Immunopotentiators

Chitosan also shows immunopotentiating activity the mechanism involves, at least in part, the production of interferon-gamma and the stimulatory effect on nitric oxide production. Chitosan-based dressings also modulate peroxide production [312,314-318]. 

Since plants used as herb medicines contain high amounts of germanium compounds, the latter have been regarded as having immunopotentiation and antitumour activities. At present, organogermanium compounds are mainly used for medical applications. For example, Ge-132 is well known to have not only an antitumour effect, but also to induce interferon (IFN) production in vivo8. 

Hiraoka, A., Shibata, H., andMasaoka, T., Immunopotentiation with Ubenimex for prevention of leukemia relapse after allogeneic BMT. The Study Group of Ubenimex for BMT, Transplant Proc, 24, 3047, 1992. 

Immunopotentiation by Cytosine-Phosphodiester-Guanine-Containing Oligodeoxynucleotides... 

Immunopotentiating reconstituted influenza virosomes (IRTV) are spherical 150-nm sized particles consisting of a phospholipid bilayer in which influenza virus A/Singapore strain-derived hemagglutinin (HA) and neuraminidase (NA) are intercalated. As such, they resemble and mimic the influenza virus envelope. The difference from conventional liposome formulations lies in the inclusion of the viral envelope proteins HA and NA as well as viral phospholipids. Especially, the inclusion of influenza virus HA provides IRIV with delivery and immimogenic capacities. IRTV are licensed for human use as adjuvant in hepatitis A vaccination and as influenza subunit vaccine (1). 

Figure 1 Continued on next page) Immunopotentiating reconstituted influenza virosomes (IRIV) induced antigen specific proliferation of CD4+CD45RO+ cells. (A) Peripheral blood mononuclear cells (PBMQ from healthy donors n=3) were cultured in the absence of stimuli (Neg), in the presence of IRIV (V), and in the presence of control liposomes (L) at the indicated dilutions. Proliferation was measured on day 6 of culture by H-thymidine incorporation. (B) Cord blood mononuclear cells from two donors were cultured in the absence of stimuli (Neg) or in the presence of phytohaemag-glutinin (PHA), concanavalin A (ConA), IRIV (V) or L at the indicated concentrations. Proliferation was measured on day 3 of culture for PHA and ConA cultures and on day 6 for IRIV and L stimulated cultures. (Q Purified CD4+ or CD8+ cells were cocultured with autologous irradiated PBMC in the absence of stimuli (Neg) and in the presence of IRIV (V) at the indicated concentrations. Proliferation was measured on day 6 of culture by H-thymidine incorporation. (D) Purified CD4/CD45RA+ cells and CD4/CD45RO-I-cells were isolated from PBMC of one healthy donor and cocultured with autologous irradiated PBMC in the presence of IRIV (V) or L at the indicated concentration. Proliferation was measured on day 6 of culture by H-thymidine incorporation. Source From Ref 6.

Figure 2 Cytokine gene expression in immunopotentiating reconstituted influenza virosomes (IRIV) stimulated peripheral blood mononuclear cells (PBMC). PBMC were cultured in the presence or absence of IRIV. On days 1 and 2, culture cells were harvested and total cellular RNA was extracted and reverse transcribed. The cDNAs thus obtained were tested in real time polymerase chain reaction assays in the presence of primers specific for the indicated cytokine genes. Source From Refs. 6 and 9.

Figure 3 Cytokine secretion in immunopotentiating reconstituted influenza viro-somes (IRIV)-stimulated peripheral blood mononuclear cells (PBMC). PBMC from a healthy donor were cultured in the absence of stimuli (Neg) or in the presence of IRIV (V, 1 50 diluted) or control liposomes (L, 1 50 diluted). On days 1, 2, and 4 supernatants were harvested and the concentrations of interferon-y (A), GM-CSF (B), TNF-a (C), and interleukin-4 (D) were determined by ELISA. Abbreviations GM-CSF, granulocyte monocyte colony stimulating factor TNF-a, tumor necrosis factor-a. Source From Ref. 6.

Figure 5 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvance on cytotoxic T-cell (CTL) induction. PBMC from a healthy donor were cultured in the presence of influenza matrix (IM)58 66 (A), IMss-eo and control liposomes (B) or IMss-ee and IRIV (C). After a seven-day culture, percentages of IMss-ee speciflc CTL within cultured cells were quantifled by HLA-A0201/IM58 gfi phosphatidylethanolamine tetramer staining (fluorescence 2) and anti CDS fluorescein isothiocyanate staining (fluorescence 1). CTL precursor frequencies detected in IMss-ee and IRIV stimulated cultures within the same experiment are shown in (D). Source From Ref 6.

Figure 6 Immunopotentiating reconstituted influenza virosomes (IRIV) adjuvant effects in the induction of tumor associated antigen-specific cytotoxic T cell. CD14-negative cells from a healthy donor peripheral blood mononuclear cells were cocultured with autologous immature dendritic cells (iDC) in the presence of Melan-A/Mart-l27-35, alone (A) or supplemented with either control liposomes (B) or IRIV (1 50, C). On day 7, culture cells were restimulated with Melan-A/MART-127-35 pulsed iDC and cultured for six further days [see Materials and Methods ]. On day 7 after restimulation cells were stained with fluorescein isothiocyanate-conjugated anti-CD8 and phosphatidylethanolamine-conjugated HL A-A0201 /Melan-A/MART -127-3 5 tetramers. Source From Ref. 6.

