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Sample records for adjuvants immunologic

  1. Characterization of the in situ immunological responses to vaccine adjuvants.

    Science.gov (United States)

    Horohov, D W; Dunham, J; Liu, C; Betancourt, A; Stewart, J C; Page, A E; Chambers, T M

    2015-03-15

    Adjuvants are included with many inactivated and some modified live vaccines to enhance immune responses to specific antigens. While early vaccines relied exclusively upon aluminum salts, still the major adjuvant used in human vaccines, other adjuvant products are used in veterinary medicine. In addition to enhancing antigen presentation, adjuvants can also enhance the development of specific immune responses. Thus, alum adjuvants often preferentially stimulate humoral immune responses. By contrast, lipid-based adjuvants are often more effective at stimulating cell-mediated immune responses. Metastim(®) is a lipid-based adjuvant reported to elicit both humoral and cellular immune responses, though the mechanism responsible for this activity remains unclear. In this study, we compared the ability of equine influenza virus vaccines containing either saline or Metastim(®) or an aluminum phosphate adjuvant to stimulate antigen presenting cell function in vivo. Six ponies were intradermally inoculated with inactivated equine influenza (KY97) mixed with either adjuvant or saline. Multiple sites were injected so that biopsies could be collected at different times post injection. The 4mm punch biopsies were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated from 2mm punch biopsies for the determination of gene expression by real-time PCR. H&E staining revealed a variety of cells recruited to the injection sites, including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR analysis of the injection site confirmed this cellular infiltration and identified increased expression of activation markers. Both vaccines also stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing Metastim(®) elicited significantly higher gene expression of interferon-γ, IL-12, CD4 and CD83 compared to alum (paluminum salt, there was also evidence of Th2 cytokine induction. Copyright © 2015 Elsevier

  2. [Immunological adjuvants. Determinant factors in the efficacy-toxicity ratio of the contemporary vaccines].

    Science.gov (United States)

    Batista-Duharte, Alexander; Lastre, Miriam; Pérez, Oliver

    2014-02-01

    To achieve effective and safe vaccines for the prevention of not yet controlled or re-emergent infectious diseases, one of the more importance aspects is to have immunological adjuvants that allow inducing a protective immune response with an appropriate safety profile. Since 1926 the aluminium compounds have been used as adjuvants for human vaccines, and only in the last 10 years have some new products been registered. Although there an enormous quantity of proposed candidates, the toxicity is the main factor that has limited their introduction into the clinic. In this work the mechanism of action are updated, and the toxicity of the immunological adjuvants are revised, especially those that have obtained clinical approval or are close to getting it. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  3. Studies on the toxicities of aluminium hydroxide and calcium phosphate as immunological adjuvants for vaccines.

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    Goto, N; Kato, H; Maeyama, J; Eto, K; Yoshihara, S

    1993-01-01

    Aluminium hydroxide (Al) and calcium phosphate (Ca) have been used for many years as immunological adjuvants for biologicals. We investigated the toxic effects of both adjuvants with different physical properties. Al-gel elicited vascular permeability-increasing and toxic effects to macrophages (M phi), while its haemolytic effect was weak. Ca-gel elicited a significantly stronger haemolytic effect, but no other toxic effect. Incubation of M phi or polymorphonuclear leucocytes with Al-suspension resulted in the largest release of lactate dehydrogenase. Ca-suspension caused haemolysis of about 50% of that caused by Ca-gel.

  4. Safety studies of aluminum in vaccines lack immunotoxicity analysis of this immunological adjuvant: Ignorance or deception?

    OpenAIRE

    Arumugham, Vinu

    2017-01-01

    The safety studies most often referred by vaccine regulators when making claims about the safety of aluminum in vaccines, have ignored the immunotoxicity of aluminum. Vaccinologists admit that they neither understand the general immunological mechanisms involved in vaccination nor do they understand the mechanisms involved in aluminum adjuvant action. Thus vaccine regulators have no scientific basis to make vaccine safety claims. Given this situation one would expect that vaccine regu...

  5. Immunological Adjuvant Activity of Pectinioside A, the Steroidal Saponin from the Starfish Patiria pectinifera.

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    Kawase, Osamu; Ohno, Osamu; Suenaga, Kiyotake; Xuan, Xuenan

    2016-05-01

    The steroidal saponin, pectinioside A, was isolated from the starfish, Patiria pectinifera. When it was subcutaneously injected into mice with ovalbumin (OVA), it facilitated the production of OVA-specific total IgG and IgG1 but not IgG2a. To our knowledge, this is the first report suggesting that starfish saponin has the potential to be an immunological adjuvant, stimulating Th2 type immune response.

  6. Haemolytic activity and immunological adjuvant effect of a new steroidal saponin from Allium ampeloprasum var. porrum.

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    Adão, Camila Rodrigues; Pereira da Silva, Bernadete; Tinoco, Luzineide Wanderley; Parente, José Paz

    2012-01-01

    A new steroidal saponin was isolated from the bulbs of Allium ampeloprasum L. var. porrum. On the basis of chemical evidence, comprehensive spectroscopic analyses, and comparison with known compounds, its structure was established as (3β,5α,6β,25R)-3-{(O-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→2)-O-[O-β-D-glucopyranosyl-(1→3)]-O-β-D-glucopyranosyl-(1→4)-β-D-galactopyranosyl)oxy}-6-hydroxyspirostan-2-one (1). Results of the present study indicated that 1 exhibited haemolytic activity in the in vitro assays, and immunological adjuvant activity on the cellular immune response against ovalbumin antigen. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

  7. Physical properties of ordered mesoporous SBA-15 silica as immunological adjuvant

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    Mariano-Neto, F.; Matos, J. R.; Cides da Silva, L. C.; Carvalho, L. V.; Scaramuzzi, K.; Sant'Anna, O. A.; Oliveira, C. P.; Fantini, M. C. A.

    2014-10-01

    This work reports a detailed analysis of the ordered mesoporous SBA-15 silica synthesis procedure that provides a matrix with mean pore diameter around 10 nm. The encapsulation of bovine serum albumin (BSA) by four different methods allowed the determination of the best imbibition condition, which is keeping the mixture under rest and solvent evaporation. Simulation of the in situ SAXS scattered intensity of the BSA release in potassium buffer solution, gastrointestinal fluids revealed a slow evolution of BSA content, independent of the media. Proton induced x-ray emission results obtained in calcined mouse organs revealed that silica is only present in the spleen after 35 days and is completely eliminated from all mouse organs after 10 weeks. Biological studies showed that Santa Barbara Amorphous-15 is an effective adjuvant when compared to the traditional Al(OH)3, and is non-toxic to mice, rats, dogs and even cells, such as macrophages and dendritic cells. Recent studies showed that the immunological response is improved by enhancing the inflammatory response and the recruitment of immune competent cells to the site of injection as by the oral route and, most importantly, by increasing the number of phagocytes of a particulate antigen by antigen presenting cells. This research is under the scope of the International Patent WO 07030901, IN248654,ZA2008/02277, KR 1089400, MX297263, JP5091863, CN101287491B.

  8. Interleukin-1 stimulates beta-cell necrosis and release of the immunological adjuvant HMGB1.

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    Sarah A Steer

    2006-02-01

    Full Text Available There are at least two phases of beta-cell death during the development of autoimmune diabetes: an initiation event that results in the release of beta-cell-specific antigens, and a second, antigen-driven event in which beta-cell death is mediated by the actions of T lymphocytes. In this report, the mechanisms by which the macrophage-derived cytokine interleukin (IL-1 induces beta-cell death are examined. IL-1, known to inhibit glucose-induced insulin secretion by stimulating inducible nitric oxide synthase expression and increased production of nitric oxide by beta-cells, also induces beta-cell death.To ascertain the mechanisms of cell death, the effects of IL-1 and known activators of apoptosis on beta-cell viability were examined. While IL-1 stimulates beta-cell DNA damage, this cytokine fails to activate caspase-3 or to induce phosphatidylserine (PS externalization; however, apoptosis inducers activate caspase-3 and the externalization of PS on beta-cells. In contrast, IL-1 stimulates the release of the immunological adjuvant high mobility group box 1 protein (HMGB1; a biochemical maker of necrosis in a nitric oxide-dependent manner, while apoptosis inducers fail to stimulate HMGB1 release. The release of HMGB1 by beta-cells treated with IL-1 is not sensitive to caspase-3 inhibition, while inhibition of this caspase attenuates beta-cell death in response to known inducers of apoptosis.These findings indicate that IL-1 induces beta-cell necrosis and support the hypothesis that macrophage-derived cytokines may participate in the initial stages of diabetes development by inducing beta-cell death by a mechanism that promotes antigen release (necrosis and islet inflammation (HMGB1 release.

  9. Interleukin-1 Stimulates beta-Cell Necrosis and Release of the Immunological Adjuvant HMGB1.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: There are at least two phases of beta-cell death during the development of autoimmune diabetes: an initiation event that results in the release of beta-cell-specific antigens, and a second, antigen-driven event in which beta-cell death is mediated by the actions of T lymphocytes. In this report, the mechanisms by which the macrophage-derived cytokine interleukin (IL-1 induces beta-cell death are examined. IL-1, known to inhibit glucose-induced insulin secretion by stimulating inducible nitric oxide synthase expression and increased production of nitric oxide by beta-cells, also induces beta-cell death. METHODS AND FINDINGS: To ascertain the mechanisms of cell death, the effects of IL-1 and known activators of apoptosis on beta-cell viability were examined. While IL-1 stimulates beta-cell DNA damage, this cytokine fails to activate caspase-3 or to induce phosphatidylserine (PS externalization; however, apoptosis inducers activate caspase-3 and the externalization of PS on beta-cells. In contrast, IL-1 stimulates the release of the immunological adjuvant high mobility group box 1 protein (HMGB1; a biochemical maker of necrosis in a nitric oxide-dependent manner, while apoptosis inducers fail to stimulate HMGB1 release. The release of HMGB1 by beta-cells treated with IL-1 is not sensitive to caspase-3 inhibition, while inhibition of this caspase attenuates beta-cell death in response to known inducers of apoptosis. CONCLUSIONS: These findings indicate that IL-1 induces beta-cell necrosis and support the hypothesis that macrophage-derived cytokines may participate in the initial stages of diabetes development by inducing beta-cell death by a mechanism that promotes antigen release (necrosis and islet inflammation (HMGB1 release.

  10. Immunology.

    Science.gov (United States)

    Toskala, Elina

    2014-09-01

    Knowledge of our immune system functions is critical for understanding allergic airway disease development as well as for selection of appropriate diagnostic and therapeutic options for patients with respiratory allergies. This review explains the current understanding of the basic immunology of the upper airways and the pathophysiology of allergic responses, including the mechanisms behind allergic rhinitis. The immune system can be divided to 2 main defense systems that function differently-innate immunity and adaptive immunity. Innate immunity includes several defensive mechanisms such as anatomic or physical barriers, physiological barriers, phagocytosis, and inflammation. The adaptive immune response is activated in an antigen-specific way to provide for the elimination of antigen and induce lasting protection. Hypersensitivity reactions occur when an exaggerated adaptive immune response is activated. Allergic rhinitis is an example of a type I, immunoglobulin E, mediated hypersensitivity reaction. Today we have several immunomodulatory treatment options for patients with allergic airway diseases, such as subcutaneous and sublingual immunotherapy. An understanding of the basics of our immune system and its method of functions is key for using these therapies appropriately. © 2014 ARS-AAOA, LLC.

  11. Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease.

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    Kanoke, Atsushi; Fujimura, Miki; Niizuma, Kuniyasu; Fujimura, Taku; Kakizaki, Aya; Ito, Akira; Sakata, Hiroyuki; Sato-Maeda, Mika; Kure, Shigeo; Tominaga, Teiji

    2016-07-01

    Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by an abnormal vascular network at the base of the brain. Recent studies identified the RNF213 gene (RNF213) as an important susceptibility gene for MMD; however, the mechanisms underlying the RNF213 abnormality related to MMD have not yet been elucidated. We previously reported that Rnf213-deficient mice and Rnf213 p. R4828K knock-in mice did not spontaneously develop MMD, indicating the importance of secondary insults in addition to genetic factors in the pathogenesis of MMD. The most influential secondary insult is considered to be an immunological reaction because RNF213 is predominantly expressed in immunological tissues. Therefore, we herein attempted to evaluate the role of an immunological stimulation as a supplementary insult to the target disruption of RNF213 in the pathophysiology of MMD. Rnf213-deficient mice were treated with strong immunological adjuvants including muramyl dipeptide (MDP)-Lys (L18), and then underwent time-sequential magnetic resonance angiography (MRA) up to 40 weeks of age. The results obtained did not reveal any characteristic finding of MMD, and no significant difference was observed in MRA findings or the anatomy of the circle of Willis between Rnf213-deficient mice and wild-type mice after the administration of MDP-Lys (L18). The ratio of regulatory T cells after the administration of MDP-Lys (L18) was significantly decreased in Rnf213-deficient mice (p<0.01), suggesting the potential role of the RNF213 abnormality in the differentiation of regulatory T cells. Although the mechanisms underlying the development of MMD currently remain unclear, the RNF213 abnormality may compromise immunological self-tolerance, thereby contributing to the development of MMD. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus

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    Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the be...

  13. Qualitative immune modulation by interleukin-2 (IL-2 adjuvant therapy in immunological non responder HIV-infected patients.

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    Francesca Sabbatini

    Full Text Available 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+<200/µl, HIV-RNA<50 cp/ml on combination antiretroviral treatment (cART were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01. Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02 and substantial reductions in IL-10 levels were observed. CONCLUSIONS: IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone.

  14. MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults.

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    Angelika Banzhoff

    Full Text Available Pathogenic avian influenza virus (H5N1 has the potential to cause a major global pandemic in humans. Safe and effective vaccines that induce immunologic memory and broad heterotypic response are needed.Healthy adults aged 18-60 and > 60 years (n = 313 and n = 173, respectively were randomized (1:1 to receive two primary and one booster injection of 7.5 microg or 15 microg doses of a subunit MF59-adjuvanted H5N1 (A/Vietnam/1194/2004 (clade 1 vaccine. Safety was monitored until 6 months after booster. Immunogenicity was assessed by hemagglutination inhibition (HI, single radial hemolysis (SRH and microneutralization assays (MN. Mild injection-site pain was the most common adverse reaction. No serious adverse events relating to the vaccine were reported. The humoral immune responses to 7.5 microg and 15 microg doses were comparable. The rates for seroprotection (HI>40; SRH>25 mm(2; MN > or = 40 after the primary vaccination ranged 72-87%. Six months after primary vaccination with the 7.5 microg dose, 18% and 21% of non-elderly and elderly adults were seroprotected; rates increased to 90% and 84%, respectively, after the booster vaccination. In the 15 microg group, seroprotection rates among non-elderly and elderly adults increased from 25% and 62% after primary vaccination to 92% and 88% after booster vaccination, respectively. A heterologous immune response to the H5N1/turkey/Turkey/05 strain was elicited after second and booster vaccinations.Both formulations of MF59-adjuvanted influenza H5N1 vaccine were well tolerated. The European Union requirement for licensure for pre-pandemic vaccines was met by the lower dose tested. The presence of cross-reactive antibodies to a clade 2 heterologous strain demonstrates that this vaccine may be appropriate for pre-pandemic programs.(ClinicalTrials.gov NCT00311480.

  15. Resiquimod as an Immunologic Adjuvant for NY-ESO-1 Protein Vaccination in Patients with High Risk Melanoma

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    Gnjatic, Sacha; Cruz, Crystal M.; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P.; Rolnitzsky, Linda; Goldberg, Judith; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A.; Bhardwaj, Nina

    2015-01-01

    The TLR7/8 agonist, Resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide with or without Resiquimod in high-risk melanoma patients. In Part I of the study, patients received 100ug full length NY-ESO-1 protein emulsified in 1.25mL Montanide (day 1) followed by topical application of 1000mg of 0.2% Resiquimod gel on days 1 and 3 (Cohort 1) versus days 1, 3, and 5 (Cohort 2) of a 21 day cycle. In Part II, patients were randomized to receive 100ug NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel (Arm-A; N=8) or 1000mg of 0.2% Resiquimod gel (Arm-B; N=12) using the dosing regimen established in Part I. The vaccine regimens were generally well-tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In Part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4+ T-cell responses. CD8+ T-cell responses were only seen in 3 of 12 patients in Arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8+ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical Resiquimod is safe and induces both antibody and CD4+ T-cell responses in the majority of patients; the small proportion of CD8+ T-cell responses suggests that the addition of topical Resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8+ T-cell responses. PMID:25633712

  16. Resiquimod as an immunologic adjuvant for NY-ESO-1 protein vaccination in patients with high-risk melanoma.

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    Sabado, Rachel Lubong; Pavlick, Anna; Gnjatic, Sacha; Cruz, Crystal M; Vengco, Isabelita; Hasan, Farah; Spadaccia, Meredith; Darvishian, Farbod; Chiriboga, Luis; Holman, Rose Marie; Escalon, Juliet; Muren, Caroline; Escano, Crystal; Yepes, Ethel; Sharpe, Dunbar; Vasilakos, John P; Rolnitzsky, Linda; Goldberg, Judith; Mandeli, John; Adams, Sylvia; Jungbluth, Achim; Pan, Linda; Venhaus, Ralph; Ott, Patrick A; Bhardwaj, Nina

    2015-03-01

    The Toll-like receptor (TLR) 7/8 agonist resiquimod has been used as an immune adjuvant in cancer vaccines. We evaluated the safety and immunogenicity of the cancer testis antigen NY-ESO-1 given in combination with Montanide (Seppic) with or without resiquimod in patients with high-risk melanoma. In part I of the study, patients received 100 μg of full-length NY-ESO-1 protein emulsified in 1.25 mL of Montanide (day 1) followed by topical application of 1,000 mg of 0.2% resiquimod gel on days 1 and 3 (cohort 1) versus days 1, 3, and 5 (cohort 2) of a 21-day cycle. In part II, patients were randomized to receive 100-μg NY-ESO-1 protein plus Montanide (day 1) followed by topical application of placebo gel [(arm A; n = 8) or 1,000 mg of 0.2% resiquimod gel (arm B; n = 12)] using the dosing regimen established in part I. The vaccine regimens were generally well tolerated. NY-ESO-1-specific humoral responses were induced or boosted in all patients, many of whom had high titer antibodies. In part II, 16 of 20 patients in both arms had NY-ESO-1-specific CD4⁺ T-cell responses. CD8⁺ T-cell responses were only seen in 3 of 12 patients in arm B. Patients with TLR7 SNP rs179008 had a greater likelihood of developing NY-ESO-1-specific CD8⁺ responses. In conclusion, NY-ESO-1 protein in combination with Montanide with or without topical resiquimod is safe and induces both antibody and CD4⁺ T-cell responses in the majority of patients; the small proportion of CD8⁺ T-cell responses suggests that the addition of topical resiquimod to Montanide is not sufficient to induce consistent NY-ESO-1-specific CD8⁺ T-cell responses. ©2015 American Association for Cancer Research.

  17. [Influenza vaccine and adjuvant].

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    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.

  18. Immunological Assessment of Three Tandem Repeat of Influenza Virus M2 Extracellular Domain with Adjuvant in Balb/c Mice Model

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    Hadiseh Shokouhi

    2016-04-01

    Full Text Available Abstract Background: Influenza A viruses are globally important respiratory pathogens which cause a high degree of morbidity and mortality during annual epidemics. M2 protein which expressed on the viral surface facilitates virus entry to the host cells. The extracellular domain of M2 protein (M2e consists of N-terminal 24 residue which shows remarkable conservation among all subtypes of influenza A viruses. In this study, we evaluated the immunogenicity of three tandem repeats of M2e along with different adjuvants in BALB/C mice model. Materials and Methods: Recombinant protein (3M2e was expressed in Escherichia coli and purified. Six weeks old BALB/c mice were immunized interdermally with three doses of 3M2e alone or supplemented with Alum/CpG motif as adjuvant. Control group was injected with PBS. Two weeks after the last immunization, specific anti-M2 was measured using ELISA method and finally mice were challenged with one lethal dose (LD90 of PR8 virus. Results: The results showed that 3M2e can induce specific antibody alone. However, 3M2e protein supplemented with Alum-CpG induced higher level of specific antibodies, so that, there was a significant difference with 3M2e group (p<0.05. Anti-M2 antibodies mostly consisted of IgG2a subclass which considered as activity index of TH1 Cells. Moreover, this group showed enhanced protection against wild-type virus (survival rate=60%. Conclusion: Applying Alum-CpG as a complex adjuvant may play a crucial role in integrating innate and acquisitive immunity. We increased density of M2e in combination with complex adjuvant and showed that this vaccine induced power immune responses and semi-protected mice against lethal challenge.

  19. Quantitation of the immunological adjuvants, monophosphoryl lipid A and Quil A in poly (lactic-co-glycolic acid) nanoparticles using high performance liquid chromatography with evaporative light scattering detection.

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    Bobbala, Sharan; McDowell, Arlene; Hook, Sarah

    2015-01-15

    Monophosphoryl lipid A (MPL) and Quil A are two immunological adjuvants commonly used in vaccines. At present no simple, validated methods for the quantification of Quil A and MPL have been previously reported therefore the aim of the current study was to develop a simple, fast and validated method to quantify MPL and Quil A using high performance liquid chromatography evaporative light scattering detection (HPLC-ELSD). The HPLC-ELSD technique was carried out using a ZORBAX Eclipse XDB-C8 column (2.1×50 mm; particle size, 3.5 μm) in an isocratic elution mode at 25 °C. MPL was eluted at a retention time of 1.8 min with methanol-water as the mobile phase and a detector temperature of 75 °C. Quil A was resolved as three peaks with retention times of 4.1, 5.5 and 6.4 min with a detector temperature of 30 °C and with water-acetonitrile and 0.01% formic acid as the mobile phase. The nebulizer pressure and gain were set at 3.5 bar and 10, respectively. Calibration curves plotted for both the adjuvants had an R(2)>0.997. Accuracy, intra- and inter-day precision were within the accepted limits. The limit of detection for MPL and Quil A were calculated as 1.343 and 2.06 μg/mL, respectively. The limit of quantification was 2.445 for MPL and 8.97 μg/mL for Quil A. This analytical method was used to quantify the entrapment and in vitro release of MPL and Quil A in a poly lactic-co-glycolic acid (PLGA) nanoparticle vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. IMMUNOLOGICAL METHODS

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    Environmental microbiology does not deal with all aspects of immunology or the immune responses per se, but instead adapts immunology-based research technologies or immunoassays for the study of microorganisms and chemical contaminants in association with the environment. The primary immunologic-bas...

