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Sample records for adjuvant induces qualitative

  1. Muramyl dipeptide-induced adjuvant arthritis.

    Nagao, S.; Tanaka, A.

    1980-01-01

    Muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine, induced adjuvant arthritis in WKA rats when injected in a water-in-oil emulsion prepared with Freund incomplete adjuvant (Difco), but not when emulsified with Drackeol and Arlacel A.

  2. Does lipophilicity per se induce adjuvant effects?

    Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.;

    2007-01-01

    ) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al......Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL...

  3. Antigens linked to synthetic microspheres induce immune responses in primates in the absence of adjuvant.

    Sedlik, C; Perraut, R; Bonnemains, B; Leclerc, C

    1996-01-01

    Although most strategies of vaccination require immunopotentiation to induce efficient immune responses, the development of new adjuvants for human vaccines is highly limited by safety problems. In order to overcome this problem, we developed a new vaccine formulation based on the covalent linkage of protein or peptide to synthetic microspheres. In previous experiments performed in mice, we demonstrated that these particulate antigens induce strong antigen-specific CD4+ T cell proliferative responses in the absence of adjuvant. In the present study, we analyzed the immunogenicity in primate Saimiri sciureus monkeys of two different proteins linked to synthetic microspheres. Immune responses induced by these particulate proteins administered without adjuvant were compared to those stimulated by the soluble antigens injected with alum. We currently demonstrated that, in monkeys, particulate antigens administered without adjuvant, induced good PBMC proliferative response and antibody production. Furthermore, the analysis of antibody responses using mAbs specific for different Saimiri sciureus immunoglobulins showed that the antibody response profiles were different in monkeys immunized with soluble versus particulate form of antigens. Results of this study demonstrate that particulate form of antigen may stimulate qualitatively different immune responses as compared to alum and therefore suggest that this new antigen formulation could be an attractive candidate for the development of vaccines. PMID:8852604

  4. CpG ODN and ISCOMATRIX Adjuvant: A Synergistic Adjuvant Combination Inducing Strong T-Cell IFN-γ Responses

    Michael J. McCluskie

    2013-01-01

    Full Text Available For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN containing immunostimulatory CpG motifs (CpG, and ISCOMATRIX adjuvant (ISCOMATRIX, composed of saponin, phospholipid, and cholesterol, which possesses both immunostimulatory and delivery properties. While both individual adjuvants have been shown effective in numerous preclinical and clinical studies, it is likely that for optimal adjuvant activity a combined adjuvant approach will be necessary. Herein, using three different antigens, namely, hepatitis B surface antigen (HBsAg, ovalbumin (OVA, and influenza A haemagglutinin antigen (HA, we show in mice that some adjuvant effects of CpG and ISCOMATRIX are further enhanced if they are used in combination. In particular, with all three antigens, IFN-γ levels were greatly increased with the CpG/ISCOMATRIX combination. The ability of the CpG/ISCOMATRIX combination to induce antitumor responses when administered with OVA following administration to mice of a highly metastatic OVA-secreting tumor cell line (B16-OVA melanoma was also demonstrated. Thus the CpG/ISCOMATRIX combination may prove to be a valuable tool in the development of novel or improved vaccines.

  5. Inducible nitric oxide synthase and guinea-pig ileitis induced by adjuvant

    N. D. Seago

    1995-01-01

    Full Text Available We sought to establish a model of inflammatory bowel disease by augmenting the activity of the local immune system with Freund's complete adjuvant, and to determine if inducible nitric oxide synthase (iNOS expression and peroxynitrite formation accompanied the inflammatory condition. In anaesthetized guinea-pigs, a loop of distal ileum received intraluminal 50% ethanol followed by Freund's complete adjuvant. Control animals were sham operated. When the animals were killed 7 or 14 days later, loop lavage fluid was examined for nitrite and PGE2 levels; mucosal levels of granulocyte and macrophages were estimated by myeloperoxidase (MPO and N-acetyl-D-glucosaminidase (NAG activity, respectively. Cellular localization if iNOS and peroxynitrite formation were determined by immunohistochemistry with polyclonal antibodies directed against peptide epitopes of mouse iNOS and nitrotyrosine, respectfully. Adjuvant administration resulted in a persistent ileitis, featuring gut thickening, crypt hyperplasia, villus tip swelling and disruption, and cellular infiltration. Lavage levels of PGE2 and nitrite were markedly elevated by adjuvant treatment. Immunoreactive iNOS and nitrotyrosine bordered on detectability in normal animals but were markedly evident with adjuvant treatment at day 7 and particularly day 14. Immunohistochemistry suggested that enteric neurons and epithelia were major sites of iNOS activity and peroxynitrite formation. We conclude that local administration of adjuvant establishes a chronic ileitis. Inducible nitric oxide synthase may contribute to the inflammatory process.

  6. Effect of Cornus officinalis glycoside on adjuvant-induced arthritis in rats

    SHI PING ZHAO; JIAN MIN LI; GUI XIANG FU; YONG ZHOU

    2006-01-01

    The aim of this study was to explore the effect of Cornus officinalis glucosides (COG) on adjuvant-induced arthritis in rats and its mechanism. Seventy-two rats were divided into six groups of normal, model, Dexasone (0. 125 mg/kg), high-dose COG (240 mg/kg), mid-dose COG (120 mg/kg),and low-dose COG (60 mg/kg). Rat arthritis was induced by injection of Freund's complete adjuvant in the hind paws. All treatment started from the day the arthritis was induced. The edema degree of the adjuvant injection location was determined on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 20, 23 and the opposite side was observed on days 11, 13, 15, 17, 20, 23 after the injection of adjuvant. All rats were sacrificed on day 24 after the injection of adjuvant for microscopic examination of the ankle, and for the study of the immunological molecular mechanism. The results showed that the COG significantly suppressed both the primary and secondary edema, improved pathological injuries of adjuvant arthritis (AA)rat ankles, significantly suppressed the proliferation of T lymphocytes and DTH reaction. It significantly suppressed IL-1, IL-6 and TNF-α production from peritoneal macrophages and PGE2 in plasma. In conclusion, the Cornus officinalis glucosides (COG) is able to prevent and cure the rat adjuvant-induced arthritis, and can suppress the production of pro-inflammatory cytokine IL-1, IL-6, TNF-α and PGE2.

  7. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine. PMID:27228647

  8. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) 2013: Unveiling the pathogenic, clinical and diagnostic aspects.

    Perricone, Carlo; Colafrancesco, Serena; Mazor, Roei D; Soriano, Alessandra; Agmon-Levin, Nancy; Shoenfeld, Yehuda

    2013-12-01

    In 2011 a new syndrome termed 'ASIA Autoimmune/Inflammatory Syndrome Induced by Adjuvants' was defined pointing to summarize for the first time the spectrum of immune-mediated diseases triggered by an adjuvant stimulus such as chronic exposure to silicone, tetramethylpentadecane, pristane, aluminum and other adjuvants, as well as infectious components, that also may have an adjuvant effect. All these environmental factors have been found to induce autoimmunity by themselves both in animal models and in humans: for instance, silicone was associated with siliconosis, aluminum hydroxide with post-vaccination phenomena and macrophagic myofasciitis syndrome. Several mechanisms have been hypothesized to be involved in the onset of adjuvant-induced autoimmunity; a genetic favorable background plays a key role in the appearance on such vaccine-related diseases and also justifies the rarity of these phenomena. This paper will focus on protean facets which are part of ASIA, focusing on the roles and mechanisms of action of different adjuvants which lead to the autoimmune/inflammatory response. The data herein illustrate the critical role of environmental factors in the induction of autoimmunity. Indeed, it is the interplay of genetic susceptibility and environment that is the major player for the initiation of breach of tolerance. PMID:24238833

  9. CpG ODN and ISCOMATRIX Adjuvant: A Synergistic Adjuvant Combination Inducing Strong T-Cell IFN-γ Responses

    Michael J. McCluskie; Weeratna, Risini D.; Evans, Dana M.; Shawn Makinen; Debbie Drane; Heather L. Davis

    2013-01-01

    For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG), and ISCOMATRIX adjuvant (ISCOMATRIX), composed of saponin, phospholipid, and cholesterol, which possesses both immunostim...

  10. An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice

    Cherukuri Anu

    2012-10-01

    Full Text Available Abstract Background Respiratory Syncytial Virus (RSV causes significant disease in the elderly, in part, because immunosenescence impairs protective immune responses to infection in this population. Despite previous and current efforts, there is no RSV vaccine currently licensed in infants or elderly adults. Adjuvanted RSV subunit vaccines have the potential to boost waning immune responses and reduce the burden of RSV disease in the elderly population. Results We used an aged BALB/c mouse model to evaluate immune responses to RSV Fusion (F protein in the absence and presence of an alum adjuvant. We demonstrate that aged BALB/c mice immunized with alum-adjuvanted RSV F protein had significantly reduced lung viral titers at day 4 following challenge with wild-type (wt RSV. Serum neutralizing antibody titers measured on day 27 correlated with protection in both young and aged vaccinated mice, although the magnitude of antibody titers was lower in aged mice. Unlike young mice, in aged mice, alum-adjuvanted RSV F did not induce lung TH2-type cytokines or eosinophil infiltration compared to non-adjuvanted F protein following wt RSV challenge. Conclusion Our studies demonstrate that neutralizing anti-RSV antibody titers correlate with protection in both young and aged BALB/c mice vaccinated with RSV F protein vaccines. The F + alum formulation mediated greater protection compared to the non-adjuvanted F protein in both young and aged mice. However, while alum can boost F-specific antibody responses in aged mice, it does not completely overcome the reduced ability of a senescent immune system to respond to the RSV F antigen. Thus, our data suggest that a stronger adjuvant may be required for the prevention of RSV disease in immunosenescent populations, to achieve the appropriate balance of protective neutralizing antibodies and effective TH1-type cytokine response along with minimal lung immunopathology.

  11. Adjuvant oil induces waves of arthritogenic lymph node cells prior to arthritis onset.

    Holm, Barbro; Lorentzen, J C; Bucht, A

    2004-01-01

    A single intradermal injection of the adjuvant-oil squalene induces T cell mediated arthritis in DA rats. The chain of events leading from nonspecific provocation of the immune system to arthritis is largely unknown. Previous studies have demonstrated that lymph node (LN) cells are of pathogenic importance, i.e. cells from LNs draining the injection site can transfer arthritis to naïve DA rats. Recently we have demonstrated cellular uptake of adjuvant oil in draining lymph nodes but also that...

  12. How do surgeons decide to refer patients for adjuvant cancer treatment? Protocol for a qualitative study

    Urquhart Robin

    2012-10-01

    Full Text Available Abstract Background Non-small cell lung cancer, breast cancer, and colorectal cancer are commonly diagnosed cancers in Canada. Patients diagnosed with early-stage non-small cell lung, breast, or colorectal cancer represent potentially curable populations. For these patients, surgery is the primary mode of treatment, with (neoadjuvant therapies (e.g., chemotherapy, radiotherapy recommended according to disease stage. Data from our research in Nova Scotia, as well as others’, demonstrate that a substantial proportion of non-small cell lung cancer and colorectal cancer patients, for whom practice guidelines recommend (neoadjuvant therapy, are not referred for an oncologist consultation. Conversely, surveillance data and clinical experience suggest that breast cancer patients have much higher referral rates. Since surgery is the primary treatment, the surgeon plays a major role in referring patients to oncologists. Thus, an improved understanding of how surgeons make decisions related to oncology services is important to developing strategies to optimize referral rates. Few studies have examined decision making for (neoadjuvant therapy from the perspective of the cancer surgeon. This study will use qualitative methods to examine decision-making processes related to referral to oncology services for individuals diagnosed with potentially curable non-small cell lung, breast, or colorectal cancer. Methods A qualitative study will be conducted, guided by the principles of grounded theory. The study design is informed by our ongoing research, as well as a model of access to health services. The method of data collection will be in-depth, semi structured interviews. We will attempt to recruit all lung, breast, and/or colorectal cancer surgeons in Nova Scotia (n ≈ 42, with the aim of interviewing a minimum of 34 surgeons. Interviews will be audiotaped and transcribed verbatim. Data will be collected and analyzed concurrently, with two investigators

  13. Influence of adjuvants on protection induced by a recombinant fusion protein against malarial infection.

    Daly, T M; Long, C A

    1996-01-01

    Previously, we described a protective immune response induced by the carboxyl-terminal region of the merozoite surface protein-1 (MSP-1) from the rodent malarial parasite Plasmodium yoelii yoelii 17XL, expressed as a fusion protein and designated glutathione S-transferase (GST)-PYC2. We also demonstrated that the humoral response induced by GST-PYC2 was the primary mechanism by which immunized animals controlled their blood-stage infections. We have now examined the influence of several adjuv...

  14. PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway

    Dool-Ri Oh

    2014-01-01

    Full Text Available Toll-like receptor (TLR ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.

  15. PMA Induces Vaccine Adjuvant Activity by the Modulation of TLR Signaling Pathway

    Oh, Dool-Ri; Kang, Hu Won; Kim, Jong-Ro; Kim, Sunoh; Park, In-Kyu; Rhee, Joon Haeng; Oh, Won Keun; Kim, Young Ran

    2014-01-01

    Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract from Croton tiglium showed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component from Croton tiglium and to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component of Croton tiglium by activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant. PMID:24948847

  16. Synergy between adjuvant arthritis and collagen-induced arthritis in rats

    1985-01-01

    Adjuvant arthritis (AA) in rats is susceptible to cell-mediated passive transfer. Collagen-induced arthritis (CIA) in rats is susceptible to passive transfer with antibody to type II collagen. We report here the development of strikingly severe arthritis in Lewis rats as the result of synergy between passively transferred antibody to type II collagen from rats with CIA and concanavalin A (Con A)-stimulated lymph node or spleen cells from syngeneic rats with AA. Similar synergy was seen in rat...

  17. Self-Adjuvanting Bacterial Vectors Expressing Pre-Erythrocytic Antigens Induce Sterile Protection against Malaria

    Elke eBergmann-Leitner

    2013-07-01

    Full Text Available Genetically inactivated, Gram-negative bacteria that express malaria vaccine candidates represent a promising novel self-adjuvanting vaccine approach. Antigens expressed on particulate bacterial carriers not only target directly to antigen-presenting cells but also provide a strong danger signal thus circumventing the requirement for potent extraneous adjuvants. E. coli expressing malarial antigens resulted in the induction of either Th1 or Th2 biased responses that were dependent on both antigen and sub-cellular localization. Some of these constructs induced higher quality humoral responses compared to recombinant protein and most importantly they were able to induce sterile protection against sporozoite challenge in a murine model of malaria. In light of these encouraging results, two major Plasmodium falciparum pre-erythrocytic malaria vaccine targets, the Cell-Traversal protein for Ookinetes and Sporozoites (CelTOS fused to the Maltose-binding protein in the periplasmic space and the Circumsporozoite Protein (CSP fused to the Outer membrane protein A in the outer membrane were expressed in a clinically relevant, attenuated Shigella strain (Shigella flexneri 2a. This type of live attenuated vector has previously undergone clinical investigations as a vaccine against shigellosis. Using this novel delivery platform for malaria, we find that vaccination with the whole organism represents an effective vaccination alternative that induces protective efficacy against sporozoite challenge. Shigella GeMI-Vax expressing malaria targets warrant further evaluation to determine their full potential as a dual disease, multivalent, self-adjuvanting vaccine system, against both shigellosis and malaria.

  18. Aluminum hydroxide adjuvant induces macrophage differentiation towards a specialized antigen-presenting cell type.

    Rimaniol, Anne-Cécile; Gras, Gabriel; Verdier, François; Capel, Francis; Grigoriev, Vladimir B; Porcheray, Fabrice; Sauzeat, Elisabeth; Fournier, Jean-Guy; Clayette, Pascal; Siegrist, Claire-Anne; Dormont, Dominique

    2004-08-13

    Aluminum hydroxide (AlOOH) has been used for many years as a vaccine adjuvant, but little is known about its mechanism of action. We investigated in this study the in vitro effect of aluminum hydroxide adjuvant on isolated macrophages. We showed that AlOOH-stimulated macrophages contain large and persistent intracellular crystalline inclusions, a characteristic property of muscle infiltrated macrophages described in animal models of vaccine injection, as well as in the recently described macrophagic myofasciitis (MMF) histological reaction in humans. AlOOH-loaded macrophages exhibited phenotypical and functional modifications, as they expressed the classical markers of myeloid dendritic cells (HLA-DR(high)/CD86(high)/CD83(+)/CD1a(-)/CD14(-)) and displayed potent ability to induce MHC-II-restricted antigen specific memory responses, but kept a macrophage morphology. This suggests a key role of macrophages, in the reaction to AlOOH-adjuvanted vaccines and these mature antigen-presenting macrophages may therefore be of particular importance in the establishment of memory responses and in vaccination mechanisms leading to long-lasting protection. PMID:15297065

  19. A Nomogram for Predicting the Benefit of Adjuvant Cytokine-Induced Killer Cell Immunotherapy in Patients with Hepatocellular Carcinoma

    Qiu-Zhong Pan; Qi-Jing Wang; Jia-Qiang Dan; Ke Pan; Yong-Qiang Li; Yao-Jun Zhang; Jing-Jing Zhao; De-Sheng Weng; Yan Tang; Li-Xi Huang; Jia He; Shi-Ping Chen; Miao-La Ke; Min-Shan Chen; Wicha, Max S.

    2015-01-01

    The benefits of adjuvant cytokine-induced killer (CIK) cell immunotherapy for hepatocellular carcinoma (HCC) remain mixed among patients. Here, we constructed a prognostic nomogram to enable individualized predictions of survival benefit of adjuvant CIK cell treatment for HCC patients. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) for patients in the hepatectomy/CIK combination group were 41 and 16 months, respectively, compared to 28 and 1...

  20. Th immune response induced by H pylori vaccine with chitosan as adjuvant and its relation to immune protection

    Yong Xie; Nan-Jin Zhou; Yan-Feng Gong; Xiao-Jiang Zhou; Jiang Chen; Si-Juan Hu; Nong-Hua Lu; Xiao-Hua Hou

    2007-01-01

    was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant (P < 0.05). After challenge, the level of IL-4 was significantly higher in the groups with chitosan particles as an adjuvant than in the group with CT as an adjuvant (P < 0.05), and in the group with chitosan solution as an adjuvant, the level of IL-4 was significantly higher than that in control group, non-adjuvant group and the groups with CT (P < 0.05 or 0.001). The ratio of anti- H pylori IgG2a/IgGl in serum was significantly lower in the groups with chitosan as an adjuvant than in the groups with CT as an adjuvant or without adjuvant (P < 0.01).CONCLUSION: H pylori vaccine with chitosan as an adjuvant can protect against H pylori infection and induce both Thl and Th2 type immune response.

  1. Gemcitabine-Induced Pulmonary Toxicity During Adjuvant Therapy in a Patient with Pancreatic Cancer

    Walid Shaib

    2008-11-01

    Full Text Available Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitabine is the accepted standard for the adjuvant and metastatic treatment of pancreatic cancer, however, it also has indications in breast, ovarian, and non-small cell lung cancers. The most common side effect is myelosuppression. Dyspnea is reported in 23% and bronchospasm occurs in less than 2% of subjects. Acute respiratory distress syndrome is rare with single agent use or in combination. Case report A 68-year-old man being treated for stage IIA pancreatic cancer after pancreaticoduodenectomy developed hypoxemic respiratory distress after the second dose of gemcitabine 1,000 mg/m2. The radiographic findings on computed tomography scans evolved from ground glass opacities to findings suggestive of cryptogenic organizing pneumonia over the course of two weeks. He was treated with antibiotics, steroids, nebulizers and oxygen. A follow-up computed tomography scan of chest four weeks after presentation showed complete resolution of pneumonitis. Conclusions We report the first case of gemcitabine-induced pneumonitis encountered during the adjuvant treatment of pancreatic cancer. Physicians seeing such patients should be aware of this rare but real pulmonary toxicity. A delay in diagnosis and treatment can lead to potentially fatal outcomes.

  2. The effect of adjuvants on the immune response induced by a DBL4e-ID4 VAR2CSA based Plasmodium falciparum vaccine against placental malaria

    Pinto, V V; Salanti, A; Joergensen, L M;

    2012-01-01

    720, Alhydrogel(®) and CAF01. Antibodies induced against DBL4¿-ID4 in combination with these adjuvants inhibited parasite binding to CSA from 82% to 99%. Although, different epitope recognition patterns were obtained for the different formulations, all adjuvant combinations induced strong Th1 and Th2...

  3. Therapeutic effects of Hominis placenta herb-acupuncture in adjuvant-induced arthritis rat

    MiJung Yeom

    2002-02-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory autoimmune disease, characterized by leukocyte infiltration, a chronic inflammation of the joint, a pannus formation and the extensive destruction of the articular cartilage and bone. Several proinflammatory cytokines such as tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β and interleukin 6 (IL-6 have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. In the Korean traditional medicine, Hominis placenta (HP as an herbal solution of herb-acupuncture has been widely used to treat the inflammatory diseases including RA. In order to study the medicinal effect of HP herb-acupuncture on rheumatoid joint, an adjuvant-induced arthritis (AIA was generated by the injection of 1.5 mg of Mycobacterium tuberculosis, emulsified in squalene, to the base of the tail of Spraque-Dawley (SD rats. After onset stage of polyarthritis, HP was daily injected to the Zusanli (ST36 acupuncture points in both of rat lags and the expression patterns of cytokines such as TNF-α, IL-1β, and IL-6 at the knee joint were analyzed using immunostaining and RT-PCR. The HP herb-acupuncture was found to be effective to alleviate the arthritic symptoms in adjuvant-induced arthritic rats as regards the joint appearance and the expression profiles of inflammatory cytokines. In conclusion, therapeutic effects of HP herb-acupuncture on the rat with AIA might be related to anti-inflammatory activities of the hurb-acupuncture.

  4. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    Shankar, J. [Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago (United States); Thippegowda, P.B., E-mail: btprabha@uic.edu [Department of Pharmacology, (M/C 868), College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Ave., Chicago, IL 60612 (United States); Kanum, S.A. [Department of Chemistry, Yuvaraj' s College, University of Mysore, Mysore (India)

    2009-09-18

    Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.

  5. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    Jing ZHANG; Pei LI; Hai-fang GUO; Li LIU; Xiao-dong LIU

    2012-01-01

    Aim:To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker.Methods:The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats.PGE2 level in the rats was measured using an enzyme immunoassay.A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production.The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE2 production in blood cells was investigated in vitro.Results:Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats.Diclofenac significantly decreased the plasma levels of PGE2 in both normal and arthritic rats.The inhibitory effect on PGE2 levels in the plasma was in proportion to the plasma concentration of diclofenac.No delay in the onset of inhibition was observed,suggesting that the effect compartment was located in the central compartment.An inhibitory effect sigmoid/max model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production in vivo.The /max model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE2 production in blood cells in vitro.Conclusion:Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats,but the pharmacodynamics of diclofenac is slightly affected.A PK-PD model characterizing an inhibitory effect sigmoid /max can be used to fit the relationship between the plasma PGE2 and diclofenac levels in both normal rats and FCA-induced arthritic rats.

  6. Qualitative Immune Modulation by Interleukin-2 (IL-2) Adjuvant Therapy in Immunological Non Responder HIV-Infected Patients

    Francesca Sabbatini; Alessandra Bandera; Giulio Ferrario; Daria Trabattoni; Giulia Marchetti; Fabio Franzetti; Mario Clerici; Andrea Gori

    2010-01-01

    BACKGROUND: Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs). METHODS AND FINDINGS: PBMC from 12 immunological non-responders (INRs) (CD4+

  7. The Potential Therapeutic Effect of Curcumin on the Adjuvant-induced Arthritis in Irradiated Rats

    Naturalistic that provide medical or health benefits, including prevention and treatment of diseases. They may be advantageous in inflammation and exposure to radiation. The study was conducted to investigate curcumin potential to modulate, counteract or prevent the inflammatory response induced in arthritic irradiated and non-irradiated rats using the adjuvant-induced arthritis model. Diclofenac was used as a reference standard non-steroidal anti-inflammatory drug (NSAID). Results indicated that exposure of rats to single dose of gamma-radiation (6 Gy) before induction of inflammation increased production of prostaglandin E2 (PGE2), tumour necrosis factor-gamma (TNF-gamma) and malondialdehyde (MDA) levels in serum. Blood glutathione (GSH) was shown to be reduced in irradiated animals. Curcumin suppressed the elevated levels of TNF-gamma, PGE2 and MDA and was able to restore blood GSH level. Reduction in liver contents of copper (Cu), zinc (Zn), selenium (Se) and iron (Fe) was recorded in animals irradiated before induction of inflammation. In addition, curcumin restored the hepatic contents of these trace elements. The present results suggest that irradiation of rats caused marked changes in the inflammatory response, while curcumin suppressed the inflammatory response in both irradiated and normal rats

  8. Experimental investigation of anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats

    Patel Pinal; Patel Dharmik; Patel Natvarlal

    2012-01-01

    Pleurotus sajorcaju (P.sajorcaju),an edible and non-toxic mushroom,was evaluated as antioxidant,antitumor,anti-inflammatory and antihypertensive activities.P.sajorcaju is a good source of carbohydrates,dietary fiber,essential amino acids,minerals,vitamin B,folic acid and steroids.Anti-inflammatory,immunomodulatory and analgesic activities of aqueous and methanolic extracts of mycelium of P.sajorcaju were investigated (data is not shown).This finding suggests that extracts of P.sajorcaju can be used against inflammatory and autoimmune disease.So,P.sajorcaju examined for its antiarthritic activity.Plant was collected and separately extracted with water and methanol.For antiarthritic activity 500 and 1 000 mg·kg-1 of both extracts were prepared and administered by oral route.Body weight,paw edema (inflammation),hematological parameter,spleen weight,radiological and histological analysis of bone damage were assessed in rats with Freund's adjuvant induced paw inflammation.Both extracts showed significant and dose-dependent anti-inflammatory and anti-arthritic effects compared to control group.

  9. Electroacupuncture Inhibits Inflammation Reaction by Upregulating Vasoactive Intestinal Peptide in Rats with Adjuvant-Induced Arthritis

    Tian-Feng He

    2011-01-01

    Full Text Available Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA. However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36, Xuanzhong (GB39; and Shenshu (BL23 markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP, a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r=−0.483, P=.0026. In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.

  10. Glutaminase Increases in Rat Dorsal Root Ganglion Neurons after Unilateral Adjuvant-Induced Hind Paw Inflammation

    E. Matthew Hoffman

    2016-01-01

    Full Text Available Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir with quantitative image analysis of L4 dorsal root ganglion (DRG neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm2, presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy.

  11. Glutaminase Increases in Rat Dorsal Root Ganglion Neurons after Unilateral Adjuvant-Induced Hind Paw Inflammation.

    Hoffman, E Matthew; Zhang, Zijia; Schechter, Ruben; Miller, Kenneth E

    2016-01-01

    Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir) with quantitative image analysis of L4 dorsal root ganglion (DRG) neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA) compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm²), presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy. PMID:26771651

  12. Xanthones from Securidaca inappendiculata exert significant therapeutic efficacy on adjuvant-induced arthritis in mice.

    Zuo, Jian; Xia, Yan; Li, Xiang; Chen, Jian-Wei

    2014-06-01

    The study was designed to investigate effects of the xanthones from Securidaca inappendiculata on adjuvant-induced arthritis (AA) mice in vivo. Arthritis severity was evaluated by arthritic score, body weight loss, paw circumference, histological changes and hyperplasia of lymphatic tissues. Plasma samples were collected for estimation of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) using enzyme-linked immunosorbent assay method. The levels of glutathione (GSH), malondialdehyde (MDA), N-acetyl glucosaminidase (NAG) and sialic acid (SA) in liver were assessed by colorimetric method. Xanthones significantly ameliorated the severity of AA indicated by the physical parameters changes, and reverted the abnormal changes of MDA, GSH, NAG and SA in liver. Levels of IL-1, TNF-α, MCP-1 and VEGF reduced dramatically meanwhile. The effects of xanthones on AA were the outcome of the multitargets activities, and probably associated with NF-κB signaling pathway. PMID:24419745

  13. The Experimental Study on Chaenomelis Fructus(木瓜) in Case of the Arthritis Induced by Injecting Freund's Complete Adjuvant

    Kwon, Kang; Park, Ki-Chul; Sohn, Seong-Hyun; Park, Hee-Soo

    2003-01-01

    Objective : We carried out this experimental study in order to investigate the effect of Chaenomelis Fructus(목과(木瓜)) extract and herbal-acupuncture on the arthritis induced by injecting Freund's complete adjuvant. Methods : 1.We categorized SD-rats into five groups as followings. ① Control: Without any Treat ② Treat I: treated by acupuncture ③ Treat II: treated by drinking 5% saline ④ Treat III: treatedbydrinking Chaenomelis Fructus(木瓜)) extract ⑤ Treat IV: treated by Chaeno...

  14. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats

    Zheng ZL

    2015-08-01

    Full Text Available Zhaoling Zheng,1,* YanHua Sun,2,* Ziliang Liu,1 Mingqin Zhang,1 Chunqing Li,1 Hui Cai3 1Department of Traditional Chinese Medicine, Dongying People’s Hospital, Dongying, 2Shandong Provincial Key Laboratory of Microparticles Drug Delivery Technology, Jinan, 3Department of Integrated Traditional Chinese Medicine and Western Medicine, Nanjing Jinling Hospital, Nanjing, People’s Republic of China *These authors contributed equally to this work Background: Rheumatoid arthritis (RA, induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM, a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1 examining the therapeutic effect of CM administered via intravenous (iv injection on RA and 2 formulating the drug into oil–water nanoemulsions (Ns to overcome the low oral bioavailability of CM and achieve oral delivery of the drug.Methods: The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high

  15. Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats.

    Sukketsiri, Wanida; Chonpathompikunlert, Pennapa; Tanasawet, Supita; Choosri, Nutjanat; Wongtawatchai, Tulaporn

    2016-06-01

    Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund's adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity. PMID:27390722

  16. Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats

    Sukketsiri, Wanida; Chonpathompikunlert, Pennapa; Tanasawet, Supita; Choosri, Nutjanat; Wongtawatchai, Tulaporn

    2016-01-01

    Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund’s adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity. PMID:27390722

  17. Imaging of Carrageenan-Induced Local Inflammation and Adjuvant-Induced Systemic Arthritis with [11C]PBR28 PET

    Shao, Xia; Wang, Xueding; English, Sean J; Desmond, Timothy; Sherman, Phillip S; Quesada, Carole A; Piert, Morand R

    2013-01-01

    Introduction [11C]PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. Methods Acute inflammation was induced by local Carrageenan-injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [11C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak 11C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [11C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. Results LPS-stimulated macrophages displayed dose-dependent increased [11C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of Carrageenan-treated paws was significantly increased compared to controls. Also, the [11C]PBR28 uptake ratio of Carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [11C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. Conclusions Based on our initial data, [11C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving

  18. Delivery of an inactivated avian influenza virus vaccine adjuvanted with poly(D,L-lactic-co-glycolic acid) encapsulated CpG ODN induces protective immune responses in chickens.

    Singh, Shirene M; Alkie, Tamiru N; Nagy, Éva; Kulkarni, Raveendra R; Hodgins, Douglas C; Sharif, Shayan

    2016-09-14

    In poultry, systemic administration of commercial vaccines consisting of inactivated avian influenza virus (AIV) requires the simultaneous delivery of an adjuvant (water-in-oil emulsion). These vaccines are often limited in their ability to induce quantitatively better local (mucosal) antibody responses capable of curtailing virus shedding. Therefore, more efficacious adjuvants with the ability to provide enhanced immunogenicity and protective anti-AIV immunity in chickens are needed. While the Toll-like receptor (TLR) 21 agonist, CpG oligodeoxynucleotides (ODNs) has been recognized as a potential vaccine adjuvant in chickens, poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles, successfully tested as vaccine delivery systems in other species, have not been extensively explored. The present study, therefore, assessed both systemic and mucosal antibody-mediated responses following intramuscular vaccination (administered at 7 and 21days post-hatch) of chickens with PLGA encapsulated H9N2 AIV plus encapsulated CpG ODN 2007 (CpG 2007), and nonencapsulated AIV plus PLGA encapsulated CpG 2007 vaccine formulations. Virus challenge was performed at 2weeks post-secondary vaccination using the oculo-nasal route. Our results showed that chickens vaccinated with the nonencapsulated AIV vaccine plus PLGA encapsulated CpG 2007 developed significantly higher systemic IgY and local (mucosal) IgY antibodies as well as haemagglutination inhibition antibody titres compared to PLGA encapsulated AIV plus encapsulated CpG 2007 vaccinated chickens. Furthermore, chickens that received CpG 2007 as an adjuvant in the vaccine formulation had antibodies exhibiting higher avidity indicating that the TLR21-mediated pathway may enhance antibody affinity maturation qualitatively. Collectively, our data indicate that vaccination of chickens with nonencapsulated AIV plus PLGA encapsulated CpG 2007 results in qualitatively and quantitatively augmented antibody responses leading to a reduction in

  19. [Influenza vaccine and adjuvant].

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  20. alpha-Galactosylceramide can act as a nasal vaccine adjuvant inducing protective immune responses against viral infection and tumor.

    Ko, Sung-Youl; Ko, Hyun-Jeong; Chang, Woo-Sung; Park, Se-Ho; Kweon, Mi-Na; Kang, Chang-Yuil

    2005-09-01

    alpha-Galactosylceramide (alpha-GalCer) is a ligand of invariant Valpha14+ NKT cells and is presented by CD1d molecule on APC. NKT cells produce a large amount of Th1 and Th2 cytokines in response to alpha-GalCer-presented APC. In this study, we assessed whether alpha-GalCer could act as an effective nasal vaccine adjuvant for mucosal vaccine that would be capable of inducing systemic as well as mucosal immune responses. When alpha-GalCer was administered with OVA via the intranasal route to C57BL/6 and BALB/c mice, significant OVA-specific mucosal secretory IgA, systemic IgG, and CTL responses were induced with mixed Th1 and Th2 cytokine profiles seen in both strains of mice. Interestingly, as BALB/c mice were intranasally immunized with PR8 hemagglutinin Ag isolated from influenza virus A/PR/8/34 together with alpha-GalCer, significant protection was afforded against influenza viral infection. When alpha-GalCer was coimmunized with a replication-deficient live adenovirus to BALB/c mice, it significantly induced both humoral and cellular immune responses. In addition, intranasal administration of OVA with alpha-GalCer showed complete protection against EG7 tumor challenge in C57BL/6. The adjuvant effects induced by intranasal coadministration with alpha-GalCer were blocked in CD1d-/- mice, indicating that the immune responses were exclusively mediated by CD1d molecule on APC. Most interestingly, intranasally coadministered alpha-GalCer activated naive T cells and triggered them to differentiate into functional effector T cells when CFSE-labeled OT-1 cells were adoptively transferred into syngeneic mice. Overall, our results are the first to show that alpha-GalCer can act as a nasal vaccine adjuvant inducing protective immune responses against viral infections and tumors. PMID:16116223

  1. Pathogen-Mimicking Polymeric Nanoparticles based on Dopamine Polymerization as Vaccines Adjuvants Induce Robust Humoral and Cellular Immune Responses.

    Liu, Qi; Jia, Jilei; Yang, Tingyuan; Fan, Qingze; Wang, Lianyan; Ma, Guanghui

    2016-04-01

    Aiming to enhance the immunogenicity of subunit vaccines, a novel antigen delivery and adjuvant system based on dopamine polymerization on the surface of poly(D,L-lactic-glycolic-acid) nanoparticles (NPs) with multiple mechanisms of immunity enhancement is developed. The mussel-inspired biomimetic polydopamine (pD) not only serves as a coating to NPs but also functionalizes NP surfaces. The method is facile and mild including simple incubation of the preformed NPs in the weak alkaline dopamine solution, and incorporation of hepatitis B surface antigen and TLR9 agonist unmethylated cytosine-guanine (CpG) motif with the pD surface. The as-constructed NPs possess pathogen-mimicking manners owing to their size, shape, and surface molecular immune-activating properties given by CpG. The biocompatibility and biosafety of these pathogen-mimicking NPs are confirmed using bone marrow-derived dendritic cells. Pathogen-mimicking NPs hold great potential as vaccine delivery and adjuvant system due to their ability to: 1) enhance cytokine secretion and immune cell recruitment at the injection site; 2) significantly activate and maturate dendritic cells; 3) induce stronger humoral and cellular immune responses in vivo. Furthermore, this simple and versatile dopamine polymerization method can be applicable to endow NPs with characteristics to mimic pathogen structure and function, and manipulate NPs for the generation of efficacious vaccine adjuvants. PMID:26849717

  2. Trypanosoma cruzi adjuvants potentiate T cell-mediated immunity induced by a NY-ESO-1 based antitumor vaccine.

    Caroline Junqueira

    Full Text Available Immunological adjuvants that induce T cell-mediate immunity (TCMI with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL and CpGs oligodeoxynucleotides (CpG ODNs derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL, lipopeptide (Pam3Cys, and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+ T and CD8(+ T cell responses. In particular, both GIPLs (GTH, and GY and CpG ODNs (B344, B297 and B128 derived from T. cruzi elicited interferon-gamma (IFN-γ production by CD4(+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception. The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+ T and CD8(+ T cell responses elicited by a specific immunological adjuvant.

  3. Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: A prospective study

    梁雪峰

    2013-01-01

    Objective To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy.Methods One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study,and they were randomized into2 groups,i.e.,treatment group,which received the therapy of CIK cells transfusion,and control group,

  4. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  5. Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

    Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

    2011-10-01

    Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. PMID:21693118

  6. Gemcitabine-Induced Pulmonary Toxicity During Adjuvant Therapy in a Patient with Pancreatic Cancer

    Walid Shaib; Frederick Lansigan; Daniel Cornfeld; Kostas Syrigos; Muhammad Wasif Saif

    2008-01-01

    Context Gemcitabine is a pyrimidine antimetabolite with activity in a number of cancers. Gemcitabine is the accepted standard for the adjuvant and metastatic treatment of pancreatic cancer, however, it also has indications in breast, ovarian, and non-small cell lung cancers. The most common side effect is myelosuppression. Dyspnea is reported in 23% and bronchospasm occurs in less than 2% of subjects. Acute respiratory distress syndrome is rare with single agent use or in combination. Case re...

  7. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A⁎02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A⁎02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties

  8. Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats.

    Jiang, Hui; Liu, Jian; Wang, Ting; Gao, Jia-Rong; Sun, Yue; Huang, Chuan-Bing; Meng, Mei; Qin, Xiu-Juan

    2016-09-01

    To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26856389

  9. Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats

    Pankaj S. Kothavade

    2015-01-01

    Full Text Available Objective. Achyranthes aspera Linn. (AA is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction of Achyranthes aspera in adjuvant-induced arthritic rats. Methods. Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine and in vivo antioxidant parameters were measured on the last day of the study. Results. SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints. Conclusion. These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats.

  10. Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules

    Liebmann, A.; Hindemith, M.; Jahns, J.; Kamprad, F.; Hildebrandt, G. [Dept. of Radiotherapy and Radiooncology, Univ. of Leipzig (Germany); Madaj-Sterba, P.; Weisheit, S. [Medical-Experimental Center, Univ. of Leipzig (Germany)

    2004-03-01

    Background and purpose: low-dose radiotherapy is widely accepted as a very effective treatment option for inflammatory symptoms associated with painful degenerative joint disorders. Radiation doses and fractionation schedules in practical use are empirical and mainly based on clinical observations. Experimental data are rare. The efficacy of low-dose X-irradiation on adjuvant induced arthritis in rats using different fractionation schemes was investigated in vivo, in order to explore whether there is a dose and fractionation dependence. Material and methods: adjuvant arthritis in female lewis rats (n = 128) was induced by intradermal injection of heat-inactivated Mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham-irradiated (group 1: days 10-14; group 2: days 15-19; group 3: days 22-26) or X-irradiated with either 5 x 1.0 Gy (group 4: days 10-14; group 6: days 15-19; group 8: days 22-26; group 10: days 10, 12, 14, 16, and 18) or 5 x 0.5 Gy (group 5: days 10-14; group 7: days 15-19; group 9: days 22-26; group 11: days 10, 12, 14, 16, and 18; group 12: days 10-14 and 22-26). The clinical parameters arthritis score (AS), hind paw volume (HPV), and body weight were determined. Results: a significant decrease of the clinical arthritis parameters was observed following 5 x 0.5 Gy or 5 x 1.0 Gy during the acute maximum of the inflammatory response (days 15-19). The most pronounced treatment effect was reached after two daily fractionated series of 5 x 0.5 Gy with an early treatment onset (days 10-14) and repetition in interval (days 22-26). After the application of 5 x 1.0 Gy on days 10-14 or in a protracted scheme (days 10, 12, 14, 16, and 18), only a nonsignificant positive trend could be detected. Daily fractionated X-irradiation in the chronic phase of adjuvant arthritis (days 22-26) did not show any positive clinical effect. Conclusion: low-dose radiotherapy is able to prevent a full-blown arthritic reaction if given during the florid phase of

  11. Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules

    Background and purpose: low-dose radiotherapy is widely accepted as a very effective treatment option for inflammatory symptoms associated with painful degenerative joint disorders. Radiation doses and fractionation schedules in practical use are empirical and mainly based on clinical observations. Experimental data are rare. The efficacy of low-dose X-irradiation on adjuvant induced arthritis in rats using different fractionation schemes was investigated in vivo, in order to explore whether there is a dose and fractionation dependence. Material and methods: adjuvant arthritis in female lewis rats (n = 128) was induced by intradermal injection of heat-inactivated Mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham-irradiated (group 1: days 10-14; group 2: days 15-19; group 3: days 22-26) or X-irradiated with either 5 x 1.0 Gy (group 4: days 10-14; group 6: days 15-19; group 8: days 22-26; group 10: days 10, 12, 14, 16, and 18) or 5 x 0.5 Gy (group 5: days 10-14; group 7: days 15-19; group 9: days 22-26; group 11: days 10, 12, 14, 16, and 18; group 12: days 10-14 and 22-26). The clinical parameters arthritis score (AS), hind paw volume (HPV), and body weight were determined. Results: a significant decrease of the clinical arthritis parameters was observed following 5 x 0.5 Gy or 5 x 1.0 Gy during the acute maximum of the inflammatory response (days 15-19). The most pronounced treatment effect was reached after two daily fractionated series of 5 x 0.5 Gy with an early treatment onset (days 10-14) and repetition in interval (days 22-26). After the application of 5 x 1.0 Gy on days 10-14 or in a protracted scheme (days 10, 12, 14, 16, and 18), only a nonsignificant positive trend could be detected. Daily fractionated X-irradiation in the chronic phase of adjuvant arthritis (days 22-26) did not show any positive clinical effect. Conclusion: low-dose radiotherapy is able to prevent a full-blown arthritic reaction if given during the florid phase of

  12. Dural administration of inflammatory soup or Complete Freund's Adjuvant induces activation and inflammatory response in the rat trigeminal ganglion

    Lukács, M; Haanes, K A; Majláth, Zs;

    2015-01-01

    induces inflammatory activation in the trigeminal ganglion. METHODS: We performed topical administration of inflammatory soup (IS) or Complete Freund's Adjuvant (CFA) onto an exposed area of the rat dura mater in vivo for 20 min. The window was closed and the rats were sacrificed after 4 h and up to 7...... previously been shown that application of inflammatory or algesic substances onto the dura mater or chemical stimulation of the dural receptive fields causes hypersensitivity to mechanical and thermal stimulation together with direct activation of the TG. We asked whether local inflammation of dura mater...... days. Myography was performed on middle meningeal arteries. The trigeminal ganglia were removed and processed for immunohistochemistry or Western blot. RESULTS: Both CFA and IS induced enhanced expression of pERK1/2, IL-1β and CGRP in the trigeminal ganglia. The pERK1/2 immunoreactivity was mainly seen...

  13. REGULAR EXPRESSION OF DISCOIDIN DOMAIN RECEPTOR 2 IN THE IMPROVED ADJUVANT-INDUCED ANIMAL MODEL FOR RHEUMATOID ARTHRITIS

    Wei Li; Yuan-qiang Zhang; Xin-ping Liu; Li-bo Yao; Lan Sun

    2005-01-01

    Objective To investigate the expression of discoidin domain receptor 2 (DDR2) of fibroblast-like synovial cells in improved adjuvant-induced animal (AIA) model for rheumatoid arthritis (RA) and to provide evidence for DDR2′s antagonist use clinically.Methods AIA was modified by administrating 0.1 mL of complete Freund′s adjuvant (CFA, mixed with 5 mg Bacillus Calmette-Guerin vaccine/mL) into rats′ right hind paws and 0.125 mL tumor necrosis factor-α (2 U/mL) into right ankles and subpatellar fatty tissue. The expression of DDR2 in fibroblast-like synovial cells was assessed using immunohistochemistry,immunofluorescence histochemistry, and in situ hybridization methods. Levels of anti-collagen Ⅱ antibody were measured using enzyme-linked immunosorbent assay.Results Given the terms mentioned above, we found a more practical rat model, apparently decreasing immunization time (average 3-5 days). DDR2 can be detected upon the 15th day of immunization; expression gradually increased with time going on, and reaching a peak 35 days after immunization before gradually decreasing. Serum anti-collagen Ⅱ antibody showed similar expression patterns as DDR2, but reached peak later than DDR2, about 40 days after immunization.Conclusion Regular expression of DDR2 in animal models infers its important role in the pathological process of RA.

  14. A self-adjuvanting vaccine induces cytotoxic T lymphocytes that suppress allergy.

    Anderson, Regan J; Tang, Ching-wen; Daniels, Naomi J; Compton, Benjamin J; Hayman, Colin M; Johnston, Karen A; Knight, Deborah A; Gasser, Olivier; Poyntz, Hazel C; Ferguson, Peter M; Larsen, David S; Ronchese, Franca; Painter, Gavin F; Hermans, Ian F

    2014-11-01

    Epitope-based peptide vaccines encompass minimal immunogenic regions of protein antigens to allow stimulation of precisely targeted adaptive immune responses. However, because efficacy is largely determined by the functional status of antigen-presenting cells (APCs) that acquire and present peptides to cells of the adaptive immune system, adjuvant compounds are needed to enhance immunogenicity. We present here a vaccine consisting of an allergen-derived peptide conjugated to a prodrug of the natural killer-like T (NKT) cell agonist α-galactosylceramide, which is highly effective in reducing inflammation in a mouse model of allergic airway inflammation. Unlike other peptide-adjuvant conjugates that directly activate APCs through pattern recognition pathways, this vaccine encourages third-party interactions with NKT cells to enhance APC function. Therapeutic efficacy was correlated with marked increases in the number and functional activity of allergen-specific cytotoxic T lymphocytes (CTLs), leading to suppression of immune infiltration into the lungs after allergen challenge in sensitized hosts. PMID:25282504

  15. Models of Inflammation: Carrageenan- or Complete Freund's Adjuvant (CFA)-Induced Edema and Hypersensitivity in the Rat.

    McCarson, Kenneth E

    2015-01-01

    Animal models of inflammation are used to assess the production of inflammatory mediators at sites of inflammation, the processing of pain sensation at CNS sites, the anti-inflammatory properties of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs), and the efficacy of putative analgesic compounds in reversing cutaneous hypersensitivity. Detailed in this unit are methods to elicit and measure carrageenan- and complete Freund's adjuvant (CFA)-induced cutaneous inflammation. Due to possible differences between the dorsal root sensory system and the trigeminal sensory system, injections into either the footpad or vibrissal pad are described. In this manner, cutaneous inflammation can be assessed in tissue innervated by the lumbar dorsal root ganglion neurons (footpad) or by the trigeminal ganglion neurons (vibrissal pad). PMID:26331888

  16. Radiofrequency Ablation–Induced Upregulation of Hypoxia-Inducible Factor-1α Can Be Suppressed with Adjuvant Bortezomib or Liposomal Chemotherapy

    Moussa, Marwan; Goldberg, S. Nahum; Kumar, Gaurav; Sawant, Rupa R.; Levchenko, Tatyana; Torchilin, Vladimir; Ahmed, Muneeb

    2014-01-01

    Purpose To characterize upregulation of hypoxia-inducible factor (HIF)-1α after radiofrequency (RF) ablation and the influence of an adjuvant HIF-1α inhibitor (bortezomib) and nanodrugs on modulating RF ablation–upregulated hypoxic pathways. Materials and Methods Fisher 344 rats (n = 68) were used. First, RF ablation–induced periablational HIF-1α expression was evaluated in normal liver or subcutaneous R3230 tumors (14–16 mm). Next, the effect of varying RF ablation thermal dose (varying tip temperature 50°C–90°C for 2–20 minutes) on HIF-1α expression was studied in R3230 tumors. Third, RF ablation was performed in R3230 tumors without or with an adjuvant HIF-1α inhibitor, bortezomib (single intraperitoneal dose 0.1 mg/kg). Finally, the combination RF ablation and intravenous liposomal chemotherapeutics with known increases in periablational cellular cytotoxicity (doxorubicin, paclitaxel, and quercetin) was assessed for effect on periablational HIF-1α. Outcome measures included immunohistochemistry of HIF-1α and heat shock protein 70 (marker of nonlethal thermal injury). Results RF ablation increased periablational HIF-1α in both normal liver and R3230 tumor, peaking at 24–72 hours. Tumor RF ablation had similar HIF-1α rim thickness but significantly greater percent cell positivity compared with hepatic RF ablation (P nanodrugs suppressed RF ablation–induced HIF-1α (ie, rim thickness and cell positivity; P < .02 for all comparisons), with liposomal doxorubicin suppressing HIF-1α the most (P < .03). Conclusions RF ablation upregulates HIF-1α in normal liver and tumor in a temperature-independent manner. This progrowth, hypoxia pathway can be successfully suppressed with an adjuvant HIF-1α-specific inhibitor, bortezomib, or non–HIF-1α-specific liposomal chemotherapy. PMID:25439675

  17. Relationship between G-proteins associated transmembrane cascades and MAPK phosphorylation induced by recombinant interleukin-α in fibroblast-like synoviocytes from rats with adjuvant arthritis

    Yong-qiuZHENG; WeiWEI; LeiZHU; Xiao-yiJIA

    2004-01-01

    AIM: To elucidate the relationship between G protein-associ-ated transmembrane cascade and mitogen-activated protein kinases (MAPKs) phosphorylation in recombinant rat IL-1α(rIL-1α)-induced fibroblast-like synoviocytes (FLS) from rats with adjuvant arthritis (AA). METHODS: The expressions of MAPKs phosphorylation, the stimulatory subunit of G alpha

  18. Ultrastructure of pulmonary granulomatosis induced in rats by intravenous complete Freund's adjuvant.

    Soler, P; Bernaudin, J F; Basset, F

    1975-10-01

    Following the intravenous injection of complete Freund's adjuvant, changes in the rat lung were studied with the electron microscope. Interstitial granulomas were produced and whereas on light microscopy these appeared to consist mainly of epitheloid cells, electron microscopy showed that the granulomas were largely made up of macrophages. Epithelioid cells were in fact few in number, atypical in appearance and limited to the periphery of some granulomas. Fenestrated capillaries were also found at the edge of the granulomas. The alveolar macrophages were increased in number and size but marked cytoplasmic vacuolation and a paucity of lysosomes are consistent with our previous suggestion that the phagocytic and migratory properties of these cells are weakened or inhibited. Alterations were found in both types of alveolar epithelial cell with the appearance of intermediate cell forms. PMID:171827

  19. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    Kawano, Masaaki [Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Morikawa, Katsuma [Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501 (Japan); Suda, Tatsuya [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Ohno, Naohito [Laboratory for Immunopharmacology of Microbial Products, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Matsushita, Sho [Department of Allergy and Immunology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Allergy Center, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Akatsuka, Toshitaka [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan); Handa, Hiroshi, E-mail: handa.h.aa@m.titech.ac.jp [Solutions Research Laboratory, Tokyo Institute of Technology, Midori-ku, Yokohama 226-8503 (Japan); Matsui, Masanori, E-mail: mmatsui@saitama-med.ac.jp [Department of Microbiology, Faculty of Medicine, Saitama Medical University, Moroyama-cho, Iruma-gun, Saitama 350-0495 (Japan)

    2014-01-05

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.

  20. A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway

    Fukasaka, Masahiro; Asari, Daisuke; Kiyotoh, Eiji; Okazaki, Arimichi; Gomi, Yasuyuki; Tanimoto, Takeshi; Takeuchi, Osamu; Akira, Shizuo; Hori, Mitsuhiko

    2015-01-01

    A lipopolysaccharide from Pantoea agglomerans (LPSpa) has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine) with LPSpa induced both HA-specific IgG (systemic) and IgA (mucosal) antibody responses, which le...

  1. A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice.

    Liu, Xun; Da, Zejiao; Wang, Yue; Niu, Hongxia; Li, Ruiying; Yu, Hongjuan; He, Shanshan; Guo, Ming; Wang, Yong; Luo, Yanping; Ma, Xingming; Zhu, Bingdong

    2016-03-01

    Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctadecylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400nm and zeta potential of 40mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell-mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41±0.38log10CFU) than traditional vaccine Bacillus Calmette-Guerin (BCG) (6.01±0.33log10CFU) and PBS control (6.53±0.26log10CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine. PMID:26845736

  2. Oral Administration of Shark Type II Collagen Suppresses Complete Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rats

    Wenhui Wu

    2012-03-01

    Full Text Available Objective: Shark type II collagen (SCII is extracted as a glycoprotein from the cartilage of blue shark (Prionace glauca. We aim to confirm the effects of oral tolerance of SCII on inflammatory and immune responses to the ankle joint of rheumatoid-arthritis rats induced by Complete Freund’s Adjuvant (CFA. Materials and Methods: The onset of rheumatoid arthritis (RA was observed 14 ± x days after injection of CFA. Rats in the control group were treated with acetic acid by oral administration (0.05 mmol kg−1d−1, days 14–28, while rats in experimental groups were treated by oral administration with SCII (1 or 3 mg kg−1d−1, days 14–28, Tripterygium wilfordii polyglycosidium (TWP (10 mg kg−1d−1, days 14–28, and bovine type II collagen from US (US-CII (1 mg kg−1d−1, days 14–28, respectively. The severity of arthritis was evaluated by the articular swelling. The immunological indexes observed included delayed type hypersensitivity (DTH reaction, the level of interleukins 10 (IL-10 in rat blood serum and morphological characterization. Mixed lymphocyte culture (MLC was performed to investigate the relationship between T cell apoptosis and specific immune tolerance induced by SCII. Results: Treatment with SCII for 2 weeks significantly attenuated the acute inflammation. The rats orally administrated with SCII at the level of 3 mg kg−1d−1 (SCII 3 and US-CII had decreased DTH reaction compared with rats in control group. Rats treated with SCII 3 had the highest level of IL-10 with 102 pg/mL. SCII with concentration of 10 μg/L could help to significantly enhance level of Fas/Apo-1 in T cell in vitro. The result of histological staining indicated that the recovery of the articular membranes of ankle joint in SCII 3 group was greatly enhanced. Conclusions: Our results suggest that appropriate dose of SCII can not only ameliorate symptoms but also modify the disease process of Complete-Freunds-Adjuvant-induced arthritis. Oral

  3. Protective antiviral immune responses to pseudorabies virus induced by DNA vaccination using dimethyldioctadecylammonium bromide as an adjuvant

    Rooij, van E.M.A.; Glansbeek, H.L.; Hilgers, L.A.T.; Lintelo, te E.G.; Visser, de Y.E.; Boersma, W.J.A.; Haagmans, B.L.; Bianchi, A.T.J.