Figure 7 Immunopotentiating reconstituted influenza virosomes (IRIV) mediated adjuvance in cytotoxic T-cell induction requires CD4+ T cells. CD8+ and CD14+ cells were cultured in the presence of autologous intact or irradiated CD4+ cells. These cultures were stimulated with influenza matrix (IM)58 66 (1 Pg/mL) alone (A) or supplemented with IRIV (1 50) (B). After seven days of incubation both cocultures were restimulated with irradiated IMss-ee pulsed CD14+ cells and cultured for six further days in the presence of interleukin-2 [see Materials and Methods ]. Six days after restimulation, cultures were stained with HLA-A0201 /IM58-66 PE-specilic tetramers and anti-CD8 fluorescein isothiocyanate monoclonal antibodies. Source. From Ref 6.

Hedyotis diffusa Willd. Bai Hua She Shi Chao (leaf) Acyl flavonol di-gycoside, iridoid glucosides, anthraquinone, essential oils, p-vinylphenol, p-vinylguaiacol, linalool 50,202,203,204,205,206 Immunopotentiation activity, treat tumours, antibacterial, antipyretic, detoxicant, diuretic, anticancer, externally applied as lotion. 

IMMUNOPOTENTIATING EFFECTS OF A GLYCOPROTEIN FROM CHLORELLA VULGARIS STRAIN CK AND ITS CHARACTERISTICS... 

Shek, P. N., and Sabiston, B. H. (1982b) Immune response mediated by liposome-associated protein antigens. II. Comparison of the effectiveness of vesicle-entrapped and surface-associated antigens in immunopotentiation. Immunology 47, 627. 

Novel opioid compounds have been synthesized that have analgesic capacity, but lack immunosuppressive effects or even potentiates immune function [60,123-126]. In this respect, Nowak et al. [123] recently reported that the delta opioid agonist SNC 80 did not alter NK cell, lymphocyte, and macrophage functions following ICV administration [123]. Furthermore, IV administration of SNC 80 was associated with ex vivo immunopotentiation, following an activating challenge. 

Garcon, N. Development and evaluation of AS04, a novel and improved adjuvant system containing MPL and aluminum salt. In Schijns, V., O Hagan, D. (eds), Immunopotentiators in Modem Vaccines. Academic Press, London (2005), pp. 161-178. 

Gluck, R. (1999), Adjuvant activity of immunopotentiating reconstituted influenza viro-somes (IRIVs), Vaccine, 17,1782-1787. 

Its biodegradability and low toxicity in humans have aided the recent increased interest in chitosan as an immunopotentiating agent. In vivo studies have demonstrated that chitosan powder and solution formulations are able to enhance the systemic and mucosal immune responses after nasal vaccine delivery [19, 22, 76],... 

Virosomes are liposomes containing viral fusion proteins that allow efficient entering into cells fusion with endosome membranes. Viral fusion proteins become activated in the low pH environment in the endosome to release its contents into the cytosol. Hepatitis A and influenza vaccines constructed on virosomes elicited fewer local adverse reactions than did their classic counterparts and displayed enhanced immunogenicity. Virosome-formulated influenza vaccine has also been shown to be safe and immunogenic when administered by the intranasal route. Other studies have suggested that immunopotentiating reconstituted influenza virosomes can be a suitable delivery system for synthetic... 

Hayashi, A. Nakanishi, T. Kunisawa, J. Kondoh, M. Imazu, S. Tsutsumi, Y. Tanaka, K. Fujiwara, H. Hamaoka, T. Mayumi, T. A novel vaccine delivery system using immunopotentiating fusogenic liposomes. Biochem. Biophys. Res. Commun. 1999, 261, 824—828. 

Poltl-Frank, F. Zurbriggen, R. Helg, A. Stuart, F. Robinson, J. Gluck, R. Pluschke, G. Use of reconstituted influenza virus virosomes as an immunopotentiating delivery system for a peptide-based vaccine. Clin. Exp. Immunol. 1999, 117, 496-503. 

Maeda YY, Hamuro J, Yamada YO, Ishimura K, Chihara G (1973) In Immunopotentiation. Wolstenholme GEW, Knight J (eds) Elsevier, Excerpta Medica, North-Holland, p 2592 Maeda YY, Chihara G (1971) Nature 229 634 Hamuro J, Rollinghoff M, Wagner H (1978) Cancer Res 38 3080... 

Most of the research on marine compounds with anti-HIV activity has focused on sulphated polysaccharides (PS) and proteins. Sulphated polymannuroguluronate is a marine sulphated PS which has entered phase II clinical trials in China as the first anti-AIDS drug candidate obtained from marine brown algae. Miao et al. [19] investigated the binding site(s) receptors of this compound in lymphocytes mediating its anti-AIDS activities. These results indicate that the interaction of this PS and CD4 may provide a mechanistic explanation of its immunopotentiating and anti-AIDS activities in HIV-infected individuals. 

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