  1. Vaccine adjuvants: Why and how.

    Science.gov (United States)

    Christensen, Dennis

    2016-10-02

    Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.

  2. Applications of nanotechnology for immunology.

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    Smith, Douglas M; Simon, Jakub K; Baker, James R

    2013-08-01

    Nanotechnology uses the unique properties of objects that function as a unit within the overall size range of 1-1,000 nanometres. The engineering of nanostructure materials, including nanoparticles, nanoemulsions or nanotubules, holds great promise for the development of new immunomodulatory agents, as such nanostructures can be used to more effectively manipulate or deliver immunologically active components to target sites. Successful applications of nanotechnology in the field of immunology will enable new generations of vaccines, adjuvants and immunomodulatory drugs that aim to improve clinical outcomes in response to a range of infectious and non-infectious diseases.

  3. Laser vaccine adjuvants

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    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  4. Immunological sterility.

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    Diniz Pereira de Carvalho, W

    1980-01-01

    The author presents the fundamental principles of the immunological process, and describes the constitution, origin, classification and action of antibodies and antigens. He identifies the 5 types of antibodies. He then comments on the classical mechanism of the immunological response. The immunological process is then related to a couple's infertility. After a short history the author calls attention to immunological problems of semen and describes a test he created to detect agglutination and/or immobilization of spermatozoa in non-diluted female blood serum. It is a test to be used as a first step in the research of infertility without an apparent cause (ESCA) in office practice. The author also presents the results of 182 cases studied and in his commentary he shows the advantages and deficiencies of the test.

  5. Silica Nanoparticles as the Adjuvant for the Immunisation of Mice Using Hepatitis B Core Virus-Like Particles: e114006

    National Research Council Canada - National Science Library

    Dace Skrastina; Ivars Petrovskis; Ilva Lieknina; Janis Bogans; Regina Renhofa; Velta Ose; Andris Dishlers; Yuri Dekhtyar; Paul Pumpens

    2014-01-01

      Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic...

  6. Wild immunology.

    Science.gov (United States)

    Pedersen, Amy B; Babayan, Simon A

    2011-03-01

    In wild populations, individuals are regularly exposed to a wide range of pathogens. In this context, organisms must elicit and regulate effective immune responses to protect their health while avoiding immunopathology. However, most of our knowledge about the function and dynamics of immune responses comes from laboratory studies performed on inbred mice in highly controlled environments with limited exposure to infection. Natural populations, on the other hand, exhibit wide genetic and environmental diversity. We argue that now is the time for immunology to be taken into the wild. The goal of 'wild immunology' is to link immune phenotype with host fitness in natural environments. To achieve this requires relevant measures of immune responsiveness that are both applicable to the host-parasite interaction under study and robustly associated with measures of host and parasite fitness. Bringing immunology to nonmodel organisms and linking that knowledge host fitness, and ultimately population dynamics, will face difficult challenges, both technical (lack of reagents and annotated genomes) and statistical (variation among individuals and populations). However, the affordability of new genomic technologies will help immunologists, ecologists and evolutionary biologists work together to translate and test our current knowledge of immune mechanisms in natural systems. From this approach, ecologists will gain new insight into mechanisms relevant to host health and fitness, while immunologists will be given a measure of the real-world health impacts of the immune factors they study. Thus, wild immunology can be the missing link between laboratory-based immunology and human, wildlife and domesticated animal health. © 2011 Blackwell Publishing Ltd.

  7. Comparative immunology.

    Science.gov (United States)

    Cooper, Edwin L

    2006-03-01

    As a discipline, comparative immunology enhances zoology and has gained wide acceptance in the biological sciences. It is an offshoot of the parent field, immunology, and is an amalgam of immunology and zoology. All animals from protozoans to humans have solved the threat of extinction by having evolved an immune-defense strategy that ensures the capacity to react against foreign, non-self microorganisms and cancers that disturb the homeostatic self. Invertebrate-type innate immune responses evolved first and they characterize the metazoans. These rapid natural responses act immediately and are often essential for the occurrence of slower, more specific, adaptive vertebrate-type immune responses. As components of the innate immune system, there is an emphasis on several major steps in the evolutionary process: (i) recognition; (ii) the phagocytic cell; and (iii) the natural killer cell. When vertebrates evolved, beginning with fish, thymus-controlled T cells first appeared, as did bone marrow-derived B cells (first found in amphibians with long bones). These were the precursors of the plasma cells that synthesize and secrete antibodies. Confirming the concept of self/non-self, invertebrates possess natural, non-adaptive, innate, non-clonal, non-anticipatory immune responses, whereas vertebrates possess adaptive, acquired, clonal, and anticipatory responses. This symposium concerns: (i) aspects of the immune spectrum in representative groups; (ii) specific findings (in particular models; e.g. earthworms); (iii) clues as to the possible biomedical application of relevant molecules derived from animals, notably invertebrates; and (iv) some views on the more practical applications of understanding immune systems of invertebrates and ectotherms, and their possible role in survival.

  8. Heroin-HIV-1 (H2) vaccine: induction of dual immunologic effects with a heroin hapten-conjugate and an HIV-1 envelope V2 peptide with liposomal lipid A as an adjuvant.

    Science.gov (United States)

    Torres, Oscar B; Matyas, Gary R; Rao, Mangala; Peachman, Kristina K; Jalah, Rashmi; Beck, Zoltan; Michael, Nelson L; Rice, Kenner C; Jacobson, Arthur E; Alving, Carl R

    2017-01-01

    A synthetic heroin analog (MorHap) and a synthetic 42 amino acid V2 loop peptide from A/E strain of HIV-1 gp120 envelope protein that was previously used in a successful phase III vaccine trial were constructed as antigens together with liposomes containing monophosphoryl lipid A as an adjuvant, to explore the feasibility of producing a dual use vaccine both for treatment of heroin addiction and prevention of HIV-1 infection among injection drug users. The V2 peptide was tethered by a palmitoyl fatty acyl tail embedded in the liposomal lipid bilayer, and the heroin analog was conjugated to tetanus toxoid as a carrier protein that was mixed with the adjuvant. Upon comparison of a linear V2 peptide with a cyclic peptide, differences were found in the secondary configurations by circular dichroism, with the tethered cyclic peptide (palm-cyclic peptide) entirely in a random coil, and the tethered linear V2 peptide (palm-linear V2 peptide) entirely in a beta-sheet. Upon immunization of mice, palm-cyclic peptide induced anti-cyclic peptide endpoint titers >10 6 and was considered to be a better immunogen overall than palm-linear V2 peptide for inducing antibodies to gp120 and gp70-V1V2. The antibodies also inhibited the binding of V2 peptide to the HIV-1 α 4 β 7 integrin receptor. Antibody titers to MorHap, even with the presence of injected cyclic peptide, were very high, and resulted in inhibition of the hyper-locomotion and antinociception effects of injected heroin. From these initial experiments, we conclude that with a potent adjuvant and mostly synthetic constituents, a vaccine directed to heroin and HIV-1 (H2 vaccine) could be a feasible objective.

  9. The 9th International Veterinary Immunology Symposium.

    Science.gov (United States)

    Lunney, Joan K; Kai, Chieko; Inumaru, Shigeki; Onodera, Takashi

    2012-07-15

    This special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune systems of numerous food animals and wildlife, probing basic immunity and the influence of stress, genetics, nutrition, endocrinology and reproduction. Major presentations addressed defense against pathogens and alternative control and prevention strategies including vaccines, adjuvants and novel biotherapeutics. A special Organisation for Economic Co-operation and Development (OECD) Co-operative Research Programme Sponsored Conference on "Vaccination and Diagnosis for Food Safety in Agriculture" highlighted the particular issue of "Immunology in Bovine Paratuberculosis". In April 2010 there was an outbreak of foot-and-mouth disease (FMD) in the southern part of Japan. This stimulated a special 9th IVIS session on FMD, sponsored by the World Organization for Animal Health (OIE) and the Ministry of Agriculture, Forestry and Fisheries (MAFF) of Japan, to discuss improvements of FMD vaccines, their use in FMD control, and risk assessment for decision management. The 9th IVIS was supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS) and included workshops for its MHC and Toolkit Committees. Finally VIC IUIS presented its 2010 Distinguished Service Award to Dr. Kazuya Yamanouchi for "outstanding contributions to the veterinary immunology community" and its 2010 Distinguished Veterinary Immunologist Award to Dr. Douglas F. Antczak for "outstanding research on equine immunology". Published by Elsevier B.V.

  10. Liver Immunology

    Science.gov (United States)

    Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

    2014-01-01

    The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

  11. Immunology of Gut Mucosal Vaccines

    Science.gov (United States)

    Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

    2011-01-01

    Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

  12. Immunology of gut mucosal vaccines.

    Science.gov (United States)

    Pasetti, Marcela F; Simon, Jakub K; Sztein, Marcelo B; Levine, Myron M

    2011-01-01

    Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. © 2010 John Wiley & Sons A/S.

  13. Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination

    NARCIS (Netherlands)

    Bol, K.F.; Aarntzen, E.H.; Hout, F.E. In 't; Schreibelt, G.; Creemers, J.H.; Lesterhuis, W.J.; Gerritsen, W.R.; Grunhagen, D.J.; Verhoef, C.; Punt, C.J.; Bonenkamp, J.J.; Wilt, J.H. de; Figdor, C.G.; Vries, I.J.M. de

    2016-01-01

    Melanoma patients with regional metastatic disease are at high risk for recurrence and metastatic disease, despite radical lymph node dissection (RLND). We investigated the immunologic response and clinical outcome to adjuvant dendritic cell (DC) vaccination in melanoma patients with regional

  14. Applications of nanomaterials as vaccine adjuvants

    Science.gov (United States)

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

  15. Virtual Immunology: Software for Teaching Basic Immunology

    Science.gov (United States)

    Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

    2013-01-01

    As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…

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

    Science.gov (United States)

    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.

  17. Trends in vaccine adjuvants

    NARCIS (Netherlands)

    Schijns, V.E.J.C.; Lavelle, E.C.

    2011-01-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a

  18. Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes

    Science.gov (United States)

    2015-01-01

    Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use. PMID:25648619

  19. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines.

    Science.gov (United States)

    Hayashi, Masayuki; Aoshi, Taiki; Haseda, Yasunari; Kobiyama, Kouji; Wijaya, Edward; Nakatsu, Noriyuki; Igarashi, Yoshinobu; Standley, Daron M; Yamada, Hiroshi; Honda-Okubo, Yoshikazu; Hara, Hiromitsu; Saito, Takashi; Takai, Toshiyuki; Coban, Cevayir; Petrovsky, Nikolai; Ishii, Ken J

    2017-02-01

    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

    Directory of Open Access Journals (Sweden)

    Masayuki Hayashi

    2017-02-01

    Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

  1. Aluminum vaccine adjuvants: are they safe?

    Science.gov (United States)

    Tomljenovic, L; Shaw, C A

    2011-01-01

    Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue.

  2. The New Cellular Immunology

    Science.gov (United States)

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  3. Laser vaccine adjuvants. History, progress, and potential.

    Science.gov (United States)

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.

  4. Roitt's essential immunology

    National Research Council Canada - National Science Library

    Delves, Peter J; Roitt, Ivan M

    2011-01-01

    ... of the immune system, the hallmark easy-reading style of Roitt's Essential Immunology clearly explains the key principles needed by medical and health sciences students, from the basis of immunity to clinical applications...

  5. Immunology Taught by Humans

    OpenAIRE

    Davis, Mark M

    2012-01-01

    After a half-century of mouse-dominated research, human immunology is making a comeback. Informed by mouse studies and powered by new techniques, human immune research is both advancing disease treatment and providing new insights into basic biology.

  6. Identification of Molecular Signatures from Different Vaccine Adjuvants in Chicken by Integrative Analysis of Microarray Data

    Directory of Open Access Journals (Sweden)

    Duk Kyung Kim

    2016-07-01

    Full Text Available The present study compared the differential functions of two groups of adjuvants, Montanide incomplete Seppic adjuvant (ISA series and Quil A, cholesterol, dimethyl dioctadecyl ammonium bromide, and Carbopol (QCDC formulations, in chicken by analyzing published microarray data associated with each type of vaccine adjuvants. In the biological function analysis for differentially expressed genes altered by two different adjuvant groups, ISA series and QCDC formulations showed differential effects when chickens were immunized with a recombinant immunogenic protein of Eimeria. Among the biological functions, six categories were modified in both adjuvant types. However, with respect to “Response to stimulus”, no biological process was modified by the two adjuvant groups at the same time. The QCDC adjuvants showed effects on the biological processes (BPs including the innate immune response and the immune response to the external stimulus such as toxin and bacterium, while the ISA adjuvants modified the BPs to regulate cell movement and the response to stress. In pathway analysis, ISA adjuvants altered the genes involved in the functions related with cell junctions and the elimination of exogenous and endogenous macromolecules. The analysis in the present study could contribute to the development of precise adjuvants based on molecular signatures related with their immunological functions.

  7. Immunological memory is associative

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.J.; Forrest, S. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Computer Science; Perelson, A.S. [Los Alamos National Lab., NM (United States)

    1996-12-31

    The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.

  8. Systems Theory in Immunology

    CERN Document Server

    Doria, Gino; Koch, Giorgio; Strom, Roberto

    1979-01-01

    This volume collects the contributions presented at the "Working Conference on System Theory in Immunology", held in Rome, May 1978. The aim of the Conference was to bring together immunologists on one side and experts in system theory and applied mathematics on the other, in order to identify problems of common interest and to establish a network of joint effort toward their solution. The methodologies of system theory for processing experimental data and for describing dynamical phenomena could indeed contribute significantly to the under­ standing of basic immunological facts. Conversely, the complexity of experimental results and of interpretative models should stimulate mathematicians to formulate new problems and to design appropriate procedures of analysis. The multitude of scientific publications in theoretical biology, appeared in recent years, confirms this trend and calls for extensive interaction between mat- matics and immunology. The material of this volume is divided into five sections, along ...

  9. Immunologic mechanism at infertility

    OpenAIRE

    Aydın, İlknur; Erci, Behice

    2006-01-01

    Infertility has been serious problem for couples that want to have a child. It is estimated that %10-15 of marriages are involuntary childless; that is, there is the serious problem of infertility. In more than 40% of infertility couples that is the reason of their infertility was unknown. In those couples, probably immunological factors were found to be responsible for the infertility. In the article, it was aimed to review the immunologic causes of male and female infertility in the light o...

  10. Vaccines, adjuvants and autoimmunity.

    Science.gov (United States)

    Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

    2015-10-01

    Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Probiotics and immunological disorders

    OpenAIRE

    Stojanov, Spase; Smilkov, Katarina

    2016-01-01

    This article presents a review of the current status of the use of probiotics in treating immunological disorders, using the reported results about the effects of different probiotic strains to the immune system. In this article, the effects of probiotics in asthma and rhinitis and the effects of probiotics in allergy animal models were specifically reviewed and elaborated.

  12. Oral Microbiology and Immunology

    DEFF Research Database (Denmark)

    Dahlén, Gunnar; Fiehn, Nils-Erik; Olsen, Ingar

    , dental assistants and trainees may find it a useful source of reference. The contents are based on general microbiology and immunology. Oral microbiology is given particular attention, with examples relevant to oral infectious diseases. Each chapter opens with a relatively short pre-reading section...

  13. The immunologic revolution: photoimmunology.

    Science.gov (United States)

    Ullrich, Stephen E; Byrne, Scott N

    2012-03-01

    UV radiation targets the skin and is a primary cause of skin cancer (both melanoma and nonmelanoma skin cancer). Exposure to UV radiation also suppresses the immune response, and UV-induced immune suppression is a major risk factor for skin cancer induction. The efforts of dermatologists and cancer biologists to understand how UV radiation exposure suppresses the immune response and contributes to skin cancer induction led to the development of the subdiscipline we call photoimmunology. Advances in photoimmunology have generally paralleled advances in immunology. However, there are a number of examples in which investigations into the mechanisms underlying UV-induced immune suppression reshaped our understanding of basic immunological concepts. Unconventional immune regulatory roles for Langerhans cells, mast cells, and natural killer T (NKT) cells, as well as the immune-suppressive function of lipid mediators of inflammation and alarmins, are just some examples of how advances in immunodermatology have altered our understanding of basic immunology. In this anniversary issue celebrating 75 years of cutaneous science, we provide examples of how concepts that grew out of efforts by immunologists and dermatologists to understand immune regulation by UV radiation affected immunology in general.

  14. Basic and clinical immunology

    Science.gov (United States)

    Chinen, Javier; Shearer, William T.

    2003-01-01

    Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.

  15. Immunology & Human Health.

    Science.gov (United States)

    Dawson, Jeffrey R.; And Others

    This monograph was designed for the high school biology curriculum. The first section reviews the major areas of importance in immunology. Section three contains six instructional activities for the high school classroom and the second section contains teacher's materials for those activities. The activities address for students some of the major…

  16. Refresher Course in Immunology

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 7; Issue 7. Refresher Course in Immunology. Information and Announcements Volume 7 Issue 7 July 2002 pp 92-92. Fulltext. Click here to view fulltext PDF. Permanent link: http://www.ias.ac.in/article/fulltext/reso/007/07/0092-0092. Resonance – Journal ...

  17. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  18. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  19. Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo

    Science.gov (United States)

    Munks, Michael W.; McKee, Amy S.; MacLeod, Megan K.; Powell, Roger L.; Degen, Jay L.; Reisdorph, Nichole A.; Kappler, John W.

    2010-01-01

    It has been recognized for nearly 80 years that insoluble aluminum salts are good immunologic adjuvants and that they form long-lived nodules in vivo. Nodule formation has long been presumed to be central for adjuvant activity by providing an antigen depot, but the composition and function of these nodules is poorly understood. We show here that aluminum salt nodules formed within hours of injection and contained the clotting protein fibrinogen. Fibrinogen was critical for nodule formation and required processing to insoluble fibrin by thrombin. DNase treatment partially disrupted the nodules, and the nodules contained histone H3 and citrullinated H3, features consistent with extracellular traps. Although neutrophils were not essential for nodule formation, CD11b+ cells were implicated. Vaccination of fibrinogen-deficient mice resulted in normal CD4 T-cell and antibody responses and enhanced CD8 T-cell responses, indicating that nodules are not required for aluminum's adjuvant effect. Moreover, the ability of aluminum salts to retain antigen in the body, the well-known depot effect, was unaffected by the absence of nodules. We conclude that aluminum adjuvants form fibrin-dependent nodules in vivo, that these nodules have properties of extracellular traps, and the nodules are not required for aluminum salts to act as adjuvants. PMID:20876456

  20. A Prescription for Human Immunology

    OpenAIRE

    Davis, Mark M

    2008-01-01

    Inbred mice have been an extremely successful tool for basic immunology, but much less so as models of disease. Thus, to maximize the use of immunologic approaches to improve human health, we need more strategically directed efforts in human immunology. This would also open up new opportunities for basic research.

  1. 75 FR 66766 - NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development

    Science.gov (United States)

    2010-10-29

    ... HUMAN SERVICES NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development Notice is hereby... Blue Ribbon Panel to provide expertise in developing a strategic plan and research agenda for the..., Immunology and Transplantation, NIAID, National Institutes of Health. BILLING CODE 4140-01-P ...

  2. Helminths and immunological tolerance

    OpenAIRE

    Johnston, Chris J C; McSorley, Henry J; Anderton, Stephen M; Wigmore, Stephen J; Maizels, Rick M

    2014-01-01

    Current immunosuppression regimens for solid-organ transplantation have shown disappointing efficacy in the prevention of chronic allograft rejection and carry unacceptable risks including toxicity, neoplasia, and life-threatening infection. Achievement of immunological tolerance (long-term antigen unresponsiveness in an immunocompetent host) presents the exciting prospect of freedom from immunosuppression for transplant recipients. It is now 60 years since the first demonstration of immunolo...

  3. Immunology and Epidemiology

    CERN Document Server

    Hraba, Tomáš

    1986-01-01

    In February 1985 a small international meeting of scientists took place at the recreation resort of the Polish Academy of Sci­ ences in Mogilany, near Cracow, Poland. The initiative for holding the workshop came from a working meeting on mathematical immunology and related topics at the International Institute for Applied Sys­ tems Analysis in Laxenburg, Austria, in November 1983. In addition to representatives of IIASA, delegates of the IIASA National Member Organizations (NMO) of Czechoslovakia, Italy, and the soviet Union took part in that working meeting. The participants came to the conclusion that IIASA could play an important role in facilitating the development of research in this field. The first step that they recommended to I IASA was to organize a workshop on mathematical immunology. The purpose of the workshop was to review the progress that has been made in applying mathematics to problems in immunology and to explore ways in which further progress might be achieved, especially by more efficie...

  4. Hematology and immunology studies

    Science.gov (United States)

    Kimzey, S. L.

    1977-01-01

    A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.

  5. Mucosal immunology and virology

    National Research Council Canada - National Science Library

    Tyring, Stephen

    2006-01-01

    .... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

  6. A history of pediatric immunology

    National Research Council Canada - National Science Library

    Stiehm, E Richard; Johnston, Jr, Richard B

    2005-01-01

    Immunology has played a prominent role in the history of medicine. Pediatric immunologists have focused on immune aberrations in pediatric disorders, particularly those involving host defense mechanisms...