    2002-01-01

    To enhance the efficacy of a DNA vaccine against pseudorabies virus (PRV), we evaluated the adjuvant properties of plasmids coding for gamma interferon or interleukin-12, of CpG immunostimulatory motifs, and of the conventional adjuvants dimethyldioctadecylammonium bromide in water (DDA) and sulfoli

  4. Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.

    Fahim, A T; Abd-el Fattah, A A; Agha, A M; Gad, M Z

    1995-01-01

    Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone. PMID:7784309

  5. In Vitro Evidence for the Use of Astragali Radix Extracts as Adjuvant against Oxaliplatin-Induced Neurotoxicity.

    Di Cesare Mannelli, Lorenzo; Zanardelli, Matteo; Bartolucci, Gianluca; Karioti, Anastasia; Bilia, Anna Rita; Vannacci, Alfredo; Mugelli, Alessandro; Ghelardini, Carla

    2015-08-01

    The repeated exposure to the anticancer drug oxaliplatin induces a disabling, painful neuropathy. The current pharmacological treatments are unsatisfactory and unable to modify the complex nervous damage induced by the platin derivative. Recently, we described a system of cellular measures of oxidative stress as a method for studying features of oxaliplatin neurotoxicity and screening new compounds able to reduce oxaliplatin-induced neuropathy. Based on this experimental design, the protective properties of Astragali radix were studied comparing aqueous and two hydroalcoholic root extracts. Aqueous and the 20 % hydroalcoholic (20 % water) extract were prepared from plant material, while the 50 % hydroalcoholic (50 % water) extract was a commercial one. All of the extracts were characterized in terms of drug extract ratio and content of typical isoflavonoids, Astragaloside IV, and related saponins. Furthermore, the molecular weight of the polysaccharide fraction was evaluated by light scattering analysis. Oxaliplatin increased the superoxide anion production both in the neuronal-derived cell line SH-SY5Y and in primary cultures of rat cortical astrocytes. Aqueous and the 50 % hydroalcoholic extract (50 µg/mL) showed significant antioxidant effects. In astrocytes, aqueous and the 50 % hydroalcoholic extract showed protective effects against oxaliplatin-induced lipid peroxidation (malonyl dialdehyde levels), protein (carbonylated proteins), and DNA oxidation (8-OH-2-dG levels). The 50 % hydroalcoholic extract was the most active in preventing the activation of the apoptotic enzyme caspase-3 and it was the only able to stimulate astrocyte viability. None of the tested extracts interfered with the toxicity elicited by oxaliplatin in the human colon adenocarcinoma cell line HT-29. The pharmacological profile of Astragali radix extracts, in particular, the aqueous and 50 % hydroalcoholic extracts, makes these natural products candidates as therapeutic

  6. In vivo evaluation of early disease progression by X-ray phase-contrast imaging in the adjuvant-induced arthritic rat

    To study the early change of bone matrix and soft tissue around articulation in adjuvant-induced arthritic (AIA) rats non-invasively by X-ray phase-contrast imaging (XPCI), a new imaging method. Adjuvant-induced arthritis was established in male Sprague-Dawley (SD) rats (n=6, age 40 days) by subcutaneous injection of Freund's complete adjuvant (FCA) into the left hindpaw. In vivo XPCI evaluation of the early soft tissue and bone changes in AIA rats was consecutively performed and correlated with changes in volumes of right hindpaws and body weights. In comparison, the changes in the AIA rats were also evaluated with absorption-contrast imaging using the same X-ray source as XPCI and conventional radiography at the same time. After the imaging evaluation, AIA rats were subjected to histological examination. There was significant difference between the score of XPCI and the other two methods in demonstrating soft tissue (P<0.01), bone details (P<0.01) and lesions (P<0.001). By day 10 after subcutaneous injection of FCA, bone changes in the right hindpaw were not obvious, but swelling of soft tissue appeared. By day 12, bone erosion in the articular facet and the area around the articular facet, was detected, along with osteoporosis, and swelling of soft tissue was aggravated. By day 14 bone erosions became fused and expanded, especially in the margin area around the articular facet. At day 16 bone erosion still existed. Joint interspaces seemed wider than normal, and swelling of soft tissue was significant. By day 18 periosteal new bone formation was seen definitely, destruction of bone decreased, bone density around the articular was enhanced, and swelling of soft tissue was relieved. XPCI could clearly distinguish all these alterations, which could not be demonstrated by absorption-contrast imaging and conventional radiography. During the test period, the volume of the right hindpaw and the body weight of the AIA rats also changed significantly compared with the

  7. Immunopotentiation of Different Adjuvants on Humoral and Cellular Immune Responses Induced by HA1-2 Subunit Vaccines of H7N9 Influenza in Mice.

    Li Song

    Full Text Available In spring 2013, human infections with a novel avian influenza A (H7N9 virus were reported in China. The number of cases has increased with over 200 mortalities reported to date. However, there is currently no vaccine available for the H7 subtype of influenza A virus. Virus-specific cellular immune responses play a critical role in virus clearance during influenza infection. In this study, we undertook a side-by-side evaluation of two different adjuvants, Salmonella typhimurium flagellin (fliC and polyethyleneimine (PEI, through intraperitoneal administration to assess their effects on the immunogenicity of the recombinant HA1-2 subunit vaccine of H7N9 influenza. The fusion protein HA1-2-fliC and HA1-2 combined with PEI could induce significantly higher HA1-2-specific IgG and hemagglutination inhibition titers than HA1-2 alone at 12 days post-boost, with superior HA1-2 specific IgG titers in the HA1-2-fliC group compared with the PEI adjuvanted group. The PEI adjuvanted vaccine induced higher IgG1/IgG2a ratio and significantly increased numbers of IFN-γ- and IL-4-producing cells than HA1-2 alone, suggesting a mixed Th1/Th2-type cellular immune response with a Th2 bias. Meanwhile, the HA1-2-fliC induced higher IgG2a and IgG1 levels, which is indicative of a mixed Th1/Th2-type profile. Consistent with this, significant levels, and equal numbers, of IFN-γ- and IL-4-producing cells were detected after HA1-2-fliC vaccination. Moreover, the marked increase in CD69 expression and the proliferative index with the HA1-2-fliC and PEI adjuvanted vaccines indicated that both adjuvanted vaccine candidates effectively induced antigen-specific cellular immune responses. Taken together, our findings indicate that the two adjuvanted vaccine candidates elicit effective and HA1-2-specific humoral and cellular immune responses, offering significant promise for the development of a successful recombinant HA1-2 subunit vaccine for H7N9 influenza.

  8. In vivo evaluation of early disease progression by X-ray phase-contrast imaging in the adjuvant-induced arthritic rat

    Yu, Yongqiang; Xiong, Zhuang; Lv, Yizhong; Qian, Yinfeng [First Affiliated Hospital of Anhui Medical University, Department of Radiology, Hefei (China); Jiang, Shiping [University of Science and Technology of China, Synchrotron Radiation Laboratory, Hefei (China); Tian, Yulian [Institute of High Energy Physics, Chinese Academy of Science, Synchrotron Radiation Laboratory, Beijing (China)

    2006-03-15

    To study the early change of bone matrix and soft tissue around articulation in adjuvant-induced arthritic (AIA) rats non-invasively by X-ray phase-contrast imaging (XPCI), a new imaging method. Adjuvant-induced arthritis was established in male Sprague-Dawley (SD) rats (n=6, age 40 days) by subcutaneous injection of Freund's complete adjuvant (FCA) into the left hindpaw. In vivo XPCI evaluation of the early soft tissue and bone changes in AIA rats was consecutively performed and correlated with changes in volumes of right hindpaws and body weights. In comparison, the changes in the AIA rats were also evaluated with absorption-contrast imaging using the same X-ray source as XPCI and conventional radiography at the same time. After the imaging evaluation, AIA rats were subjected to histological examination. There was significant difference between the score of XPCI and the other two methods in demonstrating soft tissue (P<0.01), bone details (P<0.01) and lesions (P<0.001). By day 10 after subcutaneous injection of FCA, bone changes in the right hindpaw were not obvious, but swelling of soft tissue appeared. By day 12, bone erosion in the articular facet and the area around the articular facet, was detected, along with osteoporosis, and swelling of soft tissue was aggravated. By day 14 bone erosions became fused and expanded, especially in the margin area around the articular facet. At day 16 bone erosion still existed. Joint interspaces seemed wider than normal, and swelling of soft tissue was significant. By day 18 periosteal new bone formation was seen definitely, destruction of bone decreased, bone density around the articular was enhanced, and swelling of soft tissue was relieved. XPCI could clearly distinguish all these alterations, which could not be demonstrated by absorption-contrast imaging and conventional radiography. During the test period, the volume of the right hindpaw and the body weight of the AIA rats also changed significantly compared with

  9. Autoimmunity in connection with a metal implant: a case of autoimmune/autoinflammatory syndrome induced by adjuvants.

    Loyo, Esthela; Jara, Luis J; López, Persio David; Puig, Ana Carolina

    2013-04-01

    Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome, silicosis and post-vaccination phenomena, autoimmunity related to infectious fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report the case of a 23-year-old woman who developed serial episodes of high fever, extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies, hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment abnormalities, elevated serum ferritin levels, and transient low positive antinuclear antibodies 1 year after she had a nickel-titanium chin implant for cosmetic reasons. The clinical picture simulated a variety of probable diseases: systemic lupus erythematosus, Kikuchi-Fujimoto syndrome, adult onset Still's disease, antiphospholipid syndrome, and hemophagocytic syndrome, among others, so she underwent an extensive medical investigation including two lymph node biopsies. She received treatment accordingly with steroids, methotrexate, and mofetil mycophenolate, with initial improvement of her symptoms, which recurred every time the dose was reduced. Two and a half years later the patient decided to retire the chin implant and afterwards all her systemic symptoms have disappeared. She remains in good health, without recurrence of any symptom and off medications until today. Albeit this patient fulfills proposed major ASIA criteria, to our knowledge it would be the first description of systemic features of autoinflammation in connection with a metal implant. PMID:26000140

  10. Radiation-induced brachial plexopathy and hypofractionated regimens in adjuvant irradiation of patients with breast cancer-a review

    Galecki, Jacek; Hicer-Grzenkowicz, Joanna; Grudzien-Kowalska, Malgorzata; Zalucki, Wojciech [Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw (Poland). Dept. of Radiotherapy; Michalska, Teresa [Academy of Medicine, Warsaw (Poland). Neurological Clinic, Second Dept.

    2006-04-15

    In order to increase the availability of adjuvant radiotherapy of breast cancer patients and make it more convenient and cheaper, in numerous cancer centres, the dose per fraction has been increased from 2 Gy to 2.25-2.75 Gy and the total dose has been decreased from 50 Gy to 40-45 Gy. The risk of developing any late complications after conventionally fractionated megavoltage radiotherapy is estimated to be below 1%. The aim of this review is to determine whether hypofractionated regimens increase the risk of damage to the brachial plexus. A review of the published literature shows that the use of doses per fraction in the range from 2.2 Gy to 4.58 Gy with the total doses between 43.5 Gy and 60 Gy causes a significant risk of brachial plexus injury which ranged from 1.7% up to 73%. The risk of radiation induced brachial plexopathy was smaller than 1% using regimens with doses per fraction between 2.2 and 2.5 Gy with the total doses between 34 and 40 Gy. Surgical manipulations in the axilla and chemotherapy have to be taken into account as additional factors which may increase the risk of brachial plexopathy.

  11. Suppressive effects of QFGJS, a preparation from an anti-arthritic herbal formula, on rat experimental adjuvant-induced arthritis

    To analyze the anti-arthritic effects of QFGJS (a pharmaceutical preparation from herbs) on rheumatoid arthritis, adjuvant-induced arthritis (AIA) was established in male SD rats, and two administration protocols, i.e., oral treatment with different doses of QFGJS on the day of arthritis induction or on the day when visible clinical signs of arthritis occurred, were initiated and continued until day 30. Treatments with QFGJS using both administration protocols significantly suppressed the incidence and severity of arthritis in a dose-dependent manner, showing dramatic reduction of paw swelling and ESR throughout the disease progression of AIA. Radiological and histopathological examinations showed markedly decreased tissue and bone destruction of ankle joints in the QFGJS-treated rats. The serum levels of TNF-α, IL-1β, and IL-6 were significantly decreased in the QFGJS-treated rats. QFGJS demonstrates pronounced anti-arthritic effects on AIA, indicating that this herbal preparation would be a potent candidate as a novel botanical drug for further investigation

  12. The Fluence Effects of Low-Level Laser Therapy on Inflammation, Fibroblast-Like Synoviocytes, and Synovial Apoptosis in Rats with Adjuvant-Induced Arthritis

    Hsieh, Yueh-Ling; Cheng, Yu-Jung; Huang, Fang-Chuen; Yang, Chen-Chia

    2014-01-01

    Objective: The aim of this study was to evaluate the effect of low-level laser therapy (LLLT) operating at low and high fluences on joint inflammation, fibroblast-like synoviocytes (FLS), and synovial apoptosis in rats with adjuvant-induced arthritis. Background data: Rheumatoid arthritis (RA) is characterized by pronounced inflammation and FLS proliferation within affected joints. Certain data indicate that LLLT is effective in patients with inflammation caused by RA; however, the fluence ef...

  13. Association between arthritis score at the onset of the disease and long-term locomotor outcome in adjuvant-induced arthritis in rats

    Mossiat, Claude; Laroche, Davy; Prati, Clément; Pozzo, Thierry; Demougeot, Céline; Marie, Christine

    2015-01-01

    Introduction To investigate the connection between the intensity of initial symptoms of inflammation and locomotor outcome in rheumatoid arthritis, we examined the relationship between long-term locomotor abnormalities and signs of inflammation at the onset of the disease in adjuvant-induced arthritis (AIA) in rats. Methods The arthritis score and hind-paw diameter were followed from immunization to day 195 (~7 months). At this time, locomotion was recorded during forced treadmill walking usi...

  14. Lack of causal relationship between inducibility/severity of adjuvant arthritis in the rat and disease associated changes in production of nitric oxide by macrophages.

    Zídek, Z; Franková, D; Otová, B

    1995-01-01

    OBJECTIVE--To investigate the formation of nitric oxide (NO) by peritoneal macrophages in three inbred strains of rats differing both in their susceptibility to the induction of adjuvant arthritis (AA) and in the severity of the disease. METHODS--AA was induced by intraplantar injection of Mycobacterium tuberculosis (M.tb) in paraffin oil. Isolated peritoneal macrophages were cultured for 24 hours and supernatants were assayed for nitrite using Griess reagent. RESULTS--All rats of the LEW and...

  15. Co-Administration of Molecular Adjuvants Expressing NF-Kappa B Subunit p65/RelA or Type-1 Transactivator T-bet Enhance Antigen Specific DNA Vaccine-Induced Immunity

    Devon J. Shedlock

    2014-03-01

    Full Text Available DNA vaccine-induced immunity can be enhanced by the co-delivery of synthetic gene-encoding molecular adjuvants. Many of these adjuvants have included cytokines, chemokines or co-stimulatory molecules that have been demonstrated to enhance vaccine-induced immunity by increasing the magnitude or type of immune responses and/or protective efficacy. In this way, through the use of adjuvants, immune responses can be highly customizable and functionally tailored for optimal efficacy against pathogen specific (i.e., infectious agent or non-pathogen (i.e., cancer antigens. In the novel study presented here, we examined the use of cellular transcription factors as molecular adjuvants. Specifically the co-delivery of (a RelA, a subunit of the NF-κB transcription complex or (b T-bet, a Th1-specific T box transcription factor, along with a prototypical DNA vaccine expressing HIV-1 proteins was evaluated. As well, all of the vaccines and adjuvants were administered to mice using in vivo electroporation (EP, a technology demonstrated to dramatically increase plasmid DNA transfection and subsequent transgene expression with concomitant enhancement of vaccine induced immune responses. As such, this study demonstrated that co-delivery of either adjuvant resulted in enhanced T and B cell responses, specifically characterized by increased T cell numbers, IFN-γ production, as well as enhanced antibody responses. This study demonstrates the use of cellular transcription factors as adjuvants for enhancing DNA vaccine-induced immunity.

  16. Co-adjuvant effects of retinoic acid and IL-15 induce inflammatory immunity to dietary antigens

    Under physiological conditions the gut-associated lymphoid tissues not only prevent the induction of a local inflammatory immune response, but also induce systemic tolerance to fed antigens. A notable exception is coeliac disease, where genetically susceptible individuals expressing human leukocyte...

  17. Poly(I:C/alum mixed adjuvant priming enhances HBV subunit vaccine-induced immunity in mice when combined with recombinant adenoviral-based HBV vaccine boosting.

    Xia Chuai

    Full Text Available BACKGROUND: Virus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed. METHODOLOGY/PRINCIPAL FINDINGS: To improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA, ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1-specific cellular immune response. HBSS1 immunisation with poly(I:C/alum priming also generated high-level CD4(+ and CD8(+ T cell responses in terms of Th1 cytokines (IFN-γ and IL-2. CONCLUSIONS: The protein-vaccine HBSS1 with mixed poly(I:C/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.

  18. STUDY ON EFFICACY OF TREATMENT WITH FICUS BENGHALENSIS LEAF EXTRACTS ON FREUND’S ADJUVANT INDUCED ARTHRITIS IN RATS

    Lokesh K. Bhardwaj

    2010-12-01

    Full Text Available In view of the well-established anti-inflammatory properties of bark and leaf of Ficus benghalensis, the present study was carried out to evaluate the protective effect of ethanol and aqueous leaf extracts against Freund?s adjuvant induced arthritis in rats. The ethanol and aqueous leaf extracts was administered orally at dose of 300 mg/kg body weight for 21 days. Indomethacin at dose of 10 mg/kg body weight was used as standard drug. The paw volume was measured on days 4, 8, 14, and 21. At the end of day 21 the blood was collected from retro-orbital route to all the groups of animals and various haematological parameters such as haemoglobin content, total WBC, RBC and erythrocyte sedimentation rate were estimated. The results indicate that at dose of 300 mg/kg body weight, both the extracts protects rats against the primary and secondary arthritic lesions, body weight changes and haematological perturbations induced by CFA. Daily treatment of rats with ethanol and aqueous leaf extracts, standard drug Indomethacin effectively inhibits paw edema in rats. Both the extracts significantly (p< 0.01 altered the parameters which were estimated when compared to control group rats. At the end of studies the ethanol extract shows more pronounce effect 66.88% than the aqueous extract 63.82% as compared to standard drug Indomethacin 75.42%. The phytochemical analysis of extracts revels the presence of sterols, flavonoids, phenols, tannins and saponins. However additional clinical investigations are needed to prove the efficacy of Ficus benghalensis L.in the treatment of various immuno-inflammatory disorders.

  19. Induced abortion among Brazilian female sex workers: a qualitative study

    Alberto Pereira Madeiro; Debora Diniz

    2015-01-01

    Prostitutes are vulnerable to unplanned pregnancies and abortions. In Brazil, abortion is a crime and there is no data about unsafe abortions for this population. The study describes how prostitutes perform illegal abortions and the health consequences thereof. Semi-structured interviews with 39 prostitutes from three cities in Brazil with previous induced abortion experience were conducted. Sixty-six abortions, with between one and eight occurrences per woman, were recorded. The majority of ...

  20. Induced abortion among Brazilian female sex workers: a qualitative study

    Alberto Pereira Madeiro

    2015-02-01

    Full Text Available Prostitutes are vulnerable to unplanned pregnancies and abortions. In Brazil, abortion is a crime and there is no data about unsafe abortions for this population. The study describes how prostitutes perform illegal abortions and the health consequences thereof. Semi-structured interviews with 39 prostitutes from three cities in Brazil with previous induced abortion experience were conducted. Sixty-six abortions, with between one and eight occurrences per woman, were recorded. The majority of the cases resulted from sexual activity with clients. The inconsistent use of condoms with regular clients and the consumption of alcohol during work were indicated as the main causes of unplanned pregnancies. The main method to perform abortion was the intravaginal and oral use of misoprostol, acquired in pharmacies or on the black market. Invasive measures were less frequently reported, however with more serious health complications. The fear of complaint to the police meant that most women do not inform the health team regarding induced abortion. The majority of prostitutes aborted with the use of illegally-acquired misoprostol, ending abortion in a public hospital with infection and hemorrhagic complications. The data indicate the need for a public policy focusing on the reproductive health of prostitutes.

  1. Induced abortion among Brazilian female sex workers: a qualitative study.

    Madeiro, Alberto Pereira; Diniz, Debora

    2015-02-01

    Prostitutes are vulnerable to unplanned pregnancies and abortions. In Brazil, abortion is a crime and there is no data about unsafe abortions for this population. The study describes how prostitutes perform illegal abortions and the health consequences thereof. Semi-structured interviews with 39 prostitutes from three cities in Brazil with previous induced abortion experience were conducted. Sixty-six abortions, with between one and eight occurrences per woman, were recorded. The majority of the cases resulted from sexual activity with clients. The inconsistent use of condoms with regular clients and the consumption of alcohol during work were indicated as the main causes of unplanned pregnancies. The main method to perform abortion was the intravaginal and oral use of misoprostol, acquired in pharmacies or on the black market. Invasive measures were less frequently reported, however with more serious health complications. The fear of complaint to the police meant that most women do not inform the health team regarding induced abortion. The majority of prostitutes aborted with the use of illegally-acquired misoprostol, ending abortion in a public hospital with infection and hemorrhagic complications. The data indicate the need for a public policy focusing on the reproductive health of prostitutes. PMID:25715152

  2. The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling.

    Christiane Desel

    Full Text Available Successful vaccination against intracellular pathogens requires the generation of cellular immune responses. Trehalose-6,6-dibehenate (TDB, the synthetic analog of the mycobacterial cord factor trehalose-6,6-dimycolate (TDM, is a potent adjuvant inducing strong Th1 and Th17 immune responses. We previously identified the C-type lectin Mincle as receptor for these glycolipids that triggers the FcRγ-Syk-Card9 pathway for APC activation and adjuvanticity. Interestingly, in vivo data revealed that the adjuvant effect was not solely Mincle-dependent but also required MyD88. Therefore, we dissected which MyD88-dependent pathways are essential for successful immunization with a tuberculosis subunit vaccine. We show here that antigen-specific Th1/Th17 immune responses required IL-1 receptor-mediated signals independent of IL-18 and IL-33-signaling. ASC-deficient mice had impaired IL-17 but intact IFNγ responses, indicating partial independence of TDB adjuvanticity from inflammasome activation. Our data suggest that the glycolipid adjuvant TDB triggers Mincle-dependent IL-1 production to induce MyD88-dependent Th1/Th17 responses in vivo.

  3. Gait analysis of C57BL/6 mice with complete Freund's adjuvant-induced arthritis using the CatWalk system

    Parvathy, Subramanian S; Masocha, Willias

    2013-01-01

    Background The CatWalk system, a video based automated gait analysis system developed to evaluate footfall and gait changes in rodents, has been used for studying rodent models of arthritis, mainly the rat model. However, it has not been used to study static and dynamic gait parameters in mice with Complete Freund’s adjuvant (CFA). CFA is used extensively to induce arthritis in rodents including mice. Methods The CatWalk system was used to study gait of freely moving mice with CFA-induced mon...

  4. Adjuvant-active fraction from Albizia julibrissin saponins improves immune responses by inducing cytokine and chemokine at the site of injection.

    Sun, Hongxiang; He, Shuwang; Shi, Minghua

    2014-10-01

    The total saponin from the stem bark of Albizia julibrissin (AJSt) has previously showed the adjuvant potentials in mice. In this study, AJSt was subjected to resin column chromatography to afford four fractions (AJS30, AJS50, AJS75 and AJS95), and these fractions were further compared for the hemolytic activities and adjuvant potentials on the immune response to ovalbumin (OVA) and recombinant fowl pox virus vector-based avian influenza vaccine (rFPV). AJSt, AJS50, AJS75 and AJS95 showed a slight hemolytic effect. AJSt, AJS50 and AJS75 significantly enhanced not only the concanavalin A (Con A)-, lipopolysaccharide (LPS)- and antigen-stimulated splenocyte proliferation, but also serum antigen-specific IgG, IgG1, IgG2a and IgG2b antibody titers in the mice immunized with OVA and rFPV. AJSt, AJS50 and AJS75 also significantly promoted the NK cell activity and delayed-type hypersensitivity (DTH) in the OVA-immunized mice. Furthermore, the mechanisms of adjuvant action were explored by determining the effects of AJS75 on cytokines and chemokines at the site of injection using antibody array. AJS75 induced or up-regulated the protein expression of 12 cytokines (IL-12p40, IL-12p40/p70, IFN-γ, IL-13, IL-1β, IL-6, IL-10, TNF-α, sTNFR I, sTNFR III, IL-3 and IL-9) and 10 chemokines (Eotaxin, I-TAC, MIG, MIP-1α, RANTES, TECK, Fracatlkine, FasL, M-CSF and GM-CSF) in the injected muscles. The results suggested that AJS75, the most adjuvant-active fraction of AJSt, could improve antigen-specific both cellular and humoral immune responses and simultaneously elicit a Th1/Th2 response by inducing cytokine and chemokine at the site of injection. PMID:25075718

  5. Synthetic innate defense regulator peptide combination using CpG ODN as a novel adjuvant induces long‑lasting and balanced immune responses.

    Yu, Chao-Heng; Luo, Zi-Chao; Li, Meng; Lu, Lian; Li, Zhan; Wu, Xiao-Zhe; Fan, Ying-Zi; Zhang, Hai-Long; Zhou, Bai-Ling; Wan, Yang; Men, Ke; Tian, Yao-Mei; Chen, Shuang; Yuan, Feng-Jiao; Xiang, Rong; Yang, Li

    2016-01-01

    Vaccines are critical tools for the prevention and treatment of several diseases. Adjuvants have been traditionally used to enhance immunity to vaccines and experimental antigens. In the present study, the adjuvant combination of CpG oligodeoxynucleotides (CpG ODN) and the innate defense regulator (IDR) peptide, IDR‑HH2, was evaluated for its ability to enhance and modulate the immune response when formulated with alum and the recombinant hepatitis B surface antigen (HBsAg). The CpG‑HH2 complex enhanced the secretions of tumor necrosis factor‑α, monocyte chemotactic protein 1 and interferon‑γ by human peripheral blood mononuclear cells and promoted murine bone marrow dentritic cell maturation. In addition, the present study demonstrated that IDR‑HH2 was chemotactic for human neutrophils, THP‑1 cells and RAW264.7 cells at concentrations between 2.5 and 40 µg/ml. The present study also observed that significantly higher anti‑HBs antibody titers, which were sustained at high levels for as long as 35 weeks following the boost immunization, were induced by the combination adjuvant, even when co‑administered with a commercial hepatitis B vaccine at a low antigen dose (0.1 µg HBsAg). Notably, the level of IgG2a was almost equal to the level of IgG1, indicating that a balanced T helper (Th)1/Th2 immune response was elicited by the novel vaccine, which was consistent with the ELISpot results. These data suggest that the CpG‑HH2 complex may be a potential effective adjuvant, which facilitates a reduction in the dose of antigen and induces long‑lasting, balanced immune responses. PMID:26647852

  6. Scopolin isolated from Erycibe obtusifolia Benth stems suppresses adjuvant-induced rat arthritis by inhibiting inflammation and angiogenesis

    PAN Rong; DAI Yue; GAO Xing-hua; XIA Yu-feng

    2008-01-01

    Objective To study the effects and mechanisms of scopolin isolated from the stems of Erycibe obtusifolia Benth in arthritis-associated inflammation and angiogenesis. Methods Adjuvant-induced arthritic rat, an animal model for human RA was used in this study for examining the potential remedial effect of scopolin. The swelling in both inoculated and non-inoculated paws, body weights and articular index (AI) scores were detected to evaluate the severity of the arthritis. Histologic assessment of tissue sections from rat ankles was also performed. Furthermore, the blood vessel density in the synovial tissues was quantitatively evaluated. In addition, expressions of VEGF, FGF-2, TNF-α, IL-1β and IL-6 in rat synovial tissues were determined by immunohistochemistry assay in an attempt to explain the mechanisms of scopolin for suppressing arthritis. Results Scopolin dose-dependently inhibited both inoculated and non-inoculated paw swelling in rat AIA. The mean AI scores of scopolin treated groups were also dose-dependently lower than that of model group. In addition, compared with the weights of model group, the mean body weights of rats treated with scopolin (50,100 mg·kg-1) were higher from day 13 to 22, perhaps indicative of healthier animals. The histologic architecture of the joint was highly abnormal in the model group rats, while high dose of scopolin treated rats preserved a nearly normal histologic architecture of the joint. Moreover, the new blood vessels were reduced dose-dependently in the synovial tissue of rat AIA treated with scopolin. Further, scopolin reduced the overexpression of IL-6,VEGF and FGF-2 in rat synovial tissues. Conclusions Scopolin is capable of reducing clinical symptoms of rat AIA by inhibiting inflammation and angiogenesis, and this compound may be a potent therapeutic agent for angiogenesis related diseases and can serve as structural base for screening for more potent synthetic analogs.

  7. Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.

    Eun-Do Kim

    Full Text Available The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1 virus challenge. Additionally, ocular inoculation with poly(I:C plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

  8. A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway.

    Fukasaka, Masahiro; Asari, Daisuke; Kiyotoh, Eiji; Okazaki, Arimichi; Gomi, Yasuyuki; Tanimoto, Takeshi; Takeuchi, Osamu; Akira, Shizuo; Hori, Mitsuhiko

    2015-01-01

    A lipopolysaccharide from Pantoea agglomerans (LPSpa) has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine) with LPSpa induced both HA-specific IgG (systemic) and IgA (mucosal) antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination. After sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA responses were induced at both mucosal surfaces close to the immunized site and at remote mucosal surfaces. Sublingual administration of LPSpa evoked local antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine production and the maturation and proliferation of innate immune cells via Toll-like receptor 4 in dendritic cells. Collectively, these results suggest that LPSpa can be used as an effective mucosal adjuvant to stimulate and activate local innate immune cells to improve and enhance mucosal vaccine potency against various pathogens. PMID:25978818

  9. A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway.

    Masahiro Fukasaka

    Full Text Available A lipopolysaccharide from Pantoea agglomerans (LPSpa has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine with LPSpa induced both HA-specific IgG (systemic and IgA (mucosal antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination. After sublingual administration of ovalbumin with LPSpa, ovalbumin-specific mucosal IgA responses were induced at both mucosal surfaces close to the immunized site and at remote mucosal surfaces. Sublingual administration of LPSpa evoked local antigen-uptake by dendritic cells in cervical lymph nodes. LPSpa induced cytokine production and the maturation and proliferation of innate immune cells via Toll-like receptor 4 in dendritic cells. Collectively, these results suggest that LPSpa can be used as an effective mucosal adjuvant to stimulate and activate local innate immune cells to improve and enhance mucosal vaccine potency against various pathogens.

  10. When uncommon and common coalesce: adult onset Still's disease associated with breast augmentation as part of autoimmune syndrome induced by adjuvants (ASIA).

    Dagan, A; Kogan, M; Shoenfeld, Y; Segal, G

    2016-06-01

    Adult onset Still's disease (AOSD) is an uncommon, multisystemic, auto-inflammatory disorder, while breast augmentation is a very common cosmetic procedure. We describe a case in which these two coalesce, AOSD, manifested with pleuritis and pericarditis, developed after breast mammoplasty. The pathogenetic, missing link, behind the development of AOSD following mammoplasty, is thought to be the autoimmune (auto-inflammatory) syndrome induced by adjuvants (ASIA). We reviewed other cases of AOSD associated with breast mammoplasty published to date and the literature regarding AOSD and ASIA syndrome. The review is followed by a short debate of whether silicone implants should be explanted in similar, future cases. PMID:25604318

  11. New pre-pandemic influenza vaccines: an egg- and adjuvant-independent human adenoviral vector strategy induces long-lasting protective immune responses in mice.

    Hoelscher, M A; Jayashankar, L; Garg, S; Veguilla, V; Lu, X; Singh, N; Katz, J M; Mittal, S K; Sambhara, S

    2007-12-01

    Highly pathogenic avian H5N1 influenza viruses that are currently circulating in southeast Asia may acquire the potential to cause the next influenza pandemic. A number of alternate approaches are being pursued to generate cross-protective, dose-sparing, safe, and effective vaccines, as traditional vaccine approaches, i.e., embryonated egg-grown, are not immunogenic. We developed a replication-incompetent adenoviral vector-based, adjuvant- and egg-independent pandemic influenza vaccine strategy as a potential alternative to conventional egg-derived vaccines. In this paper, we address suboptimal dose and longevity of vaccine-induced protective immunity and demonstrate that a vaccine dose as little as 1 x 10(6) plaque-forming unit (PFU) is sufficient to induce protective immune responses against a highly pathogenic H5N1 virus. Furthermore, the vaccine-induced humoral and cellular immune responses and protective immunity persisted at least for a year. PMID:17957181

  12. Total flavonoids of Bidens bipinnata L. ameliorate experimental adjuvant-induced arthritis through induction of synovial apoptosis

    Shen, Ai-Zong; Li, Xia; Hu, Wei; Chen, Fei-Hu

    2015-01-01

    Background Bidens bipinnata are widely distributed in China, which have been widely used as a traditional Chinese medicine. The aim of this study was to examine the effect of total avonoids of Bidens pilosa L. (TFB) on adjuvant arthritis (AA) and its possible mechanisms. Methods The macroscopic scoring of paw edema, secondary paw swelling, and polyarthritis index were measured. Histological examination of the joints and the serum concentrations of IL-6, IL-1beta, and TNF-alpha were examined. ...

  13. TLR9-adjuvanted pneumococcal conjugate vaccine induces antibody-independent memory responses in HIV-infected adults

    Offersen, Rasmus; Melchjorsen, Jesper; Paludan, Søren R; Østergaard, Lars; Tolstrup, Martin; Søgaard, Ole S.

    2012-01-01

    HIV-patients have excess of pneumococcal infection. We immunized 40 HIV-patients twice with pneumococcal conjugate vaccine (Prevnar, Pfizer) +/− a TLR9 agonist (CPG 7909). Peripheral blood mononuclear cells were stimulated with pneumococcal polysaccharides and cytokine concentrations measured. The CPG 7909 adjuvant group had significantly higher relative cytokine responses than the placebo group for IL-1β, IL-2R, IL-6, IFN-γ and MIP-β, which, did not correlate with IgG antibody responses. The...

  14. Qualitative and quantitative laser-induced breakdown spectroscopy of bronze objects

    Tankova, V.; Blagoev, K.; Grozeva, M.; Malcheva, G.; Penkova, P.

    2016-03-01

    Laser-induced breakdown spectroscopy (LIBS) is an analytical technique for qualitative and quantitative elemental analysis of solids, liquids and gases. In this work, the method was applied for investigation of archaeological bronze objects. The analytical information obtained by LIBS was used for qualitative determination of the elements in the material used for manufacturing of the objects under study. Quantitative chemical analysis was also performed after generating calibration curves with standard samples of similar matrix composition. Quantitative estimation of the elemental concentration of the bulk of the samples was performed, together with investigation of the surface layer of the objects. The results of the quantitative analyses gave indications about the manufacturing process of the investigated objects.

  15. Propionibacterium acnes induces an adjuvant effect in B-1 cells and affects their phagocyte differentiation via a TLR2-mediated mechanism.

    Gambero, Monica; Teixeira, Daniela; Butin, Liane; Ishimura, Mayari Eika; Mariano, Mario; Popi, Ana Flavia; Longo-Maugéri, Ieda Maria

    2016-09-01

    B-1 lymphocytes are present in large numbers in the mouse peritoneal cavity, as are macrophages, and are responsible for natural IgM production. These lymphocytes migrate to inflammatory foci and are also involved in innate immunity. It was also demonstrated that B-1 cells are able to differentiated into phagocytes (B-1CDP), which is characterized by expression of F4/80 and increased phagocytic activity. B-1 cell responses to antigens and adjuvants are poorly characterized. It has been shown that Propionibacterium acnes suspensions induce immunomodulatory effects in both macrophages and B-2 lymphocytes. We recently demonstrated that this bacterium has the ability to increase B-1 cell populations both in vitro and in vivo. P. acnes induces B-1CDP differentiation, increases the expression of TLR2, TLR4 and TLR9 and augments the expression of CD80, CD86 and CD40 in B-1 and B-1CDP cells. Because P. acnes has been shown to modulate TLR expression, in this study, we investigated the role of TLR2 and TLR4 in B-1 cell population, including B-1CDP differentiation and phagocytic activity in vitro and in vivo. Interestingly, we have demonstrated that TLR2 signaling could be involved in the increase in the B-1 cell population induced by P. acnes. Furthermore, the early differentiation of B-1CDP is also dependent of TLR2. It was also observed that TLR signals also interfere in the phagocytic ability of B-1 cells and their phagocytes. According to these data, it is clear that P. acnes promotes an important adjuvant effect in B-1 cells by inducing them to differentiate into B-1CDP cells and modulates their phagocytic functions both in vivo and in vitro. Moreover, most of these effects are mediated primarily via TLR2. These data reinforce the findings that such bacterial suspensions have powerful adjuvant properties. The responses of B-1 cells to exogenous stimulation indicate that these cells are important to the innate immune response. PMID:27233619

  16. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

    Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins) brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio). Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide) were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was assessed using chi-square test and coefficient

  17. Protection induced by Plasmodium falciparum MSP1(42 is strain-specific, antigen and adjuvant dependent, and correlates with antibody responses.

    Jeffrey A Lyon

    Full Text Available Vaccination with Plasmodium falciparum MSP1(42/complete Freund's adjuvant (FA followed by MSP1(42/incomplete FA is the only known regimen that protects Aotus nancymaae monkeys against infection by erythrocytic stage malaria parasites. The role of adjuvant is not defined; however complete FA cannot be used in humans. In rodent models, immunity is strain-specific. We vaccinated Aotus monkeys with the FVO or 3D7 alleles of MSP1(42 expressed in Escherichia coli or with the FVO allele expressed in baculovirus (bv combined with complete and incomplete FA, Montanide ISA-720 (ISA-720 or AS02A. Challenge with FVO strain P. falciparum showed that suppression of cumulative day 11 parasitemia was strain-specific and could be induced by E. coli expressed MSP1(42 in combination with FA or ISA-720 but not with AS02A. The coli42-FVO antigen induced a stronger protective effect than the bv42-FVO antigen, and FA induced a stronger protective effect than ISA-720. ELISA antibody (Ab responses at day of challenge (DOC were strain-specific and correlated inversely with c-day 11 parasitemia (r = -0.843. ELISA Ab levels at DOC meeting a titer of at least 115,000 ELISA Ab units identified the vaccinees not requiring treatment (noTx with a true positive rate of 83.3% and false positive rate of 14.3 %. Correlation between functional growth inhibitory Ab levels (GIA and cumulative day 11 parasitemia was weaker (r = -0.511, and was not as predictive for a response of noTx. The lowest false positive rate for GIA was 30% when requiring a true positive rate of 83.3%. These inhibition results along with those showing that antigen/FA combinations induced a stronger protective immunity than antigen/ISA-720 or antigen/AS02 combinations are consistent with protection as ascribed to MSP1-specific cytophilic antibodies. Development of an effective MSP1(42 vaccine against erythrocytic stage P. falciparum infection will depend not only on antigen quality, but also upon the selection of

  18. Is drug-induced toxicity a good predictor of response to neo-adjuvant chemotherapy in patients with breast cancer? -A prospective clinical study

    Singh JP

    2004-08-01

    Full Text Available Abstract Background Neo-adjuvant chemotherapy is an integral part of multi-modality approach in the management of locally advanced breast cancer and it is vital to predict the response in order to tailor the regime for a patient. The common final pathway in the tumor cell death is believed to be apoptosis or programmed cell death and chemotherapeutic drugs like other DNA-damaging agents act on rapidly multiplying cells including both the tumor and the normal cells by following the same common final pathway. This could account for both the toxic effects and the response. Absence or decreased apoptosis has been found to be associated with chemo resistance. The change in expression of apoptotic markers (Bcl-2 and Bax proteins brought about by various chemotherapeutic regimens is being used to identify drug resistance in the tumor cells. A prospective clinical study was conducted to assess whether chemotherapy induced toxic effects could serve as reliable predictors of apoptosis or response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer. Methods 50 cases of locally advanced breast cancer after complete routine and metastatic work up were subjected to trucut biopsy and the tissue evaluated immunohistochemically for apoptotic markers (bcl-2/bax ratio. Three cycles of Neoadjuvant Chemotherapy using FAC regime (5-fluorouracil, adriamycin, cyclophosphamide were given at three weekly intervals and patients assessed for clinical response as well as toxicity after each cycle. Modified radical mastectomy was performed in all patients three weeks after the last cycle and the specimen were re-evaluated for any change in the bcl-2/bax ratio. The clinical response, immunohistochemical response and the drug-induced toxicity were correlated and compared. Descriptive studies were performed with SPSS version 10 and the significance of response was assessed using paired t-test. Significance of correlation between various variables was

  19. Sublingual vaccination with sonicated Salmonella proteins and mucosal adjuvant induces mucosal and systemic immunity and protects mice from lethal enteritis.

    Huang, Ching-Feng; Wu, Tzee-Chung; Wu, Chia-Chao; Lee, Chin-Cheng; Lo, Wen-Tsung; Hwang, Kwei-Shuai; Hsu, Mu-Ling; Peng, Ho-Jen

    2011-07-01

    Salmonella enteritidis is one of the most common pathogens of enteritis. Most experimental vaccines against Salmonella infection have been applied through injections. This is a new trial to explore the effect of sublingual administration of Salmonella vaccines on systemic and mucosal immunity. Adult BALB/c mice were sublingually vaccinated with sonicated Salmonella proteins (SSP) alone, or plus adjuvant CpG DNA (CpG) or cholera toxin (CT). They were boosted 2 weeks later. Saliva specific secretory IgA (SIgA) antibody responses were significantly stimulated in the mice vaccinated with SSP only or together with CpG or CT. Whereas the mice sublingually vaccinated with SSP and CpG had higher spleen cell IFN-γ production and serum specific IgG2a antibody responses, those receiving SSP and CT showed enhanced spleen cell IL-4, IL-5 and IL-6 production, and serum specific IgG1 antibody responses. After oral challenge with live S. enteritidis, the same strain of the source of SSP, immune protection in those sublingually vaccinated with SSP and CpG or CT was found to prevent intestinal necrosis and to render a higher survival rate. In conclusion, sublingual vaccination together with mucosal adjuvant CpG or CT is a simple but effective way against enteric bacterial pathogens. PMID:21635554

  20. The A3 Adenosine Receptor Agonist CF502 Inhibits the PI3K, PKB/Akt and NF-κB Signaling Pathway in Synoviocytes from Rheumatoid Arthritis Patients and in Adjuvant Induced Arthritis Rats

    Ochaion, A.; BAR-YEHUDA, S.; Cohen, S.; Amital, H; Jacobson, K. A.; Joshi, B.V.; Gao, Z. G.; Barer, F.; PATOKA, R.; Del Valle, L; Perez-Liz, G.; Fishman, P

    2008-01-01

    The A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant and collagen induced arthritis.

  1. Recombinant HPV16 E7 assembled into particles induces an immune response and specific tumour protection administered without adjuvant in an animal model

    Giorgi Colomba

    2011-05-01

    Full Text Available Abstract Background The HPV16 E7 protein is both a tumour-specific and a tumour-rejection antigen, the ideal target for developing therapeutic vaccines for the treatment of HPV16-associated cancer and its precursor lesions. E7, which plays a key role in virus-associated carcinogenesis, contains 98 amino acids and has two finger-type structures which bind a Zn++ ion. The ability of an Escherichia coli-produced E7-preparation, assembled into particles, to induce protective immunity against a HPV16-related tumour in the TC-1-C57BL/6 mouse tumour model, was evaluated. Methods E7 was expressed in E. coli, purified via a one-step denaturing protocol and prepared as a soluble suspension state after dialysis in native buffer. The presence in the E7 preparation of particulate forms was analysed by non-reducing SDS-PAGE and negative staining electron microscopy (EM. The Zn++ ion content was analysed by mass-spectrometry. Ten μg of protein per mouse was administered to groups of animals, once, twice or three times without adjuvant. The E7-specific humoral response was monitored in mice sera using an E7-based ELISA while the cell-mediated immune response was analysed in mice splenocytes with lymphoproliferation and IFN-γ ELISPOT assays. The E7 immunized mice were challenged with TC-1 tumour cells and the tumour growth monitored for two months. Results In western blot analysis E7 appears in multimers and high molecular mass oligomers. The EM micrographs show the protein dispersed as aggregates of different shape and size. The protein appears clustered in micro-, nano-aggregates, and structured particles. Mice immunised with this protein preparation show a significant E7-specific humoral and cell-mediated immune response of mixed Th1/Th2 type. The mice are fully protected from the tumour growth after vaccination with three E7-doses of 10 μg without any added adjuvant. Conclusions This report shows that a particulate form of HPV16 E7 is able to induce

  2. Qualitative and quantitative analysis of adenovirus type 5 vector-induced memory CD8 T cells

    Steffensen, Maria Abildgaard; Holst, Peter Johannes; Steengaard, Sanne Skovvang; Jensen, Benjamin Anderschou Holbech; Bartholdy, Christina; Buus, Anette Stryhn; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2013-01-01

    It has been reported that adenovirus (Ad) primed CD8 T cells may display a distinct and partially exhausted phenotype. Given the practical implications of this claim, we decided to analyze in detail the quality of Ad-primed CD8 T cells directly comparing these cells to CD8 T cells induced through...... infection with lymphocytic choriomeningitis virus. We found that localized immunization with intermediate doses of Ad vector induce a moderate number of functional CD8 T cells, which qualitatively match those found in LCMV-infected mice. Numbers of these cells may be efficiently increased by additional...... leads to the generation of a population of memory cells characterized by relatively low CD27 expression and high CD127 and KLRG1 expression. These memory CD8 T cells are capable of proliferating in response to viral challenge, and protect against infection with live virus. Furthermore, viral challenge...

  3. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE2 and LTB4) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of arthritic rats.

  4. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    Arab, Hany H., E-mail: hany_h_arab@yahoo.com [Biochemistry Division, Department of Pharmacology and Toxicology, Faculty of Pharmacy, Taif University, Taif (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo (Egypt); El-Sawalhi, Maha M. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo (Egypt)

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

  5. Effect of Different Adjuvants on Protection and Side-Effects Induced by Helicobacter suis Whole-Cell Lysate Vaccination.

    Iris Bosschem

    Full Text Available Helicobacter suis (H. suis is a widespread porcine gastric pathogen, which is also of zoonotic importance. The first goal of this study was to investigate the efficacy of several vaccine adjuvants (CpG-DNA, Curdlan, Freund's Complete and Incomplete, Cholera toxin, administered either subcutaneously or intranasally along with H. suis whole-cell lysate, to protect against subsequent H. suis challenge in a BALB/c infection model. Subcutaneous immunization with Freund's complete (FC/lysate and intranasal immunization with Cholera toxin (CT/lysate were shown to be the best options for vaccination against H. suis, as determined by the amount of colonizing H. suis bacteria in the stomach, although adverse effects such as post-immunization gastritis/pseudo-pyloric metaplasia and increased mortality were observed, respectively. Therefore, we decided to test alternative strategies, including sublingual vaccine administration, to reduce the unwanted side-effects. A CCR4 antagonist that transiently inhibits the migration of regulatory T cells was also included as a new adjuvant in this second study. Results confirmed that immunization with CT (intranasally or sublingually is among the most effective vaccination protocols, but increased mortality was still observed. In the groups immunized subcutaneously with FC/lysate and CCR4 antagonist/lysate, a significant protection was observed. Compared to the FC/lysate immunized group, gastric pseudo-pyloric metaplasia was less severe or even absent in the CCR4 antagonist/lysate immunized group. In general, an inverse correlation was observed between IFN-γ, IL-4, IL-17, KC, MIP-2 and LIX mRNA expression and H. suis colonization density, whereas lower IL-10 expression levels were observed in partially protected animals.

  6. Antibody responses induced by recombinant ALV-A gp85 protein vaccine combining with CpG-ODN adjuvant in breeder hens and the protection for their offspring against early infection.

    Zhang, Dandan; Li, Hongmei; Zhang, Zhongsheng; Sun, Shuhong; Cheng, Ziqiang; Liu, Jianzhu; Zhao, Peng; Ren, Qingya; Guo, Huijun

    2015-04-01

    To observe the antibody responses induced by recombinant A subgroup avian leukosis virus (ALV-A) gp85 protein vaccine plus CpG-ODN adjuvant and the protection of maternal antibodies (MAbs) for the hatched chickens against early infection, the gp85 gene was amplified from the proviral cDNA of ALV-A-SDAU09C1 strain using PCR and the recombinant plasmid containing target gene was constructed and expressed in EscherichiaColi. The expressed product was confirmed using SDS-PAGE and western blot that it is about 46KD of recombinant protein. The purified recombinant proteins combining with CpG-ODN adjuvant or Freund's adjuvant were inoculated into the breeder hens, the ALV-A antibodies in serum and in egg-yolk were detected; the fertilized eggs from the vaccinated hens with different titers of egg-yolk antibody were hatched and then challenged with 10(4.2)/0.1mL TCID50 of ALV-A-SDAU09C1 strain, all the hatched chickens were weekly detected for the viremias and the cloacal swab P27 antigen and pathological lesions; the neutralizing test of antisera in vitro was conducted. The results showed that the recombinant gp85 proteins combining with CpG-ODN adjuvant could induce the breeder hens to produce better antibody responses than gp85 protein with Freund's adjuvant or without adjuvant; the MAbs with higher titers induced by CpG-ODN+gp85 proteins could obviously decrease the ratios of viremias (13% vs 33%), cloacal detoxification (20% vs 67%) and death (0% vs 22%) caused by ALV-A infection than those by gp85 protein without adjuvant. The results of the neutralizing test indicated that the antisera from the hatched chickens could neutralize the ALV-A-SDAU09C1 strain in vitro, but which depends on the antibody titers. The results of IFA confirmed that the serum antibody could combine with the ALV in DF1 cells. It can be concluded that the prepared ALV-A gp85 subunit vaccine combining with CpG-ODN adjuvant could induce the breeder hens to produce better neutralizing antibody

  7. Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

    Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas;

    2011-01-01

    Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

  8. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation

  9. Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat.

    Liao, Ai-Ho; Chung, Huan-Yu; Chen, Wen-Shiang; Yeh, Ming-Kung

    2016-08-01

    A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area. PMID:27181685

  10. Evaluation of the concomitant use of methotrexate and curcumin on Freund′s complete adjuvant-induced arthritis and hematological indices in rats

    David Banji

    2011-01-01

    Full Text Available Objective : To evaluate the concomitant administration of methotrexate and curcumin for antiarthiritic activity in rats. Materials and Methods : Arthritis was induced in rats following a single subplantar injection of Freund′s complete adjuvant (0.1 ml. Rats were divided into six groups of six animals each. Group I and II were control injected with saline and Freund′s complete adjuvant (0.1 ml, respectively. Group III arthritic rats were treated with curcumin (100 mg/kg, i.p. on alternate days. Group IV received methotrexate (MTX (2 mg/kg, i.p. once in a week. Group-V and VI were treated with MTX (1 mg/kg, i.p. once in a week and after 30 min received curcumin (30 mg/kg and 100 mg/kg, thrice a week, i.p. from 10 th to 45 th days, respectively. Body weight and the paw volume was measured on 9 th , 16 th , 23 rd , 30 th , 37 th , and 45 th days. Determination of complete blood cell counts, hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin concentration was determined on the 46 th day. Results : An improvement in body weight and a significant (P < 0.05 reduction in arthritis was observed with the combination treatment as compared to the positive control. A significant improvement in the hematological profile was also observed in rats treated with curcumin and methotrexate. Conclusion : The study showed a significant anti-arthritic action and protection from hematological toxicity with the combination treatment of methotrexate and curcumin.

  11. Three-dimensional analysis of morphological changes of rat mandibular head induced by administration of adjuvant in mandibular joint cavity

    Temporal morphological changes of human osteoarthritis (OA) related to temporomandibular joint dysfunction (TMJ) are unknown because of lack of the animal model. The author made the model as in the title. Complete Freud's adjuvant (CFA) was injected in the mandibular joint cavity of male standard deviation (SD) rats with monitoring by X-ray. The site of injection was determined previously with the machine RmCT (in vivo 3D micro-X-ray CT for laboratory animals, Rigaku Corp.), which consisted of rotatable X-ray tube and facing flat panel detector, at whose center anesthetized rat was placed. The machine was also used for observation of the mandible just and 1-14 days after CFA injection and images were processed to 2D and 3D with the software I-view-R (Rigaku Corp.). Morphological changes were seen at 7-14 days on the CT images, and pathologically at 14 days, erosion or osteophytosis in 9/12 animals and enlargement of mandibular head. The cavity treated became larger for 1-14 days persistently. These results indicated that morphological changes accompanying the chronic inflammation had occurred, which was thought useful as a model of TMJ-OA. (R.T.)

  12. Freund's adjuvant-induced inflammation: clinical findings and its effect on hepcidin mRNA expression in horses

    José P. Oliveira-Filho

    2014-01-01

    Full Text Available Hypoferremia observed during systemic inflammatory disorders is regulated by hepcidin. Hepcidin up-regulation is particularly important during acute inflammation, as it restricts the availability of iron, which is necessary for pathogenic microorganism growth before adaptive immunity occurs. The aim of this study was to evaluate the clinical findings and hepatic hepcidin mRNA expression in horses using a Freund's complete adjuvant (FCA model of inflammation. The expression of hepcidin mRNA in the liver was determined in healthy horses following two intramuscular injections of FCA at 0 h and 12 h. Plasma iron and fibrinogen concentrations were measured at multiple time points between 0 h and 240 h post-FCA injection (PI. Hepcidin mRNA expression was determined by RT-qPCR using liver biopsy samples performed at 0 h (control, 6 h and 18 h PI. The mean plasma fibrinogen level was significantly different from the control values only between 120 and 216 h PI. The mean plasma iron level was significantly lower than the control between 16 and 72 h PI, reaching the lowest levels at 30 h PI (33 % of the initial value, and returned to the reference value from 96 h PI to the end of the experiment. Hepcidin mRNA expression increased at 6 h PI and remained high at 18 h PI. The iron plasma concentration was an earlier indicator of inflammatory processes in horses when compared with fibrinogen and might be useful for the early detection of inflammation in the horse. FCA administration caused the rapid onset of hypoferremia, and this effect was likely the result of up-regulated hepatic hepcidin gene expression. This study emphasizes the importance of hepcidin and iron metabolism during inflammation in horses.

  13. Qualitative Analysis of Teeth and Evaluation of Amalgam Elements Penetration into Dental Matrix Using Laser Induced Breakdown Spectroscopy

    Gazmeh, Meisam; Bahreini, Maryam; Tavassoli, Seyed Hassan; Asnaashari, Mohammad

    2015-01-01

    Introduction: In this study, laser induced breakdown spectroscopy (LIBS) is used for qualitative analysis of healthy and carious teeth. The technique of laser ablation is receiving increasing attention for applications in dentistry, specifically for the treatment of teeth such as drilling of micro-holes and plaque removal.

  14. The role of Montanide ISA 70 as an adjuvant in immune responses against Leishmania major induced by thiol-specific antioxidant-based protein vaccine.

    Khabazzadeh Tehrani, Narges; Mahdavi, Mehdi; Maleki, Fatemeh; Zarrati, Somayeh; Tabatabaie, Fatemeh

    2016-09-01

    Leishmaniasis is a parasitic disease caused by several species of the genus Leishmania. Montanide ISA 70 is an adjuvant composed of a natural metabolizable oil and a very refined emulsifier from the manide monooleate family. The TSA (thiol-specific antioxidant) is a important antigen of Leishmania major. The purpose of this work was protein-vaccine efficacy as an protection and excellent candidate in the presence Montanide. The expression of recombinant protein was confirmed with SDS (sodium dodecyl sulfate) page and Western bloting. 48 BALB/c mice were divided into four groups (TSA/Freund,TSA/Alum + BCG, TSA/Montanide and PBS groups) and immunized with 20 μg of vaccine subcutaneously three times intervals on days 0, 14 and 28. The mice were challenged with parasite 21 days after final immunization. The lymphocyte proliferation was evaluated with Brdu method. Cytokines and also total antibody and subclasses were evaluated with ELISA method. The vaccine formulated with the recombinant TSA protein with Montanide induced lymphocytes proliferation cytokines and total antibody and subclasses as compared with the control group. PMID:27605780

  15. Mother root of Aconitum carmichaelii Debeaux exerts antinociceptive effect in Complet Freund’s Adjuvant-induced mice: roles of dynorpin/kappa-opioid system and transient receptor potential vanilloid type-1 ion channel

    Wang, Chao; Sun, Danni; LIU, CHUNFANG; Zhu, Chunyan; Jing, Xianghong; Chen, Shuping; LIU, CUILING; Zhi, Kai; Xu, Tengfei; Wang, Hui; Liu, Junling; Xu, Ying; Liu, Zhiqiang; Lin, Na

    2015-01-01

    Background Processed Chuanwu (PCW), the mother root of Aconitum carmichaelii Debeauxv, has been widely used as a classic Traditional Chinese Medicine for pain relieve for over two millennia clinically. However, its action on chronic inflammatory pain has not been clarified. Here, we investigated the antinociceptive effect of PCW in complete freund’s adjuvant (CFA)-induced mice and its possible mechanisms associated with opioid system and TRPV1 ion channel. Methods Male ICR mice were intraplan...

  16. HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice

    WANG Fu-xiang; SUN Yong-tao; WANG Lin-xu; LIU Juan

    2006-01-01

    @@ There is mounting evidence that the induction of strong mucosal and cell-mediated immune responses is key element to consider in constructing efficacious HIV-1 vaccine. Therapeutic vaccines that induce high levels of CTL specific to HIV are currently being developed worldwide.

  17. Adjuvanted HLA-supertype restricted subdominant peptides induce new T-cell immunity during untreated HIV-1-infection

    Karlsson, Ingrid; Brandt, Lea; Vinner, Lasse;

    2013-01-01

    -cell responses specific for one or more vaccine epitopes were induced in 10/10 vaccinees. The responses were dominated by CD107a and MIP1β expression. There were no significant changes in HIV-1 viral load or CD4 T-cell counts. Our study demonstrates that the peptide/CAF01 vaccine is safe and that it is possible...

  18. An Adjuvanted, Tetravalent Dengue Virus Purified Inactivated Vaccine Candidate Induces Long-Lasting and Protective Antibody Responses Against Dengue Challenge in Rhesus Macaques

    Fernandez, Stefan; Thomas, Stephen J.; De La Barrera, Rafael; Im-Erbsin, Rawiwan; Jarman, Richard G.; Baras, Benoît; Toussaint, Jean-François; Mossman, Sally; Bruce L. Innis; Schmidt, Alexander; Malice, Marie-Pierre; Festraets, Pascale; Warter, Lucile; Putnak, J. Robert; Eckels, Kenneth H.

    2015-01-01

    The immunogenicity and protective efficacy of a candidate tetravalent dengue virus purified inactivated vaccine (TDENV PIV) formulated with alum or an Adjuvant System (AS01, AS03 tested at three different dose levels, or AS04) was evaluated in a 0, 1-month vaccination schedule in rhesus macaques. One month after dose 2, all adjuvanted formulations elicited robust and persisting neutralizing antibody titers against all four dengue virus serotypes. Most of the formulations tested prevented vire...

  19. Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.

    Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-02-01

    Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20-28, 2016. © 2016 Wiley Periodicals, Inc. PMID:26763139

  20. Synthetic B- and T-cell epitope peptides of porcine reproductive and respiratory syndrome virus with Gp96 as adjuvant induced humoral and cell-mediated immunity.

    Chen, Caiwei; Li, Jing; Bi, Yuhai; Yang, Limin; Meng, Shanshan; Zhou, Yuancheng; Jia, Xiaojuan; Meng, Songdong; Sun, Lei; Liu, Wenjun

    2013-04-01

    Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) has recently caused huge economic losses in the pig industry worldwide. Commercial vaccines, including inactivated vaccines and attenuated live vaccines, are available but fail to provide sustainable protection, especially against genetically heterologous strains. Thus several approaches have been used to develop more effective PRRSV vaccines and/or immune modulators to accelerate and magnify immune responses to PRRSV vaccines. Heat shock protein Gp96 is one such modulator that enhances both the innate and adaptive immune responses. In the present study, two B-cell epitopes and seven T-cell epitopes from PRRSV and a Pan DR T-helper cell epitope were synthesized and mixed with the N-terminal 22-355 aa of Gp96 (Gp96N) as an adjuvant, and immune responses were evaluated. Our results show that Gp96N activated PRRSV-specific humoral immune responses elicited by BCE-peptides and promoted the PRRSV-specific cellular immunity induced by TCE-peptides. Moreover, higher levels of IL-12 and TNF-α and lower levels of IL-4 and IL-10 were observed in the serum of Gp96N-vaccinated piglets compared to piglets immunized with no Gp96N, displaying a predominant Th1 type of immune response induced by Gp96N. Following challenge with the virulent HP-PRRSV isolate JXwn06, piglets vaccinated with the mixture of peptides and Gp96N presented with milder clinical symptoms, lower viremia, and less pathological lesions in their lungs, however, this vaccine could not provide lasting and effective protection against HP-PRRSV infection. These data provide important bases for the development of PRRSV epitope-based synthetic peptide vaccines combined with Gp96N as attractive immunomodulators in swine. PMID:23395588

  1. ADJUVANTS IN MODERN VACCINOLOGY

    Belozersky V. I.

    2013-12-01

    Full Text Available A concept of adjuvants and their story of creation ischaracterized in the article. They’re presented thevarious types of non-specific stimulators of immunesysteme, thier excipients and classification. They’redescribed basic properties of adjuvant systems, their significant advantages and disadvantages. Particular attention is paid to the numerous antigen delivery systems, including alive vectors, nanoparticles, bacterial toxins, etc. They’re considered non-specific stimulators mechanisms of action on immune system and theirinteraction with antigens. They’re given examples of different adjuvants in licensed vaccines use.

  2. In vitro interactions between macrophages and aluminum-containing adjuvants.

    Rimaniol, Anne-Cécile; Gras, Gabriel; Clayette, Pascal

    2007-09-17

    Intramuscular administration of aluminum-adjuvanted vaccines induces an infiltration of aluminum-containing macrophages between muscle fibers. In vitro stimulation of human monocyte-derived macrophages with aluminum hydroxide (AlOOH) induces similar intracellular crystalline inclusions as well as phenotypical and functional modifications. We compared in this study the ability of other adjuvants to exert similar changes in macrophages in vitro. All mineral salts, i.e. aluminic (AlOOH, AlPO(4)) and non-aluminic mineral adjuvants (CaPO(4), FePO(4)) but not emulsion were able to increase macrophages capacity to potentiate autologous memory T lymphocyte proliferation, while only aluminic adjuvants induced CD83 expression and increased CD86 on macrophages. All together, this suggests that aluminic and non-aluminic adjuvants exerted their immunoactivities by distinct mechanisms on macrophages. PMID:17689842

  3. ADJUVANTS IN MODERN VACCINOLOGY

    Belozersky V. I; Zhdamarova L.A.; Yelyseyeva I. V; Babych Ye. M.; Isaenko Ye. Yu.; Kolpak S. A

    2013-01-01

    A concept of adjuvants and their story of creation ischaracterized in the article. They’re presented thevarious types of non-specific stimulators of immunesysteme, thier excipients and classification. They’redescribed basic properties of adjuvant systems, their significant advantages and disadvantages. Particular attention is paid to the numerous antigen delivery systems, including alive vectors, nanoparticles, bacterial toxins, etc. They’re considered non-specific stimulators mechanisms of a...

  4. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity.

    Kowalczyk, Aleksandra; Doener, Fatma; Zanzinger, Kai; Noth, Janine; Baumhof, Patrick; Fotin-Mleczek, Mariola; Heidenreich, Regina

    2016-07-19

    mRNA represents a new platform for the development of therapeutic and prophylactic vaccines with high flexibility with respect to production and application. We have previously shown that our two component self-adjuvanted mRNA-based vaccines (termed RNActive® vaccines) induce balanced immune responses comprising both humoral and cellular effector as well as memory responses. Here, we evaluated the early events upon intradermal application to gain more detailed insights into the underlying mode of action of our mRNA-based vaccine. We showed that the vaccine is taken up in the skin by both non-leukocytic and leukocytic cells, the latter being mostly represented by antigen presenting cells (APCs). mRNA was then transported to the draining lymph nodes (dLNs) by migratory dendritic cells. Moreover, the encoded protein was expressed and efficiently presented by APCs within the dLNs as shown by T cell proliferation and immune cell activation, followed by the induction of the adaptive immunity. Importantly, the immunostimulation was limited to the injection site and lymphoid organs as no proinflammatory cytokines were detected in the sera of the immunized mice indicating a favorable safety profile of the mRNA-based vaccines. Notably, a substantial boostability of the immune responses was observed, indicating that mRNA can be used effectively in repetitive immunization schedules. The evaluation of the immunostimulation following prime and boost vaccination revealed no signs of exhaustion as demonstrated by comparable levels of cytokine production at the injection site and immune cell activation within dLNs. In summary, our data provide mechanistic insight into the mode of action and a rational for the use of mRNA-based vaccines as a promising immunization platform. PMID:27269061

  5. Immunoliposome co-delivery of bufalin and anti-CD40 antibody adjuvant induces synergetic therapeutic efficacy against melanoma

    Li Y

    2014-12-01

    Full Text Available Ying Li,1,* Jiani Yuan,1,* Qian Yang,1 Wei Cao,1 Xuanxuan Zhou,1 Yanhua Xie,1 Honghai Tu,2 Ya Zhang,1 Siwang Wang1 1Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi’an, People’s Republic of China; 2Institute for Drug and Instrument Control, Xinjiang Military Area Command, Urumqi, Xinjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL conjugated with anti-CD40 antibody (anti-CD40-BFL showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm3 versus 270 mm3, respectively; the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistribution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic

  6. Prognostic Effects of Adjuvant Chemotherapy-Induced Amenorrhea and Subsequent Resumption of Menstruation for Premenopausal Breast Cancer Patients.

    Jeon, Se Jeong; Lee, Jae Il; Jeon, Myung Jae; Lee, Maria

    2016-04-01

    Chemotherapy-induced amenorrhea (CIA) is a side effect that occurs in patients with breast cancer (BC) as a result of chemotherapy. These patients require special treatments to avoid infertility and menopause. However, the factors controlling CIA, resumption of menstruation (RM), and persistence of menstruation after chemotherapy are unknown. The long-term prognosis for premenopausal patients with BC and the prognostic factors associated with CIA and RM are subject to debate. We performed a retrospective study by reviewing the medical records of 249 patients with BC (stage I to stage III) who were treated with cytotoxic chemotherapy. The median patient age was 43 (range, 26-55 years) and the median duration of follow-up was 64 months (range, 28-100 months). The medical records indicated that 219 patients (88.0%) scored as positive for the hormone receptor (HR); the majority of these patients completed chemotherapy and then received additional therapy of tamoxifen. Our analyses revealed that 88.0% (n = 219) of patients experienced CIA, and the percentage of RM during follow-up was 48.6% (n = 121). A total of 30 patients (12.0%) did not experience CIA. Disease-free survival (DFS) was affected by several factors, including tumour size ≥2 cm, node positivity, HR negative status, and body mass index ≥23 kg/m. Multivariate analysis indicated that tumour size ≥2 cm remained as a significant factor for DFS (hazard ratio = 3.3, P = 0.034). In summary, this study finds that the majority of premenopausal patients with BC (stage I to stage III) who receive chemotherapy experience CIA and subsequent RM. Although tumour size ≥2 cm is negatively associated with DFS, RM after CIA is not associated with poor prognosis. PMID:27057900

  7. Laser Induced Breakdown Spectroscopy of Prickly Pear's Spines and Glochids: A qualitative analysis

    A qualitative LIBS analysis of Prickly Pear is presented. The spectra for Q:Switch regime from cladode and spine are similar, while shows an intense electronic noise due the high absorption in spines for free-running regime

  8. Alternative inactivated poliovirus vaccines adjuvanted with Quillaja brasiliensis or Quil-a saponins are equally effective in inducing specific immune responses.

    Fernanda de Costa

    Full Text Available Inactivated polio vaccines (IPV have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV. An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control, Quil-A (50 µg, AE (400 µg or QB-90 (50 µg. Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.

  9. A rabies vaccine adjuvanted with saponins from leaves of the soap tree (Quillaja brasiliensis) induces specific immune responses and protects against lethal challenge.

    Yendo, Anna Carolina A; de Costa, Fernanda; Cibulski, Samuel P; Teixeira, Thais F; Colling, Luana C; Mastrogiovanni, Mauricio; Soulé, Silvia; Roehe, Paulo M; Gosmann, Grace; Ferreira, Fernando A; Fett-Neto, Arthur G

    2016-04-29

    Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A(®)) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P≤0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria. PMID:27032516

  10. The importance of adjuvant formulation in the development of a TB vaccine

    Baldwin, Susan L.; Bertholet, Sylvie; Reese, Valerie A.; Ching, Lance K; Reed, Steven G.; Coler, Rhea N.

    2012-01-01

    An effective protein based vaccine for tuberculosis (TB) will require a safe and effective adjuvant. There are few adjuvants in approved human vaccines, including Alum and the oil-in-water (o/w) based emulsions MF59 (Novartis Vaccines and Diagnostics), AS03 and AS04 (GlaxoSmith Kline Biologics, GSK) AF03 (Sanofi), and liposomes (Crucell). When used with pure, defined proteins, both Alum and emulsion adjuvants are effective at inducing primarily humoral responses. One of the newest adjuvants i...

  11. Vaccine Adjuvants: from 1920 to 2015 and Beyond.

    Pasquale, Alberta Di; Preiss, Scott; Silva, Fernanda Tavares Da; Garçon, Nathalie

    2015-01-01

    The concept of stimulating the body's immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

  12. Incidence of cold-induced peripheral neuropathy and dose modification of adjuvant oxaliplatin-based chemotherapy for patients with colorectal cancer

    Altaf, Rahim; Lund Brixen, Annette; Kristensen, Bent;

    2014-01-01

    BACKGROUND: The CAPOX regimen is used for adjuvant treatment of colorectal cancer. A well-known side effect of oxaliplatin, which often leads to dose modification (DM), is acute neuropathy (AN). AN is provoked by cold, and it could therefore be expected that the degree of AN and thereby DM is mor...

  13. Enhanced expressions of mRNA for neuropeptide Y and interleukin 1 beta in hypothalamic arcuate nuclei during adjuvant arthritis-induced anorexia in Lewis rats

    Stofková, A.; Haluzík, M.; Železná, Blanka; Kiss, A.; Skurlová, M.; Lacinová, Z.; Jurcovicová, J.

    2009-01-01

    Roč. 16, č. 6 (2009), s. 377-384. ISSN 1021-7401 R&D Projects: GA ČR GA305/06/0427 Institutional research plan: CEZ:AV0Z40550506 Keywords : adjuvant arthritis * anorexia * leptin * adiponectin Subject RIV: CC - Organic Chemistry Impact factor: 2.034, year: 2009

  14. Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer

    Ranran Zhang; Dongchu Ma; Xiaodong Xie; Wanqing Xie Co-first author; Tao Han; Yongye Liu; Zhaozhe Liu; Fang Guo; Yaling Han; Zhenyu Ding; Yinghui Sun

    2015-01-01

    Objective The aim of the present study was to investigate the ef ect of dendritic cel (DC)/cytokine-in-duced kil er cel (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrol ed in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, dif erences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cel levels), disease-free survival (DFS), and side ef ects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cel s and CD3+ and CD4+ T-cel subgroups significantly increased, and the proportion of CD8+ cel s decreased when they were compared before and after DC/CIK therapy (P Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the con-trol group, and was not associated with any obvious side ef ects. Therefore, DC/CIK therapy is a safe and ef ective method for the treatment of TNBC.

  15. Anti-inflammatory activity and neutrophil reductions mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis

    Meyer Debra M

    2010-08-01

    Full Text Available Abstract Background The Janus kinase (JAK family of tyrosine kinases includes JAK1, JAK2, JAK3 and TYK2, and is required for signaling through Type I and Type II cytokine receptors. CP-690,550 is a potent and selective JAK inhibitor currently in clinical trials for rheumatoid arthritis (RA and other autoimmune disease indications. In RA trials, dose-dependent decreases in neutrophil counts (PBNC were observed with CP-690,550 treatment. These studies were undertaken to better understand the relationship between JAK selectivity and PBNC decreases observed with CP-690,550 treatment. Methods Potency and selectivity of CP-690,550 for mouse, rat and human JAKs was evaluated in a panel of in vitro assays. The effect of CP-690,550 on granulopoiesis from progenitor cells was also assessed in vitro using colony forming assays. In vivo the potency of orally administered CP-690,550 on arthritis (paw edema, plasma cytokines, PBNC and bone marrow differentials were evaluated in the rat adjuvant-induced arthritis (AIA model. Results CP-690,550 potently inhibited signaling through JAK1 and JAK3 with 5-100 fold selectivity over JAK2 in cellular assays, despite inhibiting all four JAK isoforms with nM potency in in vitro enzyme assays. Dose-dependent inhibition of paw edema was observed in vivo with CP-690,550 treatment. Plasma cytokines (IL-6 and IL-17, PBNC, and bone marrow myeloid progenitor cells were elevated in the context of AIA disease. At efficacious exposures, CP-690,550 returned all of these parameters to pre-disease levels. The plasma concentration of CP-690,550 at efficacious doses was above the in vitro whole blood IC50 of JAK1 and JAK3 inhibition, but not that of JAK2. Conclusion Results from this investigation suggest that CP-690,550 is a potent inhibitor of JAK1 and JAK3 with potentially reduced cellular potency for JAK2. In rat AIA, as in the case of human RA, PBNC were decreased at efficacious exposures of CP-690,550. Inflammatory end points

  16. Effect of different adjuvant formulations on the immunogenicity and protective effect of a live Mycoplasma hyopneumoniae vaccine after intramuscular inoculation.

    Xiong, Qiyan; Wei, Yanna; Xie, Haidong; Feng, Zhixin; Gan, Yuan; Wang, Chunlai; Liu, Maojun; Bai, Fangfang; Xie, Fang; Shao, Guoqing

    2014-06-01

    Mycoplasma hyopneumoniae (M. hyopneumoniae) vaccine strain 168 is an intrapulmonically injected attenuated live vaccine that is available in the Chinese market. The aim of this study was to develop suitable adjuvants for this live vaccine to provide effective protection after intramuscular inoculation. Several adjuvant components were screened to assess their toxicity for the live vaccine, and various adjuvant formulations were then designed and prepared. Vaccines supplemented with these adjuvants were used to immunize mice intramuscularly to assess the capacity of the adjuvants to induce a specific immune response. The screened formulations were then evaluated in pigs. Seven of the eight adjuvant components did not affect the viability of the live vaccine, and seven different adjuvant formulations were then designed. In mice, the ISCOM-matrix adjuvant and the levamisole-chitosan mixture adjuvant significantly enhanced serum IgG responses against M. hyopneumoniae, while lymphocyte proliferation was enhanced by the ISCOM-matrix adjuvant, the carbomer-astragalus polysaccharide mixture adjuvant and an oil-in-water emulsion adjuvant. These four adjuvants were evaluated in pigs. Enhancement of specific lymphocyte proliferation responses was observed in the groups vaccinated with the ISCOM-matrix adjuvant and the carbomer-astragalus polysaccharide mixture adjuvant. Significant enhancement of serum IgG antibody production was observed before challenge in pigs vaccinated with the carbomer-astragalus polysaccharide mixture adjuvant and the levamisole-chitosan mixture adjuvant, while after challenge, all of the animals that received vaccines containing adjuvants had higher antibody concentrations against M. hyopneumoniae than unvaccinated animals. Animals inoculated with a vaccine containing the ISCOM-matrix adjuvant (median score 3.57) or the carbomer-astragalus polysaccharide mixture adjuvant (median score 5.28) had reduced lesion scores compared to unvaccinated animals

  17. ERM immersion vaccination and adjuvants

    Skov, J.; Chettri, J. K.; Jaafar, R. M.;

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were the...

  18. MF59- and Al(OH3-adjuvanted Staphylococcus aureus (4C-Staph vaccines induce sustained protective humoral and cellular immune responses, with a critical role for effector CD4 T cells at low antibody titers.

    Elisabetta eMonaci

    2015-09-01

    Full Text Available Staphylococcus aureus (S. aureus is an important opportunistic pathogen that may cause invasive life-threatening infections like sepsis and pneumonia. Due to increasing antibiotic-resistance, the development of an effective vaccine against S. aureus is needed. Although a correlate of protection against staphylococcal diseases is not yet established, several findings suggest that both antibodies and CD4 T cells might contribute to optimal immunity. In this study, we show that adjuvanting a multivalent vaccine (4C-Staph with MF59, an oil-in-water emulsion licensed in human vaccines, further potentiated antigen-specific IgG titers and CD4 T cell responses compared to alum and conferred protection in the peritonitis model of S. aureus infection. Moreover, we showed that MF59- and alum-adjuvanted 4C-Staph vaccines induced persistent antigen-specific humoral and T cell responses, and protected mice from infection up to 4 months after immunization. Furthermore, 4C-Staph formulated with MF59 was used to investigate which immune compartment is involved in vaccine-induced protection. Using CD4 T cell-depleted mice or B cell deficient mice, we demonstrated that both T and B cell responses contributed to 4C-Staph vaccine-mediated protective immunity. However, the role of CD4 T cells seemed more evident in the presence of low antibody responses. This study provides preclinical data further supporting the use of the adjuvanted 4C-Staph vaccines against S. aureus diseases, and provides critical insights on the correlates of protective immunity necessary to combat this pathogen.

  19. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine &Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland.

    Fox, Christopher B

    2013-09-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted. PMID:23787558

  20. Experts’ perceptions of the concept of induced demand in healthcare: A qualitative study in Isfahan, Iran

    Keyvanara, Mahmoud; Karimi, Saeed; Khorasani, Elahe; Jazi, Marzie Jafarian

    2014-01-01

    Context: One of the most important subjects in health economics and healthcare management is the theory of induced demand. There are different views about the concept of induced demand. Extensive texts have been presented on induced demand, however a compatible concept has not necessarily been provided for this phenomenon and it has not been defined explicitly. Aims: The main aim of this article is to understand the concept of induced demand with the use of experts’ perceptions of Isfahan Uni...

  1. Experimental autoimmune glomerulonephritis induced by anti-glomerular basement membrane antibody. II. Effects of injecting heterologous, homologous, or autologous glomerular basement membranes and complete Freund's adjuvant into sheep.

    Steblay, R. W.; Rudofsky, U H

    1983-01-01

    The effects of injecting human, rabbit, rat, or single-kidney homologous glomerular basement membrane (GBM) or autologous GBM, each in complete Freund's adjuvant (CFA), into 15- to 18-month-old sheep are compared. All sheep receiving heterologous GBM and 3 of 6 sheep receiving homologous GBM had anti-GBM nephritis, but such sheep did not bind autoantibodies or have Goodpasturelike lesions in their lungs. Sheep given injections of human GBM had autoantibodies to antigenic determinants shared b...

  2. Unlipidated outer membrane protein Omp16 (U-Omp16 from Brucella spp. as nasal adjuvant induces a Th1 immune response and modulates the Th2 allergic response to cow's milk proteins.

    Andrés E Ibañez

    Full Text Available The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n. induced an inflammatory immune response in bronchoalveolar lavage (BAL and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag ovalbumin (OVA increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow's Milk Protein (CMP, decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations.

  3. Immunoprotective activity of a Salmonid Alphavirus Vaccine: comparison of the immune responses induced by inactivated whole virus antigen formulations based on CpG class B oligonucleotides and poly I:C alone or combined with an oil adjuvant.

    Thim, Hanna L; Iliev, Dimitar B; Christie, Karen E; Villoing, Stéphane; McLoughlin, Marian F; Strandskog, Guro; Jørgensen, Jorunn B

    2012-07-01

    CpG oligonucleotides and polyinosinic:polycytidylic acid (poly I:C) are toll-like receptor (TLR) agonists that mimic the immunostimulatory properties of bacterial DNA and double-stranded viral RNA respectively, and which have exhibited potential to serve as vaccine adjuvants in previous experiments. Here, a combination of CpGs and poly I:C together with water- or oil-formulated Salmonid Alphavirus (SAV) antigen preparations has been used for a vaccine in Atlantic salmon and tested for protection in SAV challenge trial. The results demonstrate that vaccination with a high dose of the SAV antigen induced protection against challenge with SAV which correlated with production of neutralizing antibodies (NAbs). As the high antigen dose alone induced full protection, no beneficial effect from the addition of CpG and poly I:C could be observed. Nevertheless, these TLR ligands significantly enhanced the levels of NAbs in serum of vaccinated fish. Interestingly, gene expression analysis demonstrated that while addition of oil suppressed the CpG/poly I:C-induced expression of IFN-γ, the upregulation of IFNa1 was substantially enhanced. A low dose of the SAV antigen combined with oil did not induce any detectable levels of NAbs either with or without TLR ligands present, however the addition of CpG and poly I:C to the low SAV antigen dose formulation significantly enhanced the protection against SAV suggesting that CpG/poly I:C may have enhanced a cytotoxic response - a process which is dependent on the up-regulation of type I IFN. These results highlight the immunostimulatory properties of the tested TLR ligands and will serve as a ground for further, more detailed studies aimed to investigate their capacity to serve as adjuvants in vaccine formulations for Atlantic salmon. PMID:22634299

  4. Immunization with recombinant Brucella species outer membrane protein Omp16 or Omp19 in adjuvant induces specific CD4+ and CD8+ T cells as well as systemic and oral protection against Brucella abortus infection.

    Pasquevich, Karina A; Estein, Silvia M; García Samartino, Clara; Samartino, Clara García; Zwerdling, Astrid; Coria, Lorena M; Barrionuevo, Paula; Fossati, Carlos A; Giambartolomei, Guillermo H; Cassataro, Juliana

    2009-01-01

    Available vaccines against Brucella spp. are live attenuated Brucella strains. In order to engineer a better vaccine to be used in animals and humans, our laboratory aims to develop an innocuous subunit vaccine. Particularly, we are interested in the outer membrane proteins (OMPs) of B. abortus: Omp16 and Omp19. In this study, we assessed the use of these proteins as vaccines against Brucella in BALB/c mice. Immunization with lipidated Omp16 (L-Omp16) or L-Omp19 in incomplete Freund's adjuvant (IFA) conferred significant protection against B. abortus infection. Vaccination with unlipidated Omp16 (U-Omp16) or U-Omp19 in IFA induced a higher degree of protection than the respective lipidated versions. Moreover, the level of protection induced after U-Omp16 or U-Omp19 immunization in IFA was similar to that elicited by live B. abortus S19 immunization. Flow cytometric analysis showed that immunization with U-Omp16 or U-Omp19 induced antigen-specific CD4(+) as well as CD8(+) T cells producing gamma interferon. In vivo depletion of CD4(+) or CD8(+) T cells in mice immunized with U-Omp16 or U-Omp19 plus IFA resulted in a loss of the elicited protection, indicating that both cell types are mediating immune protection. U-Omp16 or U-Omp19 vaccination induced a T helper 1 response, systemic protection in aluminum hydroxide formulation, and oral protection with cholera toxin adjuvant against B. abortus infection. Both immunization routes exhibited a similar degree of protection to attenuated Brucella vaccines (S19 and RB51, respectively). Overall these results indicate that U-Omp16 or U-Omp19 would be a useful candidate for a subunit vaccine against human and animal brucellosis. PMID:18981242

  5. Experimental study on Cervi Cornu on Adjuvant Arthritis in rats

    Ji-Won, Shin; Jai-Young, Park; Hee-Soo,Park

    2002-01-01

    Objective: To investigate effects of Cervi Cornu on Adjuvant Athritis in rats, the edema inhibit rate, the anaJgesic effects, the number of WBC, RA facter, Platelet, the quantity of CRP, total protein, albumin and globuline in the blood serum were measured in the arthritis part. Results: The results obtained as fonows ; 1. After arthritis of Sprague dawley(SD) rats was induced by injecting Freund's complete adjuvant for 2 weeks, any treatment was not for Control group, acupunctured for Tr...

  6. Adjuvant Treatment for Ampullary Cancer

    Richard Kim; John Chabot; Muhammad Wasif Saif

    2011-01-01

    Ampullary cancer is an uncommon tumor and tends to have a better prognosis than pancreatic cancer. However, one half of patients will die from recurrent disease suggesting the need for effective adjuvant therapy. Currently, there is lack of randomized trials to guide the use of adjuvant therapy in ampullary cancer. At the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, the largest trial (Abstract #4006) evaluating adjuvant treatment of ampullary cancer was presented.

  7. Adjuvant Treatment for Ampullary Cancer

    Richard Kim

    2011-07-01

    Full Text Available Ampullary cancer is an uncommon tumor and tends to have a better prognosis than pancreatic cancer. However, one half of patients will die from recurrent disease suggesting the need for effective adjuvant therapy. Currently, there is lack of randomized trials to guide the use of adjuvant therapy in ampullary cancer. At the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, the largest trial (Abstract #4006 evaluating adjuvant treatment of ampullary cancer was presented.

  8. The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats.

    Ochaion, A; Bar-Yehuda, S; Cohen, S; Amital, H; Jacobson, K A; Joshi, B V; Gao, Z G; Barer, F; Patoka, R; Del Valle, L; Perez-Liz, G; Fishman, P

    2008-08-15

    The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant- and collagen-induced arthritis. In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappaB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant-induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 microg/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), IkappaB kinase (IKK), I kappa B (IkappaB), NF-kappaB and tumor necrosis factor-alpha (TNF-alpha) took place. In addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappaB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A(3)AR agonists for the treatment of rheumatoid arthritis. PMID:18602896

  9. The A3 Adenosine Receptor Agonist CF502 Inhibits the PI3K, PKB/Akt and NF-κB Signaling Pathway in Synoviocytes from Rheumatoid Arthritis Patients and in Adjuvant Induced Arthritis Rats

    Ochaion, A.; Bar-Yehuda, S.; Cohen, S.; Amital, H.; Jacobson, K.A.; Joshi, B.V.; Gao, Z.G.; Barer, F.; Patoka, R.; Del Valle, L.; Perez-Liz, G.; Fishman, P.

    2009-01-01

    The A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant and collagen induced arthritis. In this study we present a novel A3AR agonist, CF502, with high affinity and selectivity at the human A3AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of Adjuvant Induced Arthritis (AIA) in a rat experimental model when given orally at a low dose (100 μg/kg). As is typical of other G-protein coupled receptors, the A3AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of Protein Kinase B/Akt (PKB/Akt), IκB kinase (IKK), (I kappa B) IκB, NF-κB and tumor necrosis factor-alpha (TNF-α) took place. In addition, the expression levels of Glycogen synthase kinase-3 beta (GSK-3β), β-catenin, and Poly (ADP-ribose) polymerase (PARP), known to control the level and activity of NF-κB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A3AR agonists for the treatment of rheumatoid arthritis. PMID:18602896

  10. Formulation, High Throughput In Vitro Screening and In Vivo Functional Characterization of Nanoemulsion-Based Intranasal Vaccine Adjuvants

    Pamela T. Wong; Leroueil, Pascale R.; Smith, Douglas M.; Ciotti, Susan; Bielinska, Anna U.; Janczak, Katarzyna W.; Mullen, Catherine H.; Groom, Jeffrey V.; Taylor, Erin M; Passmore, Crystal; Makidon, Paul E.; O’Konek, Jessica J.; Myc, Andrzej; Hamouda, Tarek; Baker, James R.

    2015-01-01

    Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate ...

  11. Adjuvant Therapy Trials.

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

  12. Qualitative analysis of Pb liquid sample using laser-induced breakdown spectroscopy (LIBS)

    Qualitative analysis of liquid sample containing 1,000 ppm of Pb was performed by using LIBS technique. In order to avoid splashing off of the liquid sample during laser irradiation, a sample pretreatment was done, namely the liquid sample was absorbed by using commercial available stomach medicine. Two kinds of absorbent materials were chosen in this experiment, first containing 125 mg activated carbon and second 600 mg activated attapulgite. These absorbent materials were used since carbon sample gives better absorption of infrared laser irradiation used in this experiment. In order to characterize the absorption process, three treatments were conducted in this experiment; first, without heating the sample but varying the absorption time before laser irradiation; second by varying the heating temperature after certain time of absorption process and third by varying the temperature only. The maximum emission intensity of Pb I 405.7 nm was found in the second treatment of heating the sample till 85°C after 30 minutes absorption of the liquid sample in both absorbent materials

  13. Evaluation of several adjuvants in avian influenza vaccine to chickens and ducks

    Li Hong T

    2011-06-01

    Full Text Available Abstract The effects of three different adjuvants, mineral oil, Montanide™ ISA 70M VG, and Montanide™ ISA 206 VG, were evaluated on reverse genetics H5N3 avian influenza virus cell cultured vaccine. The immune results of SPF chickens after challenging with highly pathogenic avian influenza (HPAI virus demonstrated that mineral oil adjuvant group and 70M adjuvant group provided 100% protection efficiency, but 206 adjuvant group provided only 40%. Statistical analysis indicated that the protection effects of mineral oil adjuvant group and the 70M adjuvant showed no significant difference to each other, but with significant difference to 206 adjuvant group. All three groups could induce high titres of antibody after immunizing SPF ducks, but there was no significant difference among them. The immunization effect of 70M adjuvant group on SPF chickens were the best and showed significant difference compared with optimized 70Mi Montanide™ eight series adjuvants groups. These results suggest that 70M adjuvant could be a novel adjuvant for preparing avian influenza vaccine.

  14. Glucose utilisation during status epilepticus in an epilepsy model induced by pilocarpine: a qualitative study

    Scorza Fulvio Alexandre

    2002-01-01

    Full Text Available Status epilepticus (SE is a medical emergency and it is associated to brain damage. 2-deoxy-[14C] glucose (2-DG procedure has been used to measure the alterations in the functional activity of the brain induced by various pharmacological and toxicological agents. The aim of this study was to determine which changes occur in the seizure anatomic substrates during the SE induced by pilocarpine (PILO using [14C]-2 deoxyglucose functional mapping technique. Wistar male adult rats were submitted to SE PILO-induced for 6h and received [14C] 2-deoxyglucose injection via jugular vein 45 min before the 6th hour of SE. The control animals were submitted to all procedures but received saline and not pilocarpine. Brain sections were prepared and exposed X-ray film about seven days. The optical density of each region was obtained using a solid state digital analyser. The analysis revealed that 14C-2DG utilisation was pronounced in the SE rats on the areas corresponding to the hippocampal formation (+50.6%, caudate-putamen (+30.6%, frontoparietal cortex (+32.2%, amygdala (+31.7%, entorrinal cortex (+28.2%, thalamic nucleus (+93.5%, pre-tectal area (+50.1% and substantia nigra (+50.3% when compared to control. Our results suggest that the different activation levels of the distinct structures may be particularly important for understanding triggering and spreading mechanisms underlying epileptic activity during status epilepticus.

  15. Gemcitabine-induced radiation recall phenomenon in a post-operative and post-radiotherapy case of peri-ampullary carcinoma during adjuvant chemotherapy

    Jayanta Biswas

    2012-01-01

    Full Text Available Radiation recall phenomenon is an inflammatory process occurring at sites of previous radiation subsequent to administration of pharmacologic agents. The most common chemotherapeutic agents implicated with radiation recall phenomenon are anthracyclines and taxanes. Skin is the most common site for radiation recall. About 63% of the radiation recall events are reported to manifest as dermatitis. This finding differs from radiation recall due to Gemcitabine, in which approximately 70% cases manifested as inflammation of internal organs or tissues and 30% manifested as dermatitis. Here, we report a case of post-operative peri-ampullary carcinoma who developed radiation recall dermatitis during adjuvant chemotherapy with inj. Gemcitabine and inj. Carboplatin after concurrent chemoradiation with capecitabine.

  16. Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules.

    Davtyan, Hayk; Zagorski, Karen; Rajapaksha, Harinda; Hovakimyan, Armine; Davtyan, Arpine; Petrushina, Irina; Kazarian, Konstantin; Cribbs, David H; Petrovsky, Nikolai; Agadjanyan, Michael G; Ghochikyan, Anahit

    2016-01-01

    Although β-amyloid (Aβ) may be the primary driver of Alzheimer's disease (AD) pathology, accumulation of pathological tau correlates with dementia in AD patients. Thus, the prevention/inhibition of AD may require vaccine/s targeting Aβ and tau simultaneously or sequentially. Since high antibody titers are required for AD vaccine efficacy, we have decided to generate vaccines, targeting Aβ (AV-1959R), Tau (AV-1980R) or Aβ/tau (AV-1953R) B cell epitopes, based on immunogenic MultiTEP platform and evaluate the immunogenicity of these vaccines formulated with Advax(CpG), delta inulin, Alhydrogel(®), Montanide-ISA51, Montanide-ISA720, MPLA-SM pharmaceutical grade adjuvants. Formulation of AV-1959R in Advax(CpG) induced the highest cellular and humoral immune responses in mice. The dual-epitope vaccine, AV-1953R, or the combination of AV-1959R and AV-1980R vaccines formulated with Advax(CpG) induced robust antibody responses against various forms of both, Aβ and tau pathological molecules. While anti-Aβ antibody titers after AV-1953R immunization were similar to that in mice vaccinated with AV-1959R or AV-1959R/AV-1980R combination, anti-tau titers were significantly lower after AV-1953R injection when compared to the AV-1980R or AV-1959R/AV-1980R. In silico 3D-modeling provided insight into the differences in immunogenicity of these vaccine constructs. In sum, AV-1959R and AV-1980R formulated with Advax(CpG) adjuvant were identified as promising immunogenic vaccines for ongoing pre-clinical assessment and future human clinical trials. PMID:27363809

  17. Qualitative and Quantitative Contrast‐Enhanced Ultrasonographic Assessment of Cerulein‐Induced Acute Pancreatitis in Dogs

    Lim, S.Y.; Nakamura, K.; Morishita, K.; Sasaki, N.; M. Murakami; Osuga, T.; Ohta, H; Yamasaki, M; Takiguchi, M.

    2014-01-01

    Background Acute pancreatitis (AP) is the most common disease of the canine exocrine pancreas, and accurate noninvasive diagnosis is challenging. Hypothesis/Objectives To determine the feasibility of using quantitative contrast‐enhanced ultrasonography (CEUS) to detect pancreatic perfusional changes in cerulein‐induced AP in dogs. Animals Six adult female Beagles. Methods Each dog received 2 hours of IV infusion with 7.5 μg/kg/h of cerulein diluted in saline. As control, all dogs received 2 h...

  18. Adjuvant therapies for colorectal cancer

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  19. Laser-induced breakdown spectroscopy for in situ qualitative and quantitative analysis of mineral ores

    In this work, the potential of laser-induced breakdown spectroscopy (LIBS) for discrimination and analysis of geological materials was examined. The research was focused on classification of mineral ores using their LIBS spectra prior to quantitative determination of copper. Quantitative analysis is not a trivial task in LIBS measurement because intensities of emission lines in laser-induced plasmas (LIP) are strongly affected by the sample matrix (matrix effect). To circumvent this effect, typically matrix-matched standards are used to obtain matrix-dependent calibration curves. If the sample set consists of a mixture of different matrices, even in this approach, the corresponding matrix has to be known prior to the downstream data analysis. For this categorization, the multielemental character of LIBS spectra can be of help. In this contribution, a principal component analysis (PCA) was employed on the measured data set to discriminate individual rocks as individual matrices against each other according to their overall elemental composition. Twenty-seven igneous rock samples were analyzed in the form of fine dust, classified and subsequently quantitatively analyzed. Two different LIBS setups in two laboratories were used to prove the reproducibility of classification and quantification. A superposition of partial calibration plots constructed from the individual clustered data displayed a large improvement in precision and accuracy compared to the calibration plot constructed from all ore samples. The classification of mineral samples with complex matrices can thus be recommended prior to LIBS system calibration and quantitative analysis. - Highlights: • Twenty seven igneous rocks were measured on different LIBS systems. • Principal component analysis (PCA) was employed for classification. • The necessity of the classification of the rock (ore) samples prior to the quantification analysis is stressed. • Classification based on the whole LIP spectra and

  20. Choice and Design of Adjuvants for Parenteral and Mucosal Vaccines

    Huub F. J. Savelkoul

    2015-03-01

    Full Text Available The existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. For naive T-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals. Adjuvants, for example, are used to promote the immunogenicity of antigens in vaccines, by inducing a pro-inflammatory environment that enables the recruitment and promotion of the infiltration of phagocytic cells, particularly antigen-presenting cells (APC, to the injection site. Adjuvants can enhance antigen presentation, induce cytokine expression, activate APC and modulate more downstream adaptive immune reactions (vaccine delivery systems, facilitating immune Signal 1. In addition, adjuvants can act as immunopotentiators (facilitating Signals 2 and 3 exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3. New adjuvants should also target specific (innate immune cells in order to facilitate proper activation of downstream adaptive immune responses and homing (Signal 4. It is desirable that these adjuvants should be able to exert such responses in the context of mucosal administered vaccines. This review focuses on the understanding of the potential working mechanisms of the most well-known classes of adjuvants to be used effectively in vaccines.

  1. Learning impairment in honey bees caused by agricultural spray adjuvants.

    Timothy J Ciarlo

    Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

  2. The adjuvancy of silicones: dependency on compartmentalization.

    Klykken, P C; White, K L

    1996-01-01

    Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer 344) to investigate the adjuvancy potential of silicone mammary gel and the low molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on the experimental conditions employed, a divergent data profile emerges. If the antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4 prior to intramuscular immunization, an amplified anti-BSA IgG antibody response, as measured by multipoint ELISA methodology, is noted over the 8 week measurement period. In parallel studies, a variety of non-silicone personal care ingredients (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying this humoral response relative to the non-adjuvant phosphate buffered saline control. These observations are consistent with the empirical knowledge that hydrophobic substances tend to augment immune responses. However, under conditions in which the antigen is not blended with the silicone prior to immunization, normal immune responses are noted. In short (10 day) and long (180 day) term gel implant studies, the optimal IgM and IgG antibody responses, as determined in the antibody forming cell assay, were equivalent between the gel implanted and control animals. Moreover, under similar exposure conditions, no adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma, Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming cell studies conducted after 28 days of oral or inhalation exposure to D4 have also yielded responses similar to the non-silicone exposed vehicle controls. Collectively, these data suggest that in the absence of premixing the antigen with the silicone test material, there does not appear to be any silicone induced adjuvant response. PMID:8565549

  3. Protective role of Tinospora cordifolia extract against radiation-induced qualitative, quantitative and biochemical alterations in testes

    restoring almost normal structure at the end of experimentation. Furthermore, TCE administration inhibited radiation-induced elevation of lipid per-oxidation (LPO) and reduction of glutathione (GSH) and catalase (CAT) levels in testes. These observations signify that the Tinospora cordifolia root extract can be used as an efficient radio- protector against radiation mediated qualitative, quantitative and biochemical alterations in testes. (author)

  4. Development of CpG ODN Based Vaccine Adjuvant Formulations.

    Gursel, Mayda; Gursel, Ihsan

    2016-01-01

    Development of effective vaccine mediated immune responses relies on the use of vaccine adjuvants capable of enhancing and directing the adaptive immune response to the antigen. When used as vaccine adjuvants, type I interferon inducing agents can elicit potent effector/memory T cell responses and humoral immunity. Distinct sequences of single stranded synthetic oligodeoxynucleotides containing unmethylated cytosine-phosphate-guanine oligodeoxynucleotide motifs (CpG ODN) can generate type I interferon production via a TLR9-MyD88-IRF7-mediated signaling pathway. Here, we describe two different methods of preparing CpG ODN-based vaccine adjuvant formulations that can induce a robust IFNα response from human peripheral blood mononuclear cells. PMID:27076306

  5. Anti-inflammation effect of methyl salicylate 2-O-β-D-lactoside on adjuvant induced-arthritis rats and lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells.

    Zhang, Xue; Sun, Jialin; Xin, Wenyu; Li, Yongjie; Ni, Lin; Ma, Xiaowei; Zhang, Dan; Zhang, Dongming; Zhang, Tiantai; Du, Guanhua

    2015-03-01

    Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. Besides, MSL had potent anti-inflammatory effects on the LPS-activated RAW264.7. MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway. PMID:25637446

  6. Innate immunity and adjuvants.

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  7. Evaluation of adjuvants for a candidate conjugate vaccine against benzo[a]pyrene.

    Schellenberger, Mario T; Farinelle, Sophie; Willième, Stéphanie; Muller, Claude P

    2011-01-01

    We have recently developed an experimental vaccine based on benzo[a]pyrene (B[a]P) conjugated to tetanus toxoid as a carrier protein. In combination with Freund adjuvant, this vaccine induces high levels of B[a]P-specific antibodies to protect against detrimental effects of this carcinogen. Here we evaluate this conjugate vaccine by replacing Freund adjuvant by adjuvants that are potentially compatible with their use in humans. We showed that all adjuvants tested induced specific antibodies against B[a]P and 7,8-diol-B[a]P, its carcinogenic metabolite. The best antibody levels were obtained with Quil A, MF-59 and Alum. Biological activity in terms of enhanced retention of B[a]P was confirmed in mice immunised with Quil A, Montanide, Alum and MF-59. Our findings demonstrate that a vaccination against B[a]P is feasible in combination with adjuvants licensed in humans. PMID:21245662

  8. Immunization with the Chlamydia trachomatis mouse pneumonitis major outer membrane protein by use of CpG oligodeoxynucleotides as an adjuvant induces a protective immune response against an intranasal chlamydial challenge.

    Pal, Sukumar; Davis, Heather L; Peterson, Ellena M; de la Maza, Luis M

    2002-09-01

    Recently, we have shown that a vaccine consisting of a purified preparation of the Chlamydia trachomatis mouse pneumonitis (MoPn) major outer membrane protein (MOMP) and Freund's adjuvant can protect mice against a genital challenge. Here, we wanted to determine if CpG motifs could be used as an immune modulator to the MOMP to induce protection in mice against an intranasal (i.n.) challenge. One-week-old BALB/c mice were immunized intramuscularly and subcutaneously either once or three times at 2-week intervals with MOMP and CpG suspended in aluminum hydroxide (alum). Negative controls received ovalbumin, CpG, and alum. Positive controls were immunized i.n. with C. trachomatis MoPn elementary bodies (EB). Six weeks after the last immunization, mice were challenged i.n. with 10(4) inclusion-forming units (IFU) of the C. trachomatis MoPn serovar. Mice that received MOMP, CpG, and alum had a strong immune response, as shown by a high titer of serum antibodies to Chlamydia and significant lymphoproliferation of T-cells following stimulation with C. trachomatis EB. After the i.n. challenge mice immunized with MOMP, CpG, and alum showed significantly less body weight loss than the corresponding control mice immunized with ovalbumin, CpG, and alum. Ten days after the challenge the animals were euthanized, their lungs were weighed, and the numbers of IFU in the lungs were determined. The average weight of the lungs of the mice immunized with MOMP, CpG, and alum was significantly less than average weight of the lungs of the mice immunized with ovalbumin, CpG, and alum. Also, the average number of IFU recovered per mouse immunized with MOMP, CpG, and alum was significantly less than the average number of IFU per mouse detected in the mice inoculated with ovalbumin, CpG, and alum. In conclusion, our data show that CpG sequences can be used as an effective adjuvant with the C. trachomatis MoPn MOMP to elicit a protective immune response in mice against a chlamydial respiratory

  9. Old and new adjuvants for hepatitis B vaccines.

    Leroux-Roels, Geert

    2015-02-01

    The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market. PMID:25523196

  10. Adjuvant Therapy of Pancreatic Cancer

    Chakra P Chaulagain

    2011-07-01

    Full Text Available There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145 represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients’ survival. Another study by Fan et al. (Abstract #269 examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.

  11. Adjuvant chemotherapy and cancer cure

    The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

  12. Dynamics of antigen delivery and the functional roles of L121-adjuvant.

    Shen, Shan-Shan; Yang, Ya-Wun

    2015-08-20

    This study investigates the intracellular transport of protein antigens facilitated by L121-adjuvants and examines the associated cytotoxic T lymphocyte (CTL) effect. EL4 mouse thymoma cells were treated with L121-adjuvant and stained with AnnexinV-propidium iodide (PI) followed by flow cytometric analysis. The intracellular trafficking dynamics of bovine serum albumin (BSA)-FITC in the J774.A.1 macrophages, influenced by the L121-adjuvant, was visualized by confocal microscopy. The antigen-specific cytotoxic T lymphocyte (CTL) effect induced by the L121-adjuvant was determined by the cleavage-specific fluorogenic caspase substrate. The trafficking of BSA-FITC in the J774A.1 cells by confocal microscopy illustrated that the L121-adjuvant facilitated the intracellular transport of proteins to the subcellular compartments, including the lysosome, endoplasmic reticulum (ER), and the cis-Golgi apparatus. The L121-adjuvant also facilitated antigen delivery to the dendritic cells in the lymph nodes. Immunization of mice with the L121-adjuvant resulted in cell-mediated cytotoxic responses in the target cells, as detected by PhiPhiLux, a fluorogenic caspase substrate. Taken together, the L121-adjuvant improved the dynamics of protein delivery to antigen presenting cells, and also induced caspase activation, thereby illustrating the mechanism of antigen-specific CTL effects. PMID:25917678

  13. Characterization of the antigen-specific CD4+ T cell response induced by prime-boost strategies with CAF01 and CpG adjuvants administered by the intranasal and subcutaneous routes

    Annalisa eCiabattini

    2015-08-01

    Full Text Available The design of heterologous prime-boost vaccine combinations that optimally shape the immune response is of critical importance for the development of next generation vaccines. Here we tested different prime-boost combinations using the tuberculosis vaccine antigen H56 with CAF01 or CpG ODN 1821 adjuvants, administered by the parenteral and nasal routes. By using peptide-MHC class II tetramers, antigen-specific CD4+ T cells were tracked following primary and booster immunizations. Both parenteral priming with H56 plus CAF01 and nasal priming with H56 plus CpG elicited significant expansion of CD4+ tetramer-positive T cells in the spleen, however only parenterally primed cells responded to booster immunization. Subcutaneous priming with H56 and CAF01 followed by nasal boosting with H56 and CpG showed the greater expansion of CD4+ tetramer-positive T cells in the spleen and lungs compared to all the other homologous and heterologous prime-boost combinations. Nasal boosting exerted a recruitment of primed CD4+ T cells into lungs that was stronger in subcutaneously than nasally primed mice, in accordance with different chemokine receptor expression induced by primary immunization. These data demonstrate that subcutaneous priming is fundamental for eliciting CD4+ T cells that can be efficiently boosted by the nasal route and results in the recruitment of antigen-experienced cells into the lungs. Combination of different vaccine formulations and routes of delivery for priming and boosting is a strategic approach for improving and directing vaccine-induced immune responses.

  14. Antiarthritic effect of aqueous and ethanolic leaf extracts of Pistia stratiotes in adjuvant-induced arthritis in Sprague-Dawley rats

    Kyei, Samuel; Koffuor, George A; Boampong, Johnson N.

    2012-01-01

    Background Pistia stratiotes has been used effectively to treat a number of inflammatory conditions. This study aims to determine the antiarthritic effect of aqueous and ethanolic leaf extracts of P. stratiotes. Methods Arthritis was induced in Sprague-Dawley rats, paw swelling was measured, and arthritis indices were estimated in rats treated with aqueous and ethanolic leaf extracts of P. stratiotes (AQ PSE and ET PSE, respectively), methotrexate, diclofenac, dexamethasone, and normal saline...

  15. Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells

    Shuichi Kitayama

    2016-02-01

    Full Text Available Vα24 invariant natural killer T (iNKT cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer.

  16. Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells

    Kitayama, Shuichi; Zhang, Rong; Liu, Tian-Yi; Ueda, Norihiro; Iriguchi, Shoichi; Yasui, Yutaka; Kawai, Yohei; Tatsumi, Minako; Hirai, Norihito; Mizoro, Yasutaka; Iwama, Tatsuaki; Watanabe, Akira; Nakanishi, Mahito; Kuzushima, Kiyotaka; Uemura, Yasushi; Kaneko, Shin

    2016-01-01

    Summary Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer. PMID:26862702

  17. A Review and Prospect on Herbicide Adjuvants

    2005-01-01

    The history, present status and future prospects of adjuvants application in herbicides were briefly reviewed. Adjuvants can be separated into two groups, activator adjuvants and utility adjuvants. The former directly enhances the efficacy of a herbicide through increasement of herbicide absorption, spreading, cuticular penetration, rainfastness and retention enhancement, and photodegradation of the herbicide can also be decreased. And the latter is utilized for improving application characteristics, behaviors and physical properties of herbicides and reducing or minimizing unwanted side effects on application.

  18. Pseudo-Mannosylated DC-SIGN Ligands as Potential Adjuvants for HIV Vaccines

    Angela Berzi

    2014-01-01

    Full Text Available The development of new and effective adjuvants may play a fundamental role in improving HIV vaccine efficacy. New classes of vaccine adjuvants activate innate immunity receptors, notably toll like receptors (TLRs. Adjuvants targeting the C-Type lectin receptor DC-SIGN may be alternative or complementary to adjuvants based on TRL activation. Herein we evaluate the ability of the glycomimetic DC-SIGN ligand Polyman 19 (PM 19 to modulate innate immune responses. Results showed that PM 19 alone, or in combination with TLR agonists, induces the expression of cytokines, β chemokines and co-stimulatory molecules that may, in turn, modulate adaptive immunity and exert anti-viral effects. These results indicate that the suitability of this compound as a vaccine adjuvant should be further evaluated.

  19. Adjuvant therapy in pancreatic cancer

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  20. Cell Recruitment and Cytokines in Skin Mice Sensitized with the Vaccine Adjuvants: Saponin, Incomplete Freund’s Adjuvant, and Monophosphoryl Lipid A

    Vitoriano-Souza, Juliana; Moreira, Nádia das Dores; Teixeira-Carvalho, Andréa; Carneiro, Cláudia Martins; Siqueira, Fernando Augusto Mathias; Vieira, Paula Melo de Abreu; Giunchetti, Rodolfo Cordeiro; Moura, Sandra Aparecida de Lima; Fujiwara, Ricardo Toshio; Melo, Maria Norma; Reis, Alexandre Barbosa

    2012-01-01

    Vaccine adjuvants are substances associated with antigens that are fundamental to the formation of an intense, durable, and fast immune response. In this context, the use of vaccine adjuvants to generate an effective cellular immune response is crucial for the design and development of vaccines against visceral leishmaniasis. The objective of this study was to evaluate innate inflammatory response induced by the vaccine adjuvants saponin (SAP), incomplete Freund’s adjuvant (IFA), and monophosphoryl lipid A (MPL). After a single dose of adjuvant was injected into the skin of mice, we analyzed inflammatory reaction, selective cell migration, and cytokine production at the injection site, and inflammatory cell influx in the peripheral blood. We found that all vaccine adjuvants were able to promote cell recruitment to the site without tissue damage. In addition, they induced selective migration of neutrophils, macrophages, and lymphocytes. The influx of neutrophils was notable at 12 h in all groups, but at other time points it was most evident after inoculation with SAP. With regard to cytokines, the SAP led to production of interleukin (IL)-2, IL-6, and IL-4. IFA promoted production of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, IL-17, IL-4, and IL-10. We also observed that MPL induced high production of IL-2, TNF-α, and IFN-γ, in addition to IL-6, IL-17, and IL-10. In peripheral blood, values of certain cell populations in the local response changed after stimulation. Our data demonstrate that the three vaccine adjuvants stimulate the early events of innate immune response at the injection site, suggesting their ability to increase the immunogenicity of co-administered antigens. Moreover, this work provides relevant information about elements of innate and acquired immune response induced by vaccine adjuvants administered alone. PMID:22829882

  1. Antibody response in silver catfish (Rhamdia quelen) immunized with a model antigen associated with different adjuvants.

    Pavan, T R; Di Domenico, J; Kirsten, K S; Nied, C O; Frandoloso, R; Kreutz, L C

    2016-07-25

    Adjuvants are essential to boost the immune response to inoculated antigen and play a central role in vaccine development. In this study, we investigated the efficacy of several adjuvants in the production of anti-bovine serum albumin (BSA) antibodies in silver catfish. Two hundred and seventy juvenile silver catfish (60-80 g) of both sexes were intraperitoneally vaccinated with BSA (200 µg/fish) alone or mixed to the following adjuvants: Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), aluminum hydroxide (AlOH), Montanide, four types of cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) and three concentrations of β-glucan, and the immune enhancing property was evaluated by measuring anti-BSA antibodies in blood samples at biweekly intervals. Our results demonstrated that CpGs ODNs and β-glucan were as effective as classical adjuvants (FCA, FIA, AlOH and Montanide) in promoting anti-BSA antibodies and that the kinetics of antibody production induced by all adjuvants used in our study had a similar trend to that observed in other fish species, with a peak at 28 days post-vaccination. These results may be useful for the selection of adjuvants for vaccine formulation intended for silver catfish and for the development of vaccine and vaccination strategies to other fish species. PMID:27464022

  2. The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis.

    Pasquevich, Karina A; García Samartino, Clara; Coria, Lorena M; Estein, Silvia M; Zwerdling, Astrid; Ibañez, Andrés E; Barrionuevo, Paula; Oliveira, Fernanda Souza de; Carvalho, Natalia Barbosa; Borkowski, Julia; Oliveira, Sergio Costa; Warzecha, Heribert; Giambartolomei, Guillermo H; Cassataro, Juliana

    2010-05-01

    Knowing the inherent stimulatory properties of the lipid moiety of bacterial lipoproteins, we first hypothesized that Brucella abortus outer membrane protein (Omp)16 lipoprotein would be able to elicit a protective immune response without the need of external adjuvants. In this study, we demonstrate that Omp16 administered by the i.p. route confers significant protection against B. abortus infection and that the protective response evoked is independent of the protein lipidation. To date, Omp16 is the first Brucella protein that without the requirement of external adjuvants is able to induce similar protection levels to the control live vaccine S19. Moreover, the protein portion of Omp16 (unlipidated Omp16 [U-Omp16]) elicits a protective response when administered by the oral route. Either systemic or oral immunization with U-Omp16 elicits a Th1-specific response. These abilities of U-Omp16 indicate that it is endowed with self-adjuvanting properties. The adjuvanticity of U-Omp16 could be explained, at least in part, by its capacity to activate dendritic cells in vivo. U-Omp16 is also able to stimulate dendritic cells and macrophages in vitro. The latter property and its ability to induce a protective Th1 immune response against B. abortus infection have been found to be TLR4 dependent. The facts that U-Omp16 is an oral protective Ag and possesses a mucosal self-adjuvanting property led us to develop a plant-made vaccine expressing U-Omp16. Our results indicate that plant-expressed recombinant U-Omp16 is able to confer protective immunity, when given orally, indicating that a plant-based oral vaccine expressing U-Omp16 could be a valuable approach to controlling this disease. PMID:20351187

  3. Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+T-regulatory cells that suppress SIV positive CD4+cell activation and prevent SIV infection in the macaque model.

    Jean Marie eAndrieu

    2014-06-01

    Full Text Available A new paradigm of mucosal vaccination against HIV infection has been investigated in the macaque model. A vaccine consisting of inactivated SIVmac239 particles together with a living bacterial adjuvant (either the Calmette & Guerin bacillus, lactobacillus plantarum or Lactobacillus rhamnosus was administered to macaques via the vaginal or oral/intragastic route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8+T regulatory cells that suppressed the activation of SIV positive CD4+ T-lymphocytes. SIV reverse transcription was thereby blocked in inactivated CD4+ T-cells; the initial burst of virus replication was prevented and the vaccinated macaques were protected from a challenge infection. Three to 14 months after intragastric immunization, 24 macaques were challenged intrarectally with a high dose of SIVmac239 or with the heterologous strain SIV B670 (both strains grown on macaques PBMC. Twenty-three of these animals were found to be protected for up to 48 months while all 24 control macaques became infected. This protective effect against SIV challenge together with the concomitant identification of a robust ex-vivo correlate of protection suggests a new approach for developing an HIV vaccine in humans. The induction of this new class of CD8+ T regulatory cells could also possibly be used therapeutically for suppressing HIV replication in infected patients and this novel tolerogenic vaccine paradigm may have potential applications for treating a wide range of immune disorders and is likely to may have profound implications across immunology generally.

  4. Effect of Two Different Doses ofDexmedetomidine as Adjuvant in BupivacaineInduced Subarachnoid Block for ElectiveAbdominal Hysterectomy Operations: A Prospective, Double-blind, RandomizedControlled Study

    Anjan Das

    2015-07-01

    Full Text Available Objectives: Improvements in perioperative pain management for lower abdominal operations has been shown to reduce morbidity, induce early ambulation, and improve patients’ long-term outcomes. Dexmedetomidine, a selective alpha-2 agonist, has recently been used intrathecally as adjuvant to spinal anesthesia to prolong its efficacy. We compared two different doses of dexmedetomidine added to hyperbaric bupivacaine for spinal anesthesia. The primary endpoints were the onset and duration of sensory and motor block, and duration of analgesia.  Methods: A total of 100 patients, aged 35–60 years old, assigned to have elective abdominal hysterectomy under spinal anesthesia were divided into two equally sized groups (D5 and D10 in a randomized, double-blind fashion. The D5 group was intrathecally administered 3ml 0.5% hyperbaric bupivacaine with 5µg dexmedetomidine in 0.5ml of normal saline and the D10 group 3ml 0.5% bupivacaine with 10µg dexmedetomidine in 0.5ml of normal saline. For each patient, sensory and motor block onset times, block durations, time to first analgesic use, total analgesic need, postoperative visual analogue scale (VAS scores, hemodynamics, and side effects were recorded.  Results: Although both groups had a similar demographic profile, sensory and motor block in the D10 group (p0.050 without any appreciable side effects.  Conclusion: Spinal dexmedetomidine increases the sensory and motor block duration and time to first analgesic use, and decreases analgesic consumption in a dose-dependent manner.

  5. Improving vaccine delivery using novel adjuvant systems.

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  6. Bioactive peptide from bee venom for adjuvant-induced arthritis in rats%蜂毒活性肽对大鼠佐剂性关节炎的作用

    余晓东; 李博

    2005-01-01

    BACKGROUND: Traditionally, bee venom can treat rheumatic arthritis,rheumatoid arthritis(RA) and so on, but it has strong side effects. So it has been hoped for a long time that the effective angle component could be screened from bee venom, which can be used for the treatment of arthritis perfectly than bee venom.OBJECTIVE: To investigate whether bioactive peptide from bee venom could inhibit infection of arthritis by regulating immunological function so as to probe into a new treatment for RADESIGN: Completely randomized controlled experimental trial based on experimental animalsMETHODS: A municipal key laboratory of animal biology.MATERIALS: The experiment was carried out in the Chongqing Key Laboratory of animal biology from January 2001 to May 2002. Totally 80 rats of clean grade aged 2 to 3 months old with the body mass of 180 to 200 g were provided by Animal Experiment Center of Third Military Medical University of Chinese PLA. The experimental animal certification number was SYXK1 (army) 2002 -007. The animals were divided into 3 groups: normal control group( 10 cases), arthritis group( 10 cases), bioactive peptide group(30 cases).METHODS: Adjuvant-induced arthritis animal models were used and bioactive peptide were given to the animals by muscle injection to observe the knuckle volume and knuckle index changes.MAIN OUTCOME MEASURES: The effect of bioactive peptide from bee venom on the change of knuckle volume and knuckle index in adjuvant-induced arthritis ratsRESULTS: Ten days after injection of 0. 15 mg for each rat, the volume of the paw was (4.72 ±0. 58) mL and the knuckle index was (4.47 ±0.46) mL,which there was significant difference compared with the control group (P< 0. 05).CONCLUSION: P-peptide possibly has certain inhibitory effect on the development of the adjuvant-induced arthritis in Wistar rat, and will possibly be a potential therapeutic drug.%背景:传统上用蜜蜂粗毒治疗风湿性关节炎、类风湿性关节炎等,但有很

  7. The respiratory syncytial virus fusion protein formulated with a novel combination adjuvant induces balanced immune responses in lambs with maternal antibodies.

    Garg, R; Latimer, L; Gerdts, V; Potter, A; van Drunen Littel-van den Hurk, S

    2015-03-10

    Respiratory syncytial virus (RSV) causes severe respiratory illness in infants. There are no licensed vaccines to prevent RSV infection. The neonate receives short-term protection from maternally derived antibodies, which, however, can also interfere with the active response to vaccination. A RSV vaccine consisting of a truncated version of the fusion protein formulated with polyI:C, innate defense regulator peptide and polyphosphazene (ΔF/TriAdj), was evaluated in two to three week-old lambs. When delivered intrapulmonary, ΔF/TriAdj elicited IgA production in the lung in addition to a robust systemic response similar to that induced by intramuscular immunization. To investigate potential interference by maternal antibodies, pregnant ewes were vaccinated with ΔF/TriAdj. Lambs born to RSV F-immune or non-immune ewes were then given three vaccinations with ΔF/TriAdj at 3 days, 4 weeks and 8 weeks post-birth. Lambs immunized intramuscularly with ΔF/TriAdj vaccine developed high-affinity ΔF-specific serum IgG and virus neutralizing antibodies, and displayed an increase in the frequency of IFN-γ-secreting cells by in vitro restimulated peripheral blood mononuclear cells. Maternal antibodies did not interfere with the development of an immune response to ΔF/TriAdj in the newborn lambs. These results indicate that immunization of neonates with ΔF/TriAdj is effective even in the face of maternal antibodies. PMID:25637860

  8. Induction of CD8+ T-cell responses against subunit antigens by the novel cationic liposomal CAF09 adjuvant

    Korsholm, Karen Smith; Hansen, Jon; Karlsen, Kasper;

    2014-01-01

    previously described CTL-inducing adjuvants, CAF05 (DDA/trehalose dibehenate (TDB)/Poly(I:C)), Aluminium/monophosphoryl lipid-A (MPL) and Montanide/CpG/IL-2. The optimal effect was obtained when the CAF09-adjuvanted vaccine was administered by the i.p. route, whereas s.c. administration primed limited CD8+ T...

  9. CpG-DNA enhancement the immune elicited as adjuvant of foot- and- mouth disease vaccine

    Morshedi, A.; Daghighi, M.; Mahravani, H.

    2010-01-01

    In the present study the effect of the locally produced genetic adjuvant of ginea pig specific CpG-motif-containing oligodeoxynucleotide (CpG-ODN) in an inactivated FMD virus vaccine was evaluated. Boosting the ginea pigs with FMD vaccine along with CpG-ODN adjuvant produced relatively higher ratio (5-fold) of FMDV-specific IgG2a / IgG1 than those vaccinated in the absence of CpG-ODN. The neutralizing antibody (NA) titer induced by FMD vaccine along with CpG-ODN adjuvant was significantly hig...

  10. Adjuvant Therapy of Pancreatic Cancer

    Chakra P Chaulagain; Muhammad Wasif Saif; Goodman, Martin D.; John Ng

    2011-01-01

    There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposiu...

  11. Attenuation of antigenic immunogenicity by kynurenine, a novel suppressive adjuvant.

    Duan, Zhiqing; Duan, Yunqing; Lei, Huangui; Hu, Ningzhu; Shi, Jiandong; Shen, Dong; Wang, Xi; Hu, Yunzhang

    2014-01-01

    A novel therapeutic strategy is required for autoimmune diseases characterized by the production of autoantibody, because current clinical strategies have limitations. Vaccination against autoimmune diseases is a feasible strategy because vaccines induce immune response memory and the antigen specificity. However, no suitable adjuvant is available to direct the immune response toward tolerance or suppression. In the current study, we evaluated whether kynurenine (Kyn) could serve as a novel suppressive adjuvant to decrease the humoral immune responses against hepatitis A virus (HAV) in the ICR mouse model in vivo and lipopolysaccharide (LPS) in B cells in vitro. The underlying mechanisms of Kyn-mediated suppression of LPS-induced IgM responses were explored. The results showed that Kyn significantly decreased HAV immunogenicity when co-administered with HAV, and that Kyn (100 μM/1000 μM) impaired IgM generation compared with that induced by LPS alone. We also demonstrated that microRNA30b (miR30b) played a critical role in the process of Kyn-mediated suppression of IgM responses induced by LPS, and that Bach2, a transcriptional repressor of B cell terminal differentiation, was a novel target of miR30b. These findings suggest that Kyn can serve as a novel and effective suppressive adjuvant for vaccines. PMID:24583631

  12. Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

    Martin Kreutz

    Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

  13. The Effects of Adjuvants on Autoimmune Responses Against Testicular Antigens in Mice

    MUSHA, Muhetaerjiang; Hirai, Shuichi; Naito, Munekazu; Terayama, Hayato; Qu, Ning; Hatayama, Naoyuki; Itoh, Masahiro

    2012-01-01

    Abstract Experimental autoimmune orchitis (EAO) is a model of immunologic male infertility and pathologically characterized by lymphocytic inflammation, which causes breakdown of the testicular immune privilege with spermatogenic disturbance. Generally, murine EAO is induced by immunization with testicular homogenate (TH) from the testes of donor mice + complete Freund's adjuvant (CFA) + Bordetella pertussigens (BP), and it has been considered that treatment with these two adjuvants is requir...

  14. Adjuvant chemotherapy in stage I breast cancer. More harm than benefit.

    Mueller, C B

    1993-01-01

    Clinical trials of adjuvant chemotherapy for breast cancer have shown a prolonged disease-free interval but no improvement in survival. This review of the evidence indicates that adjuvant therapy induces an antineoplastic drug resistance that makes "salvage" therapy less effective. The benefit that is seen only in group statistics, not in an individual, must be weighed against the harm an individual incurs from the chemotherapy.

  15. Adjuvant enhancement of humoral immune response to chemically inactivated bovine viral diarrhea virus.

    Chen, K S; Johnson, D. W.; Muscoplat, C C

    1985-01-01

    Potentiation of the antibody response to inactivated bovine viral diarrhea virus by immunological adjuvants was studied in guinea pigs and cattle. The inactivated bovine viral diarrhea virus alone was demonstrated to be a weak immunogen. Addition of either 2 mg per mL diethylaminoethyl-dextran or 5% alhydrogel to inactivated bovine viral diarrhea virus did not or only slightly stimulated the antibody response; the combined adjuvants induced a significantly higher titer. A higher concentration...

  16. Influenza virosomes supplemented with GPI-0100 adjuvant: a potent vaccine formulation for antigen dose sparing

    Liu, Heng; de Vries-Idema, Jacqueline; ter Veer, Wouter; Wilschut, Jan; Huckriede, Anke

    2014-01-01

    Adjuvants can stimulate vaccine-induced immune responses and can contribute decisively to antigen dose sparing when vaccine antigen production is limited, as for example during a pandemic influenza outbreak. We earlier showed that GPI-0100, a semi-synthetic saponin derivative with amphiphilic structure, significantly stimulates the immunogenicity and protective efficacy of influenza subunit vaccine administered via a systemic route. Here, we evaluated the adjuvant effect of GPI-0100 on a viro...

  17. A Novel Laser Vaccine Adjuvant Increases the Motility of Antigen Presenting Cells

    Farinelli, Bill; Doukas, Apostolos; Gelfand, Jeffrey Alan; Anderson, Richard Rox; Mei X. Wu; Chen, Xinyuan; Kim, Pilhan; Yun, Seok-Hyun

    2010-01-01

    Background Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research. Methodology/Principal Findings We found that laser at a specific setting increased the motility of antigen presenting cells (APCs) and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA) effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive...

  18. Recombinant human migration inhibitory factor has adjuvant activity.

    Weiser, W Y; Pozzi, L M; Titus, R G; David, J R

    1992-01-01

    Recombinant human migration inhibitory factor (MIF), isolated through functional expression cloning in COS-1 cells, up-regulates expression of genes encoding HLA-DR and interleukin 1 beta (IL-1 beta) and elaboration of IL-1 beta by human monocyte-derived macrophages. Administration of soluble bovine serum albumin or human immunodeficiency virus 120-kDa glycoprotein (HIV gp120) to mice in the presence of recombinant MIF together with incomplete Freund's adjuvant induced a strong T-cell prolife...

  19. Cocoa intake attenuates oxidative stress associated with rat adjuvant arthritis

    Ramos Romero, Sara; Pérez-Cano, Francisco J.; Ramiro Puig, Emma; Franch i Masferrer, Àngels; Castell, Margarida

    2012-01-01

    Cocoa contains flavonoids with antioxidant properties. The aim of this study was to ascertain the effect of cocoa intake on oxidative stress associated with a model of chronic inflammation such as adjuvant arthritis. Female Wistar rats were fed with a 5 or 10% cocoa enriched diet or were given p.o. a quercetin suspension every other day for 10 days. Arthritis was induced by a heat killed Mycobacterium butyricum suspension. Reactive oxygen species (ROS) produced by macrophages, and splenic sup...

  20. Systemic adjuvant therapies in renal cell carcinoma

    Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni

    2012-01-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...

  1. Resistance training induces qualitative changes in muscle morphology, muscle architecture, and muscle function in elderly postoperative patients

    Suetta, Charlotte; Andersen, Jesper L; Dalgas, Ulrik;

    2008-01-01

    beneficial qualitative changes in muscle fiber morphology and muscle architecture in elderly postoperative patients. In contrast, rehabilitation regimes based on functional exercises and neuromuscular electrical stimulation had no effect. The present data emphasize the importance of resistance training in......Although the negative effects of bed rest on muscle strength and muscle mass are well established, it still remains a challenge to identify effective methods to restore physical capacity of elderly patients recovering from hospitalization. The present study compared different training regimes with...... respect to muscle strength, muscle fiber size, muscle architecture, and stair walking power in elderly postoperative patients. Thirty-six patients (60-86 yr) scheduled for unilateral hip replacement surgery due to hip osteoarthritis were randomized to either 1) resistance training (RT: 3/wk x 12 wk), 2...

  2. In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant.

    van Haren, Simon D; Ganapathi, Lakshmi; Bergelson, Ilana; Dowling, David J; Banks, Michaela; Samuels, Ronald C; Reed, Steven G; Marshall, Jason D; Levy, Ofer

    2016-07-01

    Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of TLR4, including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation (GLA-AF), as well as agonists of TLR7/8 (R848) and TLR9 (CpG). Both TLR4 agonists, MPLA and GLA-AF, induced greater concentrations of Th1 cytokines CXCL10, TNF and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and CXCL8 in newborn than in infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines. PMID:27081760

  3. Novel adjuvant formulations for delivery of anti-tuberculosis vaccine candidates.

    Agger, Else Marie

    2016-07-01

    There is an urgent need for a new and improved vaccine against tuberculosis for controlling this disease that continues to pose a global health threat. The current research strategy is to replace the present BCG vaccine or boost BCG-immunity with subunit vaccines such as viral vectored- or protein-based vaccines. The use of recombinant proteins holds a number of production advantages including ease of scalability, but requires an adjuvant inducing cell-mediated immune responses. A number of promising novel adjuvant formulations have recently been designed and show evidence of induction of cellular immune responses in humans. A common trait of effective TB adjuvants including those already in current clinical testing is a two-component approach combining a delivery system with an appropriate immunomodulator. This review summarizes the status of current TB adjuvant research with a focus on the division of labor between delivery systems and immunomodulators. PMID:26596558

  4. Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+T-regulatory cells that suppress SIV positive CD4+cell activation and prevent SIV infection in the macaque model.

    Jean Marie eAndrieu; song echen; Chunhui eLAI; weizhong eguo; Wei eLu

    2014-01-01

    A new paradigm of mucosal vaccination against HIV infection has been investigated in the macaque model. A vaccine consisting of inactivated SIVmac239 particles together with a living bacterial adjuvant (either the Calmette & Guerin bacillus, lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastic route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies n...

  5. Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial Adjuvants Induce CD8+ T-Regulatory Cells that Suppress SIV-Positive CD4+ T-Cell Activation and Prevent SIV Infection in the Macaque Model

    Andrieu, Jean-Marie; Chen, Song; Lai, Chunhui; Guo, Weizhong; Lu, Wei

    2014-01-01

    A new paradigm of mucosal vaccination against human immunodeficiency virus (HIV) infection has been investigated in the macaque model. A vaccine consisting of inactivated simian immunodeficiency virus (SIV)mac239 particles together with a living bacterial adjuvant (either the Calmette and Guerin bacillus, Lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastric route. In contrast to all established human and veterinary vaccines, the...

  6. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

    2016-01-01

    Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

  7. Adjuvants: Classification, Modus Operandi, and Licensing

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.

  8. Qualitative and Quantitative Analysis of ROS-Mediated Oridonin-Induced Oesophageal Cancer KYSE-150 Cell Apoptosis by Atomic Force Microscopy.

    Jiang Pi

    Full Text Available High levels of intracellular reactive oxygen species (ROS in cells is recognized as one of the major causes of cancer cell apoptosis and has been developed into a promising therapeutic strategy for cancer therapy. However, whether apoptosis associated biophysical properties of cancer cells are related to intracellular ROS functions is still unclear. Here, for the first time, we determined the changes of biophysical properties associated with the ROS-mediated oesophageal cancer KYSE-150 cell apoptosis using high resolution atomic force microscopy (AFM. Oridonin was proved to induce ROS-mediated KYSE-150 cell apoptosis in a dose dependent manner, which could be reversed by N-acetylcysteine (NAC pretreatment. Based on AFM imaging, the morphological damage and ultrastructural changes of KYSE-150 cells were found to be closely associated with ROS-mediated oridonin-induced KYSE-150 cell apoptosis. The changes of cell stiffness determined by AFM force measurement also demonstrated ROS-dependent changes in oridonin induced KYSE-150 cell apoptosis. Our findings not only provided new insights into the anticancer effects of oridonin, but also highlighted the use of AFM as a qualitative and quantitative nanotool to detect ROS-mediated cancer cell apoptosis based on cell biophysical properties, providing novel information of the roles of ROS in cancer cell apoptosis at nanoscale.

  9. Potent response of QS-21 as a vaccine adjuvant in the skin when delivered with the Nanopatch, resulted in adjuvant dose sparing.

    Ng, Hwee-Ing; Fernando, Germain J P; Depelsenaire, Alexandra C I; Kendall, Mark A F

    2016-01-01

    Adjuvants play a key role in boosting immunogenicity of vaccines, particularly for subunit protein vaccines. In this study we investigated the induction of antibody response against trivalent influenza subunit protein antigen and a saponin adjuvant, QS-21. Clinical trials of QS-21 have demonstrated the safety but, also a need of high dose for optimal immunity, which could possibly reduce patient acceptability. Here, we proposed the use of a skin delivery technology - the Nanopatch - to reduce both adjuvant and antigen dose but also retain its immune stimulating effects when compared to the conventional needle and syringe intramuscular (IM) delivery. We have demonstrated that Nanopatch delivery to skin requires only 1/100(th) of the IM antigen dose to induce equivalent humoral response. QS-21 enhanced humoral response in both skin and muscle route. Additionally, Nanopatch has demonstrated 30-fold adjuvant QS-21 dose sparing while retaining immune stimulating effects compared to IM. QS-21 induced localised, controlled cell death in the skin, suggesting that the danger signals released from dead cells contributed to the enhanced immunogenicity. Taken together, these findings demonstrated the suitability of reduced dose of QS-21 and the antigen using the Nanopatch to enhance humoral responses, and the potential to increase patient acceptability of QS-21 adjuvant. PMID:27404789

  10. Vaccinia virus strain NYVAC induces substantially lower and qualitatively different human antibody responses compared with strains Lister and Dryvax

    Midgley, Claire M.; Putz, Mike M.; Weber, Jonathan N.; Smith, Geoffrey L.

    2008-01-01

    The antibody responses elicited by immunization of humans with vaccinia virus (VACV) strains Lister, Dryvax and NYVAC have been determined and compared. Neutralizing antibodies against intracellular mature virus (IMV) and extracellular enveloped virus (EEV), and binding antibody titres (ELISA) against the EEV protein B5, the IMV proteins A27 and H3, and VACV-infected cell lysate were measured. Lister and Dryvax induced broadly similar antibody titres, consistent with the fact that these vacci...

  11. Isatis indigotica root polysaccharides as adjuvants for an inactivated rabies virus vaccine.

    Zhang, Weijiao; Zheng, Xuexing; Cheng, Nan; Gai, Weiwei; Xue, Xianghong; Wang, Yuxia; Gao, Yuwei; Shan, Junjie; Yang, Songtao; Xia, Xianzhu

    2016-06-01

    Adjuvants can enhance vaccine immunogenicity and induce long-term enhancement of immune responses. Thus, adjuvants are important for vaccine research. Polysaccharides isolated from select Chinese herbs have been demonstrated to possess various beneficial functions and excellent adjuvant abilities. In the present study, the polysaccharides IIP-A-1 and IIP-2 were isolated from Isatis indigotica root and compared with the common vaccine adjuvant aluminum hydroxide via intramuscular co-administration of inactivated rabies virus rCVS-11-G into mice. Blood was collected to determine virus neutralizing antibody (VNA) titers and B and T lymphocyte activation status. Inguinal lymph node samples were collected and used to measure B lymphocyte proliferation. Splenocytes were isolated, from which antigen-specific cellular immune responses were detected via ELISpot, ELISA and intracellular cytokine staining. The results revealed that both types of polysaccharides induce more rapid changes and higher VNA titers than aluminum hydroxide. Flow cytometry assays revealed that the polysaccharides activated more B lymphocytes in the lymph nodes and more B and T lymphocytes in the blood than aluminum hydroxide. Antigen-specific cellular immune responses showed that IIP-2 strongly induced T lymphocyte proliferation in the spleen and high levels of cytokine secretion from splenocytes, whereas aluminum hydroxide induced proliferation in only a small number of lymphocytes and the secretion of only small quantities of cytokines. Collectively, these data suggest that the polysaccharide IIP-2 exhibits excellent adjuvant activity and can enhance both cellular and humoral immunity. PMID:26875535

  12. Immune enhancement by novel vaccine adjuvants in autoimmune-prone NZB/W F1 mice: relative efficacy and safety

    Ghosh Swapan K

    2011-10-01

    Full Text Available Abstract Background Vaccines have profoundly impacted global health although concerns persist about their potential role in autoimmune or other adverse reactions. To address these concerns, vaccine components like immunogens and adjuvants require critical evaluation not only in healthy subjects but also in those genetically averse to vaccine constituents. Evaluation in autoimmune-prone animal models of adjuvants is therefore important in vaccine development. The objective here was to assess the effectiveness of experimental adjuvants: two phytol-derived immunostimulants PHIS-01 (phytanol and PHIS-03 (phytanyl mannose, and a new commercial adjuvant from porcine small intestinal submucosa (SIS-H, relative to a standard adjuvant alum. Phytol derivatives are hydrophobic, oil-in water diterpenoids, while alum is hydrophilic, and SIS is essentially a biodegradable and collagenous protein cocktail derived from extracellular matrices. Results We studied phthalate -specific and cross-reactive anti-DNA antibody responses, and parameters associated with the onset of autoimmune disorders. We determined antibody isotype and cytokine/chemokine milieu induced by the above experimental adjuvants relative to alum. Our results indicated that the phytol-derived adjuvant PHIS-01 exceeded alum in enhancing anti-phthalate antibody without much cross reactivity with ds-DNA. Relatively, SIS and PHIS-03 proved less robust, but they were also less inflammatory. Interestingly, these adjuvants facilitated isotype switching of anti-hapten, but not of anti-DNA response. The current study reaffirms our earlier reports on adjuvanticity of phytol compounds and SIS-H in non autoimmune-prone BALB/c and C57BL/6 mice. These adjuvants are as effective as alum also in autoimmune-prone NZB/WF1 mice, and they have little deleterious effects. Conclusion Although all adjuvants tested impacted cytokine/chemokine milieu in favor of Th1/Th2 balance, the phytol compounds fared better in

  13. Immunostimulatory Oligodeoxynucleotides Containing the CpG Motif are Effective as Immune Adjuvants in Tumor Antigen Immunization

    Weiner, George J.; Liu, Hsin-Ming; Wooldridge, James E.; Dahle, Christopher E.; Krieg, Arthur M.

    1997-09-01

    Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. One area of interest is the development of new immune adjuvants. Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can induce production of a wide variety of cytokines and activate B cells, monocytes, dendritic cells, and NK cells. Using the 38C13 B cell lymphoma model, we assessed whether CpG ODN can function as immune adjuvants in tumor antigen immunization. The idiotype served as the tumor antigen. Select CpG ODN were as effective as complete Freund's adjuvant at inducing an antigen-specific antibody response but were associated with less toxicity. These CpG ODN induced a higher titer of antigen-specific IgG2a than did complete Freund's adjuvant, suggesting an enhanced TH1 response. Mice immunized with CpG ODN as an adjuvant were protected from tumor challenge to a degree similar to that seen in mice immunized with complete Freund's adjuvant. We conclude that CpG ODN are effective as immune adjuvants and are attractive as part of a tumor immunization strategy.

  14. [Development of Nucleic Acid-Based Adjuvant for Cancer Immunotherapy].

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

    Since the discovery of the human T cell-defined tumor antigen, the cancer immunotherapy field has rapidly progressed, with the research and development of cancer immunotherapy, including cancer vaccines, being conducted actively. However, the disadvantages of most cancer vaccines include relatively weak immunogenicity and immune escape or exhaustion. Adjuvants with innate immunostimulatory activities have been used to overcome these issues, and these agents have been shown to enhance the immunogenicity of cancer vaccines and to act as mono-therapeutic anti-tumor agents. CpG ODN, an agonist for TLR9, is one of the promising nucleic acid-based adjuvants, and it is a potent inducer of innate immune effector functions. CpG ODN suppresses tumor growth in the absence of tumor antigens and peptide administration. Therefore, CpG ODN is expected to be useful as a cancer vaccine adjuvant as well as a cancer immunotherapy agent. In this review, we discuss the potential therapeutic applications and mechanisms of CpG ODN for cancer immunotherapy. PMID:26469159

  15. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    WONDIM MELKAM

    2015-01-01

    Full Text Available Glucocorticoids (GCs, synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bacterial infection. This review, therefore, summarizes various bacterial infections for which glucocorticoids are reported to be used as adjuvant therapy, strategies for administration of glucocorticoids, and challenges of using glucocorticoids as adjuvant therapy.

  16. Influence of various forms of dialyzable leukocyte extracts on rat adjuvant arthritis

    Adjuvant-induced arthritis in rats is a chronic inflammatory disease, widely as an animal model for rheumatoid arthritis. In our study the effect of various fractions of dialyzable leukocyte extract (DLE): DLE I-molecular weight below 10 kDa (commercial preparation), DLE II-molecular weight below 5 kDa (suppressor fraction), DLE III-molecular weight 5-10 kDa on rat adjuvant-induced arthritis was studied. The adjuvant arthritic (AA) rats were treated with DLE fractions i.p. in solutions containing an active substance isolated from 12.5 x 106 and 6.25 x 106 leukocytes from day 1 (adjuvant injected) through day 18, every second day (total 9 times). Various markers in inflammation, immune function and joint destruction were evaluated: hind paw volume, serum hyaluronic acid, serum albumin and biopterin in urine. All these markers showed a significant improvement after using fraction DLE II in comparison with AA controls. Fractions DLE I and DLE III influenced only some markers of inflammation and immune function. Our results demonstrated a therapeutical effect of fraction DLE II on rat adjuvant-induced arthritis. (author). 22 refs, 2 figs, 2 tabs

  17. Trichosanthin functions as Th2-type adjuvant in induction of allergic airway inflammation

    Yuan Wang; Kairui Mao; Shuhui Sun; Guomei Lin; Xiaodong Wu; Gang Yao; Bing Sun

    2009-01-01

    It is important to understand the pathogenesis of asthma induced by natural allergens, which could exclude the interference of artificial adjuvant and provide insights of natural immune response in the disease. In the present study, we show that Trichosanthin (TCS) could induce airway inflammation even without the help of alum. Further-more, TCS appeared capable of replacing alum to promote OVA-specific airway inflammation. TCS induced accu-mulation of IL-4-producing eosinophiis in peritoneum at an early stage and the adjuvant function of TCS was elimi-nated by blockage of IL-4 at this stage. Finally, the eosinophils triggered by TCS from WT mice, but not from IL-4-deficient mice were shown to function as adjuvant for the induction of OVA-specific Th2 responses. Our data indicate that TCS is not only an allergen, but also a Th2-type adjuvant modulating the switching of immune responses to a Th2 pathway. This chain of events results from IL-4 production by eosinophils at an early stage of TCS-priming. In conclusion, TCS may be useful as a Th2 adjuvant, and innate immune cells, such as eosinophils, may be a good target to study the initiation of Th2 response.

  18. Influence of various forms of dialyzable leukocyte extracts on rat adjuvant arthritis

    Stancikova, Maria; Rovensky, Jozef; Blazickova, Stanislava [Research Institute of Rheumatic Diseases, Piestany (Slovakia); Pekarek, J.; Cech, Karel [Institute of Sera and Vaccines, Prague (Czech Republic)

    1994-12-31

    Adjuvant-induced arthritis in rats is a chronic inflammatory disease, widely as an animal model for rheumatoid arthritis. In our study the effect of various fractions of dialyzable leukocyte extract (DLE): DLE I-molecular weight below 10 kDa (commercial preparation), DLE II-molecular weight below 5 kDa (suppressor fraction), DLE III-molecular weight 5-10 kDa on rat adjuvant-induced arthritis was studied. The adjuvant arthritic (AA) rats were treated with DLE fractions i.p. in solutions containing an active substance isolated from 12.5 x 10{sup 6} and 6.25 x 10{sup 6} leukocytes from day 1 (adjuvant injected) through day 18, every second day (total 9 times). Various markers in inflammation, immune function and joint destruction were evaluated: hind paw volume, serum hyaluronic acid, serum albumin and biopterin in urine. All these markers showed a significant improvement after using fraction DLE II in comparison with AA controls. Fractions DLE I and DLE III influenced only some markers of inflammation and immune function. Our results demonstrated a therapeutical effect of fraction DLE II on rat adjuvant-induced arthritis. (author). 22 refs, 2 figs, 2 tabs.

  19. Qualitative Economics

    Fast, Michael; Clark II, Woodrow W

    2013-01-01

    This chapter is about science from a book that on Qualitative Economics (Clark and Fast 2008), specifically building a science of economics, grounded in understanding of organizations and what is beneath the surface of structures and activities. Economics should be, as a science, concerned with its...... assumptions and how to develop and formulate theories of ideas and reality that produce descriptions of how to understand phenomenon that create experiences, hypotheses generation and replicable data which need to be connected to everyday business life. Economics has to start with a discussion of philosophy...... of science There is a “disconnection” between economics which focuses on structures and universal laws from those that are in contrast with the everyday of life of business activity, which are processual and dynamic. This discussion is the central issue in the paper, and is discussed from the perspective...

  20. Tocotrienols are good adjuvants for developing cancer vaccines

    Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy

  1. Tocotrienols are good adjuvants for developing cancer vaccines

    Radhakrishnan Ammu

    2010-01-01

    Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

  2. Early adjuvant radiotherapy in the treatment of atypical meningioma.

    Jenkinson, Michael D; Waqar, Mueez; Farah, Jibril Osman; Farrell, Michael; Barbagallo, Giuseppe M V; McManus, Robin; Looby, Seamus; Hussey, Deirdre; Fitzpatrick, David; Certo, Francesco; Javadpour, Mohsen

    2016-06-01

    Atypical meningiomas have a greater propensity to recur than benign meningiomas and the benefits of early adjuvant radiotherapy are unclear. Existing studies report conflicting results. This retrospective cohort study evaluated the role of early adjuvant radiotherapy following surgical resection of atypical meningioma. A triple center case-note review of adults with newly-diagnosed atypical meningiomas between 2001 and 2010 was performed. Pathology diagnosis was made according to the World Health Organization classification in use at the time of surgery. Patients with multiple meningiomas, neurofibromatosis type 2 and radiation-induced meningiomas were excluded. Extent of resection was defined as gross total resection (GTR; Simpson Grade I-III) or subtotal resection (STR; Simpson Grade IV-V). Survival analysis was performed using the Kaplan-Meier method. One hundred thirty-three patients were identified with a median age of 62years (range 22-86years) and median follow-up of 57.4months (range 0.1-152.2months). Tumors were mostly located in the convexity (50.4%) or falcine/parasagittal regions (27.1%). GTR (achieved in 85%) was associated with longer progression free survival (PFS) (5year PFS 81.2% versus 40.08%, log-rank=11.117, p=0.001) but not overall survival (OS) (5year OS 76.6% versus 39.7%, log-rank=3.652, p=0.056). Following GTR, early adjuvant radiotherapy was administered to 28.3% of patients and did not influence OS (5year OS 77.0% versus 75.7%, log-rank=0.075, p=0.784) or PFS (5year PFS 82.0% versus 79.3%, log-rank=0.059, p=0.808). Although extent of resection emerged as an important prognostic variable, early adjuvant radiotherapy did not influence outcome following GTR of atypical meningiomas. Prospective randomized controlled trials are planned. PMID:26775147

  3. Targeted vaccine adjuvants based on modified cholera toxin.

    Lycke, Nils

    2005-09-01

    The present review describes immunomodulation with targeted adjuvants that will allow for the development of efficacious mucosal vaccines. We have studied cholera toxin (CT) and derivatives thereof, to rationally design vaccine adjuvant vectors that are both highly efficacious as well as safe and non-toxic. Two strategies were exploited; the first using CT or the enzymatically inactive receptor-binding B-subunit of CT (CTB) and the second, using CTA1 or an enzymatically inactive mutant CTA1R7K., that was linked, in a fusion protein, to the B-cell targeting moiety, DD, from Staphylococcus areus proteinA. Our studies provide compelling evidence that delivery of Ag in the absence of ADP-ribosylation can promote tolerance, whereas, ADP-ribosyltransferase-active conjugates, prevent tolerance but induce IgA immunity. Our analysis revealed unique subsets of mucosal and systemic DC that appeared to be responsible for the ADP-ribosyltransferase sensitive dichotomy between tolerance and IgA immunity. Whether targeting of B cells suffice for tolerance-induction or requires participation of DCs, is at present an unresolved issue. Nevertheless, enzymatic modulation differentiates and matures the DC to promote CD4 T cell help for IgA B cell development. Ag-presentation in the absence of enzyme, as seen with CTA1R7K-DD, expands specific T cells to a similar extent as enzymatically active CTA1-DD, but fails to recruit help for germinal center expansion of activated B cells. We have given special attention to the genes that adjuvants turn on using Affymetrix technology. In particular, modulation of the expression of co-stimulatory molecules on the targeted APC; CD80, CD86, CD83 and B7RP-1, play important roles for the effect of the ADP-ribosylating CTA1-based adjuvants for the development of tolerance or active IgA immunity. PMID:16178769

  4. Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

    A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

  5. Adjuvant interferon treatment for melanoma.

    Agarwala, S S; Kirkwood, J M

    1998-08-01

    After decades of research, the adjuvant therapy of patients with melanoma has recently shown significant survival and relapse-free interval benefit for the intravenous and subcutaneous administration of maximally tolerable dosages of recombinant IFN alpha 2b in a trial conducted by the ECOG (E1684). Despite the toxicity of this therapy, retrospective analyses of its impact upon quality-of-life using Q-TWiST methods and cost-efficacy analyses all argue for the benefit and utility of this intervention, especially for node-positive patients with resectable melanoma at highest risk of relapse. A confirmatory trial has been completed and will mature in the spring of 1998. The impact of lower dosages of IFN, apparent transiently during and for a period of time following treatment has not been sustained with longer follow-up in a number of trials. Current approaches in Europe and North America focus upon refinement of dose and duration of treatment with IFN and their potential interactions with, and comparison with, active specific immunotherapy with vaccines. A recently emerging area of research is the patient with stage IIA melanoma and the potential role of an abbreviated high-dose regimen of IFN alpha in this patient subset. PMID:9759581

  6. Qualitative Economics

    Fast, Michael; Clark II, Woodrow W

                         This book is about science -- specifically, the science of economics. Or lack thereof is more accurate. The building of any science, let alone economics, is grounded in the understanding of what is beneath the "surface" of economics. Science, and hence economics, should...... be concerned with formulating ideas that express theories which produce descriptions of how to understand phenomenon and real world experiences.                       Economics must become a science, because the essence of economics in terms of human actions, group interactions and communities are in need...... of scientific inquiry. Academics and scholars need a scientific perspective that can hypothesize, theorize document, understand and analyze human dynamics from the individual to more societal interactions. And that is what qualitative economics does; it can make economics into becoming a science. The economic...

  7. Adjuvant activity of CpG-ODN formulated as a liquid crystal.

    Sánchez Vallecillo, María F; Ullio Gamboa, Gabriela V; Palma, Santiago D; Harman, María F; Chiodetti, Ana L; Morón, Gabriel; Allemandi, Daniel A; Pistoresi-Palencia, María C; Maletto, Belkys A

    2014-03-01

    The adjuvants approved in human vaccine with recombinant/purified antigens induce weak cellular immune response and so the development of new adjuvant strategies is critical. CpG-ODN has successfully been used as an adjuvant (phase I-III clinical trials) but its bioavailability needs to be improved. We investigated the adjuvant ability of CpG-ODN formulated with a liquid crystal nanostructure of 6-O-ascorbyl palmitate (Coa-ASC16). Mice immunized with OVA/CpG-ODN/Coa-ASC16 elicited a potent specific IgG1, IgG2a, Th1 and Th17 cellular response without systemic adverse effects. These responses were superior to those induced by OVA/CpG-ODN (solution of OVA with CpG-ODN) and to those induced by the formulation OVA/CpG-ODN/Al(OH)3. Immunization with OVA/CpG-ODN/Coa-ASC16 resulted in a long-lasting cell-mediated immune response (at least 6.5 months). Furthermore, Coa-ASC16 alone allows a controlled release of CpG-ODN in vitro and induces local inflammatory response, independent of TLR4 signaling, characterized by an influx of neutrophils and Ly6C(high) monocytes and pro-inflammatory cytokines. Remarkably, the adjuvant capacity of CpG-ODN co-injected with Coa-ASC16 (OVA/CpG-ODN plus Coa-ASC16) was similar to the adjuvant activity of OVA/CpG-ODN, supporting the requirement for whole formulation to help CpG-ODN adjuvanticity. These results show the potential of this formulation, opening a new avenue for the development of better vaccines. PMID:24382332

  8. CpG-DNA enhancement the immune elicited as adjuvant of foot- and- mouth disease vaccine

    Morshedi, A.

    2010-01-01

    Full Text Available In the present study the effect of the locally produced genetic adjuvant of ginea pig specific CpG-motif-containing oligodeoxynucleotide (CpG-ODN in an inactivated FMD virus vaccine was evaluated. Boosting the ginea pigs with FMD vaccine along with CpG-ODN adjuvant produced relatively higher ratio (5-fold of FMDV-specific IgG2a / IgG1 than those vaccinated in the absence of CpG-ODN. The neutralizing antibody (NA titer induced by FMD vaccine along with CpG-ODN adjuvant was significantly higher (8-fold than NA titer induced by the classical FMD vaccine in Alum adjuvant. The titer of NA and virus clearance from serum was consistently and significantly higher in animals primed with FMD vaccine and boosted by CpG-ODN than the classical FMD vaccine. The results of this study showed the potential of CpG-ODN as a genetic adjuvant to FMD vaccine in the development of Th1 responses.

  9. Effects of adjuvants on IgG subclasses elicited by virus-like Particles

    Visciano Maria Luisa

    2012-01-01

    Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

  10. Exercise as an Adjuvant Therapy for Hematopoietic Stem Cell Mobilization

    Emmons, Russell; Niemiro, Grace M.; De Lisio, Michael

    2016-01-01

    Hematopoietic stem cell transplant (HSCT) using mobilized peripheral blood hematopoietic stem cells (HSPCs) is the only curative strategy for many patients suffering from hematological malignancies. HSPC collection protocols rely on pharmacological agents to mobilize HSPCs to peripheral blood. Limitations including variable donor responses and long dosing protocols merit further investigations into adjuvant therapies to enhance the efficiency of HSPCs collection. Exercise, a safe and feasible intervention in patients undergoing HSCT, has been previously shown to robustly stimulate HSPC mobilization from the bone marrow. Exercise-induced HSPC mobilization is transient limiting its current clinical potential. Thus, a deeper investigation of the mechanisms responsible for exercise-induced HSPC mobilization and the factors responsible for removal of HSPCs from circulation following exercise is warranted. The present review will describe current research on exercise and HSPC mobilization, outline the potential mechanisms responsible for exercise-induced HSPC mobilization, and highlight potential sites for HSPC homing following exercise. We also outline current barriers to the implementation of exercise as an adjuvant therapy for HSPC mobilization and suggest potential strategies to overcome these barriers. PMID:27123008

  11. Formulation, high throughput in vitro screening and in vivo functional characterization of nanoemulsion-based intranasal vaccine adjuvants.

    Pamela T Wong

    Full Text Available Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate formulations consisting of oil-in-water nanoemulsions that contain various cationic and nonionic surfactants. To facilitate adjuvant development we first evaluated this library in a series of high-throughput, in vitro assays for activities associated with innate and adaptive immune activation in vivo. These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. We then sought to determine how these parameters related to adjuvant activity in vivo. While the in vitro assays alone were not enough to predict the in vivo adjuvant activity completely, several interesting relationships were found with immune responses in mice. Furthermore, by varying the physicochemical properties of the surfactant components (charge, surfactant polar head size and hydrophobicity and the surfactant blend ratio of the formulations, the strength and type of the immune response generated (TH1, TH2, TH17 could be modulated. These findings suggest the possibility of using high-throughput screens to aid in the design of custom adjuvants with unique immunological profiles to match specific mucosal vaccine applications.

  12. Endogenous oils derived from human adipocytes are potent adjuvants that promote IL-1 alpha-dependent inflammation.

    MOK, KENNETH; O'Farrelly, Cliona

    2014-01-01

    Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody response...

  13. The evaluation of yeast derivatives as adjuvants for the immune response to the Bm86 antigen in cattle

    Machado Héctor; Montero Carlos; Rodríguez Valle Manuel; Joglar Marisdania

    2001-01-01

    Abstract Background The Gavac™ vaccine against the cattle tick Boophilus microplus has proven its efficacy in a large number of controlled and field experiments. However, this vaccine could be further improved by searching for new alternative adjuvants that would induce a stronger long-lasting immune response. We conducted several experiments to assay the adjuvant effect of fractions of the recombinant yeast Pichia pastoris in mouse and cattle models. In previous experiments, the combination ...

  14. Review: Adjuvant effects of saponins on animal immune responses

    RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines,ISCOMs (immunostimulating complexes), Freund's complete adjuvant, Freund's incomplete adjuvant, alums, bacterial toxins etc.,are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed.

  15. Structural perturbation of diphtheria toxoid upon adsorption to aluminium hydroxide adjuvant

    Regnier, Marie; Metz, Bernard; Tilstra, Wichard; Hendriksen, Coenraad; Jiskoot, Wim; Norde, Willem; Kersten, Gideon

    2012-01-01

    Aluminium-containing adjuvants are often used to enhance the potency of vaccines. In the present work we studied whether adsorption of diphtheria toxoid to colloidal aluminium hydroxide induces conformational changes of the antigen. Diphtheria toxoid has a high affinity for the aluminium hydroxide p

  16. Beyond antigens and adjuvants: formulating future vaccines.

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033

  17. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  18. Systemic adjuvant therapies in renal cell carcinoma.

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  19. Systemic adjuvant therapies in renal cell carcinoma

    Sebastiano Buti

    2012-10-01

    Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.

  20. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer.

    Scheiermann, Julia; Klinman, Dennis M

    2014-11-12

    Synthetic oligonucleotides (ODN) that express unmethylated "CpG motifs" trigger cells that express Toll-like receptor 9. In humans this includes plasmacytoid dendritic cells and B cells. CpG ODN induce an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. Their utility as vaccine adjuvants was evaluated in a number of clinical trials. Results indicate that CpG ODN improve antigen presentation and the generation of vaccine-specific cellular and humoral responses. This work provides an up-to-date overview of the utility of CpG ODN as adjuvants for vaccines targeting infectious agents and cancer. PMID:24975812

  1. Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

    Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene;

    2014-01-01

    The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...... attractive interaction with the zwitterionic liposomes. In contrast, the net cationic lysozyme showed very little interaction with either types of liposome. Adsorption of α-lactalbumin altered its tertiary structure, affected lipid membrane packing below and above the phase transition temperature, and...... way vaccine antigens are presented to antigen-presenting cells, and may play an important role for the efficacy of the vaccine-induced immune response. These studies thus exemplify the importance of characterizing the molecular interactions between the vaccine antigen and adjuvant along with...

  2. Radiation recall secondary to adjuvant docetaxel after balloon-catheter based accelerated partial breast irradiation

    Wong, Nathan W. [Summer Intern, Mayo Clinic Arizona, Scottsdale, AZ (United States); Wong, William W., E-mail: wong.william@mayo.ed [Department of Radiation Oncology, Mayo Clinic Arizona, 13400 E. Shea Boulevard, Scottsdale, AZ 85259 (United States); Karlin, Nina J. [Division of Oncology, Mayo Clinic Arizona, Scottsdale, AZ (United States); Gray, Richard J. [Department of Surgery, Mayo Clinic Arizona, Scottsdale, AZ (United States)

    2010-08-15

    For early stage breast cancer, wide local excision and post-operative whole breast irradiation is a standard treatment. If adjuvant chemotherapy is recommended, radiation is usually given after completion of chemotherapy. In recent years, accelerated partial breast irradiation (APBI) with balloon-cathetered based brachytherapy has become an option for selected patients. For these patients, adjuvant chemotherapy would have to be administered after radiation. The sequence of treatment with radiation followed by chemotherapy results in increased risk of radiation recall reaction (RRD) in these patients. Docetaxel is becoming a more commonly used drug as adjuvant treatment for breast cancer. Here we report a case of docetaxel induced RRD after APBI with balloon-cathetered based brachytherapy. Such reaction would have an adverse impact on the cosmetic outcome and quality of life of the patient. For patients who develop an intense skin reaction after the administration of docetaxel following APBI, RRD should be considered in the differential diagnosis.

  3. Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid β peptides

    Wahi Monika M

    2008-02-01

    Full Text Available Abstract Background A recent human clinical trial of an Alzheimer's disease (AD vaccine using amyloid beta (Aβ 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine. Results All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue. Conclusion Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.

  4. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Sarma Nilendu

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.

  5. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  6. Lactic acid bacteria as adjuvants for sublingual allergy vaccines.

    Van Overtvelt, Laurence; Moussu, Helene; Horiot, Stéphane; Samson, Sandrine; Lombardi, Vincent; Mascarell, Laurent; van de Moer, Ariane; Bourdet-Sicard, Raphaëlle; Moingeon, Philippe

    2010-04-01

    We compared immunomodulatory properties of 11 strains of lactic acid bacteria as well as their capacity to enhance sublingual immunotherapy efficacy in a murine asthma model. Two types of bacterial strains were identified, including: (i) potent inducers of IL-12p70 and IL-10 in dendritic cells, supporting IFN-gamma and IL-10 production in CD4+ T cells such as Lactobacillus helveticus; (ii) pure Th1 inducers such as L. casei. Sublingual administration in ovalbumin-sensitized mice of L. helveticus, but not L. casei, reduced airways hyperresponsiveness, bronchial inflammation and proliferation of specific T cells in cervical lymph nodes. Thus, probiotics acting as a Th1/possibly Treg, but not Th1 adjuvant, potentiate tolerance induction via the sublingual route. PMID:20175969

  7. Formulation and Characterization of Nanoemulsion Intranasal Adjuvants: Effects of Surfactant Composition on Mucoadhesion and Immunogenicity

    Wong, Pamela T.; Wang, Su He; Ciotti, Susan; Makidon, Paul E.; Smith, Douglas M.; Fan, Yongyi; Schuler, Charles F.; Baker, James R.

    2013-01-01

    Development of effective intranasal vaccines is of great interest due to their potential to induce both mucosal and systemic immunity. Here we produced oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine antigens. NE induced immunogenicity and antigen delivery are believed to be facilitated through initial contact interactions between the NE droplet and mucosal surfaces which promote prolo...

  8. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    2010-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99...

  9. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    2010-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide chemicals. 182.99...

  10. Effectiveness of spray adjuvants on reduction of spray drift

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  11. Longitudinal Assessments of Quality of Life in Endometrial Cancer Patients: Effect of Surgical Approach and Adjuvant Radiotherapy

    Purpose: Adjuvant radiotherapy (RT) is often considered for endometrial cancer. We studied the effect of RT and surgical treatment on patients' quality of life (QOL). Methods and Materials: All patients referred to the gynecologic oncology clinics with biopsy findings showing endometrial cancer were recruited. QOL assessments were performed using the European Organization for Research and Treatment of Cancer QOL questionnaire-C30, version 3. Assessments were obtained at study entry and at regular 3-month intervals for a maximum of 2 years. Open-ended telephone interviews were done every 6 months. Linear mixed regression models were built using QOL domain scores as dependent variables, with the predictors of surgical treatment and adjuvant RT type. Results: A total of 40 patients were recruited; 80% of the surgeries were performed by laparotomy. Significant improvements were seen in most QOL domains with increased time from treatment. Adjuvant RT resulted in significantly more severe bowel symptoms and improvement in insomnia compared with conservative follow-up. No significant adverse effect from adjuvant RT was seen on the overall QOL. Bowel symptoms were significantly increased in patients treated with laparotomy compared with laparoscopy in the patients treated with whole pelvic RT. Qualitatively, about one-half of the patients noted improvements in their overall QOL during follow-up, with easy fatigability the most prevalent. Conclusion: No significant adverse effect was seen on patients' overall QOL with adjuvant pelvic RT after the recovery period. The acute adverse effects on patients' QOL significantly improved with an increasing interval from diagnosis.

  12. Advax-Adjuvanted Recombinant Protective Antigen Provides Protection against Inhalational Anthrax That Is Further Enhanced by Addition of Murabutide Adjuvant

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Tod J Merkel

    2014-01-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax a...

  13. Conflicts in qualitative research

    Colmenero Ruiz, María Jesús; Domínguez Garrido, María Concepción; Huber, Günter L.; Jiménez-Garrido, Amador; Khan, Shahjehan; Ernesto LÓPEZ GÓMEZ; Medina Rivilla, Antonio; Medina Domínguez, María; Medina Domínguez, Conchita; Pegalajar Palomino, María del Carmen; Pérez Navío, Eufrasio; Santoro Moreno, José María; Sládková, Jana; Center for Qualitative Psychology e.V.

    2014-01-01

    Volume 12 of the Qualitative Psychology Nexus series presents contributions to the XIV. Workshop on Qualitative Research in Psychology on the general topic of "Conflicts in Qualitative Research." It was organized by the Center for Qualitative Psychology and the Department of Pedagogy of the University of Jaén, Spain, during May 17-19, 2013. The presentations cover a broad spectrum of possible conflicts that social researchers using qualitative methods have to overcome, ranging from elabora...

  14. Qualitative Research Process

    Dewan Mahboob HOSSAIN

    2011-01-01

    This article provides with an overview of the qualitative research methods. Over last few decades, qualitative research is getting very popular in the fields of business, sociology, psychology and others. This article, in its introduction, gives a general idea about the qualitative research. Then it discusses the main differences between qualitative and quantitative research methods. The article also discusses about the ethical issues important for qualitative research. Lastly it discusses ab...

  15. Qualitative research in health

    Ligia Regina Franco Sansigolo Kerr; Carl Kendall

    2014-01-01

    Qualitative research and health has become extremely popular in the last 30 years. Since the 80’s, more and more health professionals have engaged in qualitative research. Discriminating a “qualitative research” from quantitative research, though, is a misnomer, since all research is at least part qualitative. After all, when epidemiologists or biostatisticians count something, that category is a qualitative “something”.

  16. New generation adjuvants--from empiricism to rational design.

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-01

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. PMID:26022561

  17. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  18. Evaluation of TLR agonists as potential mucosal adjuvants for HIV gp140 and tetanus toxoid in mice.

    Viviana Buffa

    Full Text Available In the present study we investigate the impact of a range of TLR ligands and chitosan as potential adjuvants for different routes of mucosal immunisation (sublingual (SL, intranasal (IN, intravaginal (IVag and a parenteral route (subcutaneous (SC in the murine model. We assess their ability to enhance antibody responses to HIV-1 CN54gp140 (gp140 and Tetanus toxoid (TT in systemic and vaginal compartments. A number of trends were observed by route of administration. For non-adjuvanted antigen, SC>SL>IN immunisation with respect to systemic IgG responses, where endpoint titres were greater for TT than for gp140. In general, co-administration with adjuvants increased specific IgG responses where IN = SC>SL, while in the vaginal compartment IN>SL>SC for specific IgA. In contrast, for systemic and mucosal IgA responses to antigen alone SL>IN = SC. A number of adjuvants increased specific systemic IgA responses where in general IN>SL>SC immunisation, while for mucosal responses IN = SL>SC. In contrast, direct intravaginal immunisation failed to induce any detectable systemic or mucosal responses to gp140 even in the presence of adjuvant. However, significant systemic IgG responses to TT were induced by intravaginal immunisation with or without adjuvant, and detectable mucosal responses IgG and IgA were observed when TT was administered with FSL-1 or Poly I∶C. Interestingly some TLRs displayed differential activity dependent upon the route of administration. MPLA (TLR4 suppressed systemic responses to SL immunisation while enhancing responses to IN or SC immunisation. CpG B enhanced SL and IN responses, while having little or no impact on SC immunisation. These data demonstrate important route, antigen and adjuvant effects that need to be considered in the design of mucosal vaccine strategies.

  19. Freund's vaccine adjuvant promotes Her2/Neu breast cancer

    Inflammation has been linked to the etiology of many organ-specific cancers. Indirect evidence suggests a possible role for inflammation in breast cancer. We investigated whether the systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis in a rat model in which cancer is induced by the neu oncogene. The effects of FA on hyperplastic mammary lesions and mammary carcinomas were determined in a neu-induced rat model. The inflammatory response to FA treatment was gauged by measuring acute phase serum haptoglobin. In addition, changes in cell proliferation and apoptosis following FA treatment were assessed. Rats receiving FA developed twice the number of mammary carcinomas as controls. Systemic inflammation following FA treatment is chronic, as shown by a doubling of the levels of the serum biomarker, haptoglobin, 15 days following initial treatment. We also show that this systemic inflammation is associated with the increased growth of hyperplastic mammary lesions. This increased growth results from a higher rate of cellular proliferation in the absence of changes in apoptosis. Our data suggests that systemic inflammation induced by Freund's adjuvant (FA) promotes mammary carcinogenesis. It will be important to determine whether adjuvants currently used in human vaccines also promote breast cancer

  20. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.

  1. Impact of adjuvant chemotherapy for gliomatosis cerebri

    Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

  2. Chitosan as an adjuvant for poliovaccine.

    Ghendon, Y; Markushin, S; Akopova, I; Koptiaeva, I; Krivtsov, G

    2011-05-01

    The use of inactivated poliomyelitis vaccine is very important for eradicating poliomyelitis. However, this vaccine is not available readily in underdeveloped countries due to the high cost. Adjuvants can improve the immunogenicity of a vaccine and reduce the antigen dose required for vaccination, thus lowering the cost of the vaccine. Chitosan glutamate solution and a chitosan sulfate micro/nanoparticle suspension were tested as adjuvants for Imovax-inactivated poliovaccine and for inactivated monovalent poliovirus type 1, 2, and 3 vaccines obtained by inactivation of the attenuated Sabin poliovirus strains. Inactivated vaccines admixed with either chitosan glutamate or chitosan sulfate micro/nanoparticles and administered to mice showed significantly enhanced immunogenicity to poliovirus type 1, 2, and 3 strains compared to the respective vaccines administered without chitosan. Chitosan preparations increased the immunogenicity of 1:2 and 1:4 diluted inactivated Sabin strain preparations in mice 8- to 16-fold, so that the neutralizing antibody titers after vaccination with adjuvanted diluted vaccine were equal to those obtained after vaccination with undiluted vaccine administered without chitosan. Neutralizing antibodies could be detected in sera of rats vaccinated with undiluted, 1:10, and 1:100 diluted Imovax vaccine admixed with chitosan sulfate micro/nanoparticles, although in the control group, vaccination only with the undiluted vaccine resulted in antibody production. These results show that the chitosan glutamate solution and chitosan sulfate micro/nanoparticle suspension can significantly improve the immunogenicity of various poliovaccines, and reduce the effective antigen dose. PMID:21412793

  3. Validity in qualitative research

    Kuzmanić, Marja

    2015-01-01

    This paper addresses several issues related to validity in qualitative research and, more specifically, explores the ways in which validity has been discussed and applied in research with qualitative interviews. The central question is to what extent, if at all, traditional positivist validity criteria are applicable, but also relevant, for evaluation of research with qualitative interviewing. The qualitative interview has been chosen as the focal point of this paper because of its peculiarit...

  4. Qualitative Research in Psychology

    Fattah Hanurawan

    2013-01-01

    "The first 'Workshop Qualitative Research in Psychology' took place in Blaubeuren, Germany from October 20-22, 2000. The meeting was organized by the Center for Qualitative Psychology of the University of Tübingen, Germany. The purpose of the meeting was to begin a network of qualitative psychologists. Thirty-two participants got to know each other, presented and discussed their research, discussed potential further developments within the field of qualitative psychology, and inspired each ot...

  5. The qualitative research proposal

    H. Klopper

    2008-01-01

    Qualitative research in the health sciences has had to overcome many prejudices and a number of misunderstandings, but today qualitative research is as acceptable as quantitative research designs and is widely funded and published. Writing the proposal of a qualitative study, however, can be a challenging feat, due to the emergent nature of the qualitative research design and the description of the methodology as a process. Even today, many sub-standard proposals at post-graduate evaluation c...

  6. Non-carrier nanoparticles adjuvant modular protein vaccine in a particle-dependent manner.

    Seth, Arjun; Ritchie, Fiona K; Wibowo, Nani; Lua, Linda H L; Middelberg, Anton P J

    2015-01-01

    Nanoparticles are increasingly used to adjuvant vaccine formulations due to their biocompatibility, ease of manufacture and the opportunity to tailor their size, shape, and physicochemical properties. The efficacy of similarly-sized silica (Si-OH), poly (D,L-lactic-co-glycolic acid) (PLGA) and poly caprolactone (PCL) nanoparticles (nps) to adjuvant recombinant capsomere presenting antigenic M2e modular peptide from Influenza A virus (CapM2e) was investigated in vivo. Formulation of CapM2e with Si-OH or PLGA nps significantly boosted the immunogenicity of modular capsomeres, even though CapM2e was not actively attached to the nanoparticles prior to injection (i.e., formulation was by simple mixing). In contrast, PCL nps showed no significant adjuvant effect using this simple-mixing approach. The immune response induced by CapM2e alone or formulated with nps was antibody-biased with very high antigen-specific antibody titer and less than 20 cells per million splenocytes secreting interferon gamma. Modification of silica nanoparticle surface properties through amine functionalization and pegylation did not lead to significant changes in immune response. This study confirms that simple mixing-based formulation can lead to effective adjuvanting of antigenic protein, though with antibody titer dependent on nanoparticle physicochemical properties. PMID:25756283

  7. Adjuvant activity of peanut, cottonseed and rice oils on cellular and humoral response

    Erika Freitas

    2013-04-01

    Full Text Available The potentiality of the usage of vegetable oils such as soybean, corn, olive, sesame, murici seed, rapeseed, linseed, rice and cashew nuts as adjuvant of the humoral and cellular immune response has been recently shown. In the present work, besides of evaluating the adjuvant action of peanut, cottonseed and rice oils on humoral and cellular immune responses against ovalbumin (OVA we also evaluated the protective immune response induced by Leishmania antigens. The peanut oil significantly increased the synthesis of anti-ovalbumin antibodies in the primary response, but it did not favor cellular response. Concerning mice immunized with L. amazonensis antigens emulsified with peanut oil exacerbated skin lesions and lymph node parasite load what suggests stimulation of the Th2 immune response and down regulation of Th1 response. The cottonseed oil was shown to have adjuvant effect to the humoral response, stimulating a secondary response and also favored the delayed-type hypersensitivity (DTH response to OVA. The rice oil stimulated a strong DTH reaction to OVA and enhanced the synthesis of antibodies after the third dose. Mice immunized with L. amazonensis antigens emulsified with rice oil or cotton seed oil were protected from developing skin lesions and lymph node parasite load. These results emphasize the interest and importance of the vegetable oils as tools in different procedures of immunization and their differential role in relation to the other adjuvant under usage.

  8. Effectively Communicating Qualitative Research

    Ponterotto, Joseph G.; Grieger, Ingrid

    2007-01-01

    This article is a guide for counseling researchers wishing to communicate the methods and results of their qualitative research to varied audiences. The authors posit that the first step in effectively communicating qualitative research is the development of strong qualitative research skills. To this end, the authors review a process model for…

  9. Additional Therapy with a Mistletoe Product during Adjuvant Chemotherapy of Breast Cancer Patients Improves Quality of Life: An Open Randomized Clinical Pilot Trial

    Wilfried Tröger; Zdravko Ždrale; Nevena Tišma; Miodrag Matijašević

    2014-01-01

    Background. Breast cancer patients receiving adjuvant chemotherapy often experience a loss of quality of life. Moreover chemotherapy may induce neutropenia. Patients report a better quality of life when additionally treated with mistletoe products during chemotherapy. Methods. In this prospective randomized open-label pilot study 95 patients were randomized into three groups. All patients were treated with an adjuvant chemotherapy. The primary objective of the study was quality of life, the s...

  10. The Driving of Immune Response by Th1 Adjuvants in Immunization of Mice with Trypanosoma cruzi marinkellei Elicits a Controversial Infection Control.

    Nascentes, Gabriel Antonio Nogueira; Hernández, César Gómez; Rabelo, Rosiley Aparecida de Souza; Coelho, Raquel Fernandes; Morais, Fabiana Rossetto de; Marques, Tatiane; Batista, Lara Rocha; Meira, Wendell Sérgio Ferreira; Oliveira, Carlo José Freire de; Lages Silva, Eliane; Ramírez, Luis Eduardo

    2016-05-01

    In previous studies, we have demonstrated that inoculation with a Trypanosoma cruzi marinkellei (avirulent RM1 strain) was able to reduce parasitemia in mice challenged with T. cruzi, although it was not able to prevent histopathological lesions. Th1 response stimulation by immunization is necessary for T. cruzi infection control, but the resistance is also dependent on immunoregulatory mechanisms, which can be induced by adjuvants. Thus, we evaluated whether inoculation of T. cruzi marinkellei associated with administration of different adjuvants would be capable of inducing different patterns of immune response to maximize the immune response against T. cruzi (virulent Romildo strain) infection. Two hundred eighty nonisogenic mice were divided into 14 groups according to the immunization scheme and the subsequent challenge with virulent Romildo T. cruzi strain. Nonimmunized groups and animals inoculated without adjuvants were also included. Immune protection was not observed with Th2 adjuvants (incomplete Freund's adjuvant [IFA] and Alum) due to high parasitemia. Th1/Th2-polarizing adjuvants also did not induce immune protection because inulin was unable to maintain survival, and immune-stimulating complexes induced intense inflammatory processes. Animals sensitized with RM1 strain without adjuvants were able to reduce parasitemia, increase survival, and protect against severe histological lesions, followed by adequate cytokine stimulation. Finally, our results demonstrate that the early and balanced IFN-γ production becomes critical to promote protection and that Th1 adjuvant elicited a controversial infection control due to increased histopathological damage. Therefore, the host's immunomodulation remains one of the most important challenges in the research for effective protection against T. cruzi infection. Similarly, the identification of protective antigens in the RM1 strain of T. cruzi marinkellei may contribute to further studies on vaccine development

  11. Parenteral Adjuvant Activities of Escherichia coli Heat-Labile Toxin and Its B Subunit for Immunization of Mice against Gastric Helicobacter pylori Infection

    Weltzin, Richard; Guy, Bruno; Thomas, William D.; Giannasca, Paul J.; Monath, Thomas P.

    2000-01-01

    The heat-labile toxin (LT) of Escherichia coli is a potent mucosal adjuvant that has been used to induce protective immunity against Helicobacter felis and Helicobacter pylori infection in mice. We studied whether recombinant LT or its B subunit (LTB) has adjuvant activity in mice when delivered with H. pylori urease antigen via the parenteral route. Mice were immunized subcutaneously or intradermally with urease plus LT, recombinant LTB, or a combination of LT and LTB prior to intragastric c...

  12. Adjuvant effects of liposomes containing lipid A: enhancement of liposomal antigen presentation and recruitment of macrophages.

    Verma, J N; Rao, M.; Amselem, S; Krzych, U; Alving, C R; Green, S J; Wassef, N M

    1992-01-01

    Liposomes containing lipid A induced potent humoral immune responses in mice against an encapsulated malaria antigen (R32NS1) containing NANP epitopes. The immune response was not enhanced by lipid A alone or by empty liposomes containing lipid A. Experiments to investigate the adjuvant mechanisms of liposomes and lipid A revealed that liposome-encapsulated R32NS1 was actively presented by bone marrow-derived macrophages to NANP-specific cloned T cells. The degree of presentation was related ...

  13. Identification of QS-21 as an Inflammasome-activating Molecular Component of Saponin Adjuvants.

    Marty-Roix, Robyn; Vladimer, Gregory I; Pouliot, Kimberly; Weng, Dan; Buglione-Corbett, Rachel; West, Kim; MacMicking, John D; Chee, Jonathan D; Wang, Shixia; Lu, Shan; Lien, Egil

    2016-01-15

    Many immunostimulants act as vaccine adjuvants via activation of the innate immune system, although in many cases it is unclear which specific molecules contribute to the stimulatory activity. QS-21 is a defined, highly purified, and soluble saponin adjuvant currently used in licensed and exploratory vaccines, including vaccines against malaria, cancer, and HIV-1. However, little is known about the mechanisms of cellular activation induced by QS-21. We observed QS-21 to elicit caspase-1-dependent IL-1β and IL-18 release in antigen-presenting cells such as macrophages and dendritic cells when co-stimulated with the TLR4-agonist adjuvant monophosphoryl lipid A. Furthermore, our data suggest that the ASC-NLRP3 inflammasome is responsible for QS-21-induced IL-1β/IL-18 release. At higher concentrations, QS-21 induced macrophage and dendritic cell death in a caspase-1-, ASC-, and NLRP3-independent manner, whereas the presence of cholesterol rescued cell viability. A nanoparticulate adjuvant that contains QS-21 as part of a heterogeneous mixture of saponins also induced IL-1β in an NLRP3-dependent manner. Interestingly, despite the role NLRP3 plays for cellular activation in vitro, NLRP3-deficient mice immunized with HIV-1 gp120 and QS-21 showed significantly higher levels of Th1 and Th2 antigen-specific T cell responses and increased IgG1 and IgG2c compared with wild type controls. Thus, we have identified QS-21 as a nonparticulate single molecular saponin that activates the NLRP3 inflammasome, but this signaling pathway may contribute to decreased antigen-specific responses in vivo. PMID:26555265

  14. Analgesic effects of methanolic extracts of the leaf or root of Moringa oleifera on complete Freund's adjuvant-induced arthritis in rats%辣木叶或根的甲醇提取物对弗氏佐剂致关节炎大鼠模型的止痛作用

    Homa Manaheji; Soheila Jafari; Jalal Zaringhalam; Shamsah Rezazadeh; Reza Taghizadfarid

    2011-01-01

    Objective: Moringa oleifera (family Moringaceae) has been widely used in African folk medicine,and researchers have recently revealed its anti-inflammatory effects in human.This study aimed to evaluate the analgesic properties of methanolic extracts of M.oleifera in complete Freund's adjuvant (CFA)-induced arthritis in rats.Methods: Adult male Wistar rats, weighing 200 to 220 g, were used in this study.Adjuvant arthritis was induced on day 0 by a single subcutaneous injection of CFA.The prepared extracts from both the root and leaf (200, 300 and 400 mg/kg) of M.oleifera were administered intraperitonealy to rats in the treatment groups 0, 3 and 6 d after CFA injection and indomethacin (5 mg/kg) was used as a positive control drug.Thermal hyperalgesia and mechanical allodynia were evaluated for the analgesic effect 0, 3 and 6 d after CFA injection.Combined methanolic root and leaf extracts of M.oleifera (200 mg/kg) were also tested for the analgesic effect.Results: The potency of the root or leaf extracts of M.oleifera (300 and 400 mg/kg) was similar to that of indomethacin, resulted in significant reductions in both thermal hyperalgesia and mechanical allodynia in rats with CFA-induced arthritis compared with the control group after 3 and 6 d,respectively (P<0.01 or P<0.05).Combined root and leaf extracts (200 mg/kg) of M.oleifera resulted in a significant reduction in thermal hyperalgesia compared with the control group after 3 and 6 d, respectively (P<0.01).Prophylactic injections of combined root and leaf extracts of M.oleifera (200 mg/kg) resulted in a significant reduction in thermal hyperalgesia compared with the control group, the root extracts group, and the leaf extracts group after 3 and 6 d, respectively (P<0.01).Conclusion: The methanolic extracts of the root or leaf of M.oleifera are effective in the reduction of pain induced by CFA in rats.A comparison of single and combination therapies of root and leaf extracts also showed a synergistic

  15. Adjuvant Therapy of Colon Cancer: Current Status and Future Developments

    Morse, Michael A.

    2005-01-01

    Options for the adjuvant therapy of resected stage III colon cancer have expanded beyond the previously well-accepted standard of 5-fluorouracil (5-FU) combined with leucovorin. The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) study confirmed that capecitabine (Xeloda) is at least as effective and is less toxic than a bolus 5-FU and leucovorin regimen for patients with stage III colon cancer. This study, in addition to National Surgical Adjuvant Breast and Bowel Project (NSABP) C-06, which...

  16. [Recent advance in adjuvant therapy for breast cancer].

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  17. Construction and preclinical evaluation of mmCT, a novel mutant cholera toxin adjuvant that can be efficiently produced in genetically manipulated Vibrio cholerae.

    Lebens, Michael; Terrinoni, Manuela; Karlsson, Stefan L; Larena, Maximilian; Gustafsson-Hedberg, Tobias; Källgård, Susanne; Nygren, Erik; Holmgren, Jan

    2016-04-19

    There is an urgent need for new adjuvants that are effective with mucosally administered vaccines. Cholera toxin (CT) is the most powerful known mucosal adjuvant but is much too toxic for human use. In an effort to develop a useful mucosal adjuvant we have generated a novel non-toxic mutant CT molecule that retains much of the adjuvant activity of native CT. This was achieved by making the enzymatically active A subunit (CTA) recalcitrant to the site-specific proteolytic cleavage ("nicking") required for toxicity, which was found to require mutations not only in the two residues rendering the molecule resistant to trypsin but also in neighboring sites protecting against cleavage by Vibrio cholerae proteases. This multiple-mutated CT (mmCT) adjuvant protein could be efficiently produced in and purified from the extracellular medium of CT-deleted V. cholerae. The mmCT completely lacked detectable enterotoxicity in an infant mouse model and had >1000-fold reduced cAMP inducing activity compared to native CT in a sensitive mammalian target cell system. It nonetheless proved to have potent adjuvant activity on mucosal and systemic antibody as well as cellular immune responses to mucosally co-administered antigens including oral cholera and intranasal influenza vaccines. We conclude that mmCT is an attractive novel non-toxic mucosal adjuvant for enhancing immune responses to co-administered mucosal vaccines. PMID:26973069

  18. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer - the RAPIDO trial

    Nilsson, Per J.; van Etten, Boudewijn; Hospers, Geke A. P.; Pahlman, Lars; van de Velde, Cornelis J. H.; Beets-Tan, Regina G. H.; Blomqvist, Lennart; Beukema, Jannet C.; Kapiteijn, Ellen; Marijnen, Corrie A. M.; Nagtegaal, Iris D.; Wiggers, Theo; Glimelius, Bengt

    2013-01-01

    Background: Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized

  19. Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

    Signe Tandrup Schmidt

    2016-03-01

    Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

  20. The role of adjuvants in therapeutic protection against paracoccidioidomycosis after immunization with the P10 peptide

    CarlosPelleschiTaborda

    2012-05-01

    Full Text Available Paracoccidioidomycosis (PCM, a common chronic mycosis in Latin America, is a granulomatous systemic disease caused by the thermo-dimorphic fungus Paracoccidioides brasiliensis. The glycoprotein gp43 is the main antigen target of P. brasiliensis and a 15-mer internal peptide (QTLIAIHTLAIRYAN, known as P10, defines a major CD4+-specific T cell epitope. Previous results have indicated that, besides having a preventive role in conventional immunizations prior to challenge with the fungus, protective anti-fungal effects can be induced in P. brasiliensis-infected mice treated with P10 administered with complete Freund’s adjuvant (CFA. The peptide elicits an IFN--dependent Th1 immune response and is the main candidate for effective immunotherapy of patients with PCM, as an adjunctive approach to conventional chemotherapy. In the present study we tested the therapeutic effects of P10 combined with different adjuvants (aluminum hydroxide, CFA, flagellin and the cationic lipid dioctadecyl-dimethylammonium bromide (DODAB in BALB/c mice previously infected with the P. brasiliensis Pb18 strain. Significant reductions in the number of colony forming units (CFUs of the fungus were detected in lungs of mice immunized with P10 associated with the different adjuvants 52 days after infection. Mice treated with DODAB and P10, followed by mice treated with P10 and flagellin, showed the most prominent effects as demonstrated by the lowest numbers of viable yeast cells as well as reductions in granuloma formation and fibrosis. Concomitantly, secretion of IFN- and TNF-, in contrast to IL-4 and IL-10, was enhanced in the lungs of mice immunized with P10 in combination with the tested adjuvants, with the best results observed in mice treated with P10 and DODAB. In conclusion, the present results demonstrate that the co-administration of the synthetic P10 peptide with several adjuvants, particularly DODAB, have significant therapeutic effects in experimental

  1. Biopersistence and brain translocation of aluminum adjuvants of vaccines

    Romain Kroum Gherardi

    2015-02-01

    Full Text Available Aluminum oxyhydroxide (alum is a crystaline compound widely used as an immunologic adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytozed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV, that obeys to CCL2 signaling the major inflammatory monocyte

  2. Modern Vaccines/Adjuvants Formulation Session 6: Vaccine & Adjuvant Formulation & Production 15-17 May 2013, Lausanne, Switzerland

    Fox, Christopher B.

    2013-01-01

    The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characte...

  3. Mechanism of the adjuvant activity of the synthetic mycobacterial cord factor analog Trehalose-6,6-dibehenate (TDB)

    Althaus, Kerstin

    2010-01-01

    The mechanism behind the adjuvant activity of the mycobacterial cord factor TDM and its synthetic analog TDB as a component of the new adjuvant system CAF01 was investigated and compared to the TLR9 ligand CpG. In vitro, TDB and TDM potently activate antigen-presenting cells via a Myd88 and TLR independent, but FcRg-Syk-Card9 dependent signaling pathway. Microarray analysis indicated that in macrophages, TDB induced genome-wide transcriptional responses similar to the Dectin-1 ligand Curdlan ...

  4. Immunostimulatory oligodeoxynucleotides containing the CpG motif are effective as immune adjuvants in tumor antigen immunization

    Weiner, George J; Liu, Hsin-Ming; Wooldridge, James E.; Dahle, Christopher E.; Krieg, Arthur M.

    1997-01-01

    Recent advances in our understanding of the immune response are allowing for the logical design of new approaches to cancer immunization. One area of interest is the development of new immune adjuvants. Immunostimulatory oligodeoxynucleotides containing the CpG motif (CpG ODN) can induce production of a wide variety of cytokines and activate B cells, monocytes, dendritic cells, and NK cells. Using the 38C13 B cell lymphoma model, we assessed whether CpG ODN can function as immune adjuvants in...

  5. Qualitative Research Methods

    Yıldırım, Ali; Orta Doğu Teknik Üniversitesi Eğitim Bilimleri Bölümü

    1999-01-01

    In this article, the basic characteristics of qualitative research methods are discussed in relation to quantitative research methods and their potential contribution to educational research. In addition, the article reviews the roots of qualitative research, the basic data collection methods used and how the results are used in practice. As the basic characteristics of qualitative research, being sensitive to natural context, the participant role of the researcher, a holistic approach, explo...

  6. Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant

    Shailbala Singh

    2014-10-01

    Full Text Available Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer, a synthetic glycolipid agonist of natural killer T (NKT cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.

  7. Adjuvant chemotherapy for soft tissue sarcoma.

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  8. Mucosal adjuvants to improve wildlife rabies vaccination.

    Fry, Tricia; Van Dalen, Kaci; Hurley, Jerome; Nash, Paul

    2012-10-01

    RABORAL V-RG(®)a is a recombinant vaccine used in oral rabies vaccination (ORV) programs for wildlife in the United States. Vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. Research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. We evaluated the possibility of using two benign compounds, chitosan and N,N,N-trimethylated chitosan (TMC), to increase the viscosity of the vaccine and potentially act as adjuvants to improve the immune response in raccoons (Procyon lotor). Forty mildly sedated raccoons were orally vaccinated via needleless syringe with either RABORAL V-RG (n = 12), chitosan+RABORAL V-RG (n = 12), TMC+ RABORAL V-RG (n = 12), or no vaccine (n = 4), on day 0 and again on day 90. We collected sera every 2-4 wk for 4 mo and evaluated rabies virus-neutralizing antibodies (rVNA). Raccoons were considered responders if rVNA titers were ≥ 0.1 IU/mL. Eleven of 12 raccoons vaccinated with TMC+RABORAL V-RG responded after one dose of vaccine, as did eight of 12 vaccinated with RABORAL V-RG, and three of 12 vaccinated with chitosan+ RABORAL V-RG. Our results suggest that the inclusion of an adjuvant, such as TMC, could increase vaccine efficacy to aid in controlling rabies virus spread in wildlife reservoirs. PMID:23060506

  9. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  10. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Paul H. Sugarbaker

    2012-01-01

    Full Text Available Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.

  11. 不同剂量白细胞介素2作为乙型肝炎病毒核酸疫苗佐剂的效应%Effects of different doses of interleukin 2 as adjuvants on immune responses induced by nucleic acid vaccines of hepatitis B virus

    李文波; 姚志强; 周永兴; 权启镇; 冯志华

    2001-01-01

    Objective To construct recombinant plasmids of pCR3.1-S encodingprotein S of hepatitis B virus as nucleic acid vaccines and investigate the effects of recombinant human interleukin 2 as adjuvants on immune responses induced by HBV nucleic acid vaccines in BALB/c mice. Methods Anti-HBs antibodies to HBV major protein was measured by ELISA assay, and the activities of lymphocyte proliferation and cytotoxity were detected by 3H-TdR incorporation assay and 4-hour 51Cr release assay. Humoral and cellular immune responses of different groups were then compared. Results The titers of anti-HBs antibodies in serum of rhIL-2 group mice were not significantly higher than those of control group mice (P>0.05). The difference of the activities of lymphocyte proliferation and cytotoxity between of control group mice and rhIL-2 group mice (every mouse with 500 U one time) was not significant (P>0.05). However, stimulation index and specific lysis rate of lymphocyte of rhIL-2 group mice (every mouse with 1 000 U or 2 000 U one time) showed significant difference compared with htose of control group mice (P<0.05). Conclusion Recombinant plasmids of pCR3.1-S as HBV nucleic acid vaccines could induced strong humoral and cellular immune responses in BALB/c mice. rhIL-2 acts as adjuvants to increase the potency of HBV nucleic acid vaccine in some certainty.%目的 构建表达乙型肝炎病毒(HBV)S蛋白的重组质粒pCR3.1-S作为核酸疫苗,观察重组人白细胞介素2(rhIL-2)作为佐剂对其诱导BALB/c小鼠产生免疫应答的影响。方法 分别以ELISA法、3H-TdR掺入法、Cr51 4h释放法等测定免疫小鼠的血清抗HBs、淋巴细胞增殖活性、淋巴细胞杀伤效应,初步研究不同免疫组体液和细胞免疫应答的差异。结果 血清抗HBsELISA效价,rhIL-2组与对照组相比较差异不显著(P>0.05);淋巴细胞增殖指数、淋巴细胞杀伤率,1000U(只.次)rhIL-2

  12. Adjuvant and anti-inflammatory properties of cigarette smoke in murine allergic airway inflammation.

    Trimble, Nancy J; Botelho, Fernando M; Bauer, Carla M T; Fattouh, Ramzi; Stämpfli, Martin R

    2009-01-01

    The impact of cigarette smoke on allergic asthma remains controversial both clinically and experimentally. The objective of this study was to investigate, in a murine model, how cigarette smoke affects immune inflammatory processes elicited by a surrogate allergen. In our experimental design, mice were concurrently exposed to cigarette smoke and ovalbumin (OVA), an innocuous antigen that, unless introduced in the context of an adjuvant, induces inhalation tolerance. We show that cigarette smoke exposure has adjuvant properties, allowing for allergic mucosal sensitization to OVA. Specifically, concurrent exposure to cigarette smoke and OVA for 2 weeks led to airway eosinophilia and goblet cell hyperplasia. In vivo OVA recall challenge 1 month after the last smoke exposure showed that concurrent exposure to OVA and cigarette smoke induced antigen-specific memory. Robust eosinophilia and OVA-specific IgG1 and IgE characterized the ensuing inflammatory response. Mechanistically, allergic sensitization was, in part, granulocyte macrophage colony-stimulating factor (GM-CSF) dependent, as a significant reduction in BAL eosinophilia was observed in mice treated with an anti-GM-CSF antibody. Of note, continuous smoke exposure attenuated the OVA recall response; decreased airway eosinophilia was observed in mice continuously exposed to cigarette smoke compared with mice that ceased the smoke exposure protocol. In conclusion, we demonstrate experimentally that while cigarette smoke acts as an adjuvant allowing for allergic sensitization, it also attenuates the ensuing eosinophilic inflammatory response. PMID:18635815

  13. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein) Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen.

    Thim, Hanna L; Villoing, Stéphane; McLoughlin, Marian; Christie, Karen Elina; Grove, Søren; Frost, Petter; Jørgensen, Jorunn B

    2014-01-01

    Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag) formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions) can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV) as the test Ag, the combined use of two Toll-like receptor (TLR) ligand adjuvants, CpG oligonucleotides (ODNs) and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV) glycoprotein (G) was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs) before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing receptor (PRR

  14. Vaccine Adjuvants in Fish Vaccines Make a Difference: Comparing Three Adjuvants (Montanide ISA763A Oil, CpG/Poly I:C Combo and VHSV Glycoprotein Alone or in Combination Formulated with an Inactivated Whole Salmonid Alphavirus Antigen

    Hanna L. Thim

    2014-03-01

    Full Text Available Most commercial vaccines offered to the aquaculture industry include inactivated antigens (Ag formulated in oil adjuvants. Safety concerns are related to the use of oil adjuvants in multivalent vaccines for fish, since adverse side effects (e.g., adhesions can appear. Therefore, there is a request for vaccine formulations for which protection will be maintained or improved, while the risk of side effects is reduced. Here, by using an inactivated salmonid alphavirus (SAV as the test Ag, the combined use of two Toll-like receptor (TLR ligand adjuvants, CpG oligonucleotides (ODNs and poly I:C, as well as a genetic adjuvant consisting of a DNA plasmid vector expressing the viral haemorrhagic septicaemia virus (VHSV glycoprotein (G was explored. VHSV-G DNA vaccine was intramuscularly injected in combination with intraperitoneal injection of either SAV Ag alone or combined with the oil adjuvant, Montanide ISA763, or the CpG/polyI:C combo. Adjuvant formulations were evaluated for their ability to boost immune responses and induce protection against SAV in Atlantic salmon, following cohabitation challenge. It was observed that CpG/polyI:C-based formulations generated the highest neutralizing antibody titres (nAbs before challenge, which endured post challenge. nAb responses for VHSV G-DNA- and oil-adjuvanted formulations were marginal compared to the CpG/poly I:C treatment. Interestingly, heat-inactivated sera showed reduced nAb titres compared to their non-heated counterparts, which suggests a role of complement-mediated neutralization against SAV. Consistently elevated levels of innate antiviral immune genes in the CpG/polyI:C injected groups suggested a role of IFN-mediated responses. Co-delivery of the VHSV-G DNA construct with either CpG/polyI:C or oil-adjuvanted SAV vaccine generated higher CD4 responses in head kidney at 48 h compared to injection of this vector or SAV Ag alone. The results demonstrate that a combination of pattern recognizing

  15. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

    Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...

  16. Spray characteristics affected by physical properties of adjuvants

    Four drift adjuvants, Array, In-Place, Vector and Control, were tested and physical properties and spray spectrum parameters measured. Array had the highest conductivity, indicating a good potential for the electrostatic charging, and the highest shear viscosity. All adjuvants had very similar neut...

  17. Protein antigen adsorption to the DDA/TDB liposomal adjuvant

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber; Christensen, Dennis; Foged, Camilla

    2013-01-01

    Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...

  18. Adjuvants in micro- to nanoscale: current state and future direction.

    Gupta, Ankur; Das, Soumen; Schanen, Brian; Seal, Sudipta

    2016-01-01

    Adjuvants have been used in vaccines for over 70 years to promote long-lived and sterilizing immunity. Since then, various adjuvant systems were developed by combining nanotechnology with natural and/or synthetic immunomodulatory molecules. These systems are biocompatible, immunogenic, and possess higher antigen carrying capacity. This article showcases advancements made in the adjuvant systems formulations, their synthesis routes, and the improvement of these adjuvants have brought in response to combat against ongoing global health threats such as malaria, hepatitis C, universal influenza, and human immunodeficiency virus. This review also highlights the interaction of adjuvants with the delivery of antigens to cells and unfolds mechanism of actions. In addition, this review discusses the physicochemical factors responsible for the efficient interaction of nanoadjuvants with antigen receptors to develop more effective, less reactogenic, and multifunctional systems for the next generation vaccines. PMID:26053286

  19. Immune adjuvant activity of the olive, soybean and corn oils

    Ana Claudia Marinho da Silva

    2016-08-01

    Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

  20. Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

    Samantha Sayers

    2012-01-01

    Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

  1. Evaluation of immune response elicited by inulin as an adjuvant with filarial antigens in mice model.

    Mahalakshmi, N; Aparnaa, R; Kaliraj, P

    2014-10-01

    Filariasis caused by infectious parasitic nematodes has been identified as the second leading source of permanent and long-term disability in Sub-Saharan Africa, Asia and Latin America. Several vaccine candidates were identified from infective third-stage larvae (L3) which involves in the critical transition from arthropod to human. Hitherto studies of these antigens in combination with alum adjuvant have shown to elicit its characteristic Th2 responses. Inulin is a safe, non-toxic adjuvant that principally stimulates the innate immune response through the alternative complement pathway. In the present study, the immune response elicited by inulin and alum as adjuvants were compared with filarial antigens from different aetiological agents: secreted larval acidic protein 1 (SLAP1) from Onchocerca volvulus and venom allergen homologue (VAH) from Brugia malayi as single or as cocktail vaccines in mice model. The study revealed that inulin can induce better humoral response against these antigens than alum adjuvant. Antibody isotyping disclosed inulin's ability to elevate the levels of IgG2a and IgG3 antibodies which mediates in complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC), respectively, in mice. Splenocyte analysis showed that T cells prestimulated with inulin have higher stimulation index (P < 0.05) than alum except for BmVAH antigen. In vitro ADCC assay showed that inulin formulation had induced higher cytotoxicity with filarial antigens (as single P < 0.01 and as cocktail P < 0.05, respectively) than alum. The results had confirmed the capability of inulin to deplete the levels of Treg and brought a balance in Th1/Th2 arms against filarial antigens in mice. PMID:25041426

  2. Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant.

    Rady, Hamada F; Dai, Guixiang; Huang, Weitao; Shellito, Judd E; Ramsay, Alistair J

    2016-01-01

    Flagellin has been tested as a protein-based vaccine adjuvant, with the majority of studies focused on antibody responses. Here, we evaluated the adjuvant activity of flagellin for both cellular and humoral immune responses in BALB/c mice in the setting of gene-based immunization, and have made several novel observations. DNA vaccines and adenovirus (Ad) vectors were engineered to encode mycobacterial protein Ag85B, with or without flagellin of Salmonella typhimurium (FliC). DNA-encoded flagellin given IM enhanced splenic CD4+ and CD8+ T cell responses to co-expressed vaccine antigen, including memory responses. Boosting either IM or intranasally with Ad vectors expressing Ag85B without flagellin led to durable enhancement of Ag85B-specific antibody and CD4+ and CD8+ T cell responses in both spleen and pulmonary tissues, correlating with significantly improved protection against challenge with pathogenic aerosolized M. tuberculosis. However, inclusion of flagellin in both DNA prime and Ad booster vaccines induced localized pulmonary inflammation and transient weight loss, with route-dependent effects on vaccine-induced T cell immunity. The latter included marked reductions in levels of mucosal CD4+ and CD8+ T cell responses following IM DNA/IN Ad mucosal prime-boosting, although antibody responses were not diminished. These findings indicate that flagellin has differential and route-dependent adjuvant activity when included as a component of systemic or mucosally-delivered gene-based prime-boost immunization. Clear adjuvant activity for both T and B cell responses was observed when flagellin was included in the DNA priming vaccine, but side effects occurred when given in an Ad boosting vector, particularly via the pulmonary route. PMID:26844553

  3. Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant.

    Hamada F Rady

    Full Text Available Flagellin has been tested as a protein-based vaccine adjuvant, with the majority of studies focused on antibody responses. Here, we evaluated the adjuvant activity of flagellin for both cellular and humoral immune responses in BALB/c mice in the setting of gene-based immunization, and have made several novel observations. DNA vaccines and adenovirus (Ad vectors were engineered to encode mycobacterial protein Ag85B, with or without flagellin of Salmonella typhimurium (FliC. DNA-encoded flagellin given IM enhanced splenic CD4+ and CD8+ T cell responses to co-expressed vaccine antigen, including memory responses. Boosting either IM or intranasally with Ad vectors expressing Ag85B without flagellin led to durable enhancement of Ag85B-specific antibody and CD4+ and CD8+ T cell responses in both spleen and pulmonary tissues, correlating with significantly improved protection against challenge with pathogenic aerosolized M. tuberculosis. However, inclusion of flagellin in both DNA prime and Ad booster vaccines induced localized pulmonary inflammation and transient weight loss, with route-dependent effects on vaccine-induced T cell immunity. The latter included marked reductions in levels of mucosal CD4+ and CD8+ T cell responses following IM DNA/IN Ad mucosal prime-boosting, although antibody responses were not diminished. These findings indicate that flagellin has differential and route-dependent adjuvant activity when included as a component of systemic or mucosally-delivered gene-based prime-boost immunization. Clear adjuvant activity for both T and B cell responses was observed when flagellin was included in the DNA priming vaccine, but side effects occurred when given in an Ad boosting vector, particularly via the pulmonary route.

  4. SU-E-T-558: An Exploratory RF Pulse Sequence Technique Used to Induce Differential Heating in Tissues Containing Iron Oxide Nanoparticles for a Possible Hyperthermic Adjuvant Effect to Radiotherapy

    Yee, S; Ionascu, D; Wilson, G [William Beaumont Hospital, Royal Oak, MI (United States); Thapa, R [Oakland University, Rochester, MI (United States)

    2014-06-01

    Purpose: In pre-clinical trials of cancer thermotherapy, hyperthermia can be induced by exposing localized super-paramagnetic iron oxide nanoparticles (SPION) to external alternating magnetic fields generated by a solenoid electrical circuit (Zhao et al., Theranostics 2012). Alternatively, an RF pulse technique implemented in a regular MRI system is explored as a possible hyperthermia induction technique . Methods: A new thermal RF pulse sequence was developed using the Philips pulse programming tool for the 3T Ingenia MRI system to provide a sinusoidal magnetic field alternating at the frequency of 1.43 kHz (multiples of sine waves of 0.7 ms period) before each excitation RF pulse for imaging. The duration of each thermal RF pulse routine was approximately 3 min, and the thermal pulse was applied multiple times to a phantom that contains different concentrations (high, medium and low) of SPION samples. After applying the thermal pulse each time, the temperature change was estimated by measuring the phase changes in the T1-weighted inversion-prepared multi-shot turbo field echo (TFE) sequence (TR=5.5 ms, TE=2.7 ms, inversion time=200 ms). Results: The phase values and relative differences among them changed as the number of applied thermal RF pulses increased. After the 5th application of the thermal RF pulse, the relative phase differences increased significantly, suggesting the thermal activation of the SPION. The increase of the phase difference was approximately linear with the SPION concentration. Conclusion: A sinusoidal RF pulse from the MRI system may be utilized to selectively thermally activate tissues containing super-paramagnetic iron oxide nanoparticles.

  5. SU-E-T-558: An Exploratory RF Pulse Sequence Technique Used to Induce Differential Heating in Tissues Containing Iron Oxide Nanoparticles for a Possible Hyperthermic Adjuvant Effect to Radiotherapy

    Purpose: In pre-clinical trials of cancer thermotherapy, hyperthermia can be induced by exposing localized super-paramagnetic iron oxide nanoparticles (SPION) to external alternating magnetic fields generated by a solenoid electrical circuit (Zhao et al., Theranostics 2012). Alternatively, an RF pulse technique implemented in a regular MRI system is explored as a possible hyperthermia induction technique . Methods: A new thermal RF pulse sequence was developed using the Philips pulse programming tool for the 3T Ingenia MRI system to provide a sinusoidal magnetic field alternating at the frequency of 1.43 kHz (multiples of sine waves of 0.7 ms period) before each excitation RF pulse for imaging. The duration of each thermal RF pulse routine was approximately 3 min, and the thermal pulse was applied multiple times to a phantom that contains different concentrations (high, medium and low) of SPION samples. After applying the thermal pulse each time, the temperature change was estimated by measuring the phase changes in the T1-weighted inversion-prepared multi-shot turbo field echo (TFE) sequence (TR=5.5 ms, TE=2.7 ms, inversion time=200 ms). Results: The phase values and relative differences among them changed as the number of applied thermal RF pulses increased. After the 5th application of the thermal RF pulse, the relative phase differences increased significantly, suggesting the thermal activation of the SPION. The increase of the phase difference was approximately linear with the SPION concentration. Conclusion: A sinusoidal RF pulse from the MRI system may be utilized to selectively thermally activate tissues containing super-paramagnetic iron oxide nanoparticles

  6. Ranitidine as adjuvant treatment in colorectal cancer

    Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;

    2002-01-01

    BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the...... postoperative infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had...

  7. Quadrantectomy and adjuvant radiotherapy for breast cancer

    The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4,4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted

  8. Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer.

    Verhoeff, S R; van Erning, F N; Lemmens, V E P P; de Wilt, J H W; Pruijt, J F M

    2016-07-01

    Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated. PMID:26914273

  9. Graphene Oxides Decorated with Carnosine as an Adjuvant To Modulate Innate Immune and Improve Adaptive Immunity in Vivo.

    Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang

    2016-02-23

    Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo. PMID:26766427

  10. CpG ODN佐剂对呼吸道合胞病毒重组疫苗诱导的细胞免疫应答的作用%Role of CpG ODN adjuvant in the cellular immune response induced by recombinant vaccine of respiratory syncytial virus

    李娜; 刘建勋; 曾瑞红

    2011-01-01

    Objective :To investigate the role of CpG ODN adjuvant in the cellular immune responses induced by recombinant protein vaccine of respiratory syncytial virus (RSV ) .Methods :BALB /c mice were immunized i .n .or i .p .with G1F/M2+ CpG or G1F/M2+Al+ CpG three times .Spleens from the immunized mice were removed two weeks after the third immunization .Specific lytic activity was assessed using a LDH Cytotoxicity Assay Kit .IFN-γ-and IL-4-secreting cells were quantified using a ELISPOT kit .Percentages of CD4+ /CD8+ effector cells or LDH memory cells in the splenic cells of mice were analyzed with flow cytometer .Results :Immunization with G1F/M2+ CpG i .n .or i .p .induced significant specific lytic activity compared to G1F/M2 .The specific lytic activity induced by G1F/M2+Al+CpG (i .p . ) was significantly higher than that by G1F/M2+CpG (i .p .) .G1F/M2+CpG i .n .or i .p .induced significant more IFn-γ-secreting cells and IL-4secreting cells than G1F/M2 i .n .or i .p .significantly .The level of IFN-γ-secreting cells or IL-4-secreting cells in G1F/M2+Al+CpG (i .p . ) group was higher than that in G1F/M2+CpG (i .p . ) group .In addition ,the level of IFN-γ-secreting cells was remarkably higher than that of IL-4-secreting cells in each group ,suggesting a Th1 biased response ,which benefited for defensing virus .G1F/M2+CpG (i .n . ) induced only CD44+ CD62L - cells .G1F/M2+Al+ CpG (i.p .) or G1F/M2+CpG (i.p .) elicited both CD44+ CD62L- cells and CD44 + CD62L+ cells . Conclusion :CpG2216 ,as an adjuvant ,can enhance significantly the cellular immune responses of RSV recombinant vaccine G1F/M2 .%目的:研究CpG2216佐剂对呼吸道合胞病毒(RSV)重组蛋白疫苗诱导的细胞免疫应答的作用.方法:重组RSV疫苗G1F/M2与CpG2216佐剂混合,或与CpG2216及常规佐剂Al(OH)3混合,鼻腔(i.n.)或腹腔注射(i.p.)免疫BALB/c小鼠三次,最后一次免疫后2周杀小鼠,取脾细胞,用乳酸脱氢酶(LDH)释放法检测脾

  11. Adjuvant radiation for vulvar carcinoma: improved local control

    Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

  12. Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model

    Villarreal, Daniel O.; Svoronos, Nikos; Wise, Megan C.; Shedlock, Devon J.; Morrow, Matthew P.; Garcia, Jose-Conejo; Weiner, David B.

    2015-01-01

    Identifying new molecular adjuvants that elicit effective vaccine-induced CD8+ T cell immunity may be critical for the elimination of many challenging diseases including Tuberculosis, HIV and cancer. Here, we report that co-administration of molecular adjuvant IL-33 during vaccination enhanced the magnitude and function of antigen (Ag)-specific CD8+ T cells against a model Ag, LCMV NP target protein. These enhanced responses were characterized by higher frequencies of Ag-specific, polyfunctional CD8+ T cells exhibiting cytotoxic characteristics. Importantly, these cells were capable of robust expansion upon Ag-specific restimulation in vivo and conferred remarkable protection against a high dose lethal LCMV challenge. In addition, we demonstrate the ability of IL-33 to amplifying the frequency of Ag-specific KLRG1+ effector CD8+ T cells. These data show that IL-33 is a promising immunoadjuvant at improving T cell immunity in a vaccine setting and suggest further development and understanding of this molecular adjuvant for strategies against many obstinate infectious diseases and cancer. PMID:25887087

  13. Bacillus subtilis spores as vaccine adjuvants: further insights into the mechanisms of action.

    Renata Damásio de Souza

    Full Text Available Bacillus subtilis spores have received growing attention regarding potential biotechnological applications, including the use as probiotics and in vaccine formulations. B. subtilis spores have also been shown to behave as particulate vaccine adjuvants, promoting the increase of antibody responses after co-administration with antigens either admixed or adsorbed on the spore surface. In this study, we further evaluated the immune modulatory properties of B. subtilis spores using a recombinant HIV gag p24 protein as a model antigen. The adjuvant effects of B. subtilis spores were not affected by the genetic background of the mouse lineage and did not induce significant inflammatory or deleterious effects after parenteral administration. Our results demonstrated that co-administration, but not adsorption to the spore surface, enhanced the immunogenicity of that target antigen after subcutaneous administration to BALB/c and C57BL/6 mice. Spores promoted activation of antigen presenting cells as demonstrated by the upregulation of MHC and CD40 molecules and enhanced secretion of pro-inflammatory cytokines by murine dendritic cells. In addition, in vivo studies indicated a direct role of the innate immunity on the immunomodulatory properties of B. subtilis spores, as demonstrated by the lack of adjuvant effects on MyD88 and TLR2 knockout mouse strains.

  14. Mutants of Escherichia coli heat-labile enterotoxin and cholera toxin as mucosal adjuvants

    FENG Qiang; CAI Shaoxi; ZOU Quanming

    2003-01-01

    Mucosal vaccination has been getting more and more recognition because of its compliance and low risk of spreading infectious disease by contaminated syringes used in subcutaneous immunization. However, most vaccines are unable to induce immune responses when given mucosally, and require the use of strong adjuvant for effective delivery systems. Heat-labile enterotoxin (LT) and Cholera toxin(CT) are powerful mucosal adjuvants when co-administered with soluble antigens. But high toxicity hampers their use in humans. Thanks to the fine knowledge of the structure-function relationship of LT and CT, many nontoxic or low toxic mutants have been generated, part of them retain high adjuvanticity of mucosal immunization. Among these mutants, LTS63K, LTA72R, LTR192G and CTE29H, CTE112K have been widely investigated. LTS63K and CTE112K are fully non toxic, whereas LTA72R and CTE29H are low toxic, and LTR192G is nontoxic in vitro(it remains the same toxicity as wild type LT in vivo). These mutants are extremely active as mucosal adjuvants when co-administrated with a variety of antigens in different animal models. They will be investigated more widely and deeply in the future. Some of them will be tested soon in human bodies.

  15. Molecular adjuvant IL-33 enhances the potency of a DNA vaccine in a lethal challenge model.

    Villarreal, Daniel O; Svoronos, Nikolaos; Wise, Megan C; Shedlock, Devon J; Morrow, Matthew P; Conejo-Garcia, Jose R; Weiner, David B

    2015-08-20

    Identifying new molecular adjuvants that elicit effective vaccine-induced CD8(+) T cell immunity may be critical for the elimination of many challenging diseases including Tuberculosis, HIV and cancer. Here, we report that co-administration of molecular adjuvant IL-33 during vaccination enhanced the magnitude and function of antigen (Ag)-specific CD8(+) T cells against a model Ag, LCMV NP target protein. These enhanced responses were characterized by higher frequencies of Ag-specific, polyfunctional CD8(+) T cells exhibiting cytotoxic characteristics. Importantly, these cells were capable of robust expansion upon Ag-specific restimulation in vivo and conferred remarkable protection against a high dose lethal LCMV challenge. In addition, we demonstrate the ability of IL-33 to amplifying the frequency of Ag-specific KLRG1(+) effector CD8(+) T cells. These data show that IL-33 is a promising immunoadjuvant at improving T cell immunity in a vaccine setting and suggest further development and understanding of this molecular adjuvant for strategies against many obstinate infectious diseases and cancer. PMID:25887087

  16. Xanthan Gum as an Adjuvant in a Subunit Vaccine Preparation against Leptospirosis

    Katia L. Bacelo

    2014-01-01

    Full Text Available Leptospiral immunoglobulin-like (Lig proteins are of great interest due to their ability to act as mediators of pathogenesis, serodiagnostic antigens, and immunogens. Purified recombinant LigA protein is the most promising subunit vaccine candidate against leptospirosis reported to date, however, as purified proteins are weak immunogens the use of a potent adjuvant is essential for the success of LigA as a subunit vaccine. In the present study, we compared xanthan pv. pruni (strain 106, aluminium hydroxide (alhydrogel, and CpG ODN as adjuvants in a LigA subunit vaccine preparation. Xanthan gum is a high molecular weight extracellular polysaccharide produced by fermentation of Xanthomonas spp., a plant-pathogenic bacterium genus. Preparations containing xanthan induced a strong antibody response comparable to that observed when alhydrogel was used. Upon challenge with a virulent strain of L. interrogans serovar Copenhageni, significant protection (Fisher test, P<0.05 was observed in 100%, 100%, and 67% of hamsters immunized with rLigANI-xanthan, LigA-CpG-xanthan, and rLigANI-alhydrogel, respectively. Furthermore, xanthan did not cause cytotoxicity in Chinese hamster ovary (CHO cells in vitro. The use of xanthan as an adjuvant is a novel alternative for enhancing the immunogenicity of vaccines against leptospirosis and possibly against other pathogens.

  17. Computers and Qualitative Research.

    Willis, Jerry; Jost, Muktha

    1999-01-01

    Discusses the use of computers in qualitative research, including sources of information; collaboration; electronic discussion groups; Web sites; Internet search engines; electronic sources of data; data collection; communicating research results; desktop publishing; hypermedia and multimedia documents; electronic publishing; holistic and…

  18. Adjuvant Strategies for Resectable Pancreatic Cancer: Have We Made Progress?

    Suzanne Russo

    2012-03-01

    Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.

  19. Adjuvant chemotherapy in early breast cancer.

    Ejlertsen, Bent

    2016-05-01

    these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS

  20. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    Mentha Gilles

    2011-06-01

    Full Text Available Abstract Background Extrahepatic biliary duct cancers (EBDC are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT in a series of patients treated in one institution. Methods Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma received 3D conformal external beam RT to a median total dose of 50.4Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%. Surgical margins were negative in 11 patients (48%, narrow in 2 (9%, and microscopically involved in 8 (35%. Eleven patients (55% had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98. Results Acute gastrointestinal grade 2 toxicity (RTOG scale was recorded in 2 patients (9%. Nausea or vomiting grade 1 and 2 was observed in 8 (35% and 2 patients (9% respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung. No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p = 0.04. The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p = 0.07. Conclusions Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor

  1. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p = 0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p = 0.07). Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location

  2. Qualitative research for international business

    Yves Doz

    2011-01-01

    Qualitative research in international business has been rare, the main research streams of the field relying more on quantitative methods. This paper first outlines why qualitative research has been scant. It then presents areas, such as theory building, where qualitative research could make a substantial contribution. Third, it reviews approaches to high standards of qualitative research and criteria for evaluating qualitative research. Finally, some possible research areas where qualitative...

  3. The differential expression of alternatively polyadenylated transcripts is a common stress-induced response mechanism that modulates mammalian mRNA expression in a quantitative and qualitative fashion.

    Hollerer, Ina; Curk, Tomaz; Haase, Bettina; Benes, Vladimir; Hauer, Christian; Neu-Yilik, Gabriele; Bhuvanagiri, Madhuri; Hentze, Matthias W; Kulozik, Andreas E

    2016-09-01

    Stress adaptation plays a pivotal role in biological processes and requires tight regulation of gene expression. In this study, we explored the effect of cellular stress on mRNA polyadenylation and investigated the implications of regulated polyadenylation site usage on mammalian gene expression. High-confidence polyadenylation site mapping combined with global pre-mRNA and mRNA expression profiling revealed that stress induces an accumulation of genes with differentially expressed polyadenylated mRNA isoforms in human cells. Specifically, stress provokes a global trend in polyadenylation site usage toward decreased utilization of promoter-proximal poly(A) sites in introns or ORFs and increased utilization of promoter-distal polyadenylation sites in intergenic regions. This extensively affects gene expression beyond regulating mRNA abundance by changing mRNA length and by altering the configuration of open reading frames. Our study highlights the impact of post-transcriptional mechanisms on stress-dependent gene regulation and reveals the differential expression of alternatively polyadenylated transcripts as a common stress-induced mechanism in mammalian cells. PMID:27407180

  4. Cognitive function after adjuvant treatment for early breast cancer

    Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer;

    2010-01-01

    start of adjuvant treatment and after 6 months by neuropsychological tests and questionnaires to evaluate cognitive function, quality of life and psychological distress. Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and......The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged <60 years who received adjuvant...... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...

  5. Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions

    Russell, L.B.

    1982-01-01

    Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences. (ERB)

  6. Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions

    Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences

  7. Advances in aluminum hydroxide-based adjuvant research and its mechanism

    He, Peng; Zou, Yening; Hu, Zhongyu

    2015-01-01

    In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully und...

  8. Second malignancies after breast cancer: The impact of adjuvant therapy

    Dong, Chunhui; Chen, Ling

    2014-01-01

    Second malignant neoplasms (SMNs) are potentially life-threatening late sequelae of the adjuvant therapy for breast cancer (BC). The increased risk of SMNs is associated with adjuvant chemotherapy (development of secondary acute myeloid leukemia and myelodysplastic syndrome) and hormonal therapy (risk of uterine cancer secondary to tamoxifen treatment). Previous studies have demonstrated an increased risk of SMNs associated with alkylating agents, topoisomerase-II inhibitors, granulocyte-stim...

  9. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle;

    2013-01-01

    The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

  10. Patient adherence to aromatase inhibitor treatment in the adjuvant setting

    Verma, S.; Madarnas, Y.; Sehdev, S.; Martin, G; Bajcar, J.

    2011-01-01

    Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider–related. To date, there is a gap in the literature concerning a comprehensive...

  11. Qualitative Robustness in Estimation

    Mohammed Nasser

    2012-07-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman","serif";} Qualitative robustness, influence function, and breakdown point are three main concepts to judge an estimator from the viewpoint of robust estimation. It is important as well as interesting to study relation among them. This article attempts to present the concept of qualitative robustness as forwarded by first proponents and its later development. It illustrates intricacies of qualitative robustness and its relation with consistency, and also tries to remove commonly believed misunderstandings about relation between influence function and qualitative robustness citing some examples from literature and providing a new counter-example. At the end it places a useful finite and a simulated version of   qualitative robustness index (QRI. In order to assess the performance of the proposed measures, we have compared fifteen estimators of correlation coefficient using simulated as well as real data sets.

  12. Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

    Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

  13. Chitosan-based mucosal adjuvants: Sunrise on the ocean.

    Xia, Yufei; Fan, Qingze; Hao, Dongxia; Wu, Jie; Ma, Guanghui; Su, Zhiguo

    2015-11-01

    Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant. PMID:26271831

  14. CpG adjuvant enhances the mucosal immunogenicity and efficacy of a Treponema pallidum DNA vaccine in rabbits

    Zhao, Feijun; Liu, Shuangquan; Zhang, Xiaohong; Yu, Jian; Zeng, Tiebing; Gu, Weiming; Cao, Xunyu; Chen, Xi; Wu, Yimou

    2013-01-01

    Objectives: The protective response against Treponema pallidum (Tp) infection of a DNA vaccine enhanced by an adjuvant CpG ODN was investigated. Results: The mucosal adjuvant CpG ODN enhanced the production of higher levels of anti-TpGpd antibodies induced by pcD/Gpd-IL-2 in rabbits. It also resulted in higher levels of secretion of IL-2 and IFN-γ, and facilitated T cell proliferation and differentiation (p 0.05). Furthermore, CpG ODN stimulated the production of mucosa-specific anti-sIgA antibodies and resulted in the lowest Tp-positive rate (6.7%) for Tp-infection of skin lesions and the lowest rates (8.3%) of ulceration lesions, thus achieving better protective effects. Methods: New Zealand rabbits were immunized with the eukaryotic vector encoding recombinant pcD/Gpd-IL-2 using intramuscular multi-injection or together with mucosal enhancement via a nasal route. The effect of the mucosal adjuvant CpG ODN was examined. Conclusions:The CpG ODN adjuvant significantly enhances the humoral and cellular immune effects of the immunization by pcD/Gpd-IL-2 with mucosal enhancement via nasal route. It also stimulates strong mucosal immune effects, thus initiating more efficient immune-protective effects. PMID:23563515

  15. Adjuvant requirement for successful immunization with recombinant derivatives of Plasmodium vivax merozoite surface protein-1 delivered via the intranasal route

    Daniel Y Bargieri

    2007-06-01

    Full Text Available Recently, we generated two bacterial recombinant proteins expressing 89 amino acids of the C-terminal domain of the Plasmodium vivax merozoite surface protein-1 and the hexa-histidine tag (His6MSP1(19. One of these recombinant proteins contained also the amino acid sequence of the universal pan allelic T-cell epitope (His6MSP1(19-PADRE. In the present study, we evaluated the immunogenic properties of these antigens when administered via the intra-nasal route in the presence of distinct adjuvant formulations. We found that C57BL/6 mice immunized with either recombinant proteins in the presence of the adjuvants cholera toxin (CT or the Escherichia coli heat labile toxin (LT developed high and long lasting titers of specific serum antibodies. The induced immune responses reached maximum levels after three immunizing doses with a prevailing IgG1 subclass response. In contrast, mice immunized by intranasal route with His6MSP1(19-PADRE in the presence of the synthetic oligonucleotides adjuvant CpG ODN 1826 developed lower antibody titers but when combined to CT, CpG addition resulted in enhanced IgG responses characterized by lower IgG1 levels. Considering the limitations of antigens formulations that can be used in humans, mucosal adjuvants can be a reliable alternative for the development of new strategies of immunization using recombinant proteins of P. vivax.

  16. Qualitative analysis of black stone and its application for detecting Ag and Pb in liquid sample by laser-induced breakdown spectroscopy (LIBS)

    Suyanto, Hery

    2016-03-01

    The aim of this research is to characterize black stone and also to know the capability to adsorb Ag and Pb elements in solution. All analysis in this research used laser-induced breakdown spectroscopy (commercial LIBS) method with laser energy of 120 mJ, accumulation 4, gate delay 1 µs and air surrounding gas at 1 atmosphere. Before soaked in 20 ml solution containing Ag and Pb of 40 ppm in 1 hour, the stone was analyzed by LIBS and it contains the main elements such as Ca, Mn, Si, K, Fe, Mg, Mo, H, O and Na until 16 laser shots. However, after immersed in solution, the stone contains impurities Ag and Pb elements with signal to noise ratio (SNR) of 9.5 and 1.2 respectively. Based on this data, the stone is predicted to be able to adsorb Ag element in solution till 12.7 ppm. The data also show that Ag element was adsorbed homogenously by stone till 16th laser shots, although it was washed with flowing demineralized water before it was analyzed.

  17. Impact of adjuvants on CD4(+) T cell and B cell responses to a protein antigen vaccine: Results from a phase II, randomized, multicenter trial.

    Leroux-Roels, Geert; Marchant, Arnaud; Levy, Jack; Van Damme, Pierre; Schwarz, Tino F; Horsmans, Yves; Jilg, Wolfgang; Kremsner, Peter G; Haelterman, Edwige; Clément, Frédéric; Gabor, Julian J; Esen, Meral; Hens, Annick; Carletti, Isabelle; Fissette, Laurence; Tavares Da Silva, Fernanda; Burny, Wivine; Janssens, Michel; Moris, Philippe; Didierlaurent, Arnaud M; Van Der Most, Robbert; Garçon, Nathalie; Van Belle, Pascale; Van Mechelen, Marcelle

    2016-08-01

    Immunogenicity and safety of different adjuvants combined with a model antigen (HBsAg) were compared. Healthy HBV-naïve adults were randomized to receive HBs adjuvanted with alum or Adjuvant Systems AS01B, AS01E, AS03A or AS04 at Days 0 and 30. Different frequencies of HBs-specific CD4+ T cells 14days post dose 2 but similar polyfunctionality profiles were induced by the different adjuvants with frequencies significantly higher in the AS01B and AS01E groups than in the other groups. Antibody concentrations 30days post-dose 2 were significantly higher in AS01B, AS01E and AS03A than in other groups. Limited correlations were observed between HBs-specific CD4+ T cell and antibody responses. Injection site pain was the most common solicited local symptom and was more frequent in AS groups than in alum group. Different adjuvants formulated with the same antigen induced different adaptive immune responses and reactogenicity patterns in healthy naïve adults. The results summary for this study (GSK study number 112115 - NCT# NCT00805389) is available on the GSK Clinical Study Register and can be accessed at www.gsk-clinicalstudyregister.com. PMID:27236001

  18. The potential of adjuvants to improve immune responses against TdaP vaccines: A preclinical evaluation of MF59 and monophosphoryl lipid A.

    Agnolon, Valentina; Bruno, Cristina; Leuzzi, Rosanna; Galletti, Bruno; D'Oro, Ugo; Pizza, Mariagrazia; Seubert, Anja; O'Hagan, Derek T; Baudner, Barbara C

    2015-08-15

    The successful approach of combining diphtheria, tetanus and pertussis antigens into a single vaccine has become a cornerstone of immunization programs. Yet, even if vaccination coverage is high, a resurgence of pertussis has been reported in many countries suggesting current vaccines may not provide adequate protection. To induce better tailored and more durable immune responses against pertussis vaccines different approaches have been proposed, including the use of novel adjuvants. Licensed aP vaccines contain aluminum salts, which mainly stimulate humoral immune responses and might not be ideal for protecting against Bordetella pertussis infection. Adjuvants inducing more balanced T-helper profiles or even Th1-prone responses might be more adequate. In this study, two adjuvants already approved for human use have been tested: MF59 emulsion and the combination of aluminum hydroxide with the Toll-Like Receptor 4 agonist MPLA. Adjuvanticity was evaluated in a mouse model using a TdaP vaccine containing three B. pertussis antigens: genetically detoxified pertussis toxin (PT-9K/129G), filamentous hemagglutinin (FHA) and pertactin (PRN) The physico-chemical compatibility of TdaP antigens with the proposed adjuvants, together with a quicker onset and changed quality of the antibody responses, fully supports the replacement of aluminum salts with a new adjuvant to enhance aP vaccines immunogenicity. PMID:26149936

  19. Qualitative and quantitative spectro-chemical analysis of dates using UV-pulsed laser induced breakdown spectroscopy and inductively coupled plasma mass spectrometry.

    Mehder, A O; Habibullah, Y B; Gondal, M A; Baig, Umair

    2016-08-01

    Laser Induced Breakdown Spectroscopy (LIBS) is demonstrated for the spectral analysis of nutritional and toxic elements present in several varieties of date fruit samples available in the Saudi Arabia market. The method analyzes the optical emission of a test sample when subjected to pulsed laser ablation. In this demonstration, our primary focus is on calcium (Ca) and magnesium (Mg), as nutritional elements, and on chromium (Cr), as a toxic element. The local thermodynamic equilibrium (LTE) condition was confirmed prior to the elemental characterization of date samples to ensure accuracy of the LIBS analysis. This was achieved by measuring parameters associated with the plasma, such as the electron temperature and the electron number density. These plasma parameters aid interpretation of processes such as ionization, dissociation, and excitation occurring in the plasma plume formed by ablating the date palm sample. The minimum detection limit was established from calibration curves that involved plotting the LIBS signal intensity as a function of standard date samples with known concentrations. The concentration of Ca and Mg detected in different varieties of date samples was between 187 and 515 and 35-196mgL(-1) respectively, while Cr concentration measured between 1.72 and 7.76mgL(-1). In order to optimize our LIBS system, we have studied how the LIBS signal intensity depends on the incident laser energy and the delay time. In order to validate our LIBS analysis results, standard techniques such as inductively coupled plasma mass spectrometry (ICP-MS) were also applied on an identical (duplicate) date samples as those used for the LIBS analysis. The LIBS results exhibit remarkable agreement with those obtained from the ICP-MS analysis. In addition, the finger print wavelengths of other elements present in date samples were also identified and are reported here, which has not been previously reported, to the best of our knowledge. PMID:27216665

  20. Qualitative Assertions as Prescriptive Statements

    Nolen, Amanda; Talbert, Tony

    2011-01-01

    The primary question regarding prescriptive appropriateness is a difficult one to answer for the qualitative researcher. While there are certainly qualitative researchers who have offered prescriptive protocols to better define and describe the terrain of qualitative research design and there are qualitative researchers who offer research…

  1. No adjuvant effect of Bacillus thuringiensis-maize on allergic responses in mice.

    Daniela Reiner

    Full Text Available Genetically modified (GM foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt-maize (MON810 on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma.

  2. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  3. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel ('nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination. PMID:20562880

  4. Histomorphometric and Microbiological Assessment of Photodynamic Therapy as an Adjuvant Treatment for Periodontitis: A Short-Term Evaluation of Inflammatory Periodontal Conditions and Bacterial Reduction in a Rat Model

    Prates, Renato A.; Yamada, Aécio M.; Suzuki, Luis C.; Cristiane M. França; Cai, Silvana; Mayer, Márcia P.A.; Ribeiro, Adriana C.; Martha S. Ribeiro

    2011-01-01

    Objective: The aim of this study was to investigate the short-term effects of photodynamic therapy (PDT) in periodontal tissue when it is used as an adjuvant treatment for periodontitis. Background data: PDT has been used as an adjuvant in the combat of local infections, such as periodontitis, and combines a photosensitizer (PS) with a light source to induce reactive oxygen species (ROS) and kill microbial cells. Methods: Fifty healthy male rats were used in this study. Periodontitis was indu...

  5. Risk of endocrine pancreatic insufficiency in patients receiving adjuvant chemoradiation for resected gastric cancer

    Background: Adjuvant radiotherapy combined with 5-fluorouracil based chemotherapy has become the new standard after curative resection in high risk gastric cancer. Beside many complications due to surgery, the addition of chemotherapy and radiotherapy as adjuvant treatment may lead to both acute and late toxicities. Pancreatic tissue irradiation during this adjuvant treatment because of incidental and unavoidable inclusion of the organ within the radiation field may affect exocrine and endocrine functions of the organ. Materials and methods: Fifty-three patients with gastric adenocarcinoma were evaluated for adjuvant chemoradiotherapy after surgery. While 37 out of 53 patients were treated postoperatively due to either serosal or adjacent organ or lymph node involvement, 16 patients without these risk factors were followed up regularly without any additional treatment and they served as the control group. Fasting blood glucose (FBG), hemoglobin A1c (HBA1c), insulin and C-peptide levels were measured in the control and study groups after the surgery and 6 months and 1 year later. Results: At the baseline there was no difference in FBG, HbA1c, C-peptide and insulin levels between the control and the study groups. At the end of the study there was a statistically significant decline in insulin and C-peptide levels in the study group, (7.5 ± 6.0 vs 4.5 ± 4.4 IU/L, p: 0.002 and 2.3 ± 0.9 vs 1.56 ± 0.9 ng/ml, p: 0.001) respectively. Conclusions: Adjuvant radiotherapy in gastric cancer leads to a decrease in beta cell function and insulin secretion capacity of the pancreas with possible diabetes risk. Radiation-induced pancreatic injury and late effects of radiation on normal pancreatic tissue are unknown, but pancreas is more sensitive to radiation than known. This organ should be studied extensively in order to determine the tolerance doses and it should be contoured during abdominal radiotherapy planning as an organ at risk

  6. Development of enhanced antibody response toward dual delivery of nano-adjuvant adsorbed human Enterovirus-71 vaccine encapsulated carrier.

    Saeed, Mohamed I; Omar, Abdul Rahman; Hussein, Mohd Z; Elkhidir, Isam M; Sekawi, Zamberi

    2015-01-01

    This study introduces a new approach for enhancing immunity toward mucosal vaccines. HEV71 killed vaccine that is formulated with nanosize calcium phosphate adjuvant and encapsulated onto chitosan and alginate delivery carriers was examined for eliciting antibody responses in serum and saliva collected at weeks 0, 1, 3, 5, 7 and 9 for viral-specific IgA & IgG levels and viral neutralizing antibody titers. The antibody responses induced in rabbits by the different formulations delivered by a single (buccal) route were compared to those of dual immunization (intradermal / mucosal) and un-immunized control. Chitosan-loaded vaccine adjuvant induced elevated IgA antibody, while Alginate-adjuvant irreversible bonding sequestered the vaccine and markedly reduced immunogenicity. The induced mucosal and parenteral antibody profiles appeared in an inverse manner of enhanced mucosal IgA antibody accompanied by lower systemic IgG following a single oral immunization route. The combined intradermal and oral dual-immunized group developed an elevated salivary IgA, systemic IgG, and virus neutralizing response. A reduced salivary neutralizing antibody titer was observed and attributed to the continual secretion exchanges in saliva. Designing a successful mucosal delivery formulation needs to take into account the vaccine delivery site, dosage, adjuvant and carrier particle size, charge, and the reversibility of component interactions. The dual immunization seems superior and is a important approach for modulating the antibody response and boosting mucosal protection against HEV71 and similar pathogens based on their transmission mode, tissue tropism and shedding sites. Finally, the study has highlighted the significant role of dual immunization for simultaneous inducing and modulating the systemic and mucosal immune responses to EV71. PMID:26186664

  7. Demystifying Interdisciplinary Qualitative Research

    Greckhamer, Thomas; Koro-Ljungberg, Mirka; Cilesiz, Sebnem; Hayes, Sharon

    2008-01-01

    This article seeks to demystify, through deconstruction, the concept of "interdisciplinarity" in the context of qualitative research to contribute to a new praxis of knowledge production through reflection on the possibilities and impossibilities of interdisciplinarity. A review and discussion of disciplinarity and interdisciplinarity leads the…

  8. Disciplining Qualitative Research

    Denzin, Norman K.; Lincoln, Yvonna S.; Giardina, Michael D.

    2006-01-01

    Qualitative research exists in a time of global uncertainty. Around the world, governments are attempting to regulate scientific inquiry by defining what counts as "good" science. These regulatory activities raise fundamental, philosophical epistemological, political and pedagogical issues for scholarship and freedom of speech in the academy. This…

  9. The Qualitative Similarity Hypothesis

    Paul, Peter V.; Lee, Chongmin

    2010-01-01

    Evidence is presented for the qualitative similarity hypothesis (QSH) with respect to children and adolescents who are d/Deaf or hard of hearing. The primary focus is on the development of English language and literacy skills, and some information is provided on the acquisition of English as a second language. The QSH is briefly discussed within…

  10. Functionalized graphene oxide serves as a novel vaccine nano-adjuvant for robust stimulation of cellular immunity

    Xu, Ligeng; Xiang, Jian; Liu, Ye; Xu, Jun; Luo, Yinchan; Feng, Liangzhu; Liu, Zhuang; Peng, Rui

    2016-02-01

    Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual-polymer modified GOs (GO-PEG-PEI) can act as a positive modulator to promote the maturation of dendritic cells (DCs) and enhance their cytokine secretion through the activation of multiple toll-like receptor (TLR) pathways while showing low toxicity. Moreover, this GO-PEG-PEI can serve as an antigen carrier to effectively shuttle antigens into DCs. These two advantages enable GO-PEG-PEI to serve as a novel vaccine adjuvant. In the subsequent in vivo experiments, compared with free Ure B and clinically used aluminum-adjuvant-based vaccine (Alum-Ure B), GO-PEG-PEI-Ure B induces stronger cellular immunity via intradermal administration, suggesting promising applications in cancer immunotherapy. Our work not only presents a novel, highly effective GO-based vaccine nano-adjuvant, but also highlights the critical roles of surface chemistry for the rational design of nano-adjuvants.Benefiting from their unique physicochemical properties, graphene derivatives have attracted great attention in biomedicine. In this study, we carefully engineered graphene oxide (GO) as a vaccine adjuvant for immunotherapy using urease B (Ure B) as the model antigen. Ure B is a specific antigen for Helicobacter pylori, which is a class I carcinogen for gastric cancer. Polyethylene glycol (PEG) and various types of polyethylenimine (PEI) were used as coating polymers. Compared with single-polymer modified GOs (GO-PEG and GO-PEI), certain dual

  11. Topical CpG Oligodeoxynucleotide Adjuvant Enhances the Adaptive Immune Response against Influenza A Infections.

    Cheng, Wing Ki; Plumb, Adam William; Lai, Jacqueline Cheuk-Yan; Abraham, Ninan; Dutz, Jan Peter

    2016-01-01

    Current influenza vaccines generate humoral immunity, targeting highly variable epitopes and thus fail to achieve long-term protection. T cells recognize and respond to several highly conserved epitopes across influenza serotypes. A strategy of raising strong cytotoxic T cell memory responses to epitopes conserved across serotypes would provide cross serotype protection, eliminating the need for annual vaccination. We explored the adjuvant potential of epicutaneous (ec) and subcutaneous (sc) delivery of CpG oligodeoxynucleotide in conjunction with sc protein immunization to improve protection against influenza A virus (IAV) infections using a mouse model. We found enhanced long-term protection with epicutaneous CpG ODN (ecCpG) compared to subcutaneous CpG ODN (scCpG) as demonstrated by reduced viral titers in the lungs. This correlated with increased antigen-specific CD8 T cells in the airways and the lungs. The memory T cell response after immunization with ecCpG adjuvant was comparable to memory response by priming with IAV infection in the lungs. In addition, ecCpG was more efficient than scCpG in inducing the generation of IFN-γ producing CD4 T cells. The adjuvant effect of ecCpG was accompanied with its ability to modulate tissue-homing molecules on T cells that may direct them to the site of infection. Together, this work provides evidence for using ecCpG to induce strong antibody and memory T cell responses to confer protection against IAV infection. PMID:27524984

  12. Adjuvant-enhanced antibody and cellular responses to inclusion bodies expressing FhSAP2 correlates with protection of mice to Fasciola hepatica.

    Rivera, Francheska; Espino, Ana M

    2016-01-01

    Fasciola hepatica saposin-like protein-2 (FhSAP2) is a protein differentially expressed in various developmental stages of F. hepatica. Recombinant FhSAP2 has demonstrated the induction of partial protection in mice and rabbits when it is administered subcutaneously (SC) in Freund's adjuvant. Because FhSAP2 is overexpressed in bacteria in the form of inclusion bodies (IBs), we isolated IBs expressing FhSAP2 and tested their immunogenicity when administered SC in mice emulsified in two different adjuvants: QS-21 and Montanide TM ISA720. Animals received three injections containing 20 μg of protein two weeks apart and 4 weeks after the third injection, mice were infected with 10 F. hepatica metacercariae by oral route. The percentages of protection induced by FhSAP2-IBs were estimated to be between 60.0 and 62.5% when compared with adjuvant-vaccinated, infected controls. By determining the levels of IgG1 and IgG2a antibodies and IL-4 and IFNγ cytokines in the serum of experimental animals, it was found that both Th1 and Th2 immune responses were significantly increased in the FhSAP2-IBs vaccinated groups compared with the adjuvant-vaccinated, infected control groups. The adjuvant-vaccinated groups had significantly lower IgG1 to IgG2a ratios and lower IL-4 to IFNγ ratios than the FhSAP2-IBs vaccinated animals, which is indicative of higher levels of Th2 immune responses. Irrespective to the adjuvant used, animals vaccinated with FhSAP2-IBs exhibited significantly higher survival percentage and less liver damage than the adjuvant-control groups. This study suggests that FhSAP2 has potential as vaccine against F. hepatica and that the protection elicited by this molecule could be linked to a mechanism driven by the CD4-Th1 cells. PMID:26632503

  13. The adjuvant activity of alphavirus replicons is enhanced by incorporating the microbial molecule flagellin into the replicon.

    Maria L Knudsen

    Full Text Available Ligands of pattern recognition receptors (PRRs including Toll-like receptors (TLRs stimulate innate and adaptive immune responses and are considered as potent adjuvants. Combinations of ligands might act in synergy to induce stronger and broader immune responses compared to stand-alone ligands. Alphaviruses stimulate endosomal TLRs 3, 7 and 8 as well as the cytoplasmic PRR MDA-5, resulting in induction of a strong type I interferon (IFN response. Bacterial flagellin stimulates TLR5 and when delivered intracellularly the cytosolic PRR NLRC4, leading to secretion of proinflammatory cytokines. Both alphaviruses and flagellin have independently been shown to act as adjuvants for antigen-specific antibody responses. Here, we hypothesized that alphavirus and flagellin would act in synergy when combined. We therefore cloned the Salmonella Typhimurium flagellin (FliC gene into an alphavirus replicon and assessed its adjuvant activity on the antibody response against co-administered antigen. In mice immunized with recombinant alphavirus, antibody responses were greatly enhanced compared to soluble FliC or control alphavirus. Both IgG1 and IgG2a/c responses were increased, indicating an enhancement of both Th1 and Th2 type responses. The adjuvant activity of FliC-expressing alphavirus was diminished but not abolished in the absence of TLR5 or type I IFN signaling, suggesting the contribution of several signaling pathways and some synergistic and redundant activity of its components. Thus, we have created a recombinant adjuvant that stimulates multiple signaling pathways of innate immunity resulting in a strong and broad antibody response.

  14. Role of Adjuvant Chemoradiotherapy for Resected Extrahepatic Biliary Tract Cancer

    Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. Methods and Materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p = .007; 32.1% vs. 26.1%, p = .041; 36.5% vs. 28.2%, p = .049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p < .05). Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.

  15. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines. PMID:24434331

  16. Who benefits most from adjuvant interferon treatment for melanoma?

    Gogas, Helen; Abali, Huseyin; Ascierto, Paolo A; Demidov, Lev; Pehamberger, Hubert; Robert, Caroline; Schachter, Jacob; Eggermont, Alexander M M; Hauschild, Axel; Espinosa, Enrique

    2015-01-01

    Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-α provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-α adjuvant therapy. Interferon-α is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed. PMID:24176884

  17. Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice

    Wu, Bing; Zou, Qiang; Hu, Yanxin; Wang, Bin

    2013-01-01

    Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we d...

  18. Activation of human antigen-presenting cells by the mycobacterial cord factor and its glycolipid adjuvant analogue trehalose-6,6’-dibehenate

    Ostrop, Jenny

    2015-01-01

    The mycobacterial cord factor trehalose-6,6’-dimycolate (TDM) is an abundant cell wall glycolipid of Mycobacterium tuberculosis and other mycobacteria. It causes inflammation and adjuvanticity, but it is also a major virulence factor of M. tuberculosis. Its synthetic analogue trehalose-6,6’-dibehenate (TDB) has robust adjuvant activity and induces a Th1/Th17 T cell response in animal models. The TDB-containing liposomal adjuvant formulation Caf01 has entered phase I clinical studies in humans...

  19. Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition.

    Vaccari, Monica; Gordon, Shari N; Fourati, Slim; Schifanella, Luca; Liyanage, Namal P M; Cameron, Mark; Keele, Brandon F; Shen, Xiaoying; Tomaras, Georgia D; Billings, Erik; Rao, Mangala; Chung, Amy W; Dowell, Karen G; Bailey-Kellogg, Chris; Brown, Eric P; Ackerman, Margaret E; Vargas-Inchaustegui, Diego A; Whitney, Stephen; Doster, Melvin N; Binello, Nicolo; Pegu, Poonam; Montefiori, David C; Foulds, Kathryn; Quinn, David S; Donaldson, Mitzi; Liang, Frank; Loré, Karin; Roederer, Mario; Koup, Richard A; McDermott, Adrian; Ma, Zhong-Min; Miller, Christopher J; Phan, Tran B; Forthal, Donald N; Blackburn, Matthew; Caccuri, Francesca; Bissa, Massimiliano; Ferrari, Guido; Kalyanaraman, Vaniambadi; Ferrari, Maria G; Thompson, DeVon; Robert-Guroff, Marjorie; Ratto-Kim, Silvia; Kim, Jerome H; Michael, Nelson L; Phogat, Sanjay; Barnett, Susan W; Tartaglia, Jim; Venzon, David; Stablein, Donald M; Alter, Galit; Sekaly, Rafick-Pierre; Franchini, Genoveffa

    2016-07-01

    A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies. PMID:27239761

  20. QSMSR QUALITATIVE MODEL

    Tahir Abdullah

    2012-02-01

    Full Text Available Software architecture design and requirement engineering are core and independent areas of engineering. A lot of research, education and practice are carried on Requirement elicitation and doing refine it, but it is a major issue of engineering. QSMSR model act as a bridge between requirement and design there is a huge gap between these two areas of software architecture and requirement engineering. The QSMSR model divide into two sub model qualitative model and Principal model in this research we focus on Qualitative model which further divide into two sub models fabricated model and classified model. Classified model make the sub groups of the role and match it with components. The Fabricated model link QSMSR Principal Model to an architecture design. At the end it provides the QSMSR Architecture model of the system as output.

  1. Qualitative research in finance

    Dan Kaczynski; Michelle Salmona; Tom Smith

    2014-01-01

    This paper provides an overview of qualitative research to encourage finance researchers to apply a more diverse approach to current research practices. Social science researchers recognize that research questions should determine what research paradigm is best for each study. Imagine the benefits to finance if we expand our empirical sources of data to include what people have to say, which then allows us to explore the complex reasoning behind these conversations. It is the intent of this p...

  2. QSMSR QUALITATIVE MODEL

    Tahir Abdullah; Shahbaz Nazeer

    2012-01-01

    Software architecture design and requirement engineering are core and independent areas of engineering. A lot of research, education and practice are carried on Requirement elicitation and doing refine it, but it is a major issue of engineering. QSMSR model act as a bridge between requirement and design there is a huge gap between these two areas of software architecture and requirement engineering. The QSMSR model divide into two sub model qualitative model and Principal model in this resear...

  3. Qualitative Psychology Nexus, Vol. I: Qualitative Research in Psychology

    2004-01-01

    The first "Workshop Qualitative Research in Psychology" took place in Blaubeuren, Germany from October 20-22, 2000. The meeting was organized by the Center for Qualitative Psychology of the University of Tübingen, Germany. The purpose of the meeting was to begin a network of qualitative psychologists. Thirty-two participants got to know each other, presented and discussed their research, discussed potential further developments within the field of qualitative psychology, and inspired eac...

  4. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial.

    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel Gw; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-12-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines--chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible. PMID:25156127

  5. The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

    Wegmann, Frank; Moghaddam, Amin E.; Schiffner, Torben; Gartlan, Kate H.; Powell, Timothy J.; Russell, Rebecca A.; Baart, Matthijs; Carrow, Emily W.

    2015-01-01

    The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8+ T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines. PMID:26135973

  6. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky;

    2012-01-01

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment...... in Dukes´ C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive...... preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes´ C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma...

  7. Adjuvant treatment and outcomes of stage III endometrial carcinoma

    Surgery with staging using FIGO (1988) classification is accepted management for stage III endometrial carcinoma. The delivery of adjuvant therapy is controversial and tends to be individualised. Retrospective review of stage III endometrial carcinoma patients who underwent radical surgery at the Royal Adelaide and Queen Elizabeth Hospitals from 1984 to 2003 was carried out. Medical records were reviewed for details of patient characteristics, surgery, histopathology, adjuvant therapy and recurrence/survival. Sixty-six patients with a median age of 69 (37-97), had a median follow-up of 26 months (1-188 ). For all stage III patients, the actuarial 5-year disease-free and overall survivals were 50 and 43% respectively. Thirty-five patients received pelvic +/- paraaortic radiotherapy, 5 whole abdominal radiotherapy, 14 vaginal brachytherapy boost, 10 chemotherapy and 13 adjuvant hormones. Forty-six percent of patients recurred in a median time of 13 months (0-95). For these patients, the sites of first recurrence were pelvis in 27%, pelvis and abdomen in 23%, abdomen alone in 13%, distant alone in 27%, distant and abdominal in 7% and all three sites in 3%. On univariate analysis disease-free survival was impacted by; age, grade, parametrial involvement, number of extrauterine sites, lymphovascular invasion, adjuvant radiotherapy to the pelvis alone and postoperative macroscopic residual disease. Lymphovascular invasion, post-operative residual disease and adjuvant pelvic radiotherapy remained significant on multivariate analysis. These outcomes for stage III endometrial carcinoma are comparable to the current literature. Ongoing research is required to establish the most appropriate adjuvant therapy in these high risk patients

  8. Does Adjuvant Radiotherapy Suppress Liver Regeneration After Partial Hepatectomy?

    Purpose: To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Methods and Materials: Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests at 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. Results: The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 ± 38.3cm3 and 81.5 ± 75.6cm3, respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. Conclusions: In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.

  9. Qualitative methodology in developmental psychology

    Demuth, Carolin; Mey, Günter

    2015-01-01

    Qualitative methodology presently is gaining increasing recognition in developmental psychology. Although the founders of developmental psychology to a large extent already used qualitative procedures, the field was long dominated by a (post) positivistic quantitative paradigm. The increasing...

  10. Protective efficacy of a live attenuated Mycoplasma hyopneumoniae vaccine with an ISCOM-matrix adjuvant in pigs.

    Xiong, Qiyan; Wei, Yanna; Feng, Zhixin; Gan, Yuan; Liu, Zhanjun; Liu, Maojun; Bai, Fangfang; Shao, Guoqing

    2014-02-01

    An attenuated Mycoplasma hyopneumoniae vaccine that requires intrathoracic administration is commercially available for use against mycoplasmal pneumonia in China. Given the limitations of such a route of administration, this study was undertaken to assess the capacity of an ISCOM-matrix adjuvant to enhance immunogenicity following intramuscular use. Immune responses in pigs following vaccination and subsequent intra-tracheal bacterial inoculation were examined using lymphocyte proliferation, serology and mucosal IgA in both nasal and saliva swabs. Vaccination induced clear lymphocyte proliferation, but only slight serum antibody responses although these were significantly increased following experimental infection. Mucosal IgA was not detected in either nasal or salivary secretions. Following bacterial challenge, animals vaccinated with the adjuvant-containing live vaccine exhibited less severe pulmonary lesions (median score 3.67) than unvaccinated pigs (median score 13.58). The degree of ciliary loss on the respiratory tract surface was reduced in vaccinated pigs compared with experimentally infected controls. The findings indicated that the adjuvant vaccine administered IM provided protection against experimentally induced mycoplasmal pneumonia and could have commercial potential. PMID:24314715

  11. Database searches for qualitative research

    Evans, David

    2002-01-01

    Interest in the role of qualitative research in evidence-based health care is growing. However, the methods currently used to identify quantitative research do not translate easily to qualitative research. This paper highlights some of the difficulties during searches of electronic databases for qualitative research. These difficulties relate to the descriptive nature of the titles used in some qualitative studies, the variable information provided in abstracts, and the differences in the ind...

  12. In vivo and in vitro effects of dexamethasone on leukocyte migration in the rat adjuvant arthritis model

    When polymorphonuclear leukocytes (PMNs) and mononuclear cells were isolated from the blood of dexamethasone-treated normal rats, in vitro mononuclear cell migration was inhibited and PMN migration was stimulated in comparison to controls. Inflammogen-induced PMNs showed inhibited cell migration due to dexamethasone treatment. Gamma camera imaging was then used to detect cells in vivo after labeling with 111In. When the dexamethasone-treated blood cells were injected into adjuvant arthritis diseased rats, mononuclear cells showed depressed migration into the inflamed paws, while PMNs showed stimulated migration into the inflamed paws in comparison to controls. When the recipient adjuvant arthritic animals were treated with dexamethasone, both normal mononuclear cell and normal PMN migration to the inflamed paws were inhibited

  13. Characterization of the structure and immunostimulatory activity of a vaccine adjuvant, de-O-acylated lipooligosaccharide.

    Ji Eun Han

    Full Text Available Lipopolysaccharide (LPS is a major component of the outer membrane of Gram-negative bacteria. LPS elicits strong immunopathological responses during bacterial infection, and the lipid A moiety of LPS is responsible for this immunostimulatory activity. Lipid A exerts its biological activity by sending signals via TLR4 present on immune cells, and TLR4 agonists have been a target for vaccine adjuvant. Previously, we demonstrated an adjuvant activity of deacylated lipooligosaccharide (dLOS to viral and bacterial antigens. In this study, we characterized the chemical structure of dLOS and evaluated its immunostimulatory activity on mouse and human immune cells in comparison with monophosphoryl lipid A (MPL. dLOS consists of the R3-type core, a glucosamine disaccharide with two phosphate groups, and two N-linked acyl groups [corrected], and two N-linked acyl groups. dLOS was similar to MPL in induction of cytokine production in mouse peritoneal macrophages, but was a more potent activator in human monocytes and dendritic cells (DCs. Results of an analysis of allogeneic T cell responses revealed that dLOS induces Th1, Th2, and Th17-type immune responses in a dose-dependent manner. The immunostimulatory activities of dLOS were completely abrogated in TLR4(-/- mice, which confirms its TLR4-dependency. These results suggest that in the presence of the core oligosaccharide, O-linked acyl groups of LPS are dispensable for activating the TLR4 signaling pathway. dLOS did not cause any pathological effects or death at 0.25, 0.5, or 1 mg per kg body weight in mice in the acute toxicity tests. This result suggests that dLOS has a low toxicity. dLOS should be considered for further development as a safe and effective adjuvant for human vaccines.

  14. Systemic antibody response to nano-size calcium phospate biocompatible adjuvant adsorbed HEV-71 killed vaccine

    2015-01-01

    Purpose Since 1980s, human enterovirus-71 virus (HEV-71) is one of the common infectious disease in Asian Pacific region since late 1970s without effective commercial antiviral or protective vaccine is unavailable yet. The work examines the role of vaccine adjuvant particle size and the route of administration on postvaccination antibody response towards HEV-71 vaccine adsorbed to calcium phosphate (CaP) adjuvant. Materials and Methods First, CaP nano-particles were compared to a commercial micro-size and vaccine alone. Secondly, intradermal reduced dosage was compared to the conventional intramuscular immunization. Killed HEV-71 vaccines adsorbed to CaP nano-size (73 nm) and commercial one of micro-size (1.7 µm) were administered through intradermal, intramuscular, rabbits received vaccine alone and unvaccinated animals. Results CaP nano-particles adsorbed HEV-71 vaccine displayed higher antibody than the micro-size or unadsorbed vaccine alone, through both parenteral immunization routes. Moreover, the intradermal route (0.5 µg/mL) of 0.1-mL volume per vaccine dose induced equal IgG antibody level to 1.0-mL intramuscular route (0.5 µg/mL). Conclusion The intradermal vaccine adsorbed CaP nano-adjuvant showed safer and significant antibody response after one-tenth reduced dose quantity (0.5 µg/mL) of only 0.1-mL volume as the most suitable protective, cost effective and affordable formulation not only for HEV-71; but also for developing further effective vaccines toward other human pathogens. PMID:25649429

  15. Evaluation of Montanide™ ISA 71 VG adjuvant during profilin vaccination against experimental coccidiosis.

    Seung I Jang

    Full Text Available Chickens were immunized subcutaneously with an Eimeria recombinant profilin protein plus Montanide™ ISA 70 VG (ISA 70 or Montanide™ ISA 71 VG (ISA 71 water-in-oil adjuvants, or with profilin alone, and comparative RNA microarray hybridizations were performed to ascertain global transcriptome changes induced by profilin/ISA 70 vs. profilin alone and by profilin/ISA 71 vs. profilin alone. While immunization with profilin/ISA 70 vs. profilin alone altered the levels of more total transcripts compared with profilin/ISA 71 vs. profilin alone (509 vs. 296, the latter was associated with a greater number of unique biological functions, and a larger number of genes within these functions, compared with the former. Further, canonical pathway analysis identified 10 pathways that were associated with genes encoding the altered transcripts in animals immunized with profilin/ISA 71 vs. profilin alone, compared with only 2 pathways in profilin/ISA 70 vs. profilin alone. Therefore, ISA 71 was selected as a candidate adjuvant in conjunction with profilin vaccination for in vivo disease protection studies. Vaccination with profilin/ISA 71 was associated with greater body weight gain following E. acervulina infection, and decreased parasite fecal shedding after E. maxima infection, compared with profilin alone. Anti-profilin antibody levels were higher in sera of E. maxima- and E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. Finally, the levels of transcripts encoding interferon-γ, interleukin (IL-2, IL-10, and IL-17A were increased in intestinal lymphocytes from E. acervulina-, E. maxima-, and/or E. tenella-infected chickens vaccinated with profilin/ISA 71 compared with profilin alone. None of these effects were seen in chickens injected with ISA 71 alone indicating that the adjuvant was not conferring non-specific immune stimulation. These results suggest that profilin plus ISA 71 augments protective immunity

  16. Programming of Influenza Vaccine Broadness and Persistence by Mucoadhesive Polymer-Based Adjuvant Systems.

    Noh, Hyun Jong; Chowdhury, Mohammed Y E; Cho, Seonghun; Kim, Jae-Hoon; Park, Hye Sun; Kim, Chul-Joong; Poo, Haryoung; Sung, Moon-Hee; Lee, Jong-Soo; Lim, Yong Taik

    2015-09-01

    The development of an anti-influenza vaccine with the potential for cross-protection against seasonal drift variants as well as occasionally emerging reassortant viruses is essential. In this study, we successfully generated a novel anti-influenza vaccine system combining conserved matrix protein 2 (sM2) and stalk domain of hemagglutinin (HA2) fusion protein (sM2HA2) and poly-γ-glutamic acid (γ-PGA)-based vaccine adjuvant systems that can act as a mucoadhesive delivery vehicle of sM2HA2 as well as a robust strategy for the incorporation of hydrophobic immunostimulatory 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21. Intranasal coadministration of sM2HA2 and the combination adjuvant γ-PGA/MPL/QS21 (CA-PMQ) was able to induce a high degree of protective mucosal, systemic, and cell-mediated immune responses. The sM2HA2/CA-PMQ immunization was able to prevent disease symptoms, confering complete protection against lethal infection with divergent influenza subtypes (H5N1, H1N1, H5N2, H7N3, and H9N2) that lasted for at least 6 mo. Therefore, our data suggest that mucosal administration of sM2HA2 in combination with CA-PMQ could be a potent strategy for a broad cross-protective influenza vaccine, and CA-PMQ as a mucosal adjuvant could be used for effective mucosal vaccines. PMID:26216889

  17. Adjuvant properties of thermal component of hyperthermia enhanced transdermal immunization: effect on dendritic cells.

    Neha Joshi

    Full Text Available Hyperthermia enhanced transdermal (HET immunization is a novel needle free immunization strategy employing application of antigen along with mild local hyperthermia (42°C to intact skin resulting in detectable antigen specific Ig in serum. In the present study, we investigated the adjuvant effect of thermal component of HET immunization in terms of maturation of dendritic cells and its implication on the quality of the immune outcome in terms of antibody production upon HET immunization with tetanus toxoid (TT. We have shown that in vitro hyperthermia exposure at 42°C for 30 minutes up regulates the surface expression of maturation markers on bone marrow derived DCs. This observation correlated in vivo with an increased and accelerated expression of maturation markers on DCs in the draining lymph node upon HET immunization in mice. This effect was found to be independent of the antigen delivered and depends only on the thermal component of HET immunization. In vitro hyperthermia also led to enhanced capacity to stimulate CD4+ T cells in allo MLR and promotes the secretion of IL-10 by BMDCs, suggesting a potential for Th2 skewing of T cell response. HET immunization also induced a systemic T cell response to TT, as suggested by proliferation of splenocytes from immunized animal upon in vitro stimulation by TT. Exposure to heat during primary immunization led to generation of mainly IgG class of antibodies upon boosting, similar to the use of conventional alum adjuvant, thus highlighting the adjuvant potential of heat during HET immunization. Lastly, we have shown that mice immunized by tetanus toxoid using HET route exhibited protection against challenge with a lethal dose of tetanus toxin. Thus, in addition to being a painless, needle free delivery system it also has an immune modulatory potential.

  18. Chinese herbal medicines as adjuvant treatment during chemo- or radio-therapy for cancer.

    Qi, Fanghua; Li, Anyuan; Inagaki, Yoshinori; Gao, Jianjun; Li, Jijun; Kokudo, Norihiro; Li, Xiao-Kang; Tang, Wei

    2010-12-01

    Numerous studies have indicated that in cancer treatment Chinese herbal medicines in combination with chemo- or radio-therapy can be used to enhance the efficacy of and diminish the side effects and complications caused by chemo- and radio-therapy. Therefore, an understanding of Chinese herbal medicines is needed by physicians and other health care providers. This review provides evidence for use of Chinese herbal medicines as adjuvant cancer treatment during chemo- or radio-therapy. First, Chinese herbal medicines (e.g. Astragalus, Turmeric, Ginseng, TJ-41, PHY906, Huachansu injection, and Kanglaite injection) that are commonly used by cancer patients for treating the cancer and/or reducing the toxicity induced by chemo- or radio-therapy are discussed. Preclinical and clinical studies have shown that these Chinese herbal medicines possess great advantages in terms of suppressing tumor progression, increasing the sensitivity of chemo- and radio-therapeutics, improving an organism's immune system function, and lessening the damage caused by chemo- and radio-therapeutics. Second, clinical trials of Chinese herbal medicines as adjuvant cancer treatment are reviewed. By reducing side effects and complications during chemo- and radio-therapy, these Chinese herbal medicines have a significant effect on reducing cancer-related fatigue and pain, improving respiratory tract infections and gastrointestinal side effects including diarrhea, nausea, and vomiting, protecting liver function, and even ameliorating the symptoms of cachexia. This review should contribute to an understanding of Chinese herbal medicines as adjuvant treatment for cancer and provide useful information for the development of more effective anti-cancer drugs. PMID:21248427

  19. Qualitative Studies in Information Systems

    Sarker, Suprateek; Xiao, Xiao; Beaulieu, Tanya

    2013-01-01

    The authors discuss a review of qualitative papers on information systems (IS) published in various journals between 2001 and 2012. They explain trends related to qualitative research in the chosen journals and the key anatomical components of a qualitative research manuscript, including the...

  20. Polymerized serum albumin beads for use as slow-release adjuvants

    Experimental vaccines have been made by covalently bonding virus particles into polymerized rabbit serum albumin beads. Using Nodamura virus as a model antigen, these model vaccines induced specific humoral antibody production, comparable with that achieved using Freund's adjuvants. Virus specific antibodies were also induced when Nodamura virus was covalently attached to the bead surface using different crosslinkers. However, when poliovirus type 2 (Sabin strain) was polymerized into beads, the levels of neutralizing antibodies were insignificant compared with control aqueous vaccines. The synthetic immunostimulator, muramyl dipeptide, was included with bead vaccines in an attempt to potentiate the immune response. Immunostimulation is achieved by a slow release of antigen coinciding with the gradual breakdown of bead structure. Methods used include radio-iodination and radioimmunoassay. 65 figs., 6 tabs., 173 refs

  1. A new rabies vaccine with an experimental adjuvant for domestic animals

    Süli Judit; Beníšek Z.; Ondrejková Ana; Ondrejka R.; Prokeš M.

    2010-01-01

    The authors had developed a new experimental adjuvant based on squalene and its efficacy was tested on target domestic animals - cats and dogs by means of different rabies vaccines. In this experiment the authors compared the immune response on the rabies vaccine without adjuvant and with aluminium adjuvant or experimental squalene adjuvant, respectively. The level of rabies antibodies was determined by rapid fluorescence focus inhibition test on days 14, 3...

  2. Parasitic wasp females are attracted to blends of host-induced plant volatiles: do qualitative and quantitative differences in the blend matter? [v1; ref status: indexed, http://f1000r.es/y3

    Masayoshi Uefune

    2013-02-01

    Full Text Available Naïve Cotesia vestalis wasps, parasitoids of diamondback moth (DBM larvae, are attracted to a synthetic blend (Blend A of host-induced plant volatiles composed of sabinene, n-heptanal, α-pinene, and (Z-3-hexenyl acetate, in a ratio of 1.8:1.3:2.0:3.0. We studied whether qualitative (adding (R-limonene: Blend B or quantitative changes (changing ratios: Blend C to Blend A affected the olfactory response of C. vestalis in the background of intact komatsuna plant volatiles. Naïve wasps showed equal preference to Blends A and B and Blends A and C in two-choice tests. Wasps with oviposition experience in the presence of Blend B preferred Blend B over Blend A, while wasps that had oviposited without a volatile blend showed no preference between the two. Likewise, wasps that had starvation experience in the presence of Blend B preferred Blend A over Blend B, while wasps that had starved without a volatile blend showed no preference between the two. Wasps that had oviposition experience either with or without Blend A showed equal preferences between Blends C and A. However, wasps that had starvation experience in the presence of Blend A preferred Blend C over Blend A, while those that starved without a volatile blend showed equal preferences between the two. By manipulating quality and quantity of the synthetic attractants, we showed to what extent C. vestalis could discriminate/learn slight differences between blends that were all, in principle, attractive.

  3. Parasitic wasp females are attracted to blends of host-induced plant volatiles: do qualitative and quantitative differences in the blend matter? [v2; ref status: indexed, http://f1000r.es/12h

    Masayoshi Uefune

    2013-04-01

    Full Text Available Naïve Cotesia vestalis wasps, parasitoids of diamondback moth (DBM larvae, are attracted to a synthetic blend (Blend A of host-induced plant volatiles composed of sabinene, n-heptanal, α-pinene, and (Z-3-hexenyl acetate, in a ratio of 1.8:1.3:2.0:3.0. We studied whether qualitative (adding (R-limonene: Blend B or quantitative changes (changing ratios: Blend C to Blend A affected the olfactory response of C. vestalis in the background of intact komatsuna plant volatiles. Naïve wasps showed equal preference to Blends A and B and Blends A and C in two-choice tests. Wasps with oviposition experience in the presence of Blend B preferred Blend B over Blend A, while wasps that had oviposited without a volatile blend showed no preference between the two. Likewise, wasps that had starvation experience in the presence of Blend B preferred Blend A over Blend B, while wasps that had starved without a volatile blend showed no preference between the two. Wasps that had oviposition experience either with or without Blend A showed equal preferences between Blends C and A. However, wasps that had starvation experience in the presence of Blend A preferred Blend C over Blend A, while those that starved without a volatile blend showed equal preferences between the two. By manipulating quality and quantity of the synthetic attractants, we showed to what extent C. vestalis could discriminate/learn slight differences between blends that were all, in principle, attractive.

  4. Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants

    Sen, Debasish; Forrest, Luette; Kepler, Thomas B.; Parker, Ian; Cahalan, Michael D.

    2010-01-01

    Dendritic cells (DCs) initiate and polarize adaptive immune responses toward varying functional outcomes. By means of intravital two-photon microscopy, we report that dermal dendritic cells (DDCs) and Langerhans cells (LCs) are differentially mobilized during contact sensitization and by adjuvants such as unmethylated CpG oligonucleotide (CpG) and LPS that induce T helper type 1 (Th1) responses, or papain that induces T helper type 2 (Th2) responses. In ear pinna, contact sensitization, CpG, ...

  5. Allergy adjuvant effect of particles from wood smoke and road traffic

    There is growing evidence that in addition to augmenting the severity of asthma and allergic diseases, particulate air pollution also increases the incidence of allergy and asthma. We studied the adjuvant effect of particles from wood smoke and road traffic on the immune response to the allergen ovalbumin (OVA). OVA with and without particles was injected into one hind footpad of Balb/cA mice. All particles together with OVA significantly increased the level of OVA-specific immunoglobulin E (IgE) in serum, compared to groups given OVA or particles alone. Reference diesel exhaust particles (DEP) with OVA induced the highest levels of IgE, whereas no clear difference was observed between particles from road traffic and wood smoke. Road traffic particles collected in the autumn induced higher IgE values with OVA than corresponding particles collected during the winter season when studded tires are used, suggesting that studded tire-generated road pavement particles have less allergy adjuvant activity than exhaust particles. Compared to OVA or particles alone, all particles with OVA increased popliteal lymph node cell numbers, cell proliferation, ex vivo secretion of IL-4 and IL-10 after ConA stimulation, and the expression of several cell surface molecules (CD19, MHC class II, CD86 and CD23). Wood smoke particles with OVA induced somewhat higher cellular responses than road traffic particles, but less than DEP with OVA which seemed to be the most potent particle in inducing cellular as well as antibody responses. Thus, wood smoke particles had about the same capacity to enhance allergic sensitization as road traffic particles, but less than diesel exhaust particles

  6. Taxanes in adjuvant and neoadjuvant therapy for breast cancer

    S. V. Limareva

    2010-01-01

    Taxanes (paclitaxel and docetaxel) are currently considered to be basic cytostatics in the treatment of all breast cancer (BC) stages. The results of conducted and ongoing clinical trials suggest that incorporation of taxanes into adjuvant and neoadjuvant chemotherapy regimens enhances the efficiency of treatment for operable BC and show it necessary to apply an individual approach depending on prognostic and predictive factors.

  7. Controversies in the Adjuvant Treatment of Pancreatic Adenocarcinoma

    Muhammad Wasif Saif

    2007-09-01

    Full Text Available There is no universally accepted standard approach to treat patients with pancreatic cancer in the adjuvant setting. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary depending on which side of the Atlantic you are on: chemo-radiotherapy followed by chemotherapy is considered the optimal therapy in North America (GITSG, RTOG while chemotherapy alone is the current standard in Europe (ESPAC-1, CONKO. Whether gemcitabine is superior to 5-FU remains to be learnt from the ESPAC-3 study currently on-going in Europe. A number of important questions have yet to be fully addressed: • What is the absolute value of radiotherapy in this setting? • How should radiotherapy be delivered, if at all? • What should be the time to deliver of either or both therapeutic modalities in the adjuvant setting? • Are there any patients who can benefit from the combined modality? • What is the most appropriate chemotherapeutic agent(s to administer in the adjuvant setting? • Is there any role of integrating the novel/targeted agents, albeit the negative studies in the metastatic setting? • What are the new developments (such as vaccines, pancreas cancer stem cells, etc. in this area? The author summarizes the evolution of adjuvant therapy for resected pancreatic cancer and highlights the controversies that originate from several studies, each fraught with its own limitations.

  8. Organic weed control with vinegar: Application volumes and adjuvants

    Preliminary results have indicated that vinegar has potential as an organic herbicide, but further research is needed to increase our understanding of the relationship between acetic acid concentrations, application volumes, adjuvants, weed species, and weed maturity on effectiveness of vinegar to c...

  9. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

    Licht, Peter B; Schytte, Tine; Jakobsen, Erik

    2014-01-01

    BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy. RESULTS: During a 6-year...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p<0.001) and comorbidity index (p=0.003) but increased with N2 status (p=0.02). No...

  10. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant. PMID:25549218

  11. Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants

    Turánek, J.; Ledvina, Miroslav; Kašná, A.; Vacek, A.; Hříbalová, V.; Krejčí, J.; Miller, A. D.

    2006-01-01

    Roč. 24, S2 (2006), S90-S91. ISSN 0264-410X R&D Projects: GA MZe(CZ) QF3115 Institutional research plan: CEZ:AV0Z40550506 Keywords : liposoma * adjuvant * muramyl glycopeptides Subject RIV: CC - Organic Chemistry Impact factor: 3.159, year: 2006

  12. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    Verheul, R.J.

    2010-01-01

    Tailorable Trimethyl Chitosans as Adjuvant for Intranasal Immunization Active vaccination has proven to be the most (cost) effective tool in the fight against infectious diseases. Nowadays, most vaccines are administered via parenteral injection. However, the risk of contaminated needles and need fo

  13. A Qualitative Report

    Sara L. Ackerman

    2012-01-01

    Full Text Available Background. No in-depth qualitative research exists about the effects of therapeutic massage with children hospitalized to undergo hematopoietic cell transplantation (HCT. The objective of this study is to describe parent caregivers' experience of the effects of massage/acupressure for their children undergoing HCT. Methods. We conducted a qualitative analysis of open-ended interviews with 15 parents of children in the intervention arm of a massage/acupressure trial. Children received both practitioner and parent-provided massage/acupressure. Results. Parents reported that their child experienced relief from pain and nausea, relaxation, and greater ease falling asleep. They also reported increased caregiver competence and closeness with their child as a result of learning and performing massage/acupressure. Parents supported a semistandardized massage protocol. Conclusion. Massage/acupressure may support symptom relief and promote relaxation and sleep among pediatric HCT patients if administered with attention to individual patients' needs and hospital routines and may relieve stress among parents, improve caregiver competence, and enhance the sense of connection between parent and child.

  14. Effects of oral administration of type Ⅱ collagen on adjuvant arthritis in rat sand its mechanisms

    胡永秀; 赵文明; 钱娴娟; 张力平

    2003-01-01

    Objective To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly.Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN-γ and TNF-α i n articular steep in rats.Results Oral administration of CⅡ was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CⅡ were stronger than those by Tripterygium Polyglycoside. Oral administration of CⅡ inhibi ted antigen-specific immune response, such as DTH and antibody reaction to CⅡ . In addition, the expression of IFN-γ and TNF-α in joints were locally dow nregulated. Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-γ and TNF-α, and the suppression of cell immunity.

  15. Clinical outcome of adjuvant chemotherapy plus intensity modulated radiotherapy after breast-conserving surgery

    Objective: To evaluate the efficacy and side effects of adjuvant chemotherapy plus intensity modulated radiotherapy (IMRT) after breast-conserving surgery for stage I and II breast cancer. Methods: After breast-conserving surgery, 108 patients received six cycles of chemotherapy followed by IMRT. The irradiation dose of the whole breast was 50 Gy given by 25 fractions, followed by 10 Gy boost to the tumor bed given by 5 fractions with electron beams. Patients with positive estrone receptor or progesterone receptor were given endocrine treatment, mostly with tamoxifen. Results: The follow-up rate was 100% by December 2007. The number of patients followed-up at 1-, 2- and 3-year was 108,88 and 58. The 1-, 2- and 3-year over survival rates were 100%, 100% and 98%. Three patients had local recurrence. Different degree of dermatitis occurred with good long-term cosmetic results. No severe side effects occurred such as radiation-induced pneumonitis, pulmonary, fibrosis and heart injury. Conclusions: Breast cancer patients treated by adjuvant chemotherapy plus IMRT after breast-conserving surgery have high survival rate and low side-effect rate. The survival quality and local control can be improved. (authors)

  16. Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model

    Liu-nan Song

    2016-01-01

    Full Text Available Introduction. Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. Methods. Adult male Wistar rats were studied in an adjuvant arthritis (AA model induced by the injection of Freund’s complete adjuvant (FCA. Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1 and transforming growth factor-β (TGF-β1 protein expression levels. Results. Pulmonary inflammation was evident in lung tissue from day 21 after FCA injection. Inflammation and mild fibrosis were observed in lung tissue on day 28 after FCA injection. Cav-1 protein expression was significantly decreased from day 7 through day 28 and TGF-β1 protein expression was significantly increased on day 28 after FCA injection compared to control (P<0.05. Conclusion. We established an AA rat model that exhibited the extra-articular complication of RA-ILD. We identified Cav-1 and TGF-β1 as protein biomarkers of RA-ILD in this model and propose their signaling pathway as a possible target for therapeutic intervention.

  17. Tocotrienol-adjuvanted dendritic cells inhibit tumor growth and metastasis: a murine model of breast cancer.

    Sitti Rahma Abdul Hafid

    Full Text Available Tocotrienol-rich fraction (TRF from palm oil is reported to possess anti-cancer and immune-enhancing effects. In this study, TRF supplementation was used as an adjuvant to enhance the anti-cancer effects of dendritic cells (DC-based cancer vaccine in a syngeneic mouse model of breast cancer. Female BALB/c mice were inoculated with 4T1 cells in mammary pad to induce tumor. When the tumor was palpable, the mice in the experimental groups were injected subcutaneously with DC-pulsed with tumor lysate (TL from 4T1 cells (DC+TL once a week for three weeks and fed daily with 1 mg TRF or vehicle. Control mice received unpulsed DC and were fed with vehicle. The combined therapy of using DC+TL injections and TRF supplementation (DC+TL+TRF inhibited (p<0.05 tumor growth and metastasis. Splenocytes from the DC+TL+TRF group cultured with mitomycin-C (MMC-treated 4T1 cells produced higher (p<0.05 levels of IFN-γ and IL-12. The cytotoxic T-lymphocyte (CTL assay also showed enhanced tumor-specific killing (p<0.05 by CD8(+ T-lymphocytes isolated from mice in the DC+TL+TRF group. This study shows that TRF has the potential to be used as an adjuvant to enhance effectiveness of DC-based vaccines.

  18. Influence of Asian dust particles on immune adjuvant effects and airway inflammation in asthma model mice.

    Jun Kurai

    Full Text Available An Asian dust storm (ADS contains airborne particles that affect conditions such as asthma, but the mechanism of exacerbation is unclear. The objective of this study was to compare immune adjuvant effects and airway inflammation induced by airborne particles collected on ADS days and the original ADS soil (CJ-1 soil in asthma model mice.Airborne particles were collected on ADS days in western Japan. NC/Nga mice were co-sensitized by intranasal instillation with ADS airborne particles and/or Dermatophagoides farinae (Df, and with CJ-1 soil and/or Df for 5 consecutive days. Df-sensitized mice were stimulated with Df challenge intranasally at 7 days after the last Df sensitization. At 24 hours after challenge, serum allergen specific antibody, differential leukocyte count and inflammatory cytokines in bronchoalveolar lavage fluid (BALF were measured, and airway inflammation was examined histopathologically.Co-sensitization with ADS airborne particles and Df increased the neutrophil and eosinophil counts in BALF. Augmentation of airway inflammation was also observed in peribronchiolar and perivascular lung areas. Df-specific serum IgE was significantly elevated by ADS airborne particles, but not by CJ-1 soil. Levels of interleukin (IL-5, IL-13, IL-6, and macrophage inflammatory protein-2 were higher in BALF in mice treated with ADS airborne particles.These results suggest that substances attached to ADS airborne particles that are not in the original ADS soil may play important roles in immune adjuvant effects and airway inflammation.

  19. Role of Adjuvant Chemoradiotherapy for Ampulla of Vater Cancer

    Purpose: To evaluate the role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Methods and Materials: Between January 1991 and December 2002, 118 patients with ampulla of Vater cancer underwent en bloc resection. Forty-one patients received adjuvant chemoradiotherapy [RT(+) group], and 77 did not [RT(-) group]. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes, for a total dose of up to 40 Gy delivered in 2-Gy fractions, with a planned 2-week rest period halfway through the treatment period. Intravenous 5-fluorouracil (500 mg/m2/day) was given on Days 1 to 3 of each split course. The median follow-up was 65 months. Results: The 5-year overall survival rate in the RT(-) and RT(+) groups was 66.9% and 52.8%, respectively (p = 0.2225). The 5-year locoregional relapse-free survival rate in the RT(-) and RT(+) groups was 79.9% and 80.2%, respectively (p = 0.9582). When age, type of operation, T stage, N stage, histologic differentiation, and the use of adjuvant chemoradiotherapy were incorporated into the Cox proportional hazard model, there was an improvement in the locoregional relapse-free survival rate (p = 0.0050) and a trend toward a longer overall survival (p = 0.0762) associated with the use of adjuvant chemoradiotherapy. Improved overall survival (p = 0.0235) and locoregional relapse-free survival (p = 0.0095) were also evident in patients with nodal metastasis. In contrast, enhanced locoregional control (p = 0.0319) did not result in longer survival in patients with locally advanced disease (p = 0.4544). Conclusions: Adjuvant chemoradiotherapy may enhance locoregional control and overall survival in patients with ampulla of Vater cancer after curative resection, especially in those with nodal involvement.

  20. Adjuvant and salvage irradiation following radical prostatectomy for prostate cancer

    Purpose: We performed a retrospective analysis to assess the durability of benefit derived from irradiation after prostatectomy for pT3N0 disease, and the possibility of cure. Methods and Materials: We studied 88 patients who were irradiated after prostatectomy and had available prostate specific antigen (PSA) data, no known nodal or metastatic disease, no hormonal treatment, and follow-up of at least 12 months from surgery. Forty patients received adjuvant therapy for a high risk of local failure with undetectable PSA. Forty-eight patients received salvage therapy for elevated PSA levels. Mean follow up was 44 months from date of surgery and 31 months from irradiation. Biochemical failure was strictly defined as a confirmed rise in PSA of > 10%, or as the ability to detect a previously undetectable PSA value. Results: After salvage irradiation, 69% of patients attained an undetectable PSA. Eighty-eight percent of adjuvant patients were biochemically and clinically free of disease (bNED) at 3 years from prostatectomy. Sixty-eight percent of those receiving salvage irradiation were bNED 3 years after surgery. On univariate analysis, treatment group (adjuvant or salvage), pre-operative PSA, and the status of seminal vesicles were significant prognostic factors. The extent of PSA elevation in the salvage group was also significant. We did not demonstrate a significant difference between those salvage patients referred for persistently elevated PSA as compared to those with a late rise in PSA. On multivariate analysis, the only significant predictor of outcome was treatment group, with adjuvant irradiation having better outcome than salvage. Conclusion: More than two-thirds of this group of patients remain biochemically disease free at 3 years following irradiation, attesting to a number of potential cures. For patients with stage pT3N0 prostate cancer following radical prostatectomy, our data support the use of either routine postoperative adjuvant irradiation or

  1. Recombinant polymorphic membrane protein D in combination with a novel, second-generation lipid adjuvant protects against intra-vaginal Chlamydia trachomatis infection in mice.

    Paes, Wayne; Brown, Naj; Brzozowski, Andrzej M; Coler, Rhea; Reed, Steve; Carter, Darrick; Bland, Martin; Kaye, Paul M; Lacey, Charles J N

    2016-07-29

    The development of a chlamydial vaccine that elicits protective mucosal immunity is of paramount importance in combatting the global spread of sexually transmitted Chlamydia trachomatis (Ct) infections. While the identification and prioritization of chlamydial antigens is a crucial prerequisite for efficacious vaccine design, it is likely that novel adjuvant development and selection will also play a pivotal role in the translational potential of preclinical Ct vaccines. Although the molecular nature of the immuno-modulatory component is of primary importance, adjuvant formulation and delivery systems may also govern vaccine efficacy and potency. Our study provides the first preclinical evaluation of recombinant Ct polymorphic membrane protein D (rPmpD) in combination with three different formulations of a novel second-generation lipid adjuvant (SLA). SLA was rationally designed in silico by modification of glucopyranosyl lipid adjuvant (GLA), a TLR4 agonistic precursor molecule currently in Phase II clinical development. We demonstrate robust protection against intra-vaginal Ct challenge in mice, evidenced by significantly enhanced resistance to infection and reduction in mean bacterial load. Strikingly, protection was found to correlate with the presence of robust anti-rPmpD serum and cervico-vaginal IgG titres, even in the absence of adjuvant-induced Th1-type cellular immune responses elicited by each SLA formulation, and we further show that anti-rPmpD antibodies recognize Ct EBs. These findings highlight the utility of SLA and rational molecular design of adjuvants in preclinical Ct vaccine development, but also suggest an important role for anti-rPmpD antibodies in protection against urogenital Ct infection. PMID:27389169

  2. Inflammasome-independent role of the apoptosis-associated speck-like protein containing CARD (ASC) in the adjuvant effect of MF59.

    Ellebedy, Ali H; Lupfer, Christopher; Ghoneim, Hazem E; DeBeauchamp, Jennifer; Kanneganti, Thirumala-Devi; Webby, Richard J

    2011-02-15

    Clinical studies have indicated that subvirion inactivated vaccines against avian influenza viruses, particularly H5N1, are poorly immunogenic in humans. As a consequence, the use of adjuvants has been championed for the efficient vaccination of a naïve population against avian influenza. Aluminum salts (alum) and the oil-in-water emulsion MF59 are safe and effective adjuvants that are being used with influenza vaccines, but the mechanism underlying their stimulation of the immune system remains poorly understood. It was shown recently that activation of a cytosolic innate immune-sensing complex known as "NLR-Pyrin domain containing 3" (NLRP3) inflammasome, also known as "cryopyrin," "cold-induced autoinflammatory syndrome 1" (CIAS1), or nacht domain-, leucine-rich repeat-, and PYD-containing protein 3 (Nalp3), is essential for the adjuvant effect of alum. Here we show that the inflammasome component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), an adapter protein within the NLRP3 inflammasome, is a crucial element in the adjuvant effect of MF59 when combined with H5N1 subunit vaccines. In the absence of ASC, H5-specific IgG antibody responses are significantly reduced, whereas the responses are intact in NLRP3(-/-) and caspase-1(-/-) mice. This defect is caused mainly by the failure of antigen-specific B cells to switch from IgM to IgG production. We conclude that ASC plays an inflammasome-independent role in the induction of antigen-specific humoral immunity after vaccination with MF59-adjuvanted influenza vaccines. These findings have important implications for the rational design of next-generation adjuvants. PMID:21270336

  3. Generation of humoral immune responses to multi-allele PfAMA1 vaccines; effect of adjuvant and number of component alleles on the breadth of response.

    Kwadwo A Kusi

    Full Text Available There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1. These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles and three (DiCo mix antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82% of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.

  4. The qualitative similarity hypothesis.

    Paul, Peter V; Lee, Chongmin

    2010-01-01

    Evidence is presented for the qualitative similarity hypothesis (QSH) with respect to children and adolescents who are d/Deaf or hard of hearing. The primary focus is on the development of English language and literacy skills, and some information is provided on the acquisition of English as a second language. The QSH is briefly discussed within the purview of two groups of cognitive models: those that emphasize the cognitive development of individuals and those that pertain to disciplinary or knowledge structures. It is argued that the QSH has scientific merit with implications for classroom instruction. Future research should examine the validity of the QSH in other disciplines such as mathematics and science and should include perspectives from social as well as cognitive models. PMID:20415280

  5. Qualitative research, tourism

    Ren, Carina Bregnholm

    2016-01-01

    various methods, which seek to deploy more inductive and explorative approaches. Such methods include interviews, participant or non-participatory observations, focus groups, text and discourse analysis, photo and video documentation or elicitation, semiotic studies, autoethnography, and virtual......) and a drastic rise in qualitative research based publications in prominent journals such as Annals of Tourism Research and, to a lesser degree, Tourism Management. Tourism as a heterogeneous field Since the turn of the century, the research community is progressively coming to terms with the contributions...... with which to study tourism not only as an industry and business, but also as a mundane, embodied, enacted, and localized practice. Since then, a focus on mobility, affect, emotions, materiality, everyday life, and performativity has increased immensely and shown how cultural or social issues...

  6. Qualitative experiments in psychology

    Wagoner, Brady

    2015-01-01

    In this article, I explore the meaning of experiments in early twentieth century psychology, focusing on the qualitative experimental methodology of psychologist Frederic BARTLETT. I begin by contextualizing BARTLETT's experiments within the continental research tradition of his time, which...... was in a state of transition from a focus on elements (the concern of psychophysics) to a focus on wholes (the concern of Gestalt psychology). The defining feature of BARTLETT's early experiments is his holistic treatment of human responses, in which the basic unit of analysis is the active person relating...... to some material within the constraints of a social and material context. This manifests itself in a number of methodological principles that contrast with contemporary understandings of experimentation in psychology. The contrast is further explored by reviewing the history of "replications...

  7. Comparison of Intranasal Outer Membrane Vesicles with Cholera Toxin and Injected MF59C.1 as Adjuvants for Malaria Transmission Blocking Antigens AnAPN1 and Pfs48/45

    Pritsch, Michael; Ben-Khaled, Najib; Chaloupka, Michael; Kobold, Sebastian; Berens-Riha, Nicole; Peter, Annabell; Liegl, Gabriele; Schubert, Sören; Hoelscher, Michael; Löscher, Thomas; Wieser, Andreas

    2016-01-01

    Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice. The intranasal adjuvant cholera toxin (CT) and parenteral adjuvant MF59C.1 were used in comparison. Vaccinations were administered intranasally or subcutaneously. Antibodies (total IgG and IgM as well as subclasses IgG1, IgG2a, IgG2b, and IgG3) were measured by ELISA. T cell responses (cytotoxic T cells, Th1, Th17, and regulatory T cells) were determined by flow cytometry. When OMV were used as adjuvant for intranasal immunization, antibody and cellular responses against all three antigens could be induced, comparable to cholera toxin and MF59C.1. Antigen-specific IgG titres above 1 : 105 could be detected in all groups. This study provides the rationale for further development of OMV as a vaccination strategy in malaria and other diseases.

  8. Ethics and the practice of qualitative research

    Shaw, Ian Frank

    2016-01-01

    Ethics and the practice of qualitative research? Qualitative Social Work 7 (4): 400-414. Reprinted......Ethics and the practice of qualitative research? Qualitative Social Work 7 (4): 400-414. Reprinted...

  9. Systemic Administration of CpG Oligodeoxynucleotide and Levamisole as Adjuvants for Gene-Gun-Delivered Antitumor DNA Vaccines

    Michal Šmahel

    2011-01-01

    Full Text Available DNA vaccines showed great promise in preclinical models of infectious and malignant diseases, but their potency was insufficient in clinical trials and is needed to be improved. In this study, we tested systemic administration of two conventional adjuvants, synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs (CpG-ODN and levamisole (LMS, and evaluated their effect on immune reactions induced by DNA vaccines delivered by a gene gun. DNA vaccination was directed either against the E7 oncoprotein of human papillomavirus type 16 or against the BCR-ABL1 oncoprotein characteristic for chronic myeloid leukemia. High doses of both adjuvants reduced activation of mouse splenic CD8+ T lymphocytes, but the overall antitumor effect was enhanced in both tumor models. High-dose CpG-ODN exhibited a superior adjuvant effect in comparison with any combination of CpG-ODN with LMS. In summary, our results demonstrate the benefit of combined therapy with gene-gun-delivered antitumor DNA vaccines and systemic administration of CpG-ODN or LMS.

  10. IL-2基因佐剂强化梅毒螺旋体外膜蛋白Tp92 DNA疫苗的免疫保护性研究%Evaluation of the protective effect of Treponema pallidum Tp92 DNA vaccine induced by genetic adjuvant IL-2

    赵飞骏; 张晓红; 吴华; 曾铁兵; 刘双全; 曹训宇; 陈曦; 余坚

    2013-01-01

    目的 观察IL-2基因佐剂与梅毒螺旋体(Treponema pallidum,Tp)膜蛋白Tp92抗原编码基因DNA疫苗联合免疫新西兰兔后对Tp皮肤感染的免疫保护效果. 方法 将体重约3kg的新西兰兔随机分为pcDNA3.1(+)/IL-2+ pcDNA3.1(+)/Tp92联合免疫组,pcDNA3.1(+)/Tp92免疫组,pcDNA3.1(+)空质粒组及PBS空白组共4组,每组18只,每隔2周免疫一次,共免疫3次,初次免疫后第10周进行Tp皮肤感染,观察并记录感染早期各组家兔皮损情况;ELISA检测感染后不同时间点免疫兔血清特异性抗体水平和脾细胞IL-2及IFN-γ水平;MTT法检测感染后不同时间点兔脾淋巴细胞增殖水平. 结果 IL-2+ Tp92 DNA疫苗联合免疫组在Tp感染后0~224 d期间的不同时间点均检测到高滴度的特异性IgG,与Tp92 DNA疫苗组及各对照组比较差异均有统计学意义(P<0.05);感染后第14 d联合免疫组兔脾细胞培养上清中IFN-γ和IL-2水平均显著高于Tp92单独免疫组(P<0.05)及空质粒对照组和空白对照组(P<0.01),感染后不同时间点兔脾细胞均有明显增殖反应,SI值显著高于同期Tp92单独免疫组(P<0.05)及空质粒对照组和空白对照组(P<0.01).Tp感染早期联合免疫组家兔皮损Tp阳性率为20%,溃疡病灶形成率为10%,皮损愈合时间为48 d. 结论 IL-2基因佐剂和Tp92 DNA联合免疫能有效地诱导新西兰兔在Tp感染期间产生稳定持久保护性免疫应答,并能阻止Tp皮肤感染部位病损的发展.%Objective To estimate the protection efficacy of Tp92 DNA vaccine-induced immune responses enhanced by an interleukin (IL)-2 expression plasmid as a genetic adjuvant in a rabbit Treponema pallidum (Tp) skin challenge model. Methods New Zealand White rabbits were divided into four groups (pIL-2 + pTp92, pTp92, pcD, and PBS groups) that were immunized with three intramuscular inoculations of Tp92 DNA vaccine alone or in combination with a plasmid expressing IL-2 at 2-week intervals. Ten

  11. The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice.

    Jessica A Hess

    2016-07-01

    Full Text Available In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses.Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2.The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.

  12. Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial

    Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer. Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life. Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative

  13. Influence of Brucella abortus lipopolysaccharide as an adjuvant on the immunogenicity of HPV-16 L1VLP vaccine in mice.

    Kianmehr, Zahra; Soleimanjahi, Hoorieh; Ardestani, Susan Kaboudanian; Fotouhi, Fatemeh; Abdoli, Asghar

    2015-04-01

    Brucella abortus lipopolysaccharide (LPS) has less toxicity and no pyrogenic properties in comparison with other bacterial LPS. It is a toll-like receptor 4 agonist and has been shown to have the potential use as a vaccine adjuvant. In this study, the immunostimulatory properties of LPS from smooth and rough strains of B. abortus (S19 and RB51) as adjuvants were investigated for the human papillomavirus type 16 (HPV16) L1 virus-like particles (L1VLPs) vaccines. C57BL/6 mice were immunized subcutaneously three times either with HPV-16 L1VLPs alone, or in combination with smooth LPS (S-LPS), rough LPS (R-LPS), aluminum hydroxide or a mixture of them as adjuvant. The humoral immunity was evaluated by measuring the specific and total IgG levels, and also the T-cell immune response of mice was evaluated by measuring different cytokines such as IFN-γ, TNF-α, IL-4, IL-10 and IL-17. Results showed that serum anti-HPV16 L1VLP IgG antibody titers was significantly higher in mice immunized with a combination of VLPs and R-LPS or S-LPS compared with other immunized groups. Co-administration of HPV-16 L1VLPs with R-LPS elicited the highest levels of splenocytes cytokines (IFN-γ, IL-4, IL-17 and TNF-α) and also effectively induced improvement of a Th1-type cytokine response characterized with a high ratio of IFN-γ/IL-10. The data indicate that B. abortus LPS particularly RB51-LPS enhances the immune responses to HPV-16 L1VLPs and suggests its potential as an adjuvant for the development of a potent prophylactic HPV vaccine and other candidate vaccines. PMID:25187406

  14. Characterization of a novel oil-in-water emulsion adjuvant for swine influenza virus and Mycoplasma hyopneumoniae vaccines.

    Galliher-Beckley, A; Pappan, L K; Madera, Rachel; Burakova, Y; Waters, A; Nickles, M; Li, X; Nietfeld, J; Schlup, J R; Zhong, Q; McVey, S; Dritz, S S; Shi, J

    2015-06-01

    Vaccines consisting of subunit or inactivated bacteria/virus and potent adjuvants are widely used to control and prevent infectious diseases. Because inactivated and subunit antigens are often less antigenic than live microbes, a growing need exists for the development of new and improved vaccine adjuvants that can elicit rapid and long-lasting immunity. Here we describe the development and characterization of a novel oil-in-water emulsion, OW-14. OW-14 contains low-cost plant-based emulsifiers and was added to antigen at a ratio of 1:3 with simple hand mixing. OW-14 was stable for prolonged periods of time at temperatures ranging from 4 to 40°C and could be sterilized by autoclaving. Our results showed that OW-14 adjuvanted inactivated swine influenza viruses (SIV; H3N2 and H1N1) and Mycoplasma hyopneumoniae (M. hyo) vaccines could be safely administered to piglets in two doses, three weeks apart. Injection sites were monitored and no adverse reactions were observed. Vaccinated pigs developed high and prolonged antibody titers to both SIV and M. hyo. Interestingly, antibody titers were either comparable or greater than those produced by commercially available FluSure (SIV) or RespiSure (M. hyo) vaccines. We also found that OW-14 can induce high antibody responses in pigs that were vaccinated with a decreased antigen dose. This study provides direct evidence that we have developed an easy-to-use and low-cost emulsion that can act as a powerful adjuvant in two common types of swine vaccines. PMID:25936722

  15. Ginsenoside Re as an adjuvant to enhance the immune response to the inactivated rabies virus vaccine in mice.

    Su, Xiaoyan; Pei, Zengyang; Hu, Songhua

    2014-06-01

    The inactivated rabies virus vaccine (RV) is a relatively expensive vaccine, prone to failure in some cases. Ginsenoside Re (Re) is a saponin isolated from Panax ginseng, and has an adjuvant property. Here the adjuvant effect of Re to improve the immune response to the RV is evaluated in mice. ICR mice were immunized with saline, 2.50mg/kg Re, 20μl RV, 100μl RV, or 20μl of RV adjuvanted with Re (1.25, 2.50 or 5.00mg/kg). Different time points after boosting, we measured serum antibodies in blood samples and separated splenocytes to detect lymphocyte proliferation and the production of IL-4, IL-10, IL-12, and IFN-γ in vitro. We also compared immunizations containing 20μl RV and 20μl RV adjuvanted with Re (5.00mg/kg) for the expression of CD4(+) and CD8(+) T-cell subsets at different time points. Results indicated that co-administration of Re significantly enhanced serum antibody titers, increased the CD4(+):CD8(+) ratio, and enhanced both proliferation responses and IL-4, IL-10, IL-12 and IFN-γ secretions. Both Th1 and Th2 immune responses were activated. The supplementation of the Re (5.00mg/kg) to 20μl of RV significantly amplified serum antibody responses and Th1/Th2 responses inducing similar protection as did 100μl of RV. This suggests that Re could be used to reduce the dose, and therefore the cost, of the RV to achieve the same effective protection. Re merits further studies for use with vaccines of mixed Th1/Th2 immune responses. PMID:24680943

  16. Presenting and Evaluating Qualitative Research

    Anderson, Claire

    2010-01-01

    The purpose of this paper is to help authors to think about ways to present qualitative research papers in the American Journal of Pharmaceutical Education. It also discusses methods for reviewers to assess the rigour, quality, and usefulness of qualitative research. Examples of different ways to present data from interviews, observations, and focus groups are included. The paper concludes with guidance for publishing qualitative research and a checklist for authors and reviewers.

  17. Common Perspectives in Qualitative Research.

    Flannery, Marie

    2016-07-01

    The primary purpose of this column is to focus on several common core concepts that are foundational to qualitative research. Discussion of these concepts is at an introductory level and is designed to raise awareness and understanding of several conceptual foundations that undergird qualitative research. Because of the variety of qualitative approaches, not all concepts are relevant to every design and tradition. However, foundational aspects were selected for highlighting. PMID:27314194

  18. Qualitative research in ophthalmic sciences

    Murthy G; Gupta Sanjeev

    1999-01-01

    Qualitative research was the preserve of social scientists before making inroads into medical sciences, as the medical fraternity was wedded to evidence-based medicine. Qualitative research methods are now being increasingly used in medicine. The goal of qualitative research is to help in the understanding of social phenomenon in their natural settings. These methods help to unravel mysteries relating to complex human interactions and to study the role of human behaviour in health and disease...

  19. Qualitative Equations: The Confluence Case

    Aubin, J.-P.

    1988-01-01

    This paper deals with a domain of Artificial Intelligence known under the name of "qualitative simulation" or "qualitative physics", to which special volumes of "Artificial Intelligence" (1984) and or "IEEE Transactions on Systems, Man and Cybernetics" (1987) have been devoted. It defines the concept of "qualitative frame" of a set, which allows to introduce strict, large and dual confluence frames of a finite dimensional vector-space. After providing a rigorous definition of standa...

  20. Qualitative methods in travel surveys

    HANNES, Els; Janssens, Davy; Wets, Geert

    2009-01-01

    This chapter explains the added value of integrating qualitative methods in travel surveys. The introduction briefly frames some general aspects of qualitative research. Distinct steps in a research process structure the remainder of this chapter. First, questions and contexts most applicable for qualitative methods are addressed. Next, its actual use, role and timing in travel surveys are discussed. Sampling and data collection issues are treated subsequently, followed by a brief account on ...

  1. Screening and appraisal for immunological adjuvant-active fractions from Platycodon grandiflorum total saponins.

    Ouyang, Ke; Chen, Liqing; Sun, Hongxiang; Du, Jing; Shi, Minghua

    2012-02-01

    In this study, the total saponins from the root of Platycodon grandiflorum (PGS(t)) was subjected to D101 macroreticular resin column chromatography to afford four fractions (PGS₃₀, PGS₅₀, PGS₇₅ and PGS₉₅). PGS(t) and its four fractions were evaluated and compared for the haemolytic activities and adjuvant potentials on the specific cellular and humoral immune responses of ICR mice against recombinant hepatitis B surface antigen (HBsAg). PGS(t), PGS₃₀, PGS₅₀, PGS₇₅, and PGS₇₅ showed a slight haemolytic effect, with their concentration inducing 50% of the maximum haemolysis (HD₅₀) being 16.13 ± 0.81, >200, 17.53 ± 0.24, 20.16 ± 0.76, 76.31 ± 2.20 μg/mL against 0.5% rabbit red blood cell, respectively. PGS(t), PGS₅₀, and PGS₇₅ significantly not only enhanced the Con A-, lipopolysaccharide-, and HBsAg-induced splenocyte proliferation, but promoted the killing activities of natural killer (NK) cells from splenocytes in HBsAg-immunized mice (P < 0.01 or P < 0.001). HBsAg-specific IgG, IgG1, IgG2a, and IgG2b antibody levels in serum were also significantly enhanced by PGS(t), PGS₅₀, and PGS₇₅ compared with HBsAg control group (P < 0.05, P < 0.01, or P < 0.001). Moreover, the adjuvant effects of PGS₅₀ and PGS₇₅ on the cellular immune responses and HBsAg-specific IgG2a and IgG2b antibody responses were more significant than those of Alum, PGS₃₀, and PGS₉₅. The results indicated that PGS₅₀ and PGS₇₅ could improve both cellular and humoral immune responses, and elicit a balanced Th1/Th2 response to HBsAg in mice, and that PGS₇₅ may be developed as an ideal candidate adjuvant for hepatitis B vaccine. PMID:21682667

  2. Formulation and characterization of nanoemulsion intranasal adjuvants: effects of surfactant composition on mucoadhesion and immunogenicity.

    Wong, Pamela T; Wang, Su He; Ciotti, Susan; Makidon, Paul E; Smith, Douglas M; Fan, Yongyi; Schuler, Charles F; Baker, James R

    2014-02-01

    The development of effective intranasal vaccines is of great interest due to their potential to induce both mucosal and systemic immunity. Here we produced oil-in-water nanoemulsion (NE) formulations containing various cationic and nonionic surfactants for use as adjuvants for the intranasal delivery of vaccine antigens. NE induced immunogenicity and antigen delivery are believed to be facilitated through initial contact interactions between the NE droplet and mucosal surfaces which promote prolonged residence of the vaccine at the site of application, and thus cellular uptake. However, the details of this mechanism have yet to be fully characterized experimentally. We have studied the physicochemical properties of the NE droplet surfactant components and demonstrate that properties such as charge and polar headgroup geometry influence the association of the adjuvant with the mucus protein, mucin. Association of NE droplets with mucin in vitro was characterized by various biophysical and imaging methods including dynamic light scattering (DLS), zeta potential (ZP), and surface plasmon resonance (SPR) measurements as well as transmission electron microscopy (TEM). Emulsion surfactant compositions were varied in a systematic manner to evaluate the effects of hydrophobicity and polar group charge/size on the NE-mucin interaction. Several cationic NE formulations were found to facilitate cellular uptake of the model antigen, ovalbumin (OVA), in a nasal epithelial cell line. Furthermore, fluorescent images of tissue sections from mice intranasally immunized with the same NEs containing green fluorescent protein (GFP) antigen demonstrated that these NEs also enhanced mucosal layer penetration and cellular uptake of antigen in vivo. NE-mucin interactions observed through biophysical measurements corresponded with the ability of the NE to enhance cellular uptake. Formulations that enhanced antigen uptake in vitro and in vivo also led to the induction of a more consistent

  3. CpG DNA as a vaccine adjuvant.

    Bode, Christian; Zhao, Gan; Steinhagen, Folkert; Kinjo, Takeshi; Klinman, Dennis M

    2011-04-01

    Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimized by maintaining ODNs and vaccine in close proximity. The adjuvant properties of CpG ODNs are observed when administered either systemically or mucosally, and persist in immunocompromised hosts. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer. Clinical trials demonstrate that CpG ODNs have a good safety profile and increase the immunogenicity of coadministered vaccines. PMID:21506647

  4. CpG Oligonucleotides as Cancer Vaccine Adjuvants

    Hidekazu Shirota

    2015-05-01

    Full Text Available Adjuvants improve host responsiveness to co-delivered vaccines through a variety of mechanisms. Agents that trigger cells expressing Toll-like receptors (TLR activate an innate immune response that enhances the induction of vaccine-specific immunity. When administered in combination with vaccines designed to prevent or slow tumor growth, TLR agonists have significantly improved the generation of cytotoxic T lymphocytes. Unfortunately, vaccines containing TLR agonists have rarely been able to eliminate large established tumors when administered systemically. To improve efficacy, attention has focused on delivering TLR agonists intra-tumorally with the intent of altering the tumor microenvironment. Agonists targeting TLRs 7/8 or 9 can reduce the frequency of Tregs while causing immunosuppressive MDSC in the tumor bed to differentiate into tumoricidal macrophages thereby enhancing tumor elimination. This work reviews pre-clinical and clinical studies concerning the utility of TLR 7/8/9 agonists as adjuvants for tumor vaccines.

  5. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fraction in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial. (author). 11 refs.; 2 figs.; 6 tabs

  6. Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.

    Ojas H Mehta

    Full Text Available Neisseria meningitidis lipopolysaccharide (LPS has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS, and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus were immunized with a recombinant PorA P1.7-2,4 (rPorA protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16, each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines.

  7. AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5

    Pérez Oliver

    2009-02-01

    Full Text Available Abstract Background Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP, to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4 and 5 (MSP5, was evaluated. Methods Complete Freund's adjuvant (CFA, which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH, T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline. Results AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses. Conclusion Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.

  8. INTRASITE VANCOMYCIN POWDER AS A PROPHYLACTIC ADJUVANT IN LUMBAR FUSION

    Jorge Álvaro González Ross; Alfredo Javier Moheno Gallardo; Eulalio Elizalde Martínez; José Manuel Pérez Atanasio; Ruth Martínez Martínez

    2016-01-01

    ABSTRACT Objective: To identify whether the use of prophylactic intrasite vancomycin as an adjuvant is a protective factor against deep tissue infection of the surgical site. Methods: Retrospective, descriptive, case-control study evaluating 210 patients, of whom 70 received intrasite vancomycin (case group) and 140 were controls. It was made a follow up for at least one year, reviewing the physical and electronic records. Data were tabulated in spreadsheets (Excel) including all variable...

  9. Carbonation of adjuvant concretes based on local Algerian resources

    Dakhmouche Chabil, Fatima-Zohra,

    2009-01-01

    The carbonation is a pathology which affects cement-based materials such as concretes and mortars.The carbonated skin of material becomes brittle and losses the protection of inner steels againstcorrosion. The corrosion products generate a degradation of the concrete which may lead to thecollapse of the structure.Six types of adjuvant concretes and two cement pastes have been designed by a rheological study inorder to study the effect of accelerated and natural carbonation on the sustainabili...

  10. Adjuvant immunotherapy with BCG in squamous cell bronchial carcinoma.

    Jansen, H.M.; The, T H; Orie, N G

    1980-01-01

    Fifty-four patients with evidence of locally advanced primary squamous cell bronchial carcinoma (SCC), and three patients with adenocarcinoma (AC) had lung resection to remove all the visible tumour. After operation an randomly chosen group of 20 SCC patients received adjuvant BCG immunostimulation by scarifications (BCG-A). An additional group of 14 SCC patients, and three AC patients received initially intrapleural BCG treatment and subsequently scarifications (BCG-B). A control group of 20...

  11. Adjuvant Radio-chemotherapy for extrahepatic biliary tract cancers

    Mentha Gilles; Roth Arnaud D; Bonet Beltrán Marta; Allal Abdelkarim S

    2011-01-01

    Abstract Background Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. Methods Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) r...

  12. Neo-adjuvant chemotherapy in advanced hypopharyngeal carcinoma

    Joshi, P.; V Patil; Joshi, A; V Norohna; Chaturvedi, P.; Chaukar, D.; P Pai; D Nair; Juvekar, S; Agarwal, J. P.; A K D′cruz; Prabhash, K

    2013-01-01

    Objective: The aim of this retrospective study was to find out the role of neo-adjuvant chemotherapy (NACT) in changing the management and outcome of advanced hypopharyngeal cancer patients. Materials and Methods: This is a retrospective analysis of 59 treatment naïve, advanced hypopharyngeal cancer patients presenting to our tertiary care center from April 2010 to October 2011. NACT was given as two (platinum with taxane) or three drug with (platinum, taxane with 5-flurouracil [5 FU]) as 3 w...

  13. Effect of polyphenols on neutrophil activation in adjuvant arthritis

    Nosáľ, R.; Bauerová, K.; Drábiková, K.; Harmatha, Juraj; Jančinová, V.; Perečko, T.; Poništ, S.

    Bratislava : Institute of Experimental Pharmacology & Toxicology SAS, 2012 - (Bauer, V.; Mach, M.; Navarová, J.; Sotníková, R.), s. 84-92 ISBN 978-80-971042-0-7. [Drugs: Their Action in Pharmacology and Toxicology. Bratislava (SK), 31.05.2012] Institutional research plan: CEZ:AV0Z40550506 Keywords : adjuvant arthritis * stilbenes * curcumin Subject RIV: CC - Organic Chemistry

  14. Post-prostatectomy radiotherapy in the adjuvant or relapse setting

    Although screening with prostate specific antigen (PSA) has led to a greater proportion of patients being diagnosed with clinically organ-confined prostate cancer, pathologic extension outside of the prostate (pathologic Stage C) is still found in 25% of patients undergoing radical prostatectomy. In the pre-PSA era, the pathologic findings at surgery were used to select patients for adjuvant therapy for pathologic Stage C prostate cancer. The presence of positive surgical margins, perforation of the prostate capsule, and/or poorly differentiated histology (Gleason score > 7) all independently predicted for an increased risk of local relapse after radical prostatectomy. Seminal vesicle involvement, while also a risk factor for local relapse, was found to be more predictive of distant metastases. Adjuvant radiotherapy was often recommended for patients with these adverse risk factors. While numerous retrospective studies have found that post-prostatectomy pelvic irradiation significantly improves local control, there are no prospective randomized trial demonstrating a survival advantage for this type of treatment. The widespread availability of PSA has enabled the clinician to detect early recurrences after radical prostatectomy. Following radical prostatectomy, the PSA should drop to undetectable levels; patients with measurable PSA in the serum after this operation almost certainly have residual cancer present. Without adjuvant therapy, 50%-75% of patients with pathologic Stage C prostate cancer will develop a rising PSA within 4 years after surgery. The addition of adjuvant pelvic radiotherapy (i.e., prior to the development of a rising PSA) can reduce this failure rate by 50%, particularly in the group of patients without seminal vesicle involvement. In contrast, if one waits to deliver pelvic radiotherapy until the PSA begins to rise, the success rate is considerably lower (< 50% disease-free survival in most series). In summary, the time to institute pelvic

  15. Controversies in the Adjuvant Therapy of Endometrial Cancer

    Sheng-Mou Hsiao; Lin-Hung Wei

    2011-01-01

    Endometrial cancer is the most common malignancy of the female genital tract. Surgical treatment includes hysterectomy, bilateral salpingo-oophorectomy, and an appropriate staging procedure. Relapse of endometrial cancer may occur in patients with high risk factors, such as old age, grade 3 cancer, deep myometrial invasion, and papillary serous and clear cell types. In recent years, several randomized trials reported the results of adjuvant therapy for patients with high risk factors. Nonethe...

  16. CpG DNA as a vaccine adjuvant

    Bode, Christian; Zhao, Gan; Steinhagen, Folkert; Kinjo, Takeshi; Klinman, Dennis M.

    2011-01-01

    Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs trigger cells that express Toll-like receptor 9 (including human plasmacytoid dendritic cells and B cells) to mount an innate immune response characterized by the production of Th1 and proinflammatory cytokines. When used as vaccine adjuvants, CpG ODNs improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. These effects are optimi...

  17. Cerebral biochemical pathways in experimental autoimmune encephalomyelitis and adjuvant arthritis: a comparative metabolomic study.

    Norbert W Lutz

    Full Text Available Many diseases, including brain disorders, are associated with perturbations of tissue metabolism. However, an often overlooked issue is the impact that inflammations outside the brain may have on brain metabolism. Our main goal was to study similarities and differences between brain metabolite profiles of animals suffering from experimental autoimmune encephalomyelitis (EAE and adjuvant arthritis (AA in Lewis rat models. Our principal objective was the determination of molecular protagonists involved in the metabolism underlying these diseases. EAE was induced by intraplantar injection of complete Freund's adjuvant (CFA and spinal-cord homogenate (SC-H, whereas AA was induced by CFA only. Naive rats served as controls (n = 9 for each group. Two weeks after inoculation, animals were sacrificed, and brains were removed and processed for metabolomic analysis by NMR spectroscopy or for immunohistochemistry. Interestingly, both inflammatory diseases caused similar, though not identical, changes in metabolites involved in regulation of brain cell size and membrane production: among the osmolytes, taurine and the neuronal marker, N-acetylaspartate, were decreased, and the astrocyte marker, myo-inositol, slightly increased in both inoculated groups compared with controls. Also ethanolamine-containing phospholipids, sources of inflammatory agents, and several glycolytic metabolites were increased in both inoculated groups. By contrast, the amino acids, aspartate and isoleucine, were less concentrated in CFA/SC-H and control vs. CFA rats. Our results suggest that inflammatory brain metabolite profiles may indicate the existence of either cerebral (EAE or extra-cerebral (AA inflammation. These inflammatory processes may act through distinct pathways that converge toward similar brain metabolic profiles. Our findings open new avenues for future studies aimed at demonstrating whether brain metabolic effects provoked by AA are pain/stress-mediated and

  18. Qualitative Analysis of Somitogenesis Models

    Maschke-Dutz E.

    2007-12-01

    Full Text Available Although recently the properties of a single somite cell oscillator have been intensively investigated, the system-level nature of the segmentation clock remains largely unknown. To elaborate qualitatively this question, we examine the possibility to transform a well-known time delay somite cell oscillator to dynamical system of differential equations allowing qualitative analysis.

  19. Quality assurance of qualitative analysis

    Ríos, Ángel; Barceló, Damiá; Buydens, Lutgarde;

    2003-01-01

    The European Commission has supported the G6MA-CT-2000-01012 project on "Metrology of Qualitative Chemical Analysis" (MEQUALAN), which was developed during 2000-2002. The final result is a document produced by a group of scientists with expertise in different areas of chemical analysis, metrology......: traceability, reliability (uncertainty), validation, and internal/external quality control for qualitative methods....

  20. Using Numbers in Qualitative Research

    Maxwell, Joseph A.

    2010-01-01

    The use of numerical/quantitative data in qualitative research studies and reports has been controversial. Prominent qualitative researchers such as Howard Becker and Martyn Hammersley have supported the inclusion of what Becker called "quasi-statistics": simple counts of things to make statements such as "some," "usually," and "most" more…

  1. [Adjuvant treatment of colon cancer MOSAIC study's main results].

    André, Thierry; Tournigand, Christophe; Achille, Emmanuel; Tubiana-Mathieu, Nicole; Lledo, Gérard; Raoul, Yves; Carola, Elisabeth; Flesch, Michel; Muron, Thierry; Boutan-Laroze, Arnaud; Guérin Meyer, Véronique; Boaziz, Catherine; Maigre, Michel; Ganem, Gérard; Mousseau, Mireille; Mounedji-Boudiaf, Lamia; de Gramont, Aimery

    2006-02-01

    Oxaliplatin in combination with 5-fluorouracil/leucovorin (LV5FU) improves the response rate and survival of patients with metastatic colorectal cancer. The objective of the Mosaic study was to evaluate the efficacy of this association in the adjuvant treatment of stage II and III colon cancer. This international study, including 2,246 patients, compared the efficacy of standard treatment with LV5FU2 alone to that of oxaliplatin-LV5FU (Folfox4 regimen) following R0 resection of the primary tumour. Both treatments were administered every two weeks for six months. At 3-year follow-up, the risk of relapse was decreased by 23% in the Folfox4 group (p = 0.002). The protocol was well tolerated, with an identical overall mortality during treatment (0.5%) in both groups. The main specific complication, peripheral sensory neuropathy was reversible in the great majority of cases. A new analysis at 4-year follow-up (median 48.6 months) confirmed the superior efficacy of the Folfox4 regimen compared to the standard treatment, the reduction in relapse risk being 24% (p = 0.0008). On the strength of these results, oxaliplatin was granted a marketing authorization for the indication adjuvant treatment of stage III colon cancer. Based on the data currently available, physicians should consider adjuvant treatment for stage II patients, making each individual decision for treatment on a case-by-case basis. PMID:16483940

  2. Immune responses to Mycoplasma bovis proteins formulated with different adjuvants.

    Prysliak, Tracy; Perez-Casal, Jose

    2016-06-01

    Most vaccines for protection against Mycoplasma bovis disease are made of bacterins, and they offer varying degrees of protection. Our focus is on the development of a subunit-based protective vaccine, and to that end, we have identified 10 novel vaccine candidates. After formulation of these candidates with TriAdj, an experimental tri-component novel vaccine adjuvant developed at VIDO-InterVac, we measured humoral and cell-mediated immune responses in vaccinated animals. In addition, we compared the immune responses after formulation with TriAdj with the responses measured in animals vaccinated with a mix of a commercial adjuvant (Emulsigen™) and 2 of the components of the TriAdj, namely polyinosinic:polycytidylic acid (poly I:C) and the cationic innate defense regulator (IDR) peptide 1002 (VQRWLIVWRIRK). In this latter trial, we detected significant IgG1 humoral immune responses to 8 out of 10 M. bovis proteins, and IgG2 responses to 7 out of 10 proteins. Thus, we concluded that the commercial adjuvant formulated with poly I:C and the IDR peptide 1002 is the best formulation for the experimental vaccine. PMID:27105454

  3. Analysis of adjuvant treatment with chemoradiation in gastric cancer

    The Hospital San Juan de Dios has analyzed the benefit of patients with gastric cancer who undergo surgery after receiving adjuvant chemoradiation. A retrospective study was performed reviewing records of patients during the period 1 January 2001 to December 31, 2005. These patients have been discharged with a diagnosis of gastric cancer and have received a complete resection with curative gastric malignancy and adjuvant chemoradiation according to the protocol established by Dr. MacDonald. In the study 0116. 743 patients were discharged to Hospital San Juan de Dios, 1 in 20 has been possible to diagnose gastric cancer at early stages for a total of 28 patients. The results obtained were compared at the Hospital San Juan de Dios with those published by Dr. MacDonald. The over-life of 3 years in the chemoradiation group in Hospital San Juan de Dios has been of 42.9% and 50% in the study MacDonald. The group that has not received adjuvant the over-life in the same period has been of 20 % in HSJD and 41% in the study MacDonald, being lower percentage of patients with this over-life, but greater range of difference.

  4. External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

    David Hajage

    Full Text Available BACKGROUND: Adjuvant! Online is a web-based application designed to provide 10 years survival probability of patients with breast cancer. Several predictors have not been assessed in the original Adjuvant! Online study. We provide the validation of Adjuvant! Online algorithm on two breast cancer datasets, and we determined whether the accuracy of Adjuvant! Online is improved with other well-known prognostic factors. PATIENTS AND METHODS: The French data set is composed of 456 women with early breast cancer. The Dutch data set is composed of 295 women less than 52 years of age. Agreement between observation and Adjuvant! Online prediction was checked, and logistic models were performed to estimate the prognostic information added by risk factors to Adjuvant! Online prediction. RESULTS: Adjuvant! Online prediction was overall well-calibrated in the French data set but failed in some subgroups of such high grade and HER2 positive patients. HER2 status, Mitotic Index and Ki67 added significant information to Adjuvant! Online prediction. In the Dutch data set, the overall 10-year survival was overestimated by Adjuvant! Online, particularly in patients less than 40 years old. CONCLUSION: Adjuvant! Online needs to be updated to adjust overoptimistic results in young and high grade patients, and should consider new predictors such as Ki67, HER2 and Mitotic Index.

  5. Al adjuvants can be tracked in viable cells by lumogallion staining.

    Mile, Irene; Svensson, Andreas; Darabi, Anna; Mold, Matthew; Siesjö, Peter; Eriksson, Håkan

    2015-07-01

    The mechanism behind the adjuvant effect of aluminum salts is poorly understood notwithstanding that aluminum salts have been used for decades in clinical vaccines. In an aqueous environment and at a nearly neutral pH, the aluminum salts form particulate aggregates, and one plausible explanation of the lack of information regarding the mechanisms could be the absence of an efficient method of tracking phagocytosed aluminum adjuvants and thereby the intracellular location of the adjuvant. In this paper, we want to report upon the use of lumogallion staining enabling the detection of phagocytosed aluminum adjuvants inside viable cells. Including micromolar concentrations of lumogallion in the culture medium resulted in a strong fluorescence signal from cells that had phagocytosed the aluminum adjuvant. The fluorescence appeared as spots in the cytoplasm and by confocal microscopy and co-staining with probes presenting fluorescence in the far-red region of the spectrum, aluminum adjuvants could to a certain extent be identified as localized in acidic vesicles, i.e., lysosomes. Staining and detection of intracellular aluminum adjuvants was achieved not only by diffusion of lumogallion into the cytoplasm, thereby highlighting the presence of the adjuvant, but also by pre-staining the aluminum adjuvant prior to incubation with cells. Pre-staining of aluminum adjuvants resulted in bright fluorescent particulate aggregates that remained fluorescent for weeks and with only a minor reduction of fluorescence upon extensive washing or incubation with cells. Both aluminum oxyhydroxide and aluminum hydroxyphosphate, two of the most commonly used aluminum adjuvants in clinical vaccines, could be pre-stained with lumogallion and were easily tracked intracellularly after incubation with phagocytosing cells. Staining of viable cells using lumogallion will be a useful method in investigations of the mechanisms behind aluminum adjuvants' differentiation of antigen-presenting cells

  6. Resiquimod and polyinosinic–polycytidylic acid formulation with aluminum hydroxide as an adjuvant for foot-and-mouth disease vaccine

    Zhou, Chun-Xue; Li, Dong; Chen, Ying-Li; Lu, Zeng-Jun; Sun, Pu; Cao, Yi-Mei; Bao, Hui-Fang; Fu, Yuan-Fang; Li, Ping-hua; Bai, Xing-Wen; Xie, Bao-Xia; Liu, Zai-Xin

    2014-01-01

    Background Toll-like receptor (TLR) agonists reportedly have potent antiviral and antitumor activities and may be a new kind of adjuvant for enhancing immune efficacy. Resiquimod (R848) is an imidazoquinoline compound with potent antiviral activity and functions through the TLR7/TLR8 MyD88-dependent signaling pathway. Polyinosinic-polycytidylic acid [poly(I:C)] is a synthetic analog of double-stranded RNA that induces the production of pro-inflammatory cytokines by the activation of NF-κB thr...

  7. Development of avian influenza virus H5 DNA vaccine and MDP-1 gene of Mycobacterium bovis as genetic adjuvant

    Jalilian, Babak; Omar, Abdul Rahman; Bejo, Mohd Hair; Alitheen, Noorjahan Banu; Rasoli, Mehdi; Matsumoto, Sohkichi

    2010-01-01

    Background Studies have shown that DNA vaccines can induce protective immunity, which demonstrated the high potential of DNA vaccines as an alternative to inactivated vaccines. Vaccines are frequently formulated with adjuvants to improve their release, delivery and presentation to the host immune system. Methods The H5 gene of H5N1 virus (A/Ck/Malaysia/5858/04) was cloned separately into pcDNA3.1 + vector. The immunogenicity of the cloned H5 DNA vaccine was tested on SPF chickens using two di...

  8. Pay more attention to the immunologically comparative evaluation of HIV-1 DNA vaccine in combination with adjuvant cytokines: a long way to go

    REN Xiao-feng

    2006-01-01

    @@ To the Editor: A recent article entitled "HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice"was published in the Chinese Medical Journal.1 The authors descriptively analyzed the adjuvant potential of an interleukin-12 (IL-12), interleukin-18 (IL-18),regulated on activation of normal T-cell expressed and secreted factor (RANTES), macrophage inflammatory protein 1 alpha (MIP-1α) or stromal cell derived factor 1 (SDF-1) plasmid when coimmunized with an HIV Gag gene-based DNA vaccine. Consequently the authors believed that IL-12, IL-18, or SDF-1 plasmid DNA potentially serves as immune adjuvants in combination with therapeutic HIV-1 DNA vaccine. The RANTES,MIP-1α plasmid DNA potentially serves as immune adjuvants in combination with HIV-1 prophylactic vaccine. Although the experiment allows us to consider such a coinoculation strategy as one of the means against HIV-1 infection, some special attentions should be highlighted.

  9. Structurally well-defined macrophage activating factor derived from vitamin D3-binding protein has a potent adjuvant activity for immunization.

    Yamamoto, N; Naraparaju, V R

    1998-06-01

    Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D3-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice. PMID:9682967

  10. 6-(4-Amino-2-butyl-imidazoquinolyl)-norleucine: Toll-like receptor 7 and 8 agonist amino acid for self-adjuvanting peptide vaccine.

    Fujita, Yoshio; Hirai, Kazuyuki; Nishida, Keigo; Taguchi, Hiroaki

    2016-05-01

    Generally, small peptides by themselves are weak to induce antibody responses. Toll-like receptor (TLR) ligands are attractive candidates of vaccine adjuvants to improve their antigenicity. The covalent conjugation of TLR ligands with antigens to produce self-adjuvanting peptide vaccine is a promising approach. Based on the structure of TLR7/8 ligands, a series of synthetic amino acids 6-imidazoquinolyl-norleucines were synthesized, wherein an imidazoquinoline structure as the TLR7/8 agonistic pharmacophores was constructed on the ε-NH2 group of Lys. Of them, 6-(4-amino-2-butyl-imidazoquinolyl)-norleucine showed the most potent TLR7 and TLR8 agonistic activities with EC50 values of 8.55 and 106 μM, respectively. Subsequently, mice were immunized with the influenza A virus M2e antigen mixed with or covalently conjugated to the TLR7/8 agonist amino acid, which led to induction of M2e specific antibody productions in the absence of other adjuvant. We successfully developed a novel efficient tool for self-adjuvanting peptide vaccines targeting TLR7/8. PMID:26874701

  11. Combined effect of space radiation and adjuvants on mice in vivo

    Sorokina, Svetlana; Zaichkina, Svetlana; Rozanova, Olga; Aptikaeva, Gella; Romanchenko, Sergei; Smirnova, Helene; Peleshko, Vladimir

    2012-07-01

    Recently we investigated the cytogenetic effects of low-dose-rate high-LET radiation on SHK mice in the radiation field behind the concrete shield of the Serpukhov accelerator with 70 GeV proton energy, that simulates the spectral and component composition of radiation fields formed in the conditions of high-altitude flights. It was found that low doses of high-LET irradiation led to an increase in the cytogenetic damage in mice which can be compared with level of spontaneous lesions. At the same time no decrease of cytogenetic damage was detected after irradiation with the challenging dose of 1.5 Gy, i. e., no adaptive response (AR) takes place in polychromatic erythrocytes (PCE) as opposed to low doses of chronic X-radiation. The goal of the present work was to determine if there is any influence of combined action of low doses of high-LET radiation and adjuvants on the cytogenetic damages and solid tumor growth in mice. Two-month-old SHK male mice were used. A search for potential adaptogens was performed among the adjuvants such as dibazol and calcium chloride. In each experiment, a group of animals was exposed to low doses of high-LET radiation and treated with dibazol or CaCl2 solutions after that mice were additionally irradiated with X-radiation according to the scheme of AR: 0.1 Gy + 1.5 Gy. After 28 h, the animals of all groups were killed by the cervical dislocation. Bone marrow specimens for calculating micronuclei (MN) in PCE were prepared by a conventional method with minor modifications. The influence of combined treatment of high-LET radiation and adjuvants on the growth of solid tumor of Ehrlich ascite carcinoma was estimated by measuring the size of the tumor at different times after the inoculation of ascitic cells into the femur. Our earlier study has shown that dibazol when used alone not only induced AR but also increased the magnitude of radiation AR when used in combination with low doses of X-radiation. In present work the obtained results

  12. Caspase-1 Dependent IL-1β Secretion and Antigen-Specific T-Cell Activation by the Novel Adjuvant, PCEP

    Sunita Awate

    2014-06-01

    Full Text Available The potent adjuvant activity of the novel adjuvant, poly[di(sodiumcarboxylatoethylphenoxyphosphazene] (PCEP, with various antigens has been reported previously. However, very little is known about its mechanisms of action. We have recently reported that intramuscular injection of PCEP induces NLRP3, an inflammasome receptor gene, and inflammatory cytokines, including IL-1β and IL-18, in mouse muscle tissue. Caspase-1 is required for the processing of pro-forms of IL-1β and IL-18 into mature forms and is a critical constituent of the NLRP3 inflammasome. Hence, in the present study, we investigated the role of caspase-1 in the secretion of IL-1β and IL-18 in PCEP-stimulated splenic dendritic cells (DCs. Caspase inhibitor YVAD-fmk-treated splenic DCs showed significantly reduced IL-1β and IL-18 secretion in response to PCEP stimulation. Further, PCEP had no effect on the expression of MHC class II or co-stimulatory molecules, CD86 and CD40, suggesting that PCEP does not induce DC maturation. However, PCEP directly activated B-cells to induce significant production of IgM. In addition, PCEP+ovalbumin (OVA immunized mice showed significantly increased production of antigen-specific IFN-γ by CD4+ and CD8+ T-cells. We conclude that PCEP activates innate immunity, leading to increased antigen-specific T-cell responses.

  13. Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

    Cheng Tsui

    2012-01-01

    Full Text Available Abstract Background Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer. Methods In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0, and to obtain the utility value by the standard gamble (SG and visual scale (VS methods. Total medical cost was assessed from the (National Health Insurance NHI payer's perspective. Results Survival at 11 years was significantly better in the groserelin group (P Conclusions Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

  14. Adjuvant endocrine and chemotherapy for early breast cancer

    Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

  15. Positivism and qualitative nursing research.

    Paley, J

    2001-01-01

    Despite the hostility to positivism shown by qualitative methodologists in nursing, as in other disciplines, the epistemological and ontological instincts of qualitative researchers seem to coincide with those of the positivists, especially Bayesian positivists. This article suggests that positivists and qualitative researchers alike are pro-observation, proinduction, pro-plausibility and pro-subjectivity. They are also anti-cause, anti-realist, anti-explanation, anti-correspondence, anti-truth. In only one respect is there a significant difference between positivist and qualitative methodologists: most positivists have believed that, methodologically, the natural sciences and the social sciences are the same; most qualitative researchers are adamant that they are not. However, if positivism fails as a philosophy of the natural sciences (which it probably does), it might well succeed as a philosophy of the social sciences, just because there is a methodological watershed between the two. Reflex antagonism to positivism might therefore be a major obstacle to understanding the real reasons why qualitative research and the natural sciences are methodologically divergent; and less hostility on the part of qualitative nurse researchers might bring certain advantages in its wake. PMID:11885869

  16. Immunogenicity of a virosomally-formulated Plasmodium falciparum GLURP-MSP3 chimeric protein-based malaria vaccine candidate in comparison to adjuvanted formulations

    Tamborrini Marco

    2011-12-01

    Full Text Available Abstract Background In clinical trials, immunopotentiating reconstituted influenza virosomes (IRIVs have shown great potential as a versatile antigen delivery platform for synthetic peptides derived from Plasmodium falciparum antigens. This study describes the immunogenicity of a virosomally-formulated recombinant fusion protein comprising domains of the two malaria vaccine candidate antigens MSP3 and GLURP. Methods The highly purified recombinant protein GMZ2 was coupled to phosphatidylethanolamine and the conjugates incorporated into the membrane of IRIVs. The immunogenicity of this adjuvant-free virosomal formulation was compared to GMZ2 formulated with the adjuvants Montanide ISA 720 and Alum in three mouse strains with different genetic backgrounds. Results Intramuscular injections of all three candidate vaccine formulations induced GMZ2-specific antibody responses in all mice tested. In general, the humoral immune response in outbred NMRI mice was stronger than that in inbred BALB/c and C57BL/6 mice. ELISA with the recombinant antigens demonstrated immunodominance of the GLURP component over the MSP3 component. However, compared to the Al(OH3-adjuvanted formulation the two other formulations elicited in NMRI mice a larger proportion of anti-MSP3 antibodies. Analyses of the induced GMZ2-specific IgG subclass profiles showed for all three formulations a predominance of the IgG1 isotype. Immune sera against all three formulations exhibited cross-reactivity with in vitro cultivated blood-stage parasites. Immunofluorescence and immunoblot competition experiments showed that both components of the hybrid protein induced IgG cross-reactive with the corresponding native proteins. Conclusion A virosomal formulation of the chimeric protein GMZ2 induced P. falciparum blood stage parasite cross-reactive IgG responses specific for both MSP3 and GLURP. GMZ2 thus represents a candidate component suitable for inclusion into a multi-valent virosomal

  17. Comparative evaluation of low-level laser and systemic steroid therapy in adjuvant-enhanced arthritis of rat temporomandibular joint: A histological study

    Khozeimeh, Faezeh; Moghareabed, Ahmad; Allameh, Maryam; Baradaran, Shahrzad

    2015-01-01

    Background: Low-level laser therapy (LLLT) has shown a promising effect in ameliorating symptoms of rheumatoid arthritis (RA). The aim of this investigation was to compare the early and late anti-inflammatory effects of LLLT and betamethasone in RA. Materials and Methods: In this animal experimental study, after inducing a model of RA in temporomandibular joint (TMJ) of 37 Wistar rats using adjuvant injection, they were randomly distributed into three experimental groups of 12 animals each: (...

  18. Combining Viral Vectored and Protein-in-adjuvant Vaccines Against the Blood-stage Malaria Antigen AMA1: Report on a Phase 1a Clinical Trial

    Susanne H. Hodgson; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Thomas W Rampling; Biswas, Sumi; Ian D Poulton; Miura, Kazutoyo; Douglas, Alexander D.; Alanine, Daniel GW; Illingworth, Joseph J.; de Cassan, Simone C.; ZHU, DAMING; Nicosia, Alfredo; Long, Carole A.

    2014-01-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines—chimpanzee adenovir...

  19. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per;

    2015-01-01

    ) radiotherapy, four randomized studies were found where use of adjuvant chemotherapy showed no benefit in survival. Three trials were found in which a subset of patients received preoperative (chemo) radiotherapy. Two of these trials showed a statistically significant benefit of adjuvant chemotherapy. Twenty......BACKGROUND: The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU...... trials were identified in which the patients did not receive preoperative (chemo) radiotherapy, including five Asian studies in which a statistically significant benefit from adjuvant chemotherapy was reported. CONCLUSIONS: Most of the data found did not support the use of postoperative adjuvant...

  20. Development of a minimal saponin vaccine adjuvant based on QS-21

    Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

    2014-07-01

    Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

  1. Qualitative Psycholgy Nexus Vol. VIII: Epistemologies for Qualitative Research

    Soini, Hannu; Kronqvist, Eeva-Liisa; Huber, Günter L.; Maxwell, Joseph; Kiegelmann, Mechthild; Gento, Samuel; Medina, Antonio; Pina, Jorge; Domínguez, María Concepción; Schweizer, Karin; Korte, Petra; Pavlovic, Jelena; Suorsa, Teemu; Feliz, Sálvora; Feliz, Tiberio

    2011-01-01

    The 9th annual meeting of the Center for Qualitative Psychology was held in Northern Finland, near to the city of Oulu. The seminar was started with two crucial questions leading the participants to the theme of the conference. The orientation followed the line of the former meetings of the Center for Qualitative Research in Psychology helping participants to reflect own ways of doing psychological research. In the beginning of the conference we asked the conference participant...

  2. GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza

    Clegg, Christopher H.; Roque, Richard; Perrone, Lucy A.; Rininger, Joseph A.; Bowen, Richard; Reed, Steven G.

    2014-01-01

    The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine ma...

  3. Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

    Xiaosong Li; Min Min; Nan Du; Ying Gu; Tomas Hode; Mark Naylor; Dianjun Chen; Nordquist, Robert E.; Chen, Wei R.

    2013-01-01

    With the development of cancer immunotherapy, cancer vaccine has become a novel modality for cancer treatment, and the important role of adjuvant has been realized recently. Chitin, chitosan, and their derivatives have shown their advantages as adjuvants for cancer vaccine. In this paper, the adjuvant properties of chitin and chitosan were discussed, and some detailed information about glycated chitosan and chitosan nanoparticles was also presented to illustrate the trend for future development.

  4. Adjuvant radiotherapy for melanoma metastatic to axillary and inguinal nodes: Regional tumor control and late effects

    Ahmed SK; Kottschade LA; Markovic SN; Garces YI; Foote RL

    2014-01-01

    Background: Adjuvant radiotherapy reduces nodal recurrence in metastatic melanoma. The purpose of this study was to examine the effects of adjuvant radiotherapy on in-field nodal control of melanoma metastatic to axillary and inguinal lymph nodes. Methods: The medical records of patients who received adjuvant radiotherapy from January 1, 2003, through December 31, 2011, at Mayo Clinic were reviewed. Results: In the 20 patients identified, the rates of 2-year overall survival, nodal control, a...

  5. Vaccination of Atlantic cod (Gadus morhua L.) against atypical furunculosis using different adjuvants

    Hamid, Lemia M.O

    2003-01-01

    In recent years increased attention has been focussed on fish vaccines and vaccination against diseases in farmed fish. In this study, efficacy and side effects of vaccination against atypical furunculosis in Atlantic cod (Gadus morhua L.) were studied in an experimental trial by using different adjuvants. The different adjuvanted vaccines were administered by intraperitoneal injection (i.p.) to Atlantic cod. The adjuvants used were CpG DNA, Aluminium hydroxide (Alhydrogel), an...

  6. EVALUATION OF N-RATIO IN SELECTING PATIENTS FOR ADJUVANT CHEMORADIOTHERAPY AFTER D2-GASTRECTOMY

    Wilson Luiz da COSTA JUNIOR; Felipe Jose Fernandez COIMBRA; Batista, Thales Paulo; RIBEIRO, Heber Salvador de Castro; DINIZ, Alessandro Landskron

    2013-01-01

    Context Whether adjuvant chemoradiotherapy may contribute to improve survival outcomes after D2-gastrectomy remains controvertial. Objective To explore the clinical utility of N-Ratio in selecting gastric cancer patients for adjuvant chemoradiotherapy after D2-gastrectomy. Methods A retrospective cohort study was carried out on gastric cancer patients who underwent D2-gastrectomy alone or D2-gastrectomy plus adjuvant chemoradiotherapy (INT-0116 protocol) at the Hospital A. C. Camargo from...

  7. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    Mold, M; Shardlow, E; Exley, C.

    2016-01-01

    Aluminium adjuvants remain the most widely used and effective adjuvants in vaccination and immunotherapy. Herein, the particle size distribution (PSD) of aluminium oxyhydroxide and aluminium hydroxyphosphate adjuvants was elucidated in attempt to correlate these properties with the biological responses observed post vaccination. Heightened solubility and potentially the generation of Al3+ in the lysosomal environment were positively correlated with an increase in cell mortality in vitro, pote...

  8. Development of a minimal saponin vaccine adjuvant based on QS-21

    Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; LIVINGSTON, PHILIP O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

    2014-01-01

    Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability, and an enigmatic molecular mechanism of action. Herein, we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the enti...

  9. Induction chemotherapy followed by radiotherapy and adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma treated

    Objective: To summarize the efficacy and toxicities of induction chemotherapy followed by radiotherapy and adjuvant chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC). Methods: From Oct. 1997 to Nov. 2000, 77 patients with histologically proven locally advanced NPC, staged according to the Fuzhou stage classification, were retrospectively studied. Before radical radio- therapy, the patients received 1-3 cycles cisplatin(PDD) 20 mg/m2 on Days 1-3 and fluorouracil(5-Fu) 500 nag/ma on Days 1-3 repeated every two weeks. Sixty-two patients also received calcium folinate (CF) 100 mg/m2 on Days 1-3. Two to four cycles of adjuvant chemotherapy was given 21 days after the completion of radiotherapy. All patients received radical radiotherapy by 60 Co to the nasopharynx and neck with a total dose of 64-78 Gy at 1.8-2.0 Gy per fraction over 7.0-7. 5 weeks to the primary site. The dose to the lymph nodes was 60-68 Gy. After-loading radiotherapy was given to the residual disease in 1 patient (20 Gy in 2 fractions). Results: The median follow-up was 60 months (ranged from 3 to 103 months). The 5-year overall urvival rate (OS), disease-free survival rate (DFS), relapse-free survival rate (RFS) and distant metastasis-free survival rate (DMSF) were 68%, 58%, 81% and 75%. The patients who received more than 3 cycles of chemotherapy or not had no significant effects on the OS (χ2=0.05, P=0.831). The incidence of grade 3 or 4 acute side-effects of radiotherapy was vomiting 1%, leukopenia 3%, mucositis 23% and skin reaction 5%, all of which eventually resolved. The most frequent late toxicities were hearing impairment (51% ). Patients with more than 3 cycles chemotherapy were more likely to have late hearing loss (z=2.06, P=0.039). Only one patient had radiation-induced brain damage. Conclusions: Induction chemo- therapy, radiotherapy and adjuvant chemotherapy for locally advanced nasopharyngeal carcinoma would result in a comparable outcome, but may

  10. Structure-function relationship of the saponins from the roots of Platycodon grandiflorum for hemolytic and adjuvant activity.

    Sun, Hongxiang; Chen, Liqing; Wang, Juanjuan; Wang, Kuiwu; Zhou, Jiyong

    2011-12-01

    To assess the contribution of the aglycone and sugar chain to the biological activity of saponins from Platycodon grandiflorum, seven structurally consecutive saponins, platycodin D (PD), D2 (PD2), D3 (PD3), platycoside A (PA), E (PE), deapioplatycoside E (DPE), and polygalacin D2 (PGD) were compared for their hemolytic activities and adjuvant potentials on the immune responses to Newcastle disease virus-based recombinant avian influenza vaccine (rL-H5) in mice. Among seven compounds, the order of the hemolytic activity was PGD ≈ PD > PD2 > PA > PD3 > PE > DPE. PD, PD2, PA, and PGD significantly not only promoted concanavalin A (Con A)-, lipopolysaccharide (LPS)- and antigen-induced splenocyte proliferation, but enhanced the NK cell activity in mice immunized with rL-H5. PD and PD2 increased the antigen specific IgG, IgG1, IgG2a, and IgG2b antibody titers, while PA and PGD only induce the IgG and IgG1 antibody responses in the immunized mice. However, the other three saponins were not observed for adjuvant activity. The results suggested that the sugar chains attached to C-3, the glycidic moiety at C-28 of aglycone, as well as aglycone affect their biological activities. Interestingly, their hemolytic and adjuvant activities increased with the retention time by reverse phase HPLC analysis. The retention time may be useful for primary estimation of fundamental adjuvanticity of saponin with the same aglycone. PMID:21945665

  11. Enhanced humoral response to influenza vaccine in aged mice with a novel adjuvant, rOv-ASP-1.

    Jiang, Jiu; Fisher, Erin M; Concannon, Mark; Lustigman, Sara; Shen, Hao; Murasko, Donna M

    2016-02-10

    Immunization is the best way to prevent seasonal epidemics and pandemics of influenza. There are two kinds of influenza vaccines available in the United States: an inactivated vaccine (TIV) and an attenuated vaccine; however, only TIV is approved for immunization of the elderly population. While the aged population has the highest rate of influenza vaccination, the protective efficacy is low as evidenced by elderly individuals having the highest mortality associated with influenza. Recently, we reported that an adjuvant derived from the helminth parasite Onchocerca volvulus, named O. volvulus activation-associated secreted protein-1 (Ov-ASP-1), can significantly enhance the protective efficacy of an inactivated vaccine (TIV) in young adult mice. In the current study, we examined whether this recombinant Ov-ASP-1 (rOv-ASP-1) can enhance the efficacy of TIV in aged mice as well. While primary immunization with TIV alone produced only a low level of influenza-specific antibodies (total IgG, IgG1, and IgG2c) in aged mice, the antibody levels were significantly increased after immunization with TIV+rOv-ASP-1. More importantly, the level of the total IgG in aged mice administered TIV+rOv-ASP-1 was comparable to that of young adult mice immunized with TIV alone. Co-administration of rOv-ASP-1 induced a low level of cross-reactive antibody and enhanced the protective efficacy of TIV in aged mice, reflected by significantly increased survival after challenge with a heterologous influenza virus. rOv-ASP-1 was also superior to the conventional adjuvant alum in inducing specific IgG after TIV immunization in aged mice, and in conferring protection after challenge. These results demonstrate that rOv-ASP-1 may serve as a potential adjuvant for influenza vaccine to improve the efficacy of protection in the elderly. PMID:26795365

  12. Response of immune response genes to adjuvants poly [di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP), CpG oligodeoxynucleotide and emulsigen at intradermal injection site in pigs.

    Magiri, R B; Lai, K; Chaffey, A M; Wilson, H L; Berry, W E; Szafron, M L; Mutwiri, G K

    2016-07-01

    Understanding the mechanisms by which adjuvants mediate their effects provide critical information on how innate immunity influences the development of adaptive immunity. Despite being a critical vaccine component, the mechanisms by which adjuvants mediate their effects are not fully understood and this is especially true when they are used in large animals. This lack of understanding limits our ability to design effective vaccines. In the present study, we administered polyphosphazene (PCEP), CpG oligodeoxynucleotides (CpG), emulsigen or saline via an intradermal injection into pigs and assessed the impact on the expression of reported 'adjuvant response genes' over time. CpG induced a strong upregulation of the chemokine CXL10 several 'Interferon Response Genes', as well as TNFα, and IL-10, and a down-regulation of IL-17 genes. Emulsigen upregulated expression of chemokines CCL2 and CCL5, proinflammatory cytokines IL-6 and TNFα, as well as TLR9, and several IFN response genes. PCEP induced the expression of chemokine CCL2 and proinflammatory cytokine IL-6. These results suggest that emulsigen and CpG may promote recruitment of innate immune cells and Th1 type cytokine production but that PCEP may promote a Th-2 type immune response through the induction of IL-6, an inducer of B cell activity and differentiation. PMID:27269793

  13. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup;

    2015-01-01

    BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database....... RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas there was no...

  14. A caprine herpesvirus 1 vaccine adjuvanted with MF59™ protects against vaginal infection and interferes with the establishment of latency in goats.

    Mariarosaria Marinaro

    Full Text Available The immunogenicity and the efficacy of a beta-propiolactone-inactivated caprine herpesvirus 1 (CpHV-1 vaccine adjuvanted with MF59™ were tested in goats. Following two subcutaneous immunizations, goats developed high titers of CpHV-1-specific serum and vaginal IgG and high serum virus neutralization (VN titers. Peripheral blood mononuclear cells (PBMC stimulated in vitro with inactivated CpHV-1 produced high levels of soluble IFN-gamma and exhibited high frequencies of IFN-gamma producing cells while soluble IL-4 was undetectable. On the other hand, control goats receiving the inactivated CpHV-1 vaccine without adjuvant produced only low serum antibody responses. A vaginal challenge with virulent CpHV-1 was performed in all vaccinated goats and in naïve goats to assess the efficacy of the two vaccines. Vaginal disease was not detected in goats vaccinated with inactivated CpHV-1 plus MF59™ and these animals had undetectable levels of infectious challenge virus in their vaginal washes. Goats vaccinated with inactivated CpHV-1 in the absence of adjuvant exhibited a less severe disease when compared to naïve goats but shed titers of challenge virus that were similar to those of naïve goats. Detection and quantitation of latent CpHV-1 DNA in sacral ganglia in challenged goats revealed that the inactivated CpHV-1 plus MF59™ vaccine was able to significantly reduce the latent viral load when compared either to the naïve goats or to the goats vaccinated with inactivated CpHV-1 in the absence of adjuvant. Thus, a vaccine composed of inactivated CpHV-1 plus MF59™ as adjuvant was strongly immunogenic and induced effective immunity against vaginal CpHV-1 infection in goats.

  15. Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies.

    Niu, Yange; Liu, Ye; Yang, Limin; Qu, Hongren; Zhao, Jingyi; Hu, Rongliang; Li, Jing; Liu, Wenjun

    2016-04-01

    Rabies, a zoonotic disease, causes > 55,000 human deaths globally and results in at least 500 million dollars in losses every year. The currently available rabies vaccines are mainly inactivated and attenuated vaccines, which have been linked with clinical diseases in animals. Thus, a rabies vaccine with high safety and efficacy is urgently needed. Peptide vaccines are known for their low cost, simple production procedures and high safety. Therefore, in this study, we examined the efficacy of multi-epitope-based vaccine candidates against rabies virus. The ability of various peptides to induce epitope-specific responses was examined, and the two peptides that possessed the highest antigenicity and conservation, i.e., AR16 and hPAB, were coated with adjuvant canine-Gp96 and used to prepare vaccines. The peptides were prepared as an emulsion of oil in water (O/W) to create three batches of bivalent vaccine products. The vaccine candidates possessed high safety. Virus neutralizing antibodies were detected on the day 14 after the first immunization in mice and beagles, reaching 5-6 IU/mL in mice and 7-9 IU/mL in beagles by day 28. The protective efficacy of the vaccine candidates was about 70%-80% in mice challenged by a virulent strain of rabies virus. Thus, a novel multi-epitope-based rabies vaccine with Gp96 as an adjuvant was developed and validated in mice and dogs. Our results suggest that synthetic peptides hold promise for the development of novel vaccines against rabies. PMID:27068655

  16. Qualitative Capacities as Imprecise Possibilities.

    Dubois, Didier; Prade, Henri; Rico, Agnés

    2013-01-01

    National audience This paper studies the structure of qualitative capacities, that is, monotonic set-functions, when they range on a finite totally ordered scale equipped with an order-reversing map. These set-functions correspond to general representations of uncertainty, as well as importance levels of groups of criteria in multicriteria decision-making. More specifically, we investigate the question whether these qualitative set-functions can be viewed as classes of simpler set-function...

  17. Designs for qualitatively orientated research

    Philipp Mayring

    2007-01-01

    It is shown that contemporary psychology appears to be hindered by its orientation to natural science and experimental methodology. An opening to more combinations of methods, to an integration of qualitative and quantitative approaches is needed. Several foundations for such an integration (pragmatism, constructivism, dialectics) are given. An integration is only possible if qualitatively orientated studies have a clear conception, a study design, and a research process model which fits into...

  18. Qualitative methods : the new orthodoxy?

    Crang, M.

    2002-01-01

    It is an interesting moment to write Progress in Human Geography’s first report on qualitative methods. In one sense, it suggests these methods have, at long last, arrived and been accepted as established approaches. That this is an overdue recognition needs little emphasizing when surveying the number of articles drawing upon, at least in part, qualitative material. However, a less encouraging omen is the recent column in the UK Economic and Social Research Council’s Social Sciences, penned ...

  19. Evolution of Long-Term Adjuvant Anti-hormone Therapy: Consequences and Opportunities. The St. Gallen Prize Lecture

    Jordan, V. Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R.; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2012-01-01

    experience described not only the unique mechanism of SERM-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5-years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The “oestrogen purge” concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs “anti-hormonal drug holidays” so that a woman’s own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the Selective ER Modulators (SERMs) with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect have advanced patient survivorship significantly and promises to reduce breast cancer incidence. PMID:22015273

  20. The St. Gallen Prize Lecture 2011: evolution of long-term adjuvant anti-hormone therapy: consequences and opportunities.

    Jordan, V Craig; Obiorah, Ifeyinwa; Fan, Ping; Kim, Helen R; Ariazi, Eric; Cunliffe, Heather; Brauch, Hiltrud

    2011-10-01

    described not only the unique mechanism of selective ER modulator (SERM)-stimulated breast cancer growth, but also a new apoptotic biology of oestradiol action in breast cancer, following 5 years of anti-hormonal treatment. Oestradiol-induced apoptotic therapy is currently shown to be successful for the short-term treatment of metastatic ER positive breast cancer following exhaustive treatment with anti-hormones. The "oestrogen purge" concept is now being integrated into trials of long-term adjuvant anti-hormone therapy. The Study of Letrazole Extension (SOLE) trial employs "anti-hormonal drug holidays" so that a woman's own oestrogen may periodically purge and kill the nascent sensitized breast cancer cells that are developing. This is the translation of an idea first proposed at the 1992 St. Gallen Conference. Although tamoxifen is the first successful targeted therapy in cancer, the pioneering medicine is more than that. A study of the pharmacology of tamoxifen opened the door for a pioneering application in cancer chemoprevention and created a new drug group: the SERMs, with group members (raloxifene and lasofoxifene) approved for the treatment and prevention of osteoporosis with a simultaneous reduction of breast cancer risk. Thus, the combined strategies of long-term anti-hormone adjuvant therapy, targeted to the breast tumour ER, coupled with the expanding use of SERMs to prevent osteoporosis and prevent breast cancer as a beneficial side effect, have advanced patient survivorship significantly and promise to reduce breast cancer incidence. PMID:22015273

  1. Long-term side effects of adjuvant breast cancer treatment

    Buijs, Ciska

    2008-01-01

    Breast cancer is the most common malignancy in women. Breast cancer accounts for one-third of all cancers in females and 24% of the patients are younger than 55 years of age. More than 10% all Dutch women will develop breast cancer and 70-80% of all breast cancer patients will survive over 5 years. In the absence of distant metastases, patients receive loco-regional therapy with or without adjuvant systemic therapy. Loco-regional therapy consists of either a modified radical mastectomy, in so...

  2. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU) and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96%) had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy) was completed by 22 patients (91.7%). Only 7 patients (36.8%) completed the total planned courses of chemotherapy. 2 local relapses (10%), 2 regional relapses (10%) and 2 distant relapses (10%) were recorded. Time to progression has not been reached. 9 patients (37.5%) died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8%) with 9 (36%) patients suffering grade 3 or 4 toxicity and 5 patients (20%) suffering from grade 3 or 4 neutropenia. 4 (17%) patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17%) and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the full planned courses of chemotherapy. This is due to

  3. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Ghosn Marwan G

    2010-06-01

    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  4. Qualitative Data Mining and Its Applications

    Bratko, Ivan; Šuc, Dorian

    2003-01-01

    In machine learning from numerical data, usually the target concept is a numerical function that facilitates quantitative prediction. In contrast to this, we consider qualitative data mining which aims at finding qualitative patterns, or qualitative relationships in numerical data. We present one approach to qualitative data mining, in which the target concepts are expressed as qualitative decision trees. We reviewsome case studies in qualitative data mining, and discuss typical application s...

  5. Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142 administered intramuscularly with adjuvant system AS01

    Otsyula Nekoye

    2013-01-01

    Full Text Available Abstract Background The development of an asexual blood stage vaccine against Plasmodium falciparum malaria based on the major merozoite surface protein-1 (MSP1 antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP142 has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites. Methods Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP142 in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP142 in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator. Results In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele previously tested at both study sites. Conclusions Given that the primary

  6. Interleukin-12 gene adjuvant increases the immunogenicity of virus-like particles of human papillomavirus type 16 regional variant strain

    Lanlan Wei

    2014-01-01

    Full Text Available Objectives: To analyze the immunogenicity of virus-like particles (VLP of human papillomavirus type 16 (HPV16 isolated in East China and the adjuvant potential of interleukin-12 (IL-12. Methods: The variant HPV16 L1VLP expressed in sf9 insect cells were purified with cesium chloride gradient centrifugation. BALB/c mice were vaccinated with VLP (L1N, VLP with Freund's adjuvant (L1A or VLP with IL-12 recombinant plasmid (L1P. HPV16 VLP specific IgG and IFN-γ level in the serum were detected by ELISA, and the percentage of CD4+ and CD8+ in spleen cells was detected with flow cytometry. Results: The titers of serum IgG antibodies in vaccinated groups were higher than in negative control and the serum antibodies mainly recognized conformation-dependent HPV16 VLP epitopes. Splenic CD4+ and CD8+ T cell subsets increased after vaccination in every experimental group, and CD8+ increased obviously in L1P group. The ratio of CD4+/CD8+ decreased in L1P group and increased in the other two groups, compared to control group. Vaccination induced specific secretion of IFN-γ in the serum of vaccinated group (p < 0.05, especially in the L1P group. Conclusions: VLP of HPV16 variant strain isolated in East China could induce humoral immunity and cellular immunity in mice, and IL-12 recombinant plasmid can enhance cellular immunity.

  7. The mycobacterial cord factor adjuvant analogue trehalose-6,6'-dibehenate (TDB) activates the Nlrp3 inflammasome.

    Schweneker, Katrin; Gorka, Oliver; Schweneker, Marc; Poeck, Hendrik; Tschopp, Jürg; Peschel, Christian; Ruland, Jürgen; Gross, Olaf

    2013-04-01

    The success of a vaccine consists in the induction of an innate immune response and subsequent activation of the adaptive immune system. Because antigens are usually not immunogenic, the addition of adjuvants that activate innate immunity is required. The mycobacterial cord factor trehalose-6,6'-dimycolate (TDM) and its synthetic adjuvant analogue trehalose-6,6'-dibehenate (TDB) rely on the C-type lectin Mincle and the signaling molecules Syk and Card9 to trigger innate immunity. In this study, we show that stimulation of bone marrow-derived dendritic cells (BMDCs) with TDB induces Nlrp3 inflammasome-dependent IL-1β secretion. While Card9 is required for NF-κB activation by TDB, it is dispensable for TDB-induced activation of the Nlrp3 inflammasome. Additionally, efflux of intracellular potassium, lysosomal rupture, and oxygen radical (ROS) production are crucial for caspase-1 processing and IL-1β secretion by TDB. In an in vivo inflammation model, we demonstrate that the recruitment of neutrophils by TDB is significantly reduced in the Nlrp3-deficient mice compared to the wild-type mice, while the production of chemokines in vitro is not influenced by the absence of Nlrp3. These results identify the Nlrp3 inflammasome as an essential mediator for the induction of an innate immune response triggered by TDB. PMID:22921586

  8. Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

    Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

  9. Development of Novel Protocol for Preclinical Monitoring the Release of Adjuvants Encapsulated Mucosal Delivery Carriers

    Mohamed Ibrahim-Saeed

    2015-12-01

    Full Text Available This work contributes in vaccines down-stream process by introducing a novel platform for in-vitro monitoring of vaccine-adjuvant delivery profile as a crucial preclinical optimizing step in mucosal vaccines. Nano and micro particles of Calcium phosphate (Cap vaccine-adjuvant were encapsulated in Chitosan and Alginate polymeric carriers. Adjuvants release profiles monitored in a permeable bag at 37°C, pH 2, incubated in isotonic buffer for 96 hours. The released Calcium in the outer buffer was monitored and compared in-addition to the carrier’s swelling and biophysical properties. The adjuvants and carriers did not interfere with the proliferation of cultured hepatocytes an indicator of their safe use; Chitosan’s viscosity and swelling were higher than Alginate. Chitosan’s Zeta-potential was significantly high positive, while Cap and Alginate were negative. The prepared CaP and Chitosan particles were in nano-size, while the ready-made CaP adjuvant and Alginate were in micro-size using zeta-seizer and scanning electron-micrograph. The release of nano-size particle was in ascending, extended and controlled manner compared to micro-size adjuvant. Moreover, nano-adjuvant release profile from Chitosan was superior compared to Alginate. The core controlling factors in vaccine-adjuvant sustained release includes; smaller adjuvant particles (nano-size, carrier’s low swelling, high viscosity and importantly carrier-adjuvant entrapment reversibility. Chitosan offers sustained ascending superior capacity in releasing Nano-Cap adjuvant. This novel in-vitro pre-clinical study answer a crucial downstream preparative step for optimizing mucosal vaccines before their direct routine in-vivo trial on animal regardless of adjuvant’s particle size or delivery kinetics.

  10. Adjuvant activity of ambient particulate matter of different sites, sizes, and seasons in a respiratory allergy mouse model

    In the framework of an EU project entitled, 'Respiratory Allergy and Inflammation due to Ambient Particles (RAIAP)', various ambient particulate matter samples were tested for their adjuvant potency in an animal allergy model to ovalbumin. Coarse (2.5-10 μm) and fine (0.15-2.5 μm) particles were collected during the spring, summer, and winter in Rome, Oslo, Lodz, and Amsterdam. Coarse and fine particles were also collected near a seaside location in the Netherlands, where prevailing winds are westerly. These latter particles served as a control, with a minimum contribution by traffic. Ottawa dust (EHC-93) was used as a standard reference sample. Immunoglobulins (IgE, IgG1, and IgG2a), histopathological changes in the lung, cytokines, and the number of cells and their differentiation in lung lavages were used as effect parameters to study the adjuvant potency of these particles. The particles (3 mg/ml) were mixed with ovalbumin (0.4 mg/ml) and intranasally administered during the sensitization or the challenge phase. Intranasal administration of ovalbumin only induced very little antibody response, but introduced a minor inflammatory response in the lung or BAL during the sensitization and challenge phase. On the contrary, after coexposure to EHC-93 and ovalbumin, a major increase was found in immunoglobulin levels specific for ovalbumin, and a major inflammatory response in lung and BAL was induced. Coexposure to ovalbumin with 4 out of 12 collected PM samples (3 mg/ml) resulted in an increase of mainly IgE and IgG1. The histopathological changes consisted of a small to severe peribronchial and perivascular inflammatory response, a hypertrophy of bronchiolar mucous cells and an increase in eosinophils and neutrophils in the BAL. Statistical evaluation of the above-mentioned parameters showed associations with PMx (coarse and fine), site, season, season x PMx, season x site and PMx x site. In addition, adjuvant activity of the PMx can be ranked as Lodz > Rome

  11. Adjuvant radiation therapy in metastatic lymph nodes from melanoma

    To analyze the outcome after adjuvant radiation therapy with standard fractionation regimen in metastatic lymph nodes (LN) from cutaneous melanoma. 86 successive patients (57 men) were treated for locally advanced melanoma in our institution. 60 patients (69%) underwent LN dissection followed by radiation therapy (RT), while 26 patients (31%) had no radiotherapy. The median number of resected LN was 12 (1 to 36) with 2 metastases (1 to 28). Median survival after the first relapse was 31.8 months. Extracapsular extension was a significant prognostic factor for regional control (p = 0.019). Median total dose was 50 Gy (30 to 70 Gy). A standard fractionation regimen was used (2 Gy/fraction). Median number of fractions was 25 (10 to 44 fractions). Patients were treated with five fractions/week. Patients with extracapsular extension treated with surgery followed by RT (total dose ≥50 Gy) had a better regional control than patients treated by surgery followed by RT with a total dose <50 Gy (80% vs. 35% at 5-year follow-up; p = 0.004). Adjuvant radiotherapy was able to increase regional control in targeted sub-population (LN with extracapsular extension)

  12. Preparation and evaluation of functional foods in adjuvant arthritis

    Al-Okbi, S. Y.; Mohamed, D. A.

    2012-07-01

    Adjuvant arthritis is an animal model that closely resembles rheumatoid arthritis in humans. It is a successful working model used to study new anti-inflammatory agents. In previous studies (animal and clinical) we have shown that evening primrose oil, fish oil and the methanol extract of date fruits and fenugreek seeds have anti-inflammatory activity and that the methanol extract of dates has an antioxidant effect. Based on these studies, the aim of the present study was to prepare 7 functional foods containing such bioactive fractions separately or in combination and to evaluate them in adjuvant arthritis in rats, study the stability of bioactive ingredients and evaluate their sensory properties. The studied biochemical parameters were erythrocyte sedimentation rate, erythrocyte superoxide dismutase, glutathione peroxidase and plasma copper, zinc and interlukin 2. Nutritional parameters, including body weight gain, food intake and food efficiency ratio were monitored during the feeding of the functional foods. The bioactive ingredients assessed were total phenolic contents and fatty acids. The results showed improvement in the biochemical parameters, body weight gain and food efficiency ratio of arthritic rats fed on the functional foods with different degrees. All the prepared functional foods were sensory accepted. The active ingredients showed stability during storage. In conclusion, all the tested functional foods showed promising antiinflammatory activity and were determined to be acceptable through sensory evaluation which means that their potential beneficial use as dietary supplements in rheumatoid arthritis patients may be recommended. (Author) 42 refs.

  13. Adjuvant chemoradiotherapy for adenocarcinoma of the stomach. A new progress?

    Frequency of local and distant failures after gastrectomy has led to extended lymph nodes dissection to obtain a better locoregional control. However, five year survival rates were not significantly different between patients undergoing D2 and D1 lymphadenectomy, and higher morbidity and post operative deaths were reported in large randomized trials (respectively 25% vs 48% and 4 vs 13%). Additionally, several met-analysis failed to demonstrate a significant survival advantage with adjuvant chemotherapy. The results of the first trial demonstrating one advantage to adjuvant post-operative chemoradiotherapy should modify the standard care. Disease free and overall survival after surgery alone and after surgery and concurrent chemoradiotherapy were respectively 31% vs 48% and 41% vs 50%. The inter-group trial demonstrate that better local control improve survival if radiation fields include stamps, tumour bed, proximal nodal chains and nodes corresponding to D2 extended lymph nodes dissection. Treatment was feasible with few severe toxic effects (1%). Of the 281 patients, 17% stopped treatment because toxic effects. Technical modalities of radiotherapy and post-operative nutrition support which are critical points of interest for this treatment, are also discussed. (authors)

  14. Alginate Nanoparticles as a Promising Adjuvant and Vaccine Delivery System

    F Sarei

    2013-01-01

    Full Text Available During last decades, diphtheria has remained as a serious disease that still outbreaks and can occur worldwide. Recently, new vaccine delivery systems have been developed by using the biodegradable and biocompatible polymers such as alginate. Alginate nanoparticles as a carrier with adjuvant and prolong release properties that enhance the immunogenicity of vaccines. In this study diphtheria toxoid loaded nanoparticles were prepared by ionic gelation technique and characterized with respect to size, zeta potential, morphology, encapsulation efficiency, release profile, and immunogenicity. Appropriate parameters (calcium chloride and sodium alginate concentration, homogenization rate and homogenization time redounded to the formation of suitable nanoparticles with a mean diameter of 70±0.5 nm. The loading studies of the nanoparticles resulted in high loading capacities (>90% and subsequent release studies showed prolong profile. The stability and antigenicity of toxoid were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis and ouchterlony test and proved that the encapsulation process did not affect the antigenic integrity and activity. Guinea pigs immunized with the diphtheria toxoid-loaded alginate nanoparticles showed highest humoral immune response than conventional vaccine. It is concluded that, with regard to the desirable properties of nanoparticles and high immunogenicity, alginate nanoparticles could be considered as a new promising vaccine delivery and adjuvant system.

  15. Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice.

    Bengtsson, Karin Lövgren; Song, Haifeng; Stertman, Linda; Liu, Ye; Flyer, David C; Massare, Michael J; Xu, Ren-Huan; Zhou, Bin; Lu, Hanxin; Kwilas, Steve A; Hahn, Timothy J; Kpamegan, Eloi; Hooper, Jay; Carrion, Ricardo; Glenn, Gregory; Smith, Gale

    2016-04-01

    Ebola virus (EBOV) causes severe hemorrhagic fever for which there is no approved treatment or preventive vaccine. Immunological correlates of protective immunity against EBOV disease are not well understood. However, non-human primate studies have associated protection of experimental vaccines with binding and neutralizing antibodies to the EBOV glycoprotein (GP) as well as EBOV GP-specific CD4(+) and CD8(+) T cells. In this report a full length, unmodified Zaire EBOV GP gene from the 2014 EBOV Makona strain (EBOV/Mak) was cloned into a baculovirus vector. Recombinant EBOV/Mak GP was produced in Sf9 insect cells as glycosylated trimers and, when purified, formed spherical 30-40nm particles. In mice, EBOV/Mak GP co-administered with the saponin adjuvant Matrix-M was significantly more immunogenic, as measured by virus neutralization titers and anti-EBOV/Mak GP IgG as compared to immunization with AlPO4 adjuvanted or non-adjuvanted EBOV/Mak GP. Similarly, antigen specific T cells secreting IFN-γ were induced most prominently by EBOV/Mak GP with Matrix-M. Matrix-M also enhanced the frequency of antigen-specific germinal center B cells and follicular helper T (TFH) cells in the spleen in a dose-dependent manner. Immunization with EBOV/Mak GP with Matrix-M was 100% protective in a lethal viral challenge murine model; whereas no protection was observed with the AlPO4 adjuvant and only 10% (1/10) mice were protected in the EBOV/Mak GP antigen alone group. Matrix-M adjuvanted vaccine induced a rapid onset of specific IgG and neutralizing antibodies, increased frequency of multifunctional CD4+ and CD8(+) T cells, specific TFH cells, germinal center B cells, and persistence of EBOV GP-specific plasma B cells in the bone marrow. Taken together, the addition of Matrix-M adjuvant to the EBOV/Mak GP nanoparticles enhanced both B and T-cell immune stimulation which may be critical for an Ebola subunit vaccine with broad and long lasting protective immunity. PMID:26921779

  16. Interleukin-22 as a molecular adjuvant facilitates IL-17-producing CD8+ T cell responses against a HBV DNA vaccine in mice.

    Wu, Bing; Zou, Qiang; Hu, Yanxin; Wang, Bin

    2013-10-01

    Interleukin-22 (IL-22) is mainly produced by activated Th1 cells, Th17 cells and NK cells and promotes anti-microbial defense, pro-inflammatory and tissue remodeling responses. However, its potential use as a vaccine adjuvant has not been tested. In this study, we tested if a DNA construct expressing IL-22 (pVAX-IL-22) could be used as a molecular adjuvant to enhance host immune responses induced by HBV DNA vaccination (pcD-S2). After immunizing mice with pcD-S2 combined with pVAX-IL-22, we didn't find enhancement of HBsAg-specific antibody responses in comparison to mice immunized with pcD-S2 alone. However, there was an enhancement of the level of IL-17 expression in antigen specific CD8(+) cytotoxic T lymphocytes (Tc17). By using CD8 T-cell knockout (KO) and IL-17 KO mice, Tc17 cells were found to be a dominant population driving cytotoxicity. Importantly, there was a correlation between pVAX-IL-22 enhancement of T lymphocytes and a reduction of HBsAg-positive hepatocytes in HBsAg transgenic mice. These results demonstrate that IL-22 might be used as an effective adjuvant to enhance cellular immune responses during HBsAg DNA vaccination since it can induce Tc17 cells to break tolerance in HBsAg transgenic mice. PMID:23941891

  17. Aluminum hydroxide adjuvant differentially activates the three complement pathways with major involvement of the alternative pathway

    Güven, Esin; Duus, Karen; Laursen, Inga;

    2013-01-01

    Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action remains poorly understood. Complement involvement in the adjuvant properties of Al(OH)3 has been suggested in several reports together with a depot effect. It is here confirmed that Al(OH)3 treatment of serum depletes c...

  18. Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology.

    Madelene Lindqvist

    Full Text Available Sexually transmitted infections (STIs unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs.

  19. Current adjuvant treatment modalities for gastric cancer: From history to the future.

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-05-15

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  20. Enhanced Protection against Bovine Tuberculosis after Coadministration of Mycobacterium bovis BCG with a Mycobacterial Protein Vaccine-Adjuvant Combination but Not after Coadministration of Adjuvant Alone▿

    Wedlock, D. Neil; Denis, Michel; Painter, Gavin F; Ainge, Gary D.; Vordermeier, H. Martin; Hewinson, R Glyn; Buddle, Bryce M.

    2008-01-01

    Current efforts are aimed at optimizing the protective efficacy of Mycobacterium bovis BCG by the use of vaccine combinations. We have recently demonstrated that the protection afforded by BCG alone is enhanced by vaccinating cattle with a combination of vaccines comprising BCG and a protein tuberculosis vaccine, namely, culture filtrate proteins (CFPs) from M. bovis plus an adjuvant. In the current study, three different adjuvant systems were compared. The CFP was formulated with a depot adj...