Natural and Synthetic Saponins as Vaccine Adjuvants

Saponin adjuvants have been extensively studied for their use in veterinary and human vaccines. Among them, QS-21 stands out owing to its unique profile of immunostimulating activity, inducing a balanced Th1/Th2 immunity, which is valuable to a broad scope of applications in combating various microbial pathogens, cancers, and other diseases. It has recently been approved for use in human vaccines as a key component of combination adjuvants, e.g., AS01b in Shingrix® for herpes zoster. Despite its usefulness in research and clinic, the cellular and molecular mechanisms of QS-21 and other saponin adjuvants are poorly understood. Extensive efforts have been devoted to studies for understanding the mechanisms of QS-21 in different formulations and in different combinations with other adjuvants, and to medicinal chemistry studies for gaining mechanistic insights and development of practical alternatives to QS-21 that can circumvent its inherent drawbacks. In this review, we briefly summarize the current understandings of the mechanism underlying QS-21’s adjuvanticity and the encouraging results from recent structure-activity-relationship (SAR) studies.

Immunostimulating Activity of Gold-modified Nanodiamond Particles

Background: The fight against infectious diseases includes two main components – immediate direct anti-infective action and stimulation of one's own immunity. Objective: In this study, we investigated the properties of diamond nanoparticles modified with gold. The use of such gold nanoparticles as indirect anti-infectious agents and immunostimulators has certain prospects. Material and Methods: Gold hydrosols were synthesized by the reduction in an aqueous solution of gold (III) with sodium citrate (Na3Cit) under heating. Modification procedure of nanodiamond by gold requires incubation, a small sample of nanodiamond in a defined volume of a gold sol for about 24 hours in a dark place. We use human blood cells as test objects. The reaction of blastic transformation of lymphocytes was applied here as a test of biological actions of modified nanodiamond. Results: Modified nanodiamond do not have a toxic influence on blood cells. Modified nanodiamond possesses stimulation effects on spontaneous proliferation of lymphocytes and does not significantly affect phytohemagglutinin-induced proliferation. Nanodiamond slightly increases phagocytosis parameters of neutrophil leucocytes. Conclusion: Thus, results showed that the nanodiamond modified by gold possesses immunostimulating activity, increases the phagocytic activity of neutrophilic leukocytes and stimulates lymphocytes in the spontaneous proliferation test. Gold-modified nanodiamond could be considered as a non-direct anti-infective agent through immune stimulation.

COMPOUNDS HAVING THE IMMUNOSTIMULATING ACTIVITY EX VIVO, AS POSSIBLE ADJUVANTS FOR GENETICALLY ENGINEERED ANTIVIRAL VACCINES

In the mouse lymphocyte culture ex vivo, the immunostimulating activity of a number of previously unexplored compounds was determined. Six of the 19 compounds showed an increase in the functional activity of T cells. These compounds are promising as adjuvants for genetically engineered vaccines.

Novel PEGylated Liposomes Enhance Immunostimulating Activity of isRNA

The performance of cationic liposomes for delivery of therapeutic nucleic acids in vivo can be improved and specifically tailored to certain types of cargo and target cells by incorporation of PEG-containing lipoconjugates in the cationic liposome’s composition. Here, we report on the synthesis of novel PEG-containing lipoconjugates with molecular masses of PEG 800, 1500 and 2000 Da. PEG-containing lipoconjugates were used as one of the components in liposome preparation with the polycationic amphiphile 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetra-azahexacosan tetrahydrochloride (2X3) and the lipid-helper dioleoylphosphatidylethanolamine (DOPE). We demonstrate that increasing the length of the PEG chain reduces the transfection activity of liposomes in vitro, but improves the biodistribution, increases the circulation time in the bloodstream and enhances the interferon-inducing activity of immunostimulating RNA in vivo.

Purification and Structural Characterization of a Novel Water-Soluble Neutral Polysaccharide from Cantharellus cibarius and Its Immunostimulating Activity in RAW264.7 Cells

Polysaccharide is one of the important active ingredients of Cantharellus cibarius. The aims of this work were to analyze preliminary characterization and to investigate immunostimulating activity of a novel water-soluble neutral polysaccharide named JP1, which was purified from the fruiting body of Cantharellus cibarius using DEAE-FF chromatography and Sephadex G-100 chromatography. The characteristics of JP1 were determined by HPGPC, FT-IR spectra, gas chromatography, and Congo Red Method. Immunostimulating activity of JP1 was investigated in RAW264.7 cells. Results indicated that JP1 consisted of L-Arabinose, D-Mannose, D-Glucose, and D-Galactose in a molar ratio of 1 : 1.06 : 1.95 : 1.17 with a molecular weight of 336 kDa. JP1 is nontoxic to RAW264.7 cells at this concentration range (62.5–1000 μg/mL). Furthermore, JP1 can promote mouse peritoneal macrophages to secrete NO and enhance the secretion of macrophages’ cytokines IL-6 in RAW264.7 cells. These results suggested that JP1 could have potential immunostimulating activity applications as medicine or functional food.