  7. Helminths and immunological tolerance.

    Science.gov (United States)

    Johnston, Chris J C; McSorley, Henry J; Anderton, Stephen M; Wigmore, Stephen J; Maizels, Rick M

    2014-01-27

    Current immunosuppression regimens for solid-organ transplantation have shown disappointing efficacy in the prevention of chronic allograft rejection and carry unacceptable risks including toxicity, neoplasia, and life-threatening infection. Achievement of immunological tolerance (long-term antigen unresponsiveness in an immunocompetent host) presents the exciting prospect of freedom from immunosuppression for transplant recipients. It is now 60 years since the first demonstration of immunological tolerance in animal models of transplantation, but translation into routine clinical practice remains elusive. Helminth parasites may provide novel strategies toward achieving this goal. Helminths are remarkably successful parasites: they currently infect more than one quarter of the world's population. It is now well established that the parasites' success is the result of active immunomodulation of their hosts' immune response. Although this primarily secures ongoing survival of the parasites, helminth-induced immunomodulation can also have a number of benefits for the host. Significant reductions in the prevalence of allergy and autoimmune conditions among helminth-infected populations are well recognized and there is now a significant body of evidence to suggest that harmful immune responses to alloantigens may be abrogated as well. Here, we review all existing studies of helminth infection and transplantation, explore the mechanisms involved, and discuss possible avenues for future translation to clinical practice.

  8. Immunology of breast milk

    Directory of Open Access Journals (Sweden)

    Patricia Palmeira

    Full Text Available Summary In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk’s immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant’s ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant’s secretory IgA production is insignificant.

  9. Optimization on Preparation Conditions of Salidroside Liposome and Its Immunological Activity on PCV-2 in Mice

    Directory of Open Access Journals (Sweden)

    Yibo Feng

    2015-01-01

    Full Text Available The aim of this study was to optimize the preparation conditions of salidroside liposome with high encapsulation efficiency (EE and to study the immunological enhancement activity of salidroside liposome as porcine circovirus type 2 virus (PCV-2 vaccine adjuvant. Response surface methodology (RSM was selected to optimize the conditions for the preparation of salidroside liposome using Design-Expert V8.0.6 software. Three kinds of salidroside liposome adjuvants were prepared to study their adjuvant activity. BALB/c mice were immunized with PCV-2 encapsulated in different kinds of salidroside liposome adjuvants. The PCV-2-specific IgG in immunized mice serum was determined with ELISA. The results showed that when the concentration of ammonium sulfate was 0.26 mol·L−1, ethanol volume 6.5 mL, temperature 43°C, ethanol injection rate 3 mL·min−1, and salidroside liposome could be prepared with high encapsulation efficiency of 94.527%. Salidroside liposome as adjuvant could rapidly induce the production of PCV-2-specific IgG and salidroside liposome I adjuvant proved to provide the best effect among the three kinds of salidroside liposome adjuvants.

  10. Carbohydrate-based immune adjuvants

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  11. Fundamentals of vaccine immunology

    Directory of Open Access Journals (Sweden)

    Angela S Clem

    2011-01-01

    Full Text Available From a literature review of the current literature, this article provides an introduction to vaccine immunology including a primer on the components of the immune system, passive vs. active immunization, the mechanism(s by which immunizations stimulate(s immunity, and the types of vaccines available. Both the innate and adaptive immune subsystems are necessary to provide an effective immune response to an immunization. Further, effective immunizations must induce long-term stimulation of both the humoral and cell-mediated arms of the adaptive system by the production of effector cells and memory cells. At least seven different types of vaccines are currently in use or in development that produce this effective immunity and have contributed greatly to the prevention of infectious disease around the world.

  12. Ideernes epidemiologi og kulturens immunologi

    DEFF Research Database (Denmark)

    Sørensen, Jesper

    2007-01-01

    , suggested by Sperber, is extended by an ‘immunology of cultural systems’. In addition to the selective forces described by Sperber and Boyer, the immunological approach argues that the relative success of new representations is largely dependent on how well they fit already existing cultural models...

  13. Self, intentionality, and immunological explanation.

    Science.gov (United States)

    Howes, M

    2000-06-01

    In this paper I propose that there are a number of conceptual reasons to preserve self-concepts in immunology. First, I contend that immunological language, including self-terminology, is neither genuinely anthropomorphic, nor perniciously teleological. Furthermore, although teleology associated with future-directed purposive intent is clearly inappropriate in biological contexts, a special type of teleology, intentionality-as-aboutness, needs to be present if there is to be functional explanation in immunology. Second, based on an analogy with the human self, a self comprised of both non-specific innate functions and somatic self-representation, I claim that self-terminology is very appropriate in immunological contexts. Finally, given the appropriateness of self-concepts in immunology, I suggest that the most satisfactory conceptual structure for self-nonself discrimination probably includes both innate and somatic mechanisms. Copyright 2000 Academic Press.

  14. Prediction model for regional or distant recurrence in endometrial cancer based on classical pathological and immunological parameters

    NARCIS (Netherlands)

    Versluis, M. A.; de Jong, R. A.; Plat, A.; Bosse, T.; Smit, V. T.; Mackay, H.; Powell, M.; Leary, A.; Mileshkin, L.; Kitchener, H. C.; Crosbie, E. J.; Edmondson, R. J.; Creutzberg, C. L.; Hollema, H.; Daemen, T.; de Bock, G. H.; Nijman, H. W.

    2015-01-01

    Background: Adjuvant therapy increases disease-free survival in endometrial cancer (EC), but has no impact on overall survival and negatively influences the quality of life. We investigated the discriminatory power of classical and immunological predictors of recurrence in a cohort of EC patients

  15. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  16. Immunology of atopic dermatitis.

    Science.gov (United States)

    Piloto Valdés, L J; Valdés Sánchez, A F; Gómez Echevarría, A H

    1988-01-01

    Thirty-two adult patients with atopic dermatitis were studied at the Allergology Service of the "Hnos. Ameijeiras" Clinical Surgical Hospital. The diagnosis was established following the criteria of Hanifin and Lobitz. A detailed medical history was written for the patients; the study of some immunological parameters, such as the serum immunoglobulin quantification, delayed skin tests with a battery of antigens, and the spontaneous rosette-test, was also carried out. Almost all the patients showed serum IgE values above 150 UI, by means of the ELISA test modified by C.E.N.I.C. The mean values of the spontaneous rosette-test were low; this was more noticeable during the exacerbation period of the lesions. Candida sp, Mantoux and Streptokinase-Streptodornase antigens showed negative results in a high proportion of patients with atopic dermatitis, in relation with the control group. In atopic dermatitis, there are humoral disorders of immunity; this was demonstrated in our group by increased values of IgE and cellular disorders due to skin anergy, and to a low percentage of rosette forming cells; this does not allow to state that these phenomena have an active participation in the etiopathogenesis of this entity.

  17. Mucosal immunology and probiotics.

    Science.gov (United States)

    Dongarrà, Maria Luisa; Rizzello, Valeria; Muccio, Letizia; Fries, Walter; Cascio, Antonio; Bonaccorsi, Irene; Ferlazzo, Guido

    2013-02-01

    The cross-talk between the mucosa-associated immune system and microbiota is critical in mucosal tissue homeostasis as well as in protection against infectious and inflammatory diseases occurring at mucosal sites. This recent evidence has paved the way to therapeutic approaches aimed at modulating the mucosa-associated immune system using probiotics. Different strains of probiotics possess the ability to finely regulate dendritic cell (DC) activation, polarizing the subsequent T cell activity toward Th1 (e.g. Lactobacillus (Lb) acidophilus), Th2 (Lb.reuteri and Bifidobacterium bifidum) or, as more recently demonstrated, Th17 responses induced by specific strains such as Lb.rhamnosus GG and Lac23a, the latter isolated in our laboratory. Here, we review some recent advances in our understanding of probiotics effects on mucosal immunology, particularly on cells of the innate immunity such as DCs. We also highlight our own experiences in modulating DC functions by commensal bacteria and discuss the relevance of probiotics administration in the treatment of human immunopathologies.

  18. Rotavirus capsid VP6 tubular and spherical nanostructures act as local adjuvants when co-delivered with norovirus VLPs.

    Science.gov (United States)

    Malm, M; Heinimäki, S; Vesikari, T; Blazevic, V

    2017-09-01

    A subunit protein vaccine candidate based on norovirus (NoV) virus-like particles (VLPs) and rotavirus (RV) VP6 protein against acute childhood gastroenteritis has been proposed recently. RV VP6 forms different oligomeric nanostructures, including tubes and spheres when expressed in vitro, which are highly immunogenic in different animal models. We have shown recently that recombinant VP6 nanotubes have an adjuvant effect on immunogenicity of NoV VLPs in mice. In this study, we investigated if the adjuvant effect is dependent upon a VP6 dose or different VP6 structural assemblies. In addition, local and systemic adjuvant effects as well as requirements for antigen co-delivery and co-localization were studied. The magnitude and functionality of NoV GII.4-specific antibodies and T cell responses were tested in mice immunized with GII.4 VLPs alone or different combinations of VLPs and VP6. A VP6 dose-dependent adjuvant effect on GII.4-specific antibody responses was observed. The adjuvant effect was found to be strictly dependent upon co-administration of NoV GII.4 VLPs and VP6 at the same anatomic site and at the same time. However, the adjuvant effect was not dependent on the types of oligomers used, as both nanotubes and nanospheres exerted adjuvant effect on GII.4-specific antibody generation and, for the first time, T cell immunity. These findings elucidate the mechanisms of VP6 adjuvant effect in vivo and support its use as an adjuvant in a combination NoV and RV vaccine. © 2017 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

  19. Immunological findings in autism.

    Science.gov (United States)

    Cohly, Hari Har Parshad; Panja, Asit

    2005-01-01

    The immunopathogenesis of autism is presented schematically in Fig. 1. Two main immune dysfunctions in autism are immune regulation involving pro-inflammatory cytokines and autoimmunity. Mercury and an infectious agent like the measles virus are currently two main candidate environmental triggers for immune dysfunction in autism. Genetically immune dysfunction in autism involves the MHC region, as this is an immunologic gene cluster whose gene products are Class I, II, and III molecules. Class I and II molecules are associated with antigen presentation. The antigen in virus infection initiated by the virus particle itself while the cytokine production and inflammatory mediators are due to the response to the putative antigen in question. The cell-mediated immunity is impaired as evidenced by low numbers of CD4 cells and a concomitant T-cell polarity with an imbalance of Th1/Th2 subsets toward Th2. Impaired humoral immunity on the other hand is evidenced by decreased IgA causing poor gut protection. Studies showing elevated brain specific antibodies in autism support an autoimmune mechanism. Viruses may initiate the process but the subsequent activation of cytokines is the damaging factor associated with autism. Virus specific antibodies associated with measles virus have been demonstrated in autistic subjects. Environmental exposure to mercury is believed to harm human health possibly through modulation of immune homeostasis. A mercury link with the immune system has been postulated due to the involvement of postnatal exposure to thimerosal, a preservative added in the MMR vaccines. The occupational hazard exposure to mercury causes edema in astrocytes and, at the molecular level, the CD95/Fas apoptotic signaling pathway is disrupted by Hg2+. Inflammatory mediators in autism usually involve activation of astrocytes and microglial cells. Proinflammatory chemokines (MCP-1 and TARC), and an anti-inflammatory and modulatory cytokine, TGF-beta1, are consistently

  20. Immunology of lymphatic filariasis.

    Science.gov (United States)

    Babu, S; Nutman, T B

    2014-08-01

    The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen-specific Th2 response and an expansion of IL-10 producing CD4(+) T cells that is accompanied by a muted Th1 response. This antigen-specific T-cell hyporesponsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4(+) T-cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T-cell hyporesponsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  1. Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety.

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2015-11-04

    There is an ongoing need for new adjuvants to facilitate development of vaccines against HIV, tuberculosis, malaria and cancer, amongst many others. Unfortunately, the most potent adjuvants are often associated with toxicity and safety issues. Inulin, a plant-derived polysaccharide, has no immunological activity in its native soluble form but when crystallized into a stable microcrystalline particulate from (delta inulin) acquires potent adjuvant activity. Delta inulin has been shown to enhance humoral and cellular immune responses against a broad range of co-administered viral, bacterial, parasitic and toxin antigens. Inulin normally crystallizes as large heterogeneous particles with a broad size distribution and variable solubility temperatures. To ensure reproducible delta inulin particles with a consistent size distribution and temperature of solubility, a current Good Manufacturing Practice (cGMP) process was designed to produce Advax™ adjuvant. In its cCMP form, Advax™ adjuvant has proved successful in human trials of vaccines against seasonal and pandemic influenza, hepatitis B and insect sting anaphylaxis, enhancing antibody and T-cell responses while being safe and well tolerated. Advax™ adjuvant represents a novel human adjuvant that enhances both humoral and cellular immunity. This review describes the discovery and development of Advax™ adjuvant and research into its unique mechanism of action. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    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 commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

  3. Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

    Science.gov (United States)

    Mody, Karishma T.; Popat, Amirali; Mahony, Donna; Cavallaro, Antonino S.; Yu, Chengzhong; Mitter, Neena

    2013-05-01

    Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.

  4. Aluminum adjuvants of vaccines injected into the muscle: Normal fate, pathology and associated disease.

    Science.gov (United States)

    Gherardi, R K; Aouizerate, J; Cadusseau, J; Yara, S; Authier, F J

    2016-06-01

    Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. A history of pediatric immunology.

    Science.gov (United States)

    Stiehm, E Richard; Johnston, Richard B

    2005-03-01

    Immunology has played a prominent role in the history of medicine. Pediatric immunologists have focused on immune aberrations in pediatric disorders, particularly those involving host defense mechanisms. These efforts have paid rich dividends in terms of fundamental knowledge of the immune system and major therapeutic advances, including 1) i.v. immunoglobulin therapy, 2) hematopoietic stem cell transplantation, and 3) gene therapy. Pediatric immunology as an organized discipline emerged in the early 1950s, when pediatricians and their basic scientist colleagues began to focus on clinical and basic research related to immunodeficiency. Since then, key organizations and infrastructure have been developed to support this research and the clinical care of immunodeficient patients. We review here the evolution of contemporary pediatric immunology, particularly in North America, from its roots in 19th-century Europe to its current expression as one of the fundamental scientific and clinical disciplines of pediatrics.

  6. CCL8 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of CCL8.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...

  7. Intensive educational course in allergy and immunology.

    Science.gov (United States)

    Elizalde, A; Perez, E E; Sriaroon, P; Nguyen, D; Lockey, R F; Dorsey, M J

    2012-09-01

    A one-day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows-in-training. © 2012 John Wiley & Sons A/S.

  8. Saponins from the Spanish saffron Crocus sativus are efficient adjuvants for protein-based vaccines.

    Science.gov (United States)

    Castro-Díaz, Nathaly; Salaun, Bruno; Perret, Rachel; Sierro, Sophie; Romero, Jackeline F; Fernández, Jose-Antonio; Rubio-Moraga, Angela; Romero, Pedro

    2012-01-05

    Protein and peptide-based vaccines provide rigorously formulated antigens. However, these purified products are only weakly immunogenic by themselves and therefore require the addition of immunostimulatory components or adjuvants in the vaccine formulation. Various compounds derived from pathogens, minerals or plants, possess pro-inflammatory properties which allow them to act as adjuvants and contribute to the induction of an effective immune response. The results presented here demonstrate the adjuvant properties of novel saponins derived from the Spanish saffron Crocus sativus. In vivo immunization studies and tumor protection experiments unambiguously establish the value of saffron saponins as candidate adjuvants. These saponins were indeed able to increase both humoral and cellular immune responses to protein-based vaccines, ultimately providing a significant degree of protection against tumor challenge when administered in combination with a tumor antigen. This preclinical study provides an in depth immunological characterization of a new saponin as a vaccine adjuvant, and encourages its further development for use in vaccine formulations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Anti-tumor response with immunologically modified carbon nanotubes and phototherapy

    Science.gov (United States)

    Acquaviva, Joseph T.; Zhou, Feifan; Boarman, Ellen; Chen, Wei R.

    2013-02-01

    While successes of different cancer therapies have been achieved in various degrees a systemic immune response is needed to effectively treat late-stage, metastatic cancers, and to establish long-term tumor resistance in the patients. A novel method for combating metastatic cancers has been developed using immunologically modified carbon nanotubes in conjunction with phototherapy. Glycated chitosan (GC) is a potent immunological adjuvant capable of increasing host immune responses, including antigen presentation by activation of dendritic cells (DCs) and causing T cell proliferation. GC is also an effective surfactant for nanomaterials. By combining single-walled carbon nanotubes (SWNTs) and GC, immunologically modified carbon nanotubes (SWNT-GC) were constructed. The SWNT-GC suspension retains the enhanced light absorption properties in the near infrared (NIR) region and the ability to enter cells, which are characteristic of SWNTs. The SWNT-GC also retains the immunological properties of GC. Cellular SWNT-GC treatments increased macrophage activity, DC activation and T cell proliferation. When cellular SWNT-GC was irradiated with a laser of an appropriate wavelength, these immune activities could be enhanced. The combination of laser irradiation and SWNT-GC induced cellular toxicity in targeted tumor cells, leading to a systemic antitumor response. Immunologically modified carbon nanotubes in conjunction with phototherapy is a novel and promising method to produce a systemic immune response for the treatment of metastatic cancers.

  10. A new era in veterinary immunology

    NARCIS (Netherlands)

    Halliwell, R.E.W.; Goudswaard, J.

    The importance of the creation of a new international journal of “Veterinary Immunology and Immunopathology” is apparent following the emergence of veterinary immunology as an identifiable discipline and the vital part played by investigations of animal models of immunological diseases of

  11. A new era in veterinary immunology

    NARCIS (Netherlands)

    Halliwell, R.E.W.; Goudswaard, J.

    1979-01-01

    The importance of the creation of a new international journal of “Veterinary Immunology and Immunopathology” is apparent following the emergence of veterinary immunology as an identifiable discipline and the vital part played by investigations of animal models of immunological diseases of

  12. 42 CFR 493.927 - General immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false General immunology. 493.927 Section 493.927 Public... Proficiency Testing Programs by Specialty and Subspecialty § 493.927 General immunology. (a) Program content and frequency of challenge. To be approved for proficiency testing for immunology, the annual program...

  13. 42 CFR 493.921 - Diagnostic immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are syphilis...

  14. Uncaria tomentosa—Adjuvant Treatment for Breast Cancer: Clinical Trial

    Directory of Open Access Journals (Sweden)

    Maria do Carmo Santos Araújo

    2012-01-01

    Full Text Available Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide, were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.

  15. Advances and challenges in mucosal adjuvant technology.

    Science.gov (United States)

    Newsted, Daniel; Fallahi, Firouzeh; Golshani, Ashkan; Azizi, Ali

    2015-05-15

    Adjuvants play attractive roles in enhancement of immune response during vaccination; however, due to several challenges, only a limited number of adjuvants are licensed by health authorities. The lack of an effective mucosal adjuvant is even more significant as none of the licensed adjuvants revealed a strong enhancement in immune system after mucosal administration. Over the past two decades, several mucosal adjuvants have been developed to deliver antigens to the target cells in the mucosal immune system and increase specific immune responses. However, the safety and efficacy of these adjuvants for testing in human trials is still an important issue, requiring further study. In this article, we briefly review the challenges associated with most common mucosal adjuvants and discuss potential strategies for targeting the mucosal immune system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Immunology of Photo(chemotherapy

    Directory of Open Access Journals (Sweden)

    Ekin Şavk

    2010-12-01

    Full Text Available Perhaps the oldest empirical therapeutic modality in the history of medicine, photo(chemotherapy has well documented benefits but its mode of action is not fully elucidated. Today, thanks to advances in photoimmunology and molecular biology we are provided with important clues as to how photo(chemotherapy works. Initial research on UV light and skin cancer has brought about the groundbreaking discovery of the immunological effects UV. UVB is the UV light most frequently used for therapeutic purposes and its mechanisms of action are best demonstrated. UV light has several distinct effects on various components of the innate and acquired immune systems, especially T lymphocyte functions the common endpoint of which is immune supression. The antiproliferative and antifibrotic therapeutic effects of UVA and UVB have so far not been directly associated with immunological mechanisms.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The immunology of smallpox vaccines

    OpenAIRE

    Kennedy, Richard B.; Ovsyannikova, Inna G.; Jacobson, Robert M.; Poland, Gregory A.

    2009-01-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccinat...

  19. Immunologic findings in confectionary workers.

    Science.gov (United States)

    Zuskin, E; Kanceljak, B; Mustajbegovic, J; Schachter, E N

    1994-12-01

    Food allergies are frequent in the general population. There are however, few studies of immunologic responses among workers in the confectionary industry. To assess immunologic and clinical findings of workers in a confectionary plant. Immunologic (skin tests and serum IgE) and respiratory findings (symptoms and lung function) were studied in a group of 71 confectionary workers (mean age: 35 years and mean exposure: 11 years). Skin prick testing with food extracts used in the manufacturing of candies and pastries demonstrated that the most frequent positive skin reaction occurred with extracts of cacao (31%), followed by reactions to chocolate (9%), cocoa (6%), hazelnut (6%), and sugar (2%). Increased serum IgE levels were found in 13.0% and increased IgM serum levels in 52.1% of these confectionary workers. The prevalence of asthma (26.1%) and dyspnea (26.1%) in workers with positive skin tests was significantly higher than in workers with negative skin tests (asthma: 2.0%, P = .004; dyspnea: 4.1%, P = .001). There was a high prevalence of acute respiratory symptoms during the work shift, but no significant association with immunologic tests was found. Similarly, both skin test positive and skin test negative workers exhibited significant across shift changes in lung function; however, no significant differences in baseline lung function or across-shift changes were noted between skin test positive and negative workers. Pre-shift administration of disodium cromoglycate (DSCG) significantly diminished across-shift reductions in FEF50 and FEF25 for both skin test positive and skin test negative workers. These data suggest that exposure to environmental factors in confectionary plants is associated with frequent respiratory symptoms of an irritative nature. Specific skin testing may be useful in characterizing confectionary workers at risk for the development of occupational asthma.

  20. Immunology taught by human genetics.

    Science.gov (United States)

    Casanova, Jean-Laurent; Abel, Laurent; Quintana-Murci, Lluis

    2013-01-01

    Human genetic studies are rarely conducted for immunological purposes. Instead, they are typically driven by medical and evolutionary goals, such as understanding the predisposition or resistance to infectious or inflammatory diseases, the pathogenesis of such diseases, and human evolution in the context of the long-standing relationships between humans and their commensal and environmental microbes. However, the dissection of these experiments of Nature has also led to major immunological advances. In this review, we draw on some of the immunological lessons learned in the three branches of human molecular genetics most relevant to immunology: clinical genetics, epidemiological genetics, and evolutionary genetics. We argue that human genetics has become a new frontier not only for timely studies of specific features of human immunity, but also for defining general principles of immunity. These studies teach us about immunity as it occurs under "natural" conditions, through the transition from the almost complete wilderness that existed worldwide until about a century ago to the current unevenly distributed medically shaped environment. Hygiene, vaccines, antibiotics, and surgery have considerably decreased the burden of infection, but these interventions have been available only recently, so have yet to have a major impact on patterns of genomic diversity, making it possible to carry out unbiased evolutionary studies at the population level. Clinical genetic studies of childhood phenotypes have not been blurred by modern medicine either. Instead, medical advances have actually facilitated such studies, by making it possible for children with life-threatening infections to survive. In addition, the prevention and treatment of infectious diseases have increased life expectancy at birth from ∼20 yr to ∼80 yr, providing unique opportunities to study the genetic basis of immunological phenomena against which there is no natural counterselection, such as

  1. Polysaccharides: Candidates of promising vaccine adjuvants.

    Science.gov (United States)

    Li, Pingli; Wang, Fengshan

    2015-04-01

    Aluminium-based adjuvants remain the only adjuvants approved for human use in the USA for over 80 years because of alum's simplicity, tolerability, safety and cost-efficiency. Recent development of vaccines, especially the increasing applications of recombinant subunit and synthetic vaccines, makes aluminium adjuvants cannot stimulate enough immunity to the antigens, since aluminium adjuvants can only induce Th2 type immune responses. So, novel adjuvants are urgent to make up the disadvantages of aluminium adjuvants. However, some major hurdles need to be overcome, not only the scientific knowledge of adjuvants but also unacceptable side-effects and toxicity. A number of carbohydrate-based polysaccharides from plant, bacterial, yeast and synthetic sources can act as pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition receptors (PRRs) on immune cells, followed by triggering innate immunity and regulating adaptive immunity. What is more, polysaccharides are safe and biodegradable without tissue deposits as observed in aluminium adjuvants. Therefore, polysaccharide-based compounds and formulations are potential vaccine adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants investigated in recent years.

  2. Adjuvant effect of green propolis on humoral immune response of bovines immunized with bovine herpesvirus type 5.

    Science.gov (United States)

    Fischer, Geferson; Cleff, Marlete Brum; Dummer, Luana Alves; Paulino, Niraldo; Paulino, Amarílis Scremin; de Oliveira Vilela, Camila; Campos, Fabrício Souza; Storch, Tiago; D'Avila Vargas, Gilberto; de Oliveira Hübner, Silvia; Vidor, Telmo

    2007-03-15

    Despite recent technological advances in vaccine production, most vaccines depend on the association with adjuvant substances. In this study, propolis, which has been attracting the attention of researchers due to its bioactive properties, was evaluated as an immunological adjuvant. The association of 40mg/dose of an ethanolic extract of green propolis with an inactivated oil vaccine against bovine herpesvirus type 5 (BoHV-5), resulted in a significant increase (Ppropolis. Besides, propolis increased the percentage of animals with high antibody titers (above 32). Phenolic compounds such as artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) and the derivatives of cinnamic acid besides other flavonoid substances were abundant in the propolis extract used, and they could be the main substances with adjuvant action. The effect of the green propolis extract on the humoral immune response can be exploited in the development of new vaccines.

  3. Immunological markers of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Agnieszka Matuszewska

    2016-03-01

    Full Text Available Rheumatoid arthritis (RA is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement. In 2010 the American College of Rheumatology (ACR and The European League Against Rheumatism (EULAR established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF and anti-citrullinated protein antibodies (anti-CCP antibodies. RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%. New immunologic markers include anti-carbamylated protein antibodies (anti-CarP and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33. Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.

  4. Immunological markers of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Agnieszka Matuszewska

    2016-03-01

    Full Text Available Rheumatoid arthritis (RA is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement.In 2010 the American College of Rheumatology (ACR and The European League Against Rheumatism (EULAR established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF and anti-citrullinated protein antibodies (anti-CCP antibodies. RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%.New immunologic markers include anti-carbamylated protein antibodies (anti-CarP and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33. Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.

  5. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    DEFF Research Database (Denmark)

    Claesson, Mogens Helweg

    2011-01-01

    A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African...... females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium...... phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence...

  6. Comparative Immunologic Activities of Polyclonal Antibodies ...

    African Journals Online (AJOL)

    Three types of Vibrio cholerae (El tor, Ogawa) whole cell antigens constituted with liquid paraffin adjuvant (LPA), Freund's incomplete adjuvant (FIA) and physiological saline (SA) were used for polyclonal antisera production in adult rabbits. Antisera were compared for serologic reactivities with homologous and ...

  7. Over-expression of gene encoding heat shock protein 70 from Mycobacterium tuberculosis and its evaluation as vaccine adjuvant

    Directory of Open Access Journals (Sweden)

    J Dhakal

    2013-01-01

    Full Text Available Background: Heat shock proteins (Hsps are evolutionary ancient and highly conserved molecular chaperons found in prokaryotes as well as eukaryotes. Hsp70 is a predominant member of Hsp family. Microbial Hsp70s (mHsp70s have acquired special significance in immunity since they have been shown to be potent activators of the innate immune system and generate specific immune responses against tumours and infectious agents. Objectives: The present study was aimed to clone express and purify recombinant Hsp70 from the Mycobacterium tuberculosis and characterise it immunologically. The study also aimed at determining the potential of recombinant M. tuberculosis heat shock protein (rMTB-Hsp70 as adjuvant or antigen carrier. Materials and Methods: Cloning of M. tuberculosis heat shock protein (MTB-Hsp70 amplicon was carried out using the pGEMT-Easy vector although for expression, pProExHTb prokaryotic expression vector was used. Purification of recombinant Hsp70 was carried out by nickel-nitrilotriacetic acid (Ni-NTA affinity chromatography. For immunological characterization and determining the adjuvant effect of MTB-Hsp70, BALB/c mice were used. The data obtained was statistically analysed. Results: Hsp70 gene was cloned, sequenced and the sequence data were submitted to National Center for Biotechnology Information (NCBI. Recombinant MTB-Hsp70 was successfully over-expressed using the prokaryotic expression system and purified to homogeneity. The protein was found to be immunodominant. Significant adjuvant effect was produced by the rMTB-Hsp70 when inoculated with recombinant outer membrane protein 31; however, effect was less than the conventionally used the Freund′s adjuvant. Conclusion: Protocol standardised can be followed for bulk production of rHsp70 in a cost-effective manner. Significant adjuvant effect was produced by rMTB-Hsp70; however, the effect was than Freund′s adjuvant. Further, studies need to be carried out to explore its

  8. Ginsenoside Rd induces protective anti-Candida albicans antibody through immunological adjuvant activity.

    Science.gov (United States)

    Han, Yongmoon; Rhew, Ki Yon

    2013-11-01

    The role of an antibody against candidiasis is controversial. However, a certain Candida albicans surface epitope produces a protective antibody. Yet, its isolation is difficult. In this study, we investigated if ginsenoside Rd from Panax ginseng has an immunoadjuvant ability to induce surface mannan extract (CASM) to produce a protective antibody. Mice were immunized twice i.p. with an emulsion form of CASM mixed with one of the following: IFA [CASM/IFA], or CFA [CASM/CFA] or Rd with IFA [CASM/Rd/IFA]. One week after the booster, these mice were challenged i.v. with live C. albicans and their survivability was measured. Results showed that four of five CASM/Rd/IFA-vaccinated mice survived during the entire 110 day-observation period, whereas CASM/IFA- or CASM/CFA-vaccinated mice died within 19 and 23 days (PRd/IFA-immunized mice transferred the protection to naïve mice, whereas antiserum from CASM/CFA-given mice was not protective although CASM/CFA induced an antibody four times greater than CASM/Rd/IFA. IgG isotyping revealed that CASM/Rd/IFA-vaccine produced the most abundant IgG and IgG2a-resulting in the highest ratio (1.32) of IgG2a to IgG, which is helpful in treating Th2-oriented candidiasis. In contrast, the formulae lacking Rd had these ratios less than 1. This strongly indicates that Rd could enhance Th1 immunity. Cytokine profiles and DTH further confirmed the Th1 dominance. Rd caused no hemolysis. Combining all of these data together, Rd can enhance Th1-response to CASM in mice. This protects mice against disseminated candidiasis by eliciting higher titers of Th1 type antibody and a Th1-dominant immune response. © 2013.

  9. Efficacy of adjuvant therapy with fenofibrate for primary biliary cirrhosis: a Meta-analysis

    Directory of Open Access Journals (Sweden)

    YU Yuan

    2015-10-01

    Full Text Available ObjectiveTo assess the efficacy of adjuvant therapy with fenofibrate for primary biliary cirrhosis (PBC. MethodsCNKI, Wanfang Data, China Biology Medicine, PubMed, Embase, and Cochrane library were searched for the pertinent literature of randomized controlled trials (RCTs of adjuvant therapy with fenofibrate for PBC published up to December 31, 2014. Data extraction and quality assessment were carried out, and the data were statistically analyzed by Stata10.1 software. Respectively, for heterogeneity test. The fixed effect model is chosen for homogeneity, and the random effect model is chosen for heterogeneity. ResultsSix RCTs met the inclusion criteria. Treatment with fenofibrate was associated with significantly reduced levels of gamma-glutamyl transpeptidase, alanine aminotransferase, and alkaline phosphatase in PBC patients (SMD=-1.595, -0.447, and -2.125, respectively, all P<0.05. There were no significant changes in the levels of aspartate aminotransferase and total bilirubin after adjuvant therapy with fenofibrate (both P>0.05. Also, fenofibrate led to no significant improvement in immunoglobulin M (P>0.05. ConclusionFenofibrate, which improves the indicators of liver function but leads to no changes in immunological indicators, appears to be an effective adjuvant therapy in PBC patients. There is a critical need for more large-scale, multi-center, high-quality RCTs to determine its effect on liver disease-related morbidity and mortality.

  10. EFFECTS OF DIFFERENT ADJUVANTS UPON IMMUNOGENICITY OF ANTI-GROUP B STREPTOCOCCAL VACCINE COMPONENTS

    Directory of Open Access Journals (Sweden)

    A. N. Suvorov

    2008-01-01

    Full Text Available Abstract. Design of an effective and safe vaccine against pathogenic streptococci is still on the agenda, in spite of numerous attempts in this area undertaken by different laboratories. In order to improve immunogenicity of recombinant vaccine preparations, a selection of effective adjuvants is necessary. Previously, two recombinant GBS polypeptides P6 and ScaAB were found to be immunogenic, and their injection in separate preparations or mixed manner boosted production of specific and protective antibodies with high affinity. Four different adjuvants (Freund adjuvant, aluminum hydroxide, Bestim and Interleukine-1β have been tested for immunization of mice with single polypeptides, or with their mixtures. As a result of vaccination, it was demonstrated that aluminum hydroxide was providing the most desirable immunological parameters of immune response among the adjuvants tested. A mixture of polypeptides containing aluminum hydroxide was found to produce specific antibodies with better opsonizing activity against group B streptococci. (Med. Immunol., 2008, vol. 10, N 2-3, pp 215-222.

  11. Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research

    Directory of Open Access Journals (Sweden)

    Elena Mata

    2013-01-01

    Full Text Available There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants as well as the immunostimulatory effect of the formulation components (immunostimulants modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.

  12. Malaria vaccine adjuvants: latest update and challenges in preclinical and clinical research.

    Science.gov (United States)

    Mata, Elena; Salvador, Aiala; Igartua, Manoli; Hernández, Rosa María; Pedraz, José Luis

    2013-01-01

    There is no malaria vaccine currently available, and the most advanced candidate has recently reported a modest 30% efficacy against clinical malaria. Although many efforts have been dedicated to achieve this goal, the research was mainly directed to identify antigenic targets. Nevertheless, the latest progresses on understanding how immune system works and the data recovered from vaccination studies have conferred to the vaccine formulation its deserved relevance. Additionally to the antigen nature, the manner in which it is presented (delivery adjuvants) as well as the immunostimulatory effect of the formulation components (immunostimulants) modulates the immune response elicited. Protective immunity against malaria requires the induction of humoral, antibody-dependent cellular inhibition (ADCI) and effector and memory cell responses. This review summarizes the status of adjuvants that have been or are being employed in the malaria vaccine development, focusing on the pharmaceutical and immunological aspects, as well as on their immunization outcomings at clinical and preclinical stages.

  13. The immunology of smallpox vaccines.

    Science.gov (United States)

    Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

    2009-06-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization.

  14. The immunology of smallpox vaccines

    Science.gov (United States)

    Kennedy, Richard B; Ovsyannikova, Inna G; Jacobson, Robert M; Poland, Gregory A

    2010-01-01

    In spite of the eradication of smallpox over 30 years ago; orthopox viruses such as smallpox and monkeypox remain serious public health threats both through the possibility of bioterrorism and the intentional release of smallpox and through natural outbreaks of emerging infectious diseases such as monkeypox. The eradication effort was largely made possible by the availability of an effective vaccine based on the immunologically cross-protective vaccinia virus. Although the concept of vaccination dates back to the late 1800s with Edward Jenner, it is only in the past decade that modern immunologic tools have been applied toward deciphering poxvirus immunity. Smallpox vaccines containing vaccinia virus elicit strong humoral and cellular immune responses that confer cross-protective immunity against variola virus for decades after immunization. Recent studies have focused on: establishing the longevity of poxvirus-specific immunity, defining key immune epitopes targeted by T and B cells, developing subunit-based vaccines, and developing genotypic and phenotypic immune response profiles that predict either vaccine response or adverse events following immunization. PMID:19524427

  15. The Basel Institute for Immunology.

    Science.gov (United States)

    Melchers, Fritz

    2012-01-01

    At the Centennial Exhibition of the Nobel Prize, the Nobel Foundation called it one of the ten cradles of creativity. The journal Nature likened its ideals to those of the French revolution--Liberté, Egalité, Fraternité--and called it a paradise devoted to the science of immune systems: the Basel Institute for Immunology (BII). Founded by Roche in 1968, inaugurated in 1971, and closed in 2000, it was home to almost 450 scientific members, over 1,000 scientific visitors, and nearly 100 scientific advisors from more than 30 countries who worked in complete academic freedom and without commercial motives on over 3,500 projects, publishing more than 3,200 scientific papers, almost all of them on the structure and functions of immune systems of different species. This review contains a first collection of historical facts and dates that describe the background of the exceptionally successful performance and the strong scientific impact of the institute on the field of immunology.

  16. Overview of Johne's disease immunology

    Directory of Open Access Journals (Sweden)

    Ashutosh Wadhwa

    2013-10-01

    Full Text Available Johne's disease or paratuberculosis is one of the most economically important diseases of the livestock. Most of the economiclosses associated with paratuberculosis are related to decreased milk production, reduced fertility and higher rates of culling.Understanding the immunology of the disease is very important for better understanding of the interplay between the host andthe causative agent, Mycobacterium avium subsp. paratuberculosis (MAP. After uptake of MAPby macrophages residing inhost's intestinal tissue, two possible scenarios may emerge; MAP may be destroyed or may establish persistent infectionwithin the macrophages. If MAPpersists in the infected macrophage, it continuously modulates adaptive immune responsesof the animal. In this short review we describe the host-pathogen interactions in Johne's disease and highlights potentialprotective mechanisms in order for future design of more effective diagnostic method and vaccine.

  17. Immunological treatments for occupational allergy.

    Science.gov (United States)

    Crivellaro, M; Senna, G; Marcer, G; Passalacqua, G

    2013-01-01

    Although avoidance of occupational triggers remains the primary step in the management of work-related allergies, immunological treatments (including biological agents and specific immunotherapy) can be regarded as potential therapeutic options for IgE-mediated diseases; for example, many studies with allergen-specific immunotherapy have been carried out on latex allergy, showing overall favorable results, at least with sublingual immunotherapy. On the other hand, only few case reports have suggested the efficacy of immunotherapy in baker's asthma as well as in laboratory animal-induced asthma. The new technologies, including component-resolved diagnosis and recombinant allergens, are expected to improve the quality and efficacy of specific immunotherapy in the future. Also the use of omalizumab may represent a suitable therapeutic choice in very selected cases of occupational allergy, as well as an approach to reduce side effects of venom immunotherapy in subjects with previous severe reactions to the treatment.

  18. Evolution and conservation of immunological activity

    Directory of Open Access Journals (Sweden)

    N.M. Vaz

    2006-12-01

    Full Text Available Paraphrasing what Gregory Bateson says on evolution, we might say that: "Immunology has long been badly taught. In particular, students - and even professional immunologists - acquire theories of immunological activity without any deep understanding of what problems these theories attempt to solve."

  19. Autoantibody profile and other immunological parameters in ...

    African Journals Online (AJOL)

    Background: An autoimmune cause and related immunological alterations resulting in recurrent spontaneous abortion (RSA) have been suggested in patients with unknown etiology. Materials and Methods: This study evaluated the autoantibody profile and other immunological parameters among RSA patients and normal ...

  20. American Academy of Allergy, Asthma, and Immunology

    Science.gov (United States)

    ... Allergy, Asthma & Immunology Life Spectrum of Asthma Meeting School-based Asthma Management Program – (SAMPRO TM ) This central resource focuses on ... AAAAI is proud to endorse HR 2285, the School-Based Respiratory Health Management Act Read Practice Matters! Allergy, Asthma & Immunology Quality ...

  1. The ninth international veterinary immunology symposium

    Science.gov (United States)

    This Introduction to the special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August, 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune...

  2. Adjuvants: Classification, Modus Operandi, and Licensing

    Directory of Open Access Journals (Sweden)

    Juliana de Souza Apostólico

    2016-01-01

    Full Text Available 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.

  3. Adjuvants and Their Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Masoumeh Foumani

    2012-09-01

    Full Text Available Adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in experimental and commercial vaccines include aluminum salts (alum, oil emulsions, saponins, immune-stimulating complexes (ISCOMs, liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds are different. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed. In this paper we review the current adjuvant types, structure and mechanism of action and their application in the design and production of animal and human vaccines to provide a source for students and researchers in related fields .

  4. Calcium phosphate: a substitute for aluminum adjuvants?

    Science.gov (United States)

    Masson, Jean-Daniel; Thibaudon, Michel; Bélec, Laurent; Crépeaux, Guillemette

    2017-03-01

    Calcium phosphate was used as an adjuvant in France in diphtheria, tetanus, pertussis and poliomyelitis vaccines. It was later completely substituted by alum salts in the late 80's, but it still remains as an approved adjuvant for the World Health Organization for human vaccination. Area covered: Thus, calcium phosphate is now considered as one of the substances that could replace alum salts in vaccines. The aim of this paper is to draw a review of existing data on calcium phosphate as an adjuvant in order to bring out the strengths and weaknesses for its use on a large scale. Expert commentary: Calcium phosphate is a compound naturally present in the organism, safe and already used in human vaccination. Beyond comparisons with the other adjuvants, calcium phosphate represents a good candidate to replace or to complete alum salts as a vaccine adjuvant.

  5. Vaccine Adjuvants: Putting Innate Immunity to Work

    Science.gov (United States)

    Coffman, Robert L.; Sher, Alan; Seder, Robert A.

    2012-01-01

    Adjuvants enhance immunity to vaccines and experimental antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide maximum protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens. PMID:21029960

  6. From stock bottle to vaccine: Elucidating the particle size distributions of aluminum adjuvants using dynamic light scattering.

    Science.gov (United States)

    Shardlow, Emma; Mold, Matthew; Exley, Christopher

    2016-12-01

    The physicochemical properties of aluminum salts are key determinants of their resultant adjuvanticity in vivo when administered as part of a vaccine. While there are links between particle size and the efficacy of the immune response, the limited literature directly characterizing the PSD of aluminum adjuvants has stymied the elucidation of such a relationship for these materials. Hence, this comparative study was undertaken to monitor the PSD of aluminum adjuvants throughout the process of vaccine formulation using DLS. A significant proportion of the stock suspensions was highly agglomerated (>6.5µm), although a large degree of disaggregation was observed upon the dilution of all materials into saline. Adju-Phos® yielded the largest particles in this diluent (4251±137nm); however, the higher affinity of BSA for the surface of Alhydrogel® resulted in a comparable size being observed for both commercial adjuvants when this protein was included in the formulation. These results suggest that the PSD of aluminum adjuvants is greatly influenced by dilution and the degree of protein adsorption experienced within the vaccine itself. The size of the resultant antigen-adjuvant complex may be important for its immunological recognition and subsequent clearance from the injection site.

  7. Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

    Science.gov (United States)

    Pal, Rishi; Chaudhary, Manju J; Tiwari, Prafulla C; Babu, Suresh; Pant, K K

    2015-12-01

    Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (ptheophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (ptheophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05). Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Biopersistence and brain translocation of aluminum adjuvants of vaccines

    Directory of Open Access Journals (Sweden)

    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

  9. Pediatric allergy and immunology in Turkey.

    Science.gov (United States)

    Celik, Gülfem; Bakirtas, Arzu; Sackesen, Cansin; Reisli, Ismail; Tuncer, Ayfer

    2011-06-01

    Allergic diseases constitute a significant health problem in Turkey. According to a recent multicenter study, which used the ISAAC questionnaire, the mean prevalence of wheezing, rhinoconjunctivitis, and eczema in 10-yr-old school children during the past year was 15.8%, 23.5%, and 8.1%, respectively. A healthcare level system, regulated by Ministry of Health, is available in Turkey. Pediatric allergists and pediatric immunologists provide patient care at the tertiary level. Currently, 48 centers deliver care for allergic and immunologic diseases in children. There are 136 pediatric and 61 adult allergists/immunologists. Although the number of allergy/clinical immunology specialists is limited, these centers are capable of delivering many of the procedures required for the proper management and diagnosis of allergy/immunology. Pediatric allergy and/or immunology is a subspecialty lasting 3 yr and follows a 4-yr pediatric specialist training. Fellow training involves gaining knowledge in basic and clinical allergy and immunology as well as the performance and interpretation of laboratory procedures in the field of allergy and clinical immunology. The Turkish National Society of Allergy and Clinical Immunology (TNSACI) was officially established in 1989 and currently has 356 members. The society organizes a national congress annually and winter schools for fellowship training as well as training courses for patients and their relatives. TNSACI also has a strong representation in European Academy of Allergy and Clinical Immunology (EAACI) and European Society for Immunodeficiencies (ESID) through its participation in the executive committee, consensus reports, and initiatives in the diagnosis of allergic and immunologic diseases of children. The 30th Congress of the EAACI is also due to be held in Istanbul, Turkey, between June 11 and 15, 2011. © 2011 John Wiley & Sons A/S.

  10. Safety of vaccine adjuvants: focus on autoimmunity.

    Science.gov (United States)

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

  11. Exposure to Mercury and Aluminum in Early Life: Developmental Vulnerability as a Modifying Factor in Neurologic and Immunologic Effects

    Directory of Open Access Journals (Sweden)

    José G. Dórea

    2015-01-01

    Full Text Available Currently, ethylmercury (EtHg and adjuvant-Al are the dominating interventional exposures encountered by fetuses, newborns, and infants due to immunization with Thimerosal-containing vaccines (TCVs. Despite their long use as active agents of medicines and fungicides, the safety levels of these substances have never been determined, either for animals or for adult humans—much less for fetuses, newborns, infants, and children. I reviewed the literature for papers reporting on outcomes associated with (a multiple exposures and metabolism of EtHg and Al during early life; (b physiological and metabolic characteristics of newborns, neonates, and infants relevant to xenobiotic exposure and effects; (c neurobehavioral, immunological, and inflammatory reactions to Thimerosal and Al-adjuvants resulting from TCV exposure in infancy. Immunological and neurobehavioral effects of Thimerosal-EtHg and Al-adjuvants are not extraordinary; rather, these effects are easily detected in high and low income countries, with co-exposure to methylmercury (MeHg or other neurotoxicants. Rigorous and replicable studies (in different animal species have shown evidence of EtHg and Al toxicities. More research attention has been given to EtHg and findings have showed a solid link with neurotoxic effects in humans; however, the potential synergic effect of both toxic agents has not been properly studied. Therefore, early life exposure to both EtHg and Al deserves due consideration.

  12. Immunological control of fish diseases.

    Science.gov (United States)

    Magnadottir, Bergljot

    2010-08-01

    All metazoans possess innate immune defence system whereas parameters of the adaptive immune system make their first appearance in the gnathostomata, the jawed vertebrates. Fish are therefore the first animal phyla to possess both an innate and adaptive immune system making them very interesting as regards developmental studies of the immune system. The massive increase in aquaculture in recent decades has also put greater emphasis on studies of the fish immune system and defence against diseases commonly associated with intensive fish rearing. Some of the main components of the innate and adaptive immune system of fish are described. The innate parameters are at the forefront of immune defence in fish and are a crucial factor in disease resistance. The adaptive response of fish is commonly delayed but is essential for lasting immunity and a key factor in successful vaccination. Some of the inherent and external factors that can manipulate the immune system of fish are discussed, the main fish diseases are listed and the pathogenicity and host defence discussed. The main prophylactic measures are covered, including vaccination, probiotics and immunostimulation. A key element in the immunological control of fish diseases is the great variation in disease susceptibility and immune defence of different fish species, a reflection of the extended time the present day teleosts have been separated in evolution. Future research will probably make use of molecular and proteomic tools both to study important elements in immune defence and prophylactic measures and to assist with breeding programmes for disease resistance.

  13. Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

    Directory of Open Access Journals (Sweden)

    Dace Skrastina

    Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

  14. Biosensors in immunology: the story so far

    NARCIS (Netherlands)

    Pathak, S.S.; Savelkoul, H.F.J.

    1997-01-01

    Optical biosensors are finding a range of applications in immunology. They enable biomolecular interactions to be characterized in real time without the need to label reactants, and, because individual binding steps can be visualized, are particularly suited to complex assays

  15. Immunological and hematological reference values for apparently ...

    African Journals Online (AJOL)

    admin

    Abstract. Background: Immunological and hematological reference values differ among different human beings with respect to sex, ethnicity, nutrition, altitude and health conditions. These could not be exceptional in the Ethiopian heterogeneous population. However, there are no nationally established reference values.

  16. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 10, No 2 (2012) >. Log in or Register to get access to full text downloads.

  17. Modeling-Enabled Systems Nutritional Immunology

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    Meghna eVerma

    2016-02-01

    Full Text Available This review highlights the fundamental role of nutrition in the maintenance of health, the immune response and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition and the immune system interact to delineate health and disease. The review sets an unconventional path to applying complex science methodologies to nutritional immunology research, discovery and development through ‘use cases’ centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, that include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism.

  18. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 5, No 2 (2007) >. Log in or Register to get access to full text downloads.

  19. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 5, No 1 (2007) >. Log in or Register to get access to full text downloads.

  20. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 9, No 1 (2011) >. Log in or Register to get access to full text downloads.

  1. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 13, No 1 (2015) >. Log in or Register to get access to full text downloads.

  2. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT · Advanced Search · Current Issue · Archives · Journal Home > Vol 8, No 1 (2010) >. Log in or Register to get access to full text downloads.

  3. Clinical immunology - Autoimmunity in the Netherlands

    NARCIS (Netherlands)

    Tervaert, Jan Willem Cohen; Kallenberg, Cees G. M.

    2014-01-01

    Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking

  4. Extended Adjuvant Therapy for Breast Cancer

    Science.gov (United States)

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  5. Immunology of root resorption: A literature review

    Directory of Open Access Journals (Sweden)

    Silva Luciano

    2008-01-01

    Full Text Available Root resorption seems to be related to a complex combination of mechanical factors and biological activity, which comprehends the role of immunologic structures including specialized cells. The aim of this research was to explain the development of the process - from mineralization to the destruction of hard tissues - and the possible relationship between root resorption and immunology, along with discussing current concepts described in the literature.

  6. Immunological Principles Guiding the Rational Design of Particles for Vaccine Delivery.

    Science.gov (United States)

    Gause, Katelyn T; Wheatley, Adam K; Cui, Jiwei; Yan, Yan; Kent, Stephen J; Caruso, Frank

    2017-01-24

    Despite the immense public health successes of immunization over the past century, effective vaccines are still lacking for globally important pathogens such as human immunodeficiency virus, malaria, and tuberculosis. Exciting recent advances in immunology and biotechnology over the past few decades have facilitated a shift from empirical to rational vaccine design, opening possibilities for improved vaccines. Some of the most important advancements include (i) the purification of subunit antigens with high safety profiles, (ii) the identification of innate pattern recognition receptors (PRRs) and cognate agonists responsible for inducing immune responses, and (iii) developments in nano- and microparticle fabrication and characterization techniques. Advances in particle engineering now allow highly tunable physicochemical properties of particle-based vaccines, including composition, size, shape, surface characteristics, and degradability. Enhanced collaborative efforts between researchers in immunology and materials science are expected to rise to next-generation vaccines. This process will be significantly aided by a greater understanding of the immunological principles guiding vaccine antigenicity, immunogenicity, and efficacy. With specific emphasis on PRR-targeted adjuvants and particle physicochemical properties, this review aims to provide an overview of the current literature to guide and focus rational particle-based vaccine design efforts.

  7. An immunologic portrait of cancer

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2011-08-01

    Full Text Available Abstract The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns commonly observed during the inflammatory response against pathogens, which leads to elimination of infected cells. As these signatures are observed in growing cancers, they are not sufficient to entirely clear the organism of neoplastic cells but they sustain, as in chronic infections, a self-perpetuating inflammatory process. Yet, several studies determined an association between this inflammatory status and a favorable natural history of the disease or a better responsiveness to cancer immune therapy. Moreover, these signatures overlap with those observed during immune-mediated cancer rejection and, more broadly, immune-mediated tissue-specific destruction in other immune pathologies. Thus, a discussion concerning this cancer phenotype is warranted as it remains unknown why it occurs in immune competent hosts. It also remains uncertain whether a genetically determined response of the host to its own cancer, the genetic makeup of the neoplastic process or a combination of both drives the inflammatory process. Here we reflect on commonalities and discrepancies among studies and on the genetic or somatic conditions that may cause this schism in cancer behavior.

  8. An immunologic portrait of cancer.

    Science.gov (United States)

    Ascierto, Maria Libera; De Giorgi, Valeria; Liu, Qiuzhen; Bedognetti, Davide; Spivey, Tara L; Murtas, Daniela; Uccellini, Lorenzo; Ayotte, Ben D; Stroncek, David F; Chouchane, Lotfi; Manjili, Masoud H; Wang, Ena; Marincola, Francesco M

    2011-08-29

    The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns commonly observed during the inflammatory response against pathogens, which leads to elimination of infected cells. As these signatures are observed in growing cancers, they are not sufficient to entirely clear the organism of neoplastic cells but they sustain, as in chronic infections, a self-perpetuating inflammatory process. Yet, several studies determined an association between this inflammatory status and a favorable natural history of the disease or a better responsiveness to cancer immune therapy. Moreover, these signatures overlap with those observed during immune-mediated cancer rejection and, more broadly, immune-mediated tissue-specific destruction in other immune pathologies. Thus, a discussion concerning this cancer phenotype is warranted as it remains unknown why it occurs in immune competent hosts. It also remains uncertain whether a genetically determined response of the host to its own cancer, the genetic makeup of the neoplastic process or a combination of both drives the inflammatory process. Here we reflect on commonalities and discrepancies among studies and on the genetic or somatic conditions that may cause this schism in cancer behavior.

  9. Adjuvant therapy of melanoma with interferon: lessons of the past decade

    Directory of Open Access Journals (Sweden)

    Kirkwood John M

    2008-10-01

    Full Text Available Abstract The effect of interferon alpha (IFNα2 given alone or in combination has been widely explored in clinical trials over the past 30 years. Despite the number of adjuvant studies that have been conducted, controversy remains in the oncology community regarding the role of this treatment. Recently an individual patient data (IPD meta-analysis at longer follow-up was reported, showing a statistically significant benefit for IFN in relation to relapse-free survival, without any difference according to dosage (p = 0.2 or duration of IFN therapy (p = 0.5. Most interestingly, there was a statistically significant benefit of IFN upon overall survival (OS that translates into an absolute benefit of at least 3% (CI 1–5% at 5 years. Thus, both the individual trials and this meta-analysis provide evidence that adjuvant IFNα2 significantly reduces the risk of relapse and mortality of high-risk melanoma, albeit with a relatively small absolute improvement in survival in the overall population. We have surveyed the international literature from the meta-analysis (2006 to summarize and assimilate current biological evidence that indicates a potent impact of this molecule upon the tumor microenvironment and STAT signaling, as well as the immunological polarization of the tumor tissue in vivo. In conclusion, we argue that there is a compelling rationale for new research upon IFN, especially in the adjuvant setting where the most pronounced effects of this agent have been discovered. These efforts have already shed light upon the immunological and proinflammatory predictors of therapeutic benefit from this agent – that may allow practitioners to determine which patients may benefit from IFN therapy, and approaches that may enable us to overcome resistance or enhance the efficacy of IFN. Future efforts may well build toward patient-oriented therapy based upon the knowledge of the unique molecular features of this disease and the immune system of each

  10. Mucosal adjuvants for vaccines to control upper respiratory infections in the elderly.

    Science.gov (United States)

    Fujihashi, Kohtaro; Sato, Shintaro; Kiyono, Hiroshi

    2014-06-01

    Influenza virus and Streptococcus pneumoniae are two major pathogens that lead to significant morbidity and mortality in the elderly. Since both pathogens enter the host via the mucosa, especially the upper respiratory tract (URT), it is essential to elicit pathogen-specific secretory IgA (SIgA) antibody (Ab) responses at mucosal surfaces for defense of the elderly. However, as aging occurs, alterations in the mucosal immune system of older individuals result in a failure to induce SIgA Abs for protection from these infections. To overcome mucosal immunosenescence, we have developed a mucosal dendritic cell targeting, novel double adjuvant system which we show to be an attractive and effective immunological modulator. This system induces a more balanced Th1- and Th2-type cytokine response which supports both mucosal SIgA and systemic IgG1 and IgG2a Ab responses. Thus, adaptation of this adjuvant system to nasal vaccines for influenza virus and S. pneumoniae could successfully provide protection by supporting pathogen-specific SIgA Ab responses in the URT in the mouse model of aging. In summary, a double adjuvant system is considered to be an attractive and potentially important strategy for the future development of mucosal vaccines for the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Preclinical safety study of a recombinant Streptococcus pyogenes vaccine formulated with aluminum adjuvant.

    Science.gov (United States)

    HogenEsch, Harm; Dunham, Anisa; Burlet, Elodie; Lu, Fangjia; Mosley, Yung-Yi C; Morefield, Garry

    2017-02-01

    A recombinant vaccine composed of a fusion protein formulated with aluminum hydroxide adjuvant is under development for protection against diseases caused by Streptococcus pyogenes. The safety and local reactogenicity of the vaccine was assessed by a comprehensive series of clinical, pathologic and immunologic tests in preclinical experiments. Outbred mice received three intramuscular injections of 1/5th of the human dose (0.1 ml) and rabbits received two injections of the full human dose. Control groups received adjuvant or protein antigen. The vaccine did not cause clinical evidence of systemic toxicity in mice or rabbits. There was a transient increase of peripheral blood neutrophils after the third vaccination of mice. In addition, the concentration of acute phase proteins serum amyloid A and haptoglobin was significantly increased 1 day after injection of the vaccine in mice. There was mild transient swelling and erythema of the injection site in both mice and rabbits. Treatment-related pathology was limited to inflammation at the injection site and accumulation of adjuvant-containing macrophages in the draining lymph nodes. In conclusion, the absence of clinical toxicity in two animal species suggest that the vaccine is safe for use in a phase I human clinical trial. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. 21 CFR 866.5735 - Prothrombin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin immunological test system. 866.5735 Section 866.5735 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5735 Prothrombin immunological test system. (a)...

  13. 21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radioallergosorbent (RAST) immunological test... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5750 Radioallergosorbent (RAST) immunological test system. (a) Identification. A...

  14. 21 CFR 866.5240 - Complement components immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement components immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5240 Complement components immunological test system. (a) Identification. A complement components...

  15. Immunological aspects of blood transfusions.

    Science.gov (United States)

    Brand, A

    2000-09-01

    Donor selection based on blood group phenotypes, and blood processing such as leukocyte-depletion, gamma-irradiation or washing to remove plasma, are approaches for therapeutic or preventive use to manage the immunological complications of transfusion. Indications for specific components are prescribed in guidelines provided by (inter)national Transfusion Societies. Although the use of guidelines and protocols is in line with modern medicine, these can create a state of tension with the political sense of values to improve the viral safety of blood products and with the commercial exploitation of pooled plasma-products.A century of blood transfusion therapy has facilitated cancer treatment and advanced surgical interventions. The transfusion product has improved progressively, although mostly in response to disasters such as wars and AIDS. Every blood transfusion interacts with the immune system of the recipient. There are, however, very few quantitative figures to estimate the consequences. This review is based on the available literature on the clinical consequences of transfusion induced immunization and modulation. To a large degree the clinical consequences of transfusion induced immune effects are still a mystery.A blood transfusion is a medical intervention, which in many cases remains experimental with respect to the benefit/risk ratio. Ideally, this uncertainty should be communicated to patients and every transfusion included in a study. Such studies preferentially should be randomized because the perceived need for transfusion is associated with clinical conditions with a worse prognosis than those that do not receive transfusion. This difference may mask the interpretation of the transfusion effect. Since the blood supply services in almost all Western countries have been reorganized and nationalized, or at least operate to national quality standards, the measurement of risk: benefit of transfusion, whether political or evidence-based, needs to be

  16. 21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... aid in the diagnosis of copper metabolism disorders. (b) Classification. Class II (performance...

  17. SPECIAL ISSUE VETERINARY IMMUNOLOGY IMMUNOPATHOLOGY: PROCEEDINGS 8TH INTERNATIONAL VETERINARY IMMUNOLOGY SYMPOSIUM

    Science.gov (United States)

    This is the Special Issue of Vet. Immunol. Immunopathol. that summarizes the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto, Brazil. The 8 th IVIS highlighted the importance of veterinary immunology for animal health, vaccinology, reproducti...

  18. [The sick building syndrome as a part of 'ASIA' (autoimmune/auto-inflammatory syndrome induced by adjuvants)].

    Science.gov (United States)

    Maoz-Segal, Ramit; Agmon-Levin, Nancy; Israeli, Eitan; Shoenfeld, Yehuda

    2015-02-01

    The entity 'sick building syndrome' is poorly defined and comprises of a set of symptoms resulting from environmental exposure to a work or a living environment. The symptoms are mainly "allergic"-like and include nasal, eye, and mucous membrane irritation, dry skin as well as respiratory symptoms and general symptoms such as fatigue, lethargy, headaches and fever. The Autoimmune [Auto-inflammatory] Syndrome Induced by Adjuvants (ASIA) is a wider term which describes the role of various environmental factors in the pathogenesis of immune mediated diseases. Factors entailing an immune adjuvant activity such as infectious agents, silicone, aluminium salts and others were found in association with defined and non-defined immune mediated diseases. The sick building syndrome and ASIA share a similar complex of signs and symptoms and probably the same immunological mechanisms which further support a common denominator.

  19. Pediatric allergy and immunology in Israel.

    Science.gov (United States)

    Geller-Bernstein, Carmi; Etzioni, Amos

    2013-03-01

    After the geographic and sociodemographic settings as well as the health care in Israel are briefly described, the scope of pediatric allergy and immunology in Israel is presented. This includes specific disorders commonly encountered, the environment that induces symptoms, the specialists who treat them, and the common challenges of patients, parents, doctors, and allied health personnel who collaborate to manage the maladies and patient care. Allergies usually affect some overall 15-20% of the pediatric population. The main allergens are inhaled, ingested, or injected (insects stings). Generally, the incidence of the various allergens affecting children in Israel, is similar to other parts of the Western world. Owing to the high consanguinity rate in the Israeli population, the prevalence of the various immunodeficiency conditions (in the adaptive as well as the innate system) is higher than that reported worldwide. Pediatric allergists/immunologists also treat autoimmune disorders affecting the pediatric group. Pediatric allergy and clinical immunology are not separate specialties. The 25 specialists who treat children with allergic/immunologic diseases have undergone a basic training in Pediatrics. They also received an additional 2-yr training in allergy and clinical immunology and then have to pass the board examinations. They work mainly in pediatric allergy units, in several hospitals that are affiliated to the five medical schools in the country. Aside from clinical work, most of the centers are also heavily involved in clinical and basic research in allergy and immunology. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Trypanosoma cruzi Adjuvants Potentiate T Cell-Mediated Immunity Induced by a NY-ESO-1 Based Antitumor Vaccine

    Science.gov (United States)

    Junqueira, Caroline; Guerrero, Ana Tereza; Galvão-Filho, Bruno; Andrade, Warrison A.; Salgado, Ana Paula C.; Cunha, Thiago M.; Ropert, Catherine; Campos, Marco Antônio; Penido, Marcus L. O.; Mendonça-Previato, Lúcia; Previato, José Oswaldo; Ritter, Gerd; Cunha, Fernando Q.; Gazzinelli, Ricardo T.

    2012-01-01

    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 (TLR)4 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. PMID:22567144

  2. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Science.gov (United States)

    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.

  3. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Richard James Payne

    2015-10-01

    Full Text Available 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.

  4. Comparative anatomy of phagocytic and immunological synapses

    Directory of Open Access Journals (Sweden)

    Florence eNiedergang

    2016-01-01

    Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

  5. Surgical adjuvant immunotherapy for colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Enker, W.E.; Jacobitz, J.L.; Craft, K.; Wissler, R.W.

    1978-01-01

    One hundred forty-four Wistar-Furth rats in 12 therapeutic groups have been studied in a long-term comparison of the effectiveness of nonspecific immunotherapy with MER (methanol extraction residue) vs active-specific immunotherapy with neuraminidase-modified tumor cells. Six months after surgical adjuvant immunotherapy a 100% improvement in survival was achieved with MER immunotherapy compared to untreated control animals. In addition, the use of MER enhanced the value of active-specific immunotherapy where both modalities were combined in sequence. The predicted value of MER-BCG (Bacillus Calmette-Guerin) for the immunotherapy of solid tumors was borne out by these results suggesting that present ongoing clinical trials of MER as adjuvant therapy for large bowel cancer should prove to be successful if properly controlled. The pattern of survival in these experiments suggests that surgical adjuvant immunotherapy is cytostatic rather than cytocidal, and implies the need for long-term, repeated immunizations.

  6. Clinical immunology--autoimmunity in the Netherlands.

    Science.gov (United States)

    Tervaert, Jan Willem Cohen; Kallenberg, Cees G M

    2014-12-01

    Clinical immunology is in the Netherlands a separate clinical specialty within internal medicine and pediatrics. Clinical immunologists work closely together with nephrologists, rheumatologists and many other medical specialists. Apart from research and teaching, clinical immunologists are taking care of patients with immune-deficiencies, vasculitides and systemic auto-immune diseases. Clinical immunology in the Netherlands has always been an important contributor to basic and clinical science in the Netherlands. Major scientific contributions were made in the field of Systemic Lupus Erythematosus and ANCA associated vasculitis. These Dutch contributions will be reviewed in this article. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. The early history of Stanford Immunology.

    Science.gov (United States)

    Jones, Patricia P; Herzenberg, Leonore A

    2014-05-01

    From its 1960 beginnings in a pair of windowless Genetics Department laboratories under the Stanford Medical School Dean's Office to its current broad-based program, which joins faculty members from departments across the Medical School, the Stanford Immunology Program has played a central role in shaping both basic and clinical immunology thinking. In this article, we tell the story of the beginnings of this odyssey in a reminiscence-based format that brings the flavor of the time in the words of people who lived and built the history.

  8. Immunologic Abnormalities, Treatments, and Recurrent Pregnancy Loss

    DEFF Research Database (Denmark)

    Wang, Nathalie F; Kolte, Astrid M; Larsen, Elisabeth C

    2016-01-01

    Recurrent pregnancy loss, depending on the definition, affects 1% to 3% of women aiming to have a child. Little is known about the direct causes of recurrent pregnancy loss, and the condition is considered to have a multifactorial and complex pathogenesis. The aim of this review was to summarize ...... the evaluation and the management of the condition with specific emphasis on immunologic biomarkers identified as risk factors as well as current immunologic treatment options. The review also highlights and discusses areas in need of further research....

  9. Mixed Adjuvant Formulations Reveal a New Combination That Elicit Antibody Response Comparable to Freund's Adjuvants

    Science.gov (United States)

    Lai, Rachel P. J.; Seaman, Michael S.; Tonks, Paul; Wegmann, Frank; Seilly, David J.; Frost, Simon D. W.; LaBranche, Celia C.; Montefiori, David C.; Dey, Antu K.; Srivastava, Indresh K.; Sattentau, Quentin; Barnett, Susan W.; Heeney, Jonathan L.

    2012-01-01

    Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA), are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs) was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (pCarbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (pCarbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes. PMID:22509385

  10. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

    Science.gov (United States)

    Lai, Rachel P J; Seaman, Michael S; Tonks, Paul; Wegmann, Frank; Seilly, David J; Frost, Simon D W; LaBranche, Celia C; Montefiori, David C; Dey, Antu K; Srivastava, Indresh K; Sattentau, Quentin; Barnett, Susan W; Heeney, Jonathan L

    2012-01-01

    Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA), are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs) was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (pCarbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (pCarbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes.

  11. Mixed adjuvant formulations reveal a new combination that elicit antibody response comparable to Freund's adjuvants.

    Directory of Open Access Journals (Sweden)

    Rachel P J Lai

    Full Text Available Adjuvant formulations capable of inducing high titer and high affinity antibody responses would provide a major advance in the development of vaccines to viral infections such as HIV-1. Although oil-in-water emulsions, such as Freund's adjuvant (FCA/FIA, are known to be potent, their toxicity and reactogenicity make them unacceptable for human use. Here, we explored different adjuvants and compared their ability to elicit antibody responses to FCA/FIA. Recombinant soluble trimeric HIV-1 gp140 antigen was formulated in different adjuvants, including FCA/FIA, Carbopol-971P, Carbopol-974P and the licensed adjuvant MF59, or combinations of MF59 and Carbopol. The antigen-adjuvant formulation was administered in a prime-boost regimen into rabbits, and elicitation of antigen binding and neutralizing antibodies (nAbs was evaluated. When used individually, only FCA/FIA elicited significantly higher titer of nAbs than the control group (gp140 in PBS (p<0.05. Sequential prime-boost immunizations with different adjuvants did not offer improvements over the use of FCA/FIA or MF59. Remarkably however, the concurrent use of the combination of Carbopol-971P and MF59 induced potent adjuvant activity with significantly higher titer nAbs than FCA/FIA (p<0.05. This combination was not associated with any obvious local or systemic adverse effects. Antibody competition indicated that the majority of the neutralizing activities were directed to the CD4 binding site (CD4bs. Increased antibody titers to the gp41 membrane proximal external region (MPER and gp120 V3 were detected when the more potent adjuvants were used. These data reveal that the combination of Carbopol-971P and MF59 is unusually potent for eliciting nAbs to a variety of HIV-1 nAb epitopes.

  12. [Serological response of the dog after primary antirabies vaccination using adjuvant or non-adjuvant vaccines].

    Science.gov (United States)

    Koutchoukali, M A; Blancou, J; Chappuis, G; Tixier, G; Eloit, M; Ganiere, J P; Chantal, J; Simon, S; Berthier, A; Toma, B

    1985-01-01

    The serological responses following a primary vaccination carried out one year before in two groups of dogs which received an inactivated cell culture vaccine containing or not an adjuvant (alumine-hydroxide) are compared. Neutralizing antibody titers assayed in mice, obtained with only one injection of the adjuvanted vaccine are at the same or a greater level than those induced by two injections of the non-adjuvanted vaccine administered two to four weeks apart (statutory schedule of rabies primary vaccination applied in France).

  13. [ADJUVANTED INFLUENZA VACCINES: DATA FROM DIRECT COMPARATIVE STUDIES].

    Science.gov (United States)

    Chernikova, M I; Vasiliev, Yu M

    2015-01-01

    Vaccines are the cornerstone of influenza control, however available vaccines are subject to certain limitations. Adjuvanted vaccines are a promising approach, however available adjuvants have a suboptimal effectiveness and safety profile. Data from direct comparative trials are necessary for selection of optimal adjuvants among currently available and search for novel safe and effective adjuvants for next generation influenza vaccines. Data from published direct comparative studies of adjuvants for influenza vaccines are summarized, a lack of such studies is noted, especially those using adequate methods and designs and comparing adjuvants of major groups (nature/source and mechanism of action). Several promising approaches of adjuvant research and development could be identified: chitosan-based adjuvants, oil-in-water emulsions and multi-component formulations (depot + immune modulating components).

  14. Adjuvanted vaccines: Aspects of immunosafety and modes of action

    NARCIS (Netherlands)

    van Aalst, S.

    2017-01-01

    New developments in vaccine design shift towards safe, though sometimes less immunogenic, subunit and synthetic antigens. Therefore, the majority of current vaccines require adjuvants to increase immunogenicity. Most adjuvants available were developed empirically and their mode of action is only

  15. Haematological and immunological effect of coadministration of ...

    African Journals Online (AJOL)

    This study evaluated the effect of co-administration of extracts of Vernonia amygdalina Del. (VA) and Azadirachta indica Linn.(AI) on haemapoietic and immunological indices of normal and diabetic rats. White blood cells which were non-significantly decreased (p>0.05) in diabetic control rats relative to the normal control, ...

  16. immunological arthritis Prevalence of biochemical and abnormalities ...

    African Journals Online (AJOL)

    1991-02-02

    Feb 2, 1991 ... Tile prevalence of biochemical and immunological abnormali- ties was studied in a group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52 blacks). The most common biochemical abnormalities detected were a reduction in the serum creatinine value (43,4%), raised globulins (39 ...

  17. Prevalence of biochemical and immunological abnormalities in ...

    African Journals Online (AJOL)

    Tile prevalence of biochemical and immunological abnormalities was studied in a group of 256 patients with rheumatoid arthritis (104 coloureds, 100 whites and 52 blacks). The most common biochemical abnormalities detected were a reduction in the serum creatinine value (43,4%), raised globulins (39,7%), raised serum ...

  18. Information and Announcements Refresher Course in Immunology ...

    Indian Academy of Sciences (India)

    Organised by Moving Academy of Medicine and Biomedicine and. Interdisciplinary School of Health Sciences, Pune sponsored by Indian Academy of Sciences, Bangalore. A Refresher Course in Immunology will be held for college/university teachers at the Interdisciplinary School of Health Sciences, University of Pune, ...

  19. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 1 (2017) >. Log in or Register to get access to full text downloads.

  20. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 2 (2017) >. Log in or Register to get access to full text downloads.

  1. Egyptian Journal of Pediatric Allergy and Immunology

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 11, No 2 (2013) >. Log in or Register to get access to full text downloads.

  2. Trypanosoma evansi: A clinical, parasitological and immunological ...

    African Journals Online (AJOL)

    Ibrahim Eldaghayes

    2012-08-13

    Aug 13, 2012 ... We evaluated the clinical, parasitological and immunological effects of a Venezuelan strain of Trypanosoma evansi. (T. evansi) ..... 54, 8-18. Brener, Z. 1962. Therapeutic activity and criterion of cure on mice experimentally infected with. Trypanosoma cruzi. Rev. Inst. Med. Trop. São. Paulo 4, 389-396.

  3. Immunological aspects of oral vaccination in fish

    NARCIS (Netherlands)

    Joosten, P.H.M.

    1997-01-01


    In this thesis immunological consequences of oral vaccination in fish have been described. The efficacy of oral vaccination can be increased by protection of the antigen against degradation in the foregut, in order to reach the hindgut in sufficient quantities for uptake and

  4. Simple Calculation Programs for Biology Immunological Methods

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Simple Calculation Programs for Biology Immunological Methods. Computation of Ab/Ag Concentration from EISA data. Graphical Method; Raghava et al., 1992, J. Immuno. Methods 153: 263. Determination of affinity of Monoclonal Antibody. Using non-competitive ...

  5. Growth performance and immunological responses of broiler ...

    African Journals Online (AJOL)

    The immunological response of experimental birds to ND vaccinations was not significantly different (p>0.05) among dietary treatments. The antibody titre values of birds fed diet III and IV were the highest (log27 and log28) after the first and second ND vaccinations compared to those given other test diets.

  6. Interleukin-2 based systemic and locoregional immunology

    NARCIS (Netherlands)

    S.H. Goey (Swan Hoo)

    1997-01-01

    textabstractThe major impact of recent clinical research with interleukin-2 (IL2) has been the demonstration that a strictly immunological manipulation can mediate the regression of established cancer in humans through the activation of cytotoxic lymphocytes and the release of secondary

  7. Advances in basic and clinical immunology.

    Science.gov (United States)

    Chinen, Javier; Finkelman, Fred; Shearer, William T

    2006-08-01

    This review comments on basic and clinical immunology articles that were published in 2005, with a focus on those that appeared in the Journal of Allergy and Clinical Immunology. In the area of basic immunology, mechanisms of the innate immune system and its interaction with the adaptive immune system were described, with special consideration to applications in biodefense strategies. T regulatory cells were further characterized in their role for the control of allergic, autoimmune, and neoplastic disorders. The function of the thymus Hassall's corpuscles was reported to be the generation of T regulatory cells. Flavonoid molecules obtained from medicinal herbs, including astilbin and epigallocatechin gallate, were discovered to have immunomodulatory properties. Advances in clinical immunology resulted from efforts to develop a newborn screening test for severe combined immunodeficiency and the elucidation of the crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane receptor transmembrane activator and calcium modulator and cyclophilin ligand interactor were found in patients with common variable immunodeficiency. New therapeutic options are described, such as the use of infliximab for granulomas and GM-CSF for chronic ulcers in patients with common variable immunodeficiency. The importance of mucosal immunity in acute HIV infection is cited, as is the role of CD8+ T-cell activation in HIV disease progression in children.

  8. What's so special about chicken immunology?

    Science.gov (United States)

    What’s so special about chickens? Firstly, chickens are not only an invaluable model for studying immunology, they also provide the world’s main source of meat and will be a key protein source needed to feed the growing human population into the future. Poultry meat production is highly efficient ...

  9. The Immunological Relationship between Typanosoma evansi and ...

    African Journals Online (AJOL)

    Trypanosoma evansi and Trypanosoma vivax show very high cross-reactivity in serology. This suggests that there is a close immunological relationship between the two parasite species and the possibility that antiserum against one species contains lytic antibodies against the other species was investigated. T. evansi and ...

  10. IP-I0 BASED IMMUNOLOGICAL MONITORING

    DEFF Research Database (Denmark)

    2008-01-01

    The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of IP-10.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...

  11. Immunology of Paratuberculosis Infection and Disease

    Science.gov (United States)

    The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...

  12. Trypanosoma evansi : A clinical, parasitological and immunological ...

    African Journals Online (AJOL)

    We evaluated the clinical, parasitological and immunological effects of a Venezuelan strain of Trypanosoma evansi (T. evansi) throughout in experimentally inoculated rabbits over the course of infection and compared them with the same aspect in healthy animals. Body temperature was recorded in degrees Celsius, animal ...

  13. Immunological and hematological reference values for apparently ...

    African Journals Online (AJOL)

    Background: Immunological and hematological reference values differ among different human beings with respect to sex, ethnicity, nutrition, altitude and health conditions. These could not be exceptional in the Ethiopian heterogeneous population. However, there are no nationally established reference values. Objective: ...

  14. Working together: interactions between vaccine antigens and adjuvants

    OpenAIRE

    Fox, Christopher B.; Kramer, Ryan M.; Barnes V, Lucien; Dowling, Quinton M.; Vedvick, Thomas S.

    2013-01-01

    The development of vaccines containing adjuvants has the potential to enhance antibody and cellular immune responses, broaden protective immunity against heterogeneous pathogen strains, enable antigen dose sparing, and facilitate efficacy in immunocompromised populations. Nevertheless, the structural interplay between antigen and adjuvant components is often not taken into account in the published literature. Interactions between antigen and adjuvant formulations should be well characterized ...

  15. Adjuvants in the Driver’s Seat: How Magnitude, Type, Fine Specificity and Longevity of Immune Responses Are Driven by Distinct Classes of Immune Potentiators

    Directory of Open Access Journals (Sweden)

    Elke S. Bergmann-Leitner

    2014-04-01

    Full Text Available The mechanism by which vaccine adjuvants enhance immune responses has historically been considered to be the creation of an antigen depot. From here, the antigen is slowly released and provided to immune cells over an extended period of time. This “depot” was formed by associating the antigen with substances able to persist at the injection site, such as aluminum salts or emulsions. The identification of Pathogen-Associated Molecular Patterns (PAMPs has greatly advanced our understanding of how adjuvants work beyond the simple concept of extended antigen release and has accelerated the development of novel adjuvants. This review focuses on the mode of action of different adjuvant classes in regards to the stimulation of specific immune cell subsets, the biasing of immune responses towards cellular or humoral immune response, the ability to mediate epitope spreading and the induction of persistent immunological memory. A better understanding of how particular adjuvants mediate their biological effects will eventually allow them to be selected for specific vaccines in a targeted and rational manner.

  16. Designing CAF-adjuvanted dry powder vaccines : Spray drying preserves the adjuvant activity of CAF01

    NARCIS (Netherlands)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Morck; Yang, Mingshi; Foged, Camilla

    2013-01-01

    Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties

  17. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants

    Directory of Open Access Journals (Sweden)

    E.N. Miyaji

    2011-06-01

    Full Text Available Aluminum salts have been widely used in vaccine formulations and, after their introduction more than 80 years ago, only few vaccine formulations using new adjuvants were developed in the last two decades. Recent advances in the understanding of how innate mechanisms influence the adaptive immunity opened up the possibility for the development of new adjuvants in a more rational design. The purpose of this review is to discuss the recent advances in this field regarding the attempts to determine the molecular basis and the general mechanisms underlying the development of new adjuvants, with particular emphasis on the activation of receptors of innate immune recognition. One can anticipate that the use of these novel adjuvants will also provide a window of opportunities for the development of new vaccines.

  18. Trends in adjuvant development for vaccines: DAMPs and PAMPs as potential new adjuvants.

    Science.gov (United States)

    Miyaji, E N; Carvalho, E; Oliveira, M L S; Raw, I; Ho, P L

    2011-06-01

    Aluminum salts have been widely used in vaccine formulations and, after their introduction more than 80 years ago, only few vaccine formulations using new adjuvants were developed in the last two decades. Recent advances in the understanding of how innate mechanisms influence the adaptive immunity opened up the possibility for the development of new adjuvants in a more rational design. The purpose of this review is to discuss the recent advances in this field regarding the attempts to determine the molecular basis and the general mechanisms underlying the development of new adjuvants, with particular emphasis on the activation of receptors of innate immune recognition. One can anticipate that the use of these novel adjuvants will also provide a window of opportunities for the development of new vaccines.

  19. Archives: Egyptian Journal of Pediatric Allergy and Immunology (The)

    African Journals Online (AJOL)

    Items 1 - 30 of 30 ... Archives: Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home > Archives: Egyptian Journal of Pediatric Allergy and Immunology (The). Log in or Register to get access to full text downloads.

  20. Egyptian Journal of Pediatric Allergy and Immunology (The): About ...

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The): About this journal. Journal Home > Egyptian Journal of Pediatric Allergy and Immunology (The): About this journal. Log in or Register to get access to full text downloads.

  1. Utility of adjuvant systemic therapy in melanoma.

    NARCIS (Netherlands)

    A.M.M. Eggermont (Alexander); A. Testori (Alessandro); J. Marsden (Jeremy); P. Hersey (Peter); I. Quirt (Ian); T. Petrella; H. Gogas (Helen); R.M. MacKie; A. Hauschild (Axel)

    2009-01-01

    textabstractThe lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in

  2. Adjuvant treatment delay in breast cancer patients

    Directory of Open Access Journals (Sweden)

    Damila Cristina Trufelli

    2015-10-01

    Full Text Available Summary Background: to evaluate if time between surgery and the first adjuvant treatment (chemotherapy, radiotherapy or hormone therapy in patients with breast cancer is a risk factor for lower overall survival (OS. Method: data from a five-year retrospective cohort study of all women diagnosed with invasive breast cancer at an academic oncology service were collected and analyzed. Results: three hundred forty-eight consecutive women were included. Time between surgery and the first adjuvant treatment was a risk factor for shorter overall survival (HR=1.3, 95CI 1.06-1.71, p=0.015, along with negative estrogen receptor, the presence of lymphovascular invasion and greater tumor size. A delay longer than 4 months between surgery and the first adjuvant treatment was also associated with shorter overall survival (cumulative survival of 80.9% for delays ≤ 4 months vs. 72.6% for delays > 4 months; p=0.041, log rank test. Conclusion: each month of delay between surgery and the first adjuvant treatment in women with invasive breast cancer increases the risk of death in 1.3-fold, and this effect is independent of all other well-established risk factors. Based on these results, we recommend further public strategies to decrease this interval.

  3. Adjuvant Trastuzumab: Does Time Really Matter?

    OpenAIRE

    Swain, Sandra M

    2013-01-01

    Trastuzumab is now the standard of care for metastatic and early breast cancer; however, questions remain regarding the optimal schedule of trastuzumab in the adjuvant setting. This commentary discusses the results from recent clinical trials with regard to the optimal duration of trastuzumab treatment, as well as the benefits of providing trastuzumab sequentially versus concurrently to chemotherapy.

  4. Adjuvant Biological Therapies in Chronic Leg Ulcers

    Directory of Open Access Journals (Sweden)

    Natalia Burgos-Alonso

    2017-11-01

    Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

  5. DNA Vaccine Electroporation and Molecular Adjuvants

    Science.gov (United States)

    2016-03-16

    vaccination, delivery methods, electroporation, molecular adjuvants, intramuscular, intradermal 1. Introduction The Filoviridae family of viruses is...a malaria DNA vaccine by immunization with a needle-free jet device. Vaccine, 2001. 20(1-2): p. 275-80. 20. Choi, A.H., et al., Protection of mice

  6. Induction of lupus autoantibodies by adjuvants

    Science.gov (United States)

    Satoh, M.; Kuroda, Y.; Yoshida, H.; Behney, K.M.; Mizutani, A.; Akaogi, J.; Nacionales, D.C.; Lorenson, T.D.; Rosenbauer, R.J.; Reeves, W.H.

    2003-01-01

    Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNF?? production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies. The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines. ?? 2003 Elsevier Ltd. All rights reserved.

  7. Adjuvant mitotane treatment for adrenocortical carcinoma.

    Science.gov (United States)

    Terzolo, Massimo; Angeli, Alberto; Fassnacht, Martin; Daffara, Fulvia; Tauchmanova, Libuse; Conton, Pier Antonio; Rossetto, Ruth; Buci, Lisa; Sperone, Paola; Grossrubatscher, Erika; Reimondo, Giuseppe; Bollito, Enrico; Papotti, Mauro; Saeger, Wolfgang; Hahner, Stefanie; Koschker, Ann-Cathrin; Arvat, Emanuela; Ambrosi, Bruno; Loli, Paola; Lombardi, Gaetano; Mannelli, Massimo; Bruzzi, Paolo; Mantero, Franco; Allolio, Bruno; Dogliotti, Luigi; Berruti, Alfredo

    2007-06-07

    Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival. We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery. Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2). Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively. Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients. Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma. Copyright 2007 Massachusetts Medical Society.

  8. Egyptian Journal of Pediatric Allergy and Immunology (The)

    African Journals Online (AJOL)

    This journal is the official journal of the Egyptian Society of Pediatric Allergy and Immunology. It is he first Egyptian Journal specialized in the field of allergy and immunology in the pediatric age group. It is a forum for the presentation and promotion of new researches in the field of allergy and immunology, for maintaining ...

  9. Egyptian Journal of Pediatric Allergy and Immunology (The ...

    African Journals Online (AJOL)

    Focus and Scope. This journal is the official journal of the Egyptian Society of Pediatric Allergy and Immunology. It is he first Egyptian Journal specialized in the field of allergy and immunology in the pediatric age group. It is a forum for the presentation and promotion of new researches in the field of allergy and immunology, ...

  10. 21 CFR 866.5640 - Infectious mononucleosis immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious mononucleosis immunological test system is a device that consists of the reagents used to measure by...

  11. 21 CFR 866.5570 - Lactoferrin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactoferrin immunological test system. 866.5570... Lactoferrin immunological test system. (a) Identification. A lactoferrin immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the lactoferrin (an iron...

  12. 42 CFR 493.833 - Condition: Diagnostic immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis serology...

  13. 42 CFR 493.1208 - Condition: General immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§ 493...

  14. Pediatric allergy and immunology in Italy.

    Science.gov (United States)

    Tozzi, Alberto E; Armenio, Lucio; Bernardini, Roberto; Boner, Attilio; Calvani, Mauro; Cardinale, Fabio; Cavagni, Giovanni; Dondi, Arianna; Duse, Marzia; Fiocchi, Alessandro; Marseglia, Gian L; del Giudice, Michele Miraglia; Muraro, Antonella; Pajno, Giovanni B; Paravati, Francesco; Peroni, Diego; Tripodi, Salvatore; Ugazio, Alberto G; Indinnimeo, Luciana

    2011-05-01

    In Italy, according to the International Study on Asthma and Allergies in Childhood study, the prevalence of current asthma, allergic rhinoconjunctivitis, and atopic eczema in 2006 was 7.9%, 6.5%, and 10.1% among children aged 6-7 and 8.4%, 15.5%, and 7.75% among children aged 13-14 yr. University education in this field is provided by the Postgraduate Schools of Pediatrics and those of Allergology and Clinical Immunology, as well as several annual Master courses. The Italian Society of Pediatric Allergology and Immunology (SIAIP) was founded in 1996 and counts about 1000 members. SIAIP promotes evidence-based management of allergic children and disseminates information to patients and their families through a quite innovative website and the National Journal 'Rivista Italiana di Allergologia Pediatrica'. In the last decade, four major regional, inter-regional, and national web-based networks have been created to link pediatric allergy centers and to share their clinical protocols and epidemiologic data. In addition, National Registers of Primary Immune-deficiencies and on Pediatric HIV link all clinical excellence centers. Research projects in the field of pediatric allergy and immunology are founded by the Italian Ministry of Education, University and Research (MIUR) and by the National Research Council (CNR), but the overall investments in this research area are quite low. Only a handful Italian excellence centers participate in European Projects on Pediatric Allergy and Immunology within the 7th Framework Program. The European Academy of Allergy and Clinical Immunology currently hosts two Italians in its Executive Committee (EC) and one in the EC of the Pediatric Section; moreover, major European Academy of Allergy and Clinical Immunology meetings and courses in the area of pediatrics (e.g., PAAM, Venice, 2009) have been held in Italy in the last 3 yr. Italian hallmarks in the management of allergic diseases in childhood are a quite alive and spread interest in

  15. Findings of interest from immunology and psychoneuroimmunology.

    Science.gov (United States)

    Alford, Les

    2007-05-01

    The biopsychosocial paradigm is now the main model when dealing with most human health disorders. One of the strengths of this model is that it encourages broader thinking when assessing and managing patients. It also encourages broader reading into areas not traditionally associated with manual therapy. Immunology and neuroscience are amongst the fastest growing medical sciences. These fields come together in the relatively new area of psychoneuroimmunolgy. This article examines some findings from these fields that are not widely discussed in the physical therapy professions. These findings are of relevance to many of the disciplines within the physical therapies. It is the authors aim to stimulate further interest in the relevant, yet often under explored areas of immunology and psychoneuroimmunology.

  16. Advances in clinical immunology in 2015.

    Science.gov (United States)

    Chinen, Javier; Notarangelo, Luigi D; Shearer, William T

    2016-12-01

    Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. Immunologic Consequences of Hypoxia during Critical Illness

    Science.gov (United States)

    Kiers, Harmke D.; Scheffer, Gert-Jan; van der Hoeven, Johannes G.; Eltzschig, Holger K.; Pickkers, Peter; Kox, Matthijs

    2016-01-01

    Hypoxia and immunity are highly intertwined at the clinical, cellular, and molecular level. The prevention of tissue hypoxia and modulation of systemic inflammation are cornerstones of daily practice in the Intensive Care Unit. Potentially, immunologic effects of hypoxia may contribute to outcome and represent possible therapeutic targets. Hypoxia and activation of downstream signaling pathways result in enhanced innate immune responses, aimed to augment pathogen clearance. On the other hand, hypoxia also exerts anti-inflammatory and tissue-protective effects in lymphocytes and other tissues. Although human data on the net immunologic effects of hypoxia and pharmacological modulation of downstream pathways are limited, preclinical data support the concept of tailoring the immune response through modulation of the oxygen status or pharmacological modulation of hypoxia-signaling pathways in critically ill patients. PMID:27183167

  18. Immunological effects of ayahuasca in humans.

    Science.gov (United States)

    dos Santos, Rafael Guimarães

    2014-01-01

    Ayahuasca is a botanical hallucinogen traditionally used by indigenous groups of the northwest Amazon. In the last decade, the use of ayahuasca has spread from Brazil, Colombia, Ecuador, and Peru to the U.S., Europe, Asia, and Africa. Despite acute and long-term evidence of good tolerability and safety for ayahuasca administered in the laboratory or ritually consumed in religious contexts, little is known about the immunological impact of ayahuasca on humans. Since ayahuasca is used by an increasing number of consumers, and considering its therapeutic potential, more information is needed regarding ayahuasca potential risks. This article presents a brief overview of the available data regarding the immunological impact of ayahuasca in humans.

  19. Engineering antigen-specific immunological tolerance.

    Energy Technology Data Exchange (ETDEWEB)

    Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.

    2015-05-01

    Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.

  20. Synthetic immunology: modulating the human immune system.

    Science.gov (United States)

    Geering, Barbara; Fussenegger, Martin

    2015-02-01

    Humans have manipulated the immune system to dampen or boost the immune response for thousands of years. As our understanding of fundamental immunology and biotechnological methodology accumulates, we can capitalize on this combined knowledge to engineer biological devices with the aim of rationally manipulating the immune response. We address therapeutic approaches based on the principles of synthetic immunology that either ameliorate disorders of the immune system by interfering with the immune response, or improve diverse pathogenic conditions by exploiting immune cell effector functions. We specifically highlight synthetic proteins investigated in preclinical and clinical trials, summarize studies that have used engineered immune cells, and finish with a discussion of possible future therapeutic concepts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. What Can Vampires Teach Us about Immunology?

    Science.gov (United States)

    Schneider, David S

    2016-04-01

    Speculative fiction examines the leading edge of science and can be used to introduce ideas into the classroom. For example, most students are already familiar with the fictional infectious diseases responsible for vampire and zombie outbreaks. The disease dynamics of these imaginary ailments follow the same rules we see for real diseases and can be used to remind students that they already understand the basic rules of disease ecology and immunology. By engaging writers of this sort of fiction in an effort to solve problems in immunology we may be able to perform a directed evolution experiment where we follow the evolution of plots rather than genetic traits. Copyright © 2016. Published by Elsevier Ltd.

  2. Biotechnology approaches to produce potent, self-adjuvanting antigen-adjuvant fusion protein subunit vaccines.

    Science.gov (United States)

    Moyle, Peter Michael

    Traditional vaccination approaches (e.g. live attenuated or killed microorganisms) are among the most effective means to prevent the spread of infectious diseases. These approaches, nevertheless, have failed to yield successful vaccines against many important pathogens. To overcome this problem, methods have been developed to identify microbial components, against which protective immune responses can be elicited. Subunit antigens identified by these approaches enable the production of defined vaccines, with improved safety profiles. However, they are generally poorly immunogenic, necessitating their administration with potent immunostimulatory adjuvants. Since few safe and effective adjuvants are currently used in vaccines approved for human use, with those available displaying poor potency, or an inability to stimulate the types of immune responses required for vaccines against specific diseases (e.g. cytotoxic lymphocytes (CTLs) to treat cancers), the development of new vaccines will be aided by the availability of characterized platforms of new adjuvants, improving our capacity to rationally select adjuvants for different applications. One such approach, involves the addition of microbial components (pathogen-associated molecular patterns; PAMPs), that can stimulate strong immune responses, into subunit vaccine formulations. The conjugation of PAMPs to subunit antigens provides a means to greatly increase vaccine potency, by targeting immunostimulation and antigen to the same antigen presenting cell. Thus, methods that enable the efficient, and inexpensive production of antigen-adjuvant fusions represent an exciting mean to improve immunity towards subunit antigens. Herein we review four protein-based adjuvants (flagellin, bacterial lipoproteins, the extra domain A of fibronectin (EDA), and heat shock proteins (Hsps)), which can be genetically fused to antigens to enable recombinant production of antigen-adjuvant fusion proteins, with a focus on their

  3. Immunological Characterization of Pectinatus cerevisiophilus Strains

    OpenAIRE

    Haikara, Auli

    1983-01-01

    Eleven Pectinatus cerevisiophilus strains of brewery origin were classified serologically by gel diffusion precipitin tests, immunoelectrophoresis, and the fluorescent antibody staining technique. The Pectinatus strains could be assigned immunologically to three different groups. Groups I and III were found to be very closely related, and only some of the antisera used showed differences. The antisera against the strains belonging to group II contained a common group antigen. A strong precipi...

  4. Evaluation of synergistic effect of biodegradable polymeric nanoparticles and aluminum based adjuvant for improving vaccine efficacy.

    Science.gov (United States)

    Bansal, Vivek; Kumar, Manoj; Dalela, Manu; Brahmne, H G; Singh, Harpal

    2014-08-25

    Aluminum based adjuvants have been used widely to induce long lasting protective immunity through vaccination. But reported incidences of toxicity and side effects of aluminum have raised concerns regarding their safety in childhood vaccines. The present study demonstrates the synergistic effect of admixture of polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. The immunological activity of the admixture formulation was maintained up to 180 days of storage at 5 °C±3 °C. Percent adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture formulation as compared to 55% in conventional vaccine. Admixture preparation (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival respectively, even at 180 days as compared to 30% survival observed in the conventional tetanus vaccine. The present study established the feasibility to formulate a dosage form with improved efficacy and reduced aluminum concentration for vaccination. Copyright © 2014. Published by Elsevier B.V.

  5. Adjuvant effects of salidroside from Rhodiola rosea L. on the immune responses to ovalbumin in mice.

    Science.gov (United States)

    Guan, Shuang; He, Jiakang; Guo, Weixiao; Wei, Jingyuan; Lu, Jing; Deng, Xuming

    2011-12-01

    Salidroside, a major component of Rhodiola rosea L., was evaluated for its adjuvant effects on the immune responses in mice by ovalbumin (OVA) stimulation. BALB/c mice were immunized subcutaneously with OVA 100 μg or OVA 100 μg dissolved in saline containing alum (100 μg) or salidroside (12.5, 25, or 50 μg) on Days 1 and 15. Two weeks later (Day 28), blood samples were collected to analyze OVA-specific IgG, IgG1, and IgG2b antibodies. Meanwhile, splenocytes were harvested to assess lymphocyte proliferation, cytokines (IL-2, IL-4, and IFN-γ) production, and CD4(+), CD8(+) lymphocyte subsets. The results indicated that co-administration of salidroside with OVA significantly enhanced the ConA-, LPS-, and OVA-induced splenocyte proliferation, produced more IL-2, IL-4, IFN-γ, and IgG, IgG1, and IgG2b antibody levels, and increased the percentage of CD4(+), CD8(+) lymphocyte subsets than OVA alone. Thus, salidroside possess immunological adjuvant activity by regulating humoral and cellular immune responses in mice.

  6. Can myofascial techniques modify immunological parameters?

    Science.gov (United States)

    Fernández-Pérez, Antonio Manuel; Peralta-Ramírez, Maria Isabel; Pilat, Andrzej; Moreno-Lorenzo, Carmen; Villaverde-Gutiérrez, Carmen; Arroyo-Morales, Manuel

    2013-01-01

    The objective was to determine the effect of myofascial techniques on the modulation of immunological variables. Thirty-nine healthy male volunteers were randomly assigned to an experimental or control group. The experimental group underwent three manual therapy modalities: suboccipital muscle release, so-called fourth intracranial ventricle compression, and deep cervical fascia release. The control group remained in a resting position for the same time period under the same environmental conditions. Changes in counts of CD3, CD4, CD8, CD19, and natural killer (NK) cells (as immunological markers) between baseline and 20 minutes post-intervention. Repeated-measures ANOVA revealed a significant time × groups interaction (F(1,35)=9.33; p=0.004) for CD19. There were no significant time × group interaction effects on CD3, CD4, CD8, or NK cell counts. Intrasubject analyses showed a higher CD19 count in the experimental group post-intervention versus baseline (t=-4.02; p=0.001), with no changes in the control group (t=0.526; p=0.608). A major immunological modulation, with an increased B lymphocyte count, was observed at 20 minutes after the application of craniocervical myofascial induction techniques.

  7. From Immunologically Archaic to Neoteric Glycovaccines

    Directory of Open Access Journals (Sweden)

    Marco Cavallari

    2017-01-01

    Full Text Available Polysaccharides (PS are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection.

  8. From Immunologically Archaic to Neoteric Glycovaccines.

    Science.gov (United States)

    Cavallari, Marco; De Libero, Gennaro

    2017-01-27

    Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection.

  9. Pediatric allergy and immunology in Brazil.

    Science.gov (United States)

    Rosario-Filho, Nelson A; Jacob, Cristina M; Sole, Dirceu; Condino-Neto, Antonio; Arruda, Luisa K; Costa-Carvalho, Beatriz; Cocco, Renata R; Camelo-Nunes, Inês; Chong-Neto, Herberto J; Wandalsen, Gustavo F; Castro, Ana P M; Yang, Ariana C; Pastorino, Antonio C; Sarinho, Emanuel S

    2013-06-01

    The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X-linked hyper-IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  10. The parallel evolution of immunology and pharmacology.

    Science.gov (United States)

    Conti, A A

    2010-01-01

    Immunology is the systematic evaluation of the means through which human beings protect themselves and respond to the attack of internal and external agents, and Edward Jenner (1749-1823) and Louis Pasteur (1822-1895) are considered pioneers of this field. Jenner observed the protective effect of cowpox against smallpox and inoculated the cowpox in human beings to protect them from the often lethal smallpox. Pasteur developed in his laboratory a vaccine against rabies and elaborated methods for attenuating the virulence of pathogenic microorganisms while maintaining their immunogenicity. Pharmacology is the area of medical science dealing with drugs and their uses, and it was during the nineteenth century that it assumed its status of scientific specialty, mainly in German-speaking Europe, through the establishment of pharmacological institutes and dedicated laboratories. The discovery and the synthesis of drugs and the systematic evaluation of their activity have constituted through time a scientific field in which immunology and pharmacology have met and given origin to notable progress in the history of science. The development of chemotherapy, as well as of organ and tissue transplantation, in the twentieth century has been decisively promoted by both immunology and pharmacology. In the last three decades the relationship between these two scientific branches has become increasingly closer in basic research, clinical science, medical education and also editorial scientific activity, as documented by the Journal hosting this paper.

  11. History of immunology in Australia: events and identities.

    Science.gov (United States)

    Mackay, I R

    2006-06-01

    Immunology originated in Europe during the latter 1900s, and applications can be discerned in colonial Australia. The actual beginnings of immunology in Australia followed Burnet's enunciation of two fundamental principles: natural immune tolerance as an acquired characteristic in 1948 and clonal selection theory in 1957. Laboratory and clinical immunology flourished at various centres from the 1950s. The Australian Society of Immunology was founded in 1971. The merger of clinical immunology with allergy in 1991 created the Australian Society of Clinical Immunology and Allergy, exemplary for the reamalgamation of these related specialties. Australian immunology over the past 50 years has become recognized nationally and abroad as a highly visible component of the academic, research and biomedical scene and is still on a rising trajectory.

  12. Does lipophilicity per se induce adjuvant effects?

    DEFF Research Database (Denmark)

    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(OH)3...... respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is......, additional structural properties are required....

  13. The adjuvant mechanism of cationic dimethyldioctadecylammonium liposomes

    DEFF Research Database (Denmark)

    Korsholm, Karen Smith; Agger, Else Marie; Foged, Camilla

    2007-01-01

    Cationic liposomes are being used increasingly as efficient adjuvants for subunit vaccines but their precise mechanism of action is still unknown. Here, we investigated the adjuvant mechanism of cationic liposomes based on the synthetic amphiphile dimethyldioctadecylammonium (DDA). The liposomes...... concentrations. This efficient adsorption onto the liposomes led to an enhanced uptake of OVA by BM-DCs as assessed by flow cytometry and confocal fluorescence laser-scanning microscopy. This was an active process, which was arrested at 4 degrees and by an inhibitor of actin-dependent endocytosis, cytochalasin D....... In vivo studies confirmed the observed effect because adsorption of OVA onto DDA liposomes enhanced the uptake of the antigen by peritoneal exudate cells after intraperitoneal injection. The liposomes targeted antigen preferentially to antigen-presenting cells because we only observed a minimal uptake...

  14. Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines.

    Science.gov (United States)

    Kashiwagi, Yasuyo; Maeda, Mika; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-06-05

    Aluminum-adjuvanted vaccines are administered through an intramuscular injection (IM) in the US and EU, however, a subcutaneous injection (SC) has been recommended in Japan because of serious muscle contracture previously reported following multiple IMs of antibiotics. Newly introduced adjuvanted vaccines, such as the human papillomavirus (HPV) vaccines, have been recommended through IM. In the present study, currently available vaccines were evaluated through IM in mice. Aluminum-adjuvanted vaccines induced inflammatory nodules at the injection site, which expanded into the intra-muscular space without any muscle degeneration or necrosis, whereas non-adjuvanted vaccines did not. These nodules consisted of polymorph nuclear neutrophils with some eosinophils within the initial 48h, then monocytes/macrophages 1 month later. Inflammatory nodules were observed 6 months after IM, had decreased in size, and were absorbed 12 months after IM, which was earlier than that after SC. Cytokine production was examined in the injected muscular tissues and AS04 adjuvanted HPV induced higher IL-1β, IL-6, KC, MIP-1, and G-CSF levels in muscle tissues than any other vaccine, but similar serum cytokine profiles were observed to those induced by the other vaccines. Currently available vaccines did not induce muscular degeneration or fibrotic scar as observed with muscle contracture caused by multiple IMs of antibiotics in the past. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Liposomal adjuvant development for leishmaniasis vaccines.

    Science.gov (United States)

    Askarizadeh, Anis; Jaafari, Mahmoud Reza; Khamesipour, Ali; Badiee, Ali

    2017-08-01

    Leishmaniasis is a parasitic disease that ranges in severity from skin lesions to fatality. Since long-lasting protection is induced upon recovery from cutaneous leishmaniasis, development of an effective vaccine is promising. However, there is no vaccine for use in humans yet. It seems limited efficacy in leishmaniasis vaccines is due to lack of an appropriate adjuvant or delivery system. Hence, the use of particulate adjuvants such as liposomes for effective delivery to the antigen presenting cells (APCs) is a valuable strategy to enhance leishmaniasis vaccine efficacy. The extraordinary versatility of liposomes because of their unique amphiphilic and biphasic nature allows for using antigens or immunostimulators within the core, on the surface or within the bilayer, and modulates both the magnitude and the T-helper bias of the immune response. In this review article, we attempt to summarize the role of liposomal adjuvants in the development of Leishmania vaccines and describe the main physicochemical properties of liposomes like phospholipid composition, surface charge, and particle size during formulation design. We also suggest potentially useful formulation strategies in order for future experiments to have a chance to succeed as liposomal vaccines against leishmaniasis.

  16. Adjuvant chemotherapy for advanced endometrial cancer.

    Science.gov (United States)

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  17. [Adjuvant antioxidant therapy in varicocele infertility].

    Science.gov (United States)

    Gamidov, S I; Ovchinnikov, R I; Popova, A Yu; Avakyan, A Yu; Sukhikh, G T

    2017-06-01

    Infertility affects an estimated 15% of couples globally. Male factor infertility accounts for about a half of infertility cases. About 40% of infertile men have varicocele. The aim of this study was to investigate the efficacy and safety of a complex of acetyl-L-carnitine, L-carnitine fumarate and alpha-lipoic acid (SpermActin-forte) (SA) for adjuvant antioxidant therapy after microsurgical varicocelectomy (MVE) in men with varicocele and assess its impact on the level of DNA fragmentation in sperm cells. This is an open, prospective, randomized trial comprising 114 men aged 25-45 (mean 34.1+/-12.1) years who underwent MVE. The patients were allocated to receive either adjuvant SA (n=38), SA in combination with a vitamin complex (VC) (n=38) or no adjuvant therapy (n=38). The efficacy was assessed at 3 months by testing standard semen parameters and the level of sperm DNA fragmentation. MVE led to a 21.7% increase in the progressive sperm motility compared to the baseline level. In patients receiving SA, this was by 76.7% due to active sperm motility (category A) at 3 months. MVE with concurrent supplementation of SA resulted in a 22.3% decrease in the level of sperm DNA fragmentation at 3 months. When used in the postoperative period after MVE, SA and VC resulted in a 27% increase in the sperm concentration at 3 months. There were no side effects of pharmacotherapy. The statistical significance of the change in variables was calculated using the Wilcoxon test. Critical level =0.05 was established for all criteria. Using nutraceuticals (SA) after MVE is an effective and safe adjuvant antioxidant therapy of male infertility in patients with varicocele which leads to an improvement in the basic sperm parameters (sperm concentration and motility) and a decrease in the level of sperm DNA fragmentation in the short term. Adjuvant antioxidant therapy of varicocele infertility potentiates the effects of monotherapy (both medical and surgical), leads to an increase in its

  18. The impact of size on particulate vaccine adjuvants.

    Science.gov (United States)

    Shah, Ruchi R; O'Hagan, Derek T; Amiji, Mansoor M; Brito, Luis A

    2014-12-01

    Particulate adjuvants have been successful at inducing increased immune responses against many poorly immunogenic antigens. However, the mechanism of action of these adjuvants often remains unclear. As more potential vaccine targets are emerging, it is becoming necessary to broaden our knowledge on the factors involved in generating potent immune responses to recombinant antigens with adjuvants. While composition of adjuvants is integral in defining the overall performance of an adjuvant, some physical parameters such as particle size, surface charge and surface modification may also contribute to the potency. In this review, we will try to highlight the role of particle size in controlling the immune responses to adjuvanted vaccines, with a focus on insoluble aluminum salts, oil-in-water emulsions, polymeric particles and liposomes.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Cutaneous drug hypersensitivity : Immunological and genetic perspective

    Directory of Open Access Journals (Sweden)

    Kisalay Ghosh

    2011-01-01

    Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.

  1. Parasitic Helminths: New Weapons against Immunological Disorders

    Directory of Open Access Journals (Sweden)

    Yoshio Osada

    2010-01-01

    Full Text Available The prevalence of allergic and autoimmune diseases is increasing in developed countries, possibly due to reduced exposure to microorganisms in childhood (hygiene hypothesis. Epidemiological and experimental evidence in support of this hypothesis is accumulating. In this context, parasitic helminths are now important candidates for antiallergic/anti-inflammatory agents. Here we summarize antiallergic/anti-inflammatory effects of helminths together along with our own study of the effects of Schistosoma mansoni on Th17-dependent experimental arthritis. We also discuss possible mechanisms of helminth-induced suppression according to the recent advances of immunology.

  2. Immunological Characterization of Pectinatus cerevisiophilus Strains.

    Science.gov (United States)

    Haikara, A

    1983-11-01

    Eleven Pectinatus cerevisiophilus strains of brewery origin were classified serologically by gel diffusion precipitin tests, immunoelectrophoresis, and the fluorescent antibody staining technique. The Pectinatus strains could be assigned immunologically to three different groups. Groups I and III were found to be very closely related, and only some of the antisera used showed differences. The antisera against the strains belonging to group II contained a common group antigen. A strong precipitation band found near the antigen was shown to represent the interaction of the lipopolysaccharide antibody and the respective antigen.

  3. Basic Genetics and Immunology of Candida Infections.

    Science.gov (United States)

    Wang, Xiaowen; van de Veerdonk, Frank L; Netea, Mihai G

    2016-03-01

    Candida infections can cause superficial and invasive disease. Several essential mechanisms underlying the pathogenesis of these infections were known for some time, such as neutropenia predisposing to invasive disease, and CD4 lymphopenia causing increased susceptibility to mucosal candidiasis. However, the development of novel genetic screening techniques has led to several new insights in the genetics and immunology of candida infections. This article highlights novel insights in the pathogenesis of mucocutaneous and invasive candidiasis that have been identified in recent years. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Towards an understanding of the adjuvant action of aluminium

    Science.gov (United States)

    Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

    2011-01-01

    The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

  5. Methods to Prepare Aluminum Salt-Adjuvanted Vaccines.

    Science.gov (United States)

    Thakkar, Sachin G; Cui, Zhengrong

    2017-01-01

    Many human vaccines contain certain insoluble aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate as vaccine adjuvants to boost the immunogenicity of the vaccines. Aluminum salts have been used as vaccine adjuvants for decades and have an established, favorable safety profile. However, preparing aluminum salts and aluminum salt-adjuvanted vaccines in a consistent manner remains challenging. This chapter discusses methods to prepare aluminum salts and aluminum salt-adjuvanted vaccines, factors to consider during preparation, and methods to characterize the vaccines after preparation.

  6. The Use of Xanthan Gum as Vaccine Adjuvant: An Evaluation of Immunostimulatory Potential in BALB/c Mice and Cytotoxicity In Vitro

    Directory of Open Access Journals (Sweden)

    Rodrigo Andrade Schuch

    2017-01-01

    Full Text Available The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3, and assessed the levels of IFN-γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN-γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant.

  7. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Annual Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-04-16

    The goal of this proposal is to demonstrate that co-localization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of recombinant subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. NLPs are are biocompatible, high-density lipoprotein mimetics that are amenable to the incorporation of multiple, chemically-disparate adjuvant and antigen molecules. We hypothesize that the ability to co-localize optimized adjuvant formulations with subunit antigens within a single particle will enhance the stimulation and activation of key immune effector cells, increasing the protective efficacy of subunit antigen-based vaccines. While Burkholderia spp. and F. tularensis subunit antigens are the focus of this proposal, we anticipate that this approach is applicable to a wide range of DOD-relevant biothreat agents. The F344 rat aerosol challenge model for F. tularensis has been successfully established at Battelle under this contract, and Year 3 efficacy studies performed at Battelle demonstrated that an NLP vaccine formulation was able to enhance survival of female F344 rats relative to naïve animals. In addition, Year 3 focused on the incorporation of multiple Burkholderia antigens (both polysaccharides and proteins) onto adjuvanted NLPs, with immunological analysis poised to begin in the next quarter.

  8. Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events.

    Science.gov (United States)

    Sobolev, Olga; Binda, Elisa; O'Farrell, Sean; Lorenc, Anna; Pradines, Joel; Huang, Yongqing; Duffner, Jay; Schulz, Reiner; Cason, John; Zambon, Maria; Malim, Michael H; Peakman, Mark; Cope, Andrew; Capila, Ishan; Kaundinya, Ganesh V; Hayday, Adrian C

    2016-02-01

    Adjuvanted vaccines afford invaluable protection against disease, and the molecular and cellular changes they induce offer direct insight into human immunobiology. Here we show that within 24 h of receiving adjuvanted swine flu vaccine, healthy individuals made expansive, complex molecular and cellular responses that included overt lymphoid as well as myeloid contributions. Unexpectedly, this early response was subtly but significantly different in people older than ∼35 years. Wide-ranging adverse clinical events can seriously confound vaccine adoption, but whether there are immunological correlates of these is unknown. Here we identify a molecular signature of adverse events that was commonly associated with an existing B cell phenotype. Thus immunophenotypic variation among healthy humans may be manifest in complex pathophysiological responses.

  9. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-13

    The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the third quarter of the third year, F344 rats vaccinated with adjuvanted NLP formulations were challenged with F. tularensis SCHU S4 at Battelle. Preliminary data indicate that up to 65% of females vaccinated intranasally with an NLP-based formulation survived this challenge, compared to only 20% survival of naïve animals. In addition, NLPs were successfully formulated with Burkholderia protein antigens. IACUC approval for immunological assessments in BALB/c mice was received and we anticipate that these assessments will begin by March 2015, pending ACURO approval.

  10. Influence of adjuvants and interactions between herbicides and weed species by determination of relative adjuvant-effect on herbicide dose

    Directory of Open Access Journals (Sweden)

    Brathuhn, Arne

    2014-02-01

    Full Text Available When adjuvants are used as a partner for herbicides in tank-mixtures, they can have a positive influence on herbicidal efficacy in certain situations. The addition of adjuvants can contribute to an enhanced effect of the herbicide when applying the maximum registered dose or when securing weed control of reduced application rates. The influence of adjuvants depends on weather factors, the herbicide partner and the particular weed species. This study examined the influence of different herbicide-adjuvant-combinations on various weed species. The objective of the study was to clarify, if the addition of an adjuvant to a herbicide leads to comparable results within the examined weed species or if the influence of an adjuvant use varies. The determination of relative adjuvant effects allowed comparisons of the data. The influence of six herbicideadjuvant-combinations on six weed species was evaluated in greenhouse trials. All herbicides used were from the group of ALS-inhibitors (HRAC-group B. Data of the greenhouse experiments were compared to results from field trials, which were conducted at five sites in Rhineland-Palatinate. One herbicide with and without an addition of an adjuvant was applied per site. Data of the studies reveal that the use of adjuvants results in a positive influence on herbicidal efficacy in most cases. However, strong differences in intensity as well as quality of adjuvant effects regarding the response of different weed species were observed. The efficacy of the herbicide BIATHLON® for example was improved by addition of an adjuvant for Galium aparine by a factor 364.56. For Daucus carota this factor was 2.98. Growers should necessarily take account of these differences when using adjuvants, especially when they are used to secure reduced application rates.

  11. Immunological and Toxinological Responses to Jellyfish Stings

    Science.gov (United States)

    Tibballs, James; Yanagihara, Angel A.; Turner, Helen C.; Winkel, Ken

    2013-01-01

    Just over a century ago, animal responses to injections of jellyfish extracts unveiled the phenomenon of anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact, jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically, both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier therapy. The current challenge for immunotoxinologists is to deconstruct the actions of venom components to target therapeutic modalities for sting treatment. PMID:21824077

  12. Norovirus immunology: Of mice and mechanisms

    Science.gov (United States)

    Newman, Kira L; Leon, Juan S

    2015-01-01

    Summary Noroviruses (NoVs) are the most common cause of sporadic and epidemic gastroenteritis in the United States and Europe and are responsible for 20% of acute gastroenteritis worldwide. Over the past decade, the understanding of NoV immunology has grown immensely. Studies of the natural immune response to NoV in humans and animal models have laid the foundation for innovations in cell culture systems for NoV and development of new therapeutics. Evidence from animal models, NoV surrogates, observational human research, and human challenge studies suggest that the innate immune response is critical for limiting NoV infection but is insufficient for viral clearance. NoV may antagonize the innate immune response to establish or prolong infection. However, once a robust adaptive immune response is initiated, the immune system clears the infection through the action of T cells and B cells, simultaneously generating highly specific protective immunologic memory. We review here both the current knowledge on norovirus immunity and exciting new developments, with a focus on ongoing vaccine development work, novel cell culture systems, and advances in understanding the role of the gut microbiome. These changes reinforce the need for a better understanding of the human immune response to NoV and suggest novel hypotheses. PMID:26256101

  13. Modern mucosal vaccines, adjuvants and microbicides.

    Science.gov (United States)

    Cranage, Martin P; Manoussaka, Maria

    2009-02-01

    Preventing infection at the pathogen portal of entry through induction of mucosal immunity and the use of microbicides has always been an exciting prospect. Moreover, the promise of needle-free prophylaxis is attractive for many reasons. This meeting report highlights some of the critical issues that were discussed concerning recent advances in the field. New routes of vaccination and modalities of delivery are still being discovered, and important advances are occurring in the development of safe mucosal adjuvants. Protection of mucosal surfaces is likely to be particularly crucial to prevent infections with pathogens, such as HIV, that can be sequestered rapidly.

  14. Postoperative adjuvant chemoradiotherapy in rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Sei Kyung; Kim, Jong Woo; Oh, Do Yeun; Chong, So Young; Shin, Hyun Soo [Bundang CHA General Hospital, Pochon CHA University, Seongnam (Korea, Republic of)

    2006-09-15

    To evaluate the role of postoperative adjuvant chemoradiotherapy in rectal cancer, we retrospectively analyzed the treatment outcome of patients with rectal cancer taken curative surgical resection and postoperative adjuvant chemoradiotherapy. A total 46 patients with AJCC stage II and III carcinoma of rectum were treated with curative surgical resection and postoperative adjuvant chemoradiotherapy. T3 and T4 stage were 38 and 8 patients, respectively. N0, N1, and N2 stage were 12, 16, 18 patients, respectively. Forty patients received bolus infusions of 5-fluorouracil (500 mg/m{sup 2}/day) with leucovorin (20 mg/m{sup 2}/day), every 4 weeks interval for 6 cycles. Oral Uracil/Tegafur on a daily basis for 6 {approx} 12 months was given in 6 patients. Radiotherapy with 45 Gy was delivered to the surgical bed and regional pelvic lymph node area, followed by 5.4 {approx} 9 Gy boost to the surgical bed. The follow up period ranged from 8 to 75 months with a median 35 months. Treatment failure occurred in 17 patients (37%). Locoregional failure occurred in 4 patients (8.7%) and distant failure in 16 patients (34.8%). There was no local failure only. Five year actuarial overall survival (OS) was 51.5% and relapse free survival (RFS) was 58.7%. The OS and RFS were 100%, 100% in stage N0 patients, 53.7%, 47.6% in N1 patients, and 0%, 41.2% in N2 patients ({rho} = 0.012, {rho} = 0.009). The RFS was 55%, 78.5%, and 31.2% in upper, middle, and lower rectal cancer patients, respectively ({rho} = 0.006). Multivariate analysis showed that N stage ({rho} = 0.012) was significant prognostic factor for OS and that N stage ({rho} = 0.001) and location of tumor ({rho} = 0.006) were for RFS. Bowel complications requiring surgery occurred in 3 patients. Postoperative adjuvant chemoradiotherapy was an effective modality for locoregional control of rectal cancer. But further investigations for reducing the distant failure rate are necessary because distant failure rate is still high.

  15. Nanolipoprotein Particles (NLPs) as Versatile Vaccine Platforms for Co-delivery of Multiple Adjuvants with Subunit Antigens from Burkholderia spp. and F. tularensis - Technical Report

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-01-06

    The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the second quarter of the third year, LLNL finalized all immunological assessments of NLP vaccine formulations in the F344 model. Battelle has immunized rats with three unique NLP formulations by either intramuscular or intranasal administration. All inoculations have been completed, and protective efficacy against an aerosolized challenge will begin at the end of October, 2014.

  16. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Directory of Open Access Journals (Sweden)

    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.

  17. A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer.

    Science.gov (United States)

    Fenoglio, Daniela; Traverso, Paolo; Parodi, Alessia; Tomasello, Laura; Negrini, Simone; Kalli, Francesca; Battaglia, Florinda; Ferrera, Francesca; Sciallero, Stefania; Murdaca, Giuseppe; Setti, Maurizio; Sobrero, Alberto; Boccardo, Francesco; Cittadini, Giuseppe; Puppo, Francesco; Criscuolo, Domenico; Carmignani, Giorgio; Indiveri, Francesco; Filaci, Gilberto

    2013-06-01

    Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. GX301 was administered by intradermally injecting 500 μg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. No grade 3-4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.

  18. Vaccine Adjuvants: from 1920 to 2015 and Beyond

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

    Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber

    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...... of dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB)....

  20. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    Science.gov (United States)

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Evaluation of different adjuvants formulations for bluetongue vaccine

    Directory of Open Access Journals (Sweden)

    Ludmila Branco Macedo

    2013-12-01

    Full Text Available This study investigated the adjuvant potential of W/O/W multiple emulsions and microemulsions, comparing them with traditional aluminum hydroxide and oil-in-water emulsion adjuvants against bluetongue vaccine (BTV. Local inflammatory reactions were assessed in rabbits by measuring the temperature of the animals and the skin thickness at the site of application. Antibodies titers were determined by serum-neutralization test. Histological analyses of lesions at the site of adjuvants application were done. Results showed that multiple emulsion and microemulsion maintained their stability even in the presence of complex components and presented adequate characteristics for subcutaneous administration. They were able to induce immune response against BTV, but it was smaller than the traditional adjuvants. Despite microemulsion adjuvant showed lower antibodies titre, it was easier to prepare more stable at 4°C and it was the only one that did not induce any local reaction.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Targeting Specific Immunologic Pathways in Crohn's Disease.

    Science.gov (United States)

    Ramos, Guilherme Piovezani; Faubion, William A; Papadakis, Konstantinos A

    2017-09-01

    Understanding the immunologic pathways in intestinal inflammation is crucial for the development of new therapies that can maximize patient response and minimize toxicity. Targeting integrins and cytokines is intended to control leukocyte migration to effector sites or inhibit the action of proinflammatory cytokines. New approaches to preventing leukocyte migration may target integrin receptors expressed on the intestinal vascular endothelium. The interleukin (IL)-12/IL-23 pathway has been a therapeutic target of interest in controlling active Crohn's disease (CD). New therapeutic approaches in CD may involve the enhancement of anti-inflammatory cytokine pathways and modulation of cellular responses and intranuclear signals associated with intestinal inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Immunology of term and preterm labor

    Directory of Open Access Journals (Sweden)

    Peltier Morgan R

    2003-12-01

    Full Text Available Abstract During pregnancy there is an alteration in maternal immunity within the uterus where innate, proinflammatory immune responses are tightly regulated to prevent immunological rejection of the fetal allograft. Disruption of the delicate balance of cytokines by bacteria or other factors increases the production of proinflammatory cytokines at the maternal-fetal interface and activates the parturition mechanism prematurely. Despite years of searching, there is still no broadly effective strategy for preventing preterm labor and most therapies are directed at inhibiting myometrial contractions and improving neonatal outcome. Recent studies with progestins and interleukin-10 (IL-10, however, are showing promise in randomized clinical trials and animal studies. Furthermore, the identification of the Toll-like receptors as upstream mediators of inflammation may offer alternative therapeutic targets for preventing this common pregnancy complication.

  6. Clinical and Immunological Responses in Ocular Demodecosis

    Science.gov (United States)

    Kim, Jae Hoon; Chun, Yeoun Sook

    2011-01-01

    The purpose of this study was to investigate clinical and immunological responses to Demodex on the ocular surface. Thirteen eyes in 10 patients with Demodex blepharitis and chronic ocular surface disorders were included in this study and treated by lid scrubbing with tea tree oil for the eradication of Demodex. We evaluated ocular surface manifestations and Demodex counts, and analyzed IL-1β, IL-5, IL-7, IL-12, IL-13, IL-17, granulocyte colony-stimulating factor, and macrophage inflammatory protein-1β in tear samples before and after the treatment. All patients exhibited ocular surface manifestations including corneal nodular opacity, peripheral corneal vascularization, refractory corneal erosion and infiltration, or chronic conjunctival inflammatory signs before treatment. After treatment, Demodex was nearly eradicated, tear concentrations of IL-1β and IL-17 were significantly reduced and substantial clinical improvement was observed in all patients. In conclusion, we believe that Demodex plays an aggravating role in inflammatory ocular surface disorders. PMID:21935281

  7. Update in clinical allergy and immunology.

    Science.gov (United States)

    von Gunten, S; Marsland, B J; von Garnier, C; Simon, D

    2012-12-01

    In the recent years, a tremendous body of studies has addressed a broad variety of distinct topics in clinical allergy and immunology. In this update, we discuss selected recent data that provide clinically and pathogenetically relevant insights or identify potential novel targets and strategies for therapy. The role of the microbiome in shaping allergic immune responses and molecular, as well as cellular mechanisms of disease, is discussed separately and in the context of atopic dermatitis, as an allergic model disease. Besides summarizing novel evidence, this update highlights current areas of uncertainties and debates that, as we hope, shall stimulate scientific discussions and research activities in the field. © 2012 John Wiley & Sons A/S.

  8. The Immunological Basis of Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Francesca A. R. Silva

    2016-01-01

    Full Text Available Inflammatory bowel diseases (IBDs are chronic ailments, Crohn’s disease and ulcerative colitis being the most important. These diseases present an inflammatory profile and they differ according to pathophysiology, the affected area in the gastrointestinal tract, and the depth of the inflammation in the intestinal wall. The immune characteristics of IBD arise from abnormal responses of the innate and adaptive immune system. The number of Th17 cells increases in the peripheral blood of IBD patients, while Treg cells decrease, suggesting that the Th17/Treg proportion plays an important role in the development and maintenance of inflammation. The purpose of this review was to determine the current state of knowledge on the immunological basis of IBD. Many studies have shown the need for further explanation of the development and maintenance of the inflammatory process.

  9. Reproductive immunology: biomarkers of compromised pregnancies

    Energy Technology Data Exchange (ETDEWEB)

    Faulk, W.P.; Coulam, C.B.; McIntyre, J.A.

    1987-10-01

    The objective of this paper is to consider several catagories of biomarkers of human pregnancy. The design of the report is to discuss useful and promising markers and techniques. Research gaps, needs, and priorities are also defined. Useful markers are mixed lymphocyte culture reactions, measures of lymphocytotoxic antibodies, histocompatibility (HLA) typing, and immunohematological evaluations. Promising markers are measures of major basic protein and early pregnancy factor, as well as determinations of trophoblast-lymphocyte cross-reactive (TLX) antigens. Promising techniques are flourescence-activated cell-sorter analysis of maternal blood for fetal and extraembryonic tissues and immunotherapy with TLX and other antigens to prevent spontaneous abortion. It is concluded that immunology has much to offer the development of biomarkers of human pregnancy.

  10. Immunological HCV-Associated Thrombocytopenia: Short Review

    Directory of Open Access Journals (Sweden)

    Dimitrios Dimitroulis

    2012-01-01

    Full Text Available Infection with Hepatitis C virus (HCV is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature.

  11. The dendritic cell side of the immunological synapse

    NARCIS (Netherlands)

    Verboogen, D.R.J.; Dingjan, I.; Revelo, N.H.; Visser, L.J.; Beest, M.B.A. ter; Bogaart, G. van den

    2016-01-01

    Immune responses are initiated by the interactions between antigen-presenting cells (APCs), such as dendritic cells (DCs), with responder cells, such as T cells, via a tight cellular contact interface called the immunological synapse. The immunological synapse is a highly organized subcellular

  12. Origins and evolution of reproductive immunology: a personal perspective.

    Science.gov (United States)

    Billington, W David

    2015-04-01

    This is a brief personal assessment of the origins and development of the field of reproductive immunology from the 19th century to the present day, with special reference to the founding of the Journal of Reproductive Immunology in 1979. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. 21 CFR 866.5870 - Thyroid autoantibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... thyroid autoantibodies may aid in the diagnosis of certain thyroid disorders, such as Hashimoto's disease... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid autoantibody immunological test system....5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody...

  14. Immunological Response of Hiv-Infected Children to Highly Active ...

    African Journals Online (AJOL)

    For all statistical significance tests, the cut-off value was p<0.05. Poison Regression was used for further analysis. RESULTS: ... Low CD4 count at initiation, undisclosed HIV status and lack of good adherence were found to cause low immunological response to HAART. KEYWORDS: HAART, CD4, Immunologic response ...

  15. Veterinary Immunology Committee Toolkit Workