Effects of dietary quillaja saponin and curcumin on the performance and immune status of weaned piglets. (1/15)

The objective of this study was to determine whether dietary quillaja saponin and curcumin (extract of turmeric) can modify piglet immune status and performance immediately after weaning. Piglets (n = 192) were weaned at 29 +/- 0.1 d and allocated to treatment (six replicates of eight pig per treatment) accounting for weight, litter, and gender, using a 2 x 2 factorial arrangement. Factors were diets with or without (as-fed basis) quillaja saponin (750 mg/kg during wk 1, 300 mg/kg during wk 2 to 3) and with or without dietary curcumin (200 mg/kg). Diets were fed ad libitum for 20 d after weaning. Feed intake was measured daily. Piglets were weighed at weaning, d 7, 14, and 20 after weaning. On each of d 6 and 20 after weaning, eight pigs per treatment were sacrificed for blood and tissue collection. Treatment had no effect on piglet growth. The ADFI and G:F were similar for all treatments between d 0 and 14 of the trial. Between d 15 and 20, ADFI and G:F were lower in quillaja-supplemented piglets (ADFI = 621 vs. 572 g/d; G:F = 0.75 vs. 0.85; P < 0.05). Serum immunoglobulin (Ig) G, IgA, interferon-gamma, and C-reactive protein (CRP) did not differ among treatments on d 6 after weaning. On d 20, IgG and CRP were greater (P < 0.05) in saponin-supplemented pigs (IgG = 17.5 vs. 11.4 mg/mL; CRP = 26.98 vs. 12.5 mg/mL). Small intestine villus and crypt measurements did not differ among treatments on either d 6 or 20. Saponin supplementation during the postweaning period seemed to potentiate an immune response in the weaned piglet but had a detrimental effect on the utilization of feed. Dietary curcumin had no influence on any measured aspect of pig performance or immune status.  (+info)

Synthetic studies of complex immunostimulants from Quillaja saponaria: synthesis of the potent clinical immunoadjuvant QS-21Aapi. (2/15)

QS-21 is one of the most promising new adjuvants for immune response potentiation and dose-sparing in vaccine therapy given its exceedingly high level of potency and its favorable toxicity profile. Melanoma, breast cancer, small cell lung cancer, prostate cancer, HIV-1, and malaria are among the numerous maladies targeted in more than 80 recent and ongoing vaccine therapy clinical trials involving QS-21 as a critical adjuvant component for immune response augmentation. QS-21 is a natural product immunostimulatory adjuvant, eliciting both T-cell- and antibody-mediated immune responses with microgram doses. Herein is reported the synthesis of QS-21A(api) in a highly modular strategy, applying novel glycosylation methodologies to a convergent construction of the potent saponin immunostimulant. The chemical synthesis of QS-21 offers unique opportunities to probe its mode of biological action through the preparation of otherwise unattainable nonnatural saponin analogues.  (+info)

Antiviral activity obtained from aqueous extracts of the Chilean soapbark tree (Quillaja saponaria Molina). (3/15)

Natural, aqueous extracts of Quillaja saponaria, the Chilean soapbark tree, contain several physiologically active triterpenoid saponins that display strong adjuvant activity when used in either human or animal vaccines. In this paper, we describe studies that demonstrate a novel antiviral activity of Quillaja extracts against six viruses: vaccinia virus, herpes simplex virus type 1, varicella zoster virus, human immunodeficiency viruses 1 and 2 (HIV-1, HIV-2) and reovirus. We demonstrate that microgram amounts of extract, while exhibiting no cell cytotoxicity or direct virucidal activity, prevent each of the six viruses tested from infecting their host cells. In addition, the presence of residual amounts of extract continue to block virus infection and render cells resistant to infection for at least 16 h after the removal of the extract from the cell culture medium. We demonstrate that a Quillaja extract possesses strong antiviral activity at concentrations more than 100-fold lower than concentrations that exhibit cell cytotoxicity. Extract concentrations as high as 100 microg ml(-1) are not cytotoxic, but concentrations as low as 0.1 microg ml(-1) are able to block HIV-1 and HIV-2 virus attachment and infection.  (+info)

Synthesis and structure verification of the vaccine adjuvant QS-7-Api. Synthetic access to homogeneous Quillaja saponaria immunostimulants. (4/15)

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ISCOMATRIX adjuvant induces efficient cross-presentation of tumor antigen by dendritic cells via rapid cytosolic antigen delivery and processing via tripeptidyl peptidase II. (5/15)

Cancer vaccines aim to induce antitumor CTL responses, which require cross-presentation of tumor Ag to CTLs by dendritic cells (DCs). Adjuvants that facilitate cross-presentation of vaccine Ag are therefore key for inducing antitumor immunity. We previously reported that human DCs could not efficiently cross-present the full-length cancer/testis Ag NY-ESO-1 to CTL unless formulated as either an immune complex (NY-ESO-1/IC) or with ISCOMATRIX adjuvant. We now demonstrate that NY-ESO-1/ICs induce cross-presentation of HLA-A2- and HLA-Cw3-restricted epitopes via a proteasome-dependent pathway. In contrast, cross-presentation of NY-ESO-1/ISCOMATRIX vaccine was proteasome independent and required the cytosolic protease tripeptidyl peptidase II. Trafficking studies revealed that uptake of ICs and ISCOMATRIX vaccine by DCs occurred via endocytosis with delivery to lysosomes. Interestingly, ICs were retained in lysosomes, whereas ISCOMATRIX adjuvant induced rapid Ag translocation into the cytosol. Ag translocation was dependent on endosomal acidification and IL-4-driven differentiation of monocytes into DCs. This study demonstrates that Ag formulation determines Ag processing and supports a role for tripeptidyl peptidase II in cross-presentation of CTL epitopes restricted to diverse HLA alleles.  (+info)

Design and synthesis of potent Quillaja saponin vaccine adjuvants. (6/15)

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Nanoparticulate Quillaja saponin induces apoptosis in human leukemia cell lines with a high therapeutic index. (7/15)

Saponin fractions of Quillaja saponaria Molina (QS) have cytotoxic activity against cancer cells in vitro, but are too toxic to be useful in the clinic. The toxic effect was abolished by converting QS fractions into stable nanoparticles through the binding of QS to cholesterol. Two fractions of QS were selected for particle formation, one with an acyl-chain (ASAP) was used to form killing and growth-inhibiting (KGI) particles, and the other without the acyl-chain (DSAP) was used to formulate blocking and balancing effect (BBE) particles. KGI showed significant growth inhibiting and cancer cell-killing activities in nine of 10 cell lines while BBE showed that on one cell line. The monoblastoid lymphoma cell line U937 was selected for analyzing the mode of action. Low concentrations of KGI (0.5 and 2 microg/mL) induced irreversible exit from the cell cycle, differentiation measured by cytokine production, and eventually programmed cell death (apoptosis). Compared to normal human monocytes, the U937 cells were 30-fold more sensitive to KGI. The nontoxic BBE blocked the cell killing effect of KGI in a concentration-dependent manner. In conclusion, the formulation of QS into nanoparticles has the potential of becoming a new class of anticancer agents.  (+info)

Prevention of rotavirus infections in vitro with aqueous extracts of Quillaja Saponaria Molina. (8/15)

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