cells, Th2,TH 2 Cell,TH 2 Cells,Type 2 Helper T Cell,Type 2 Helper T Cells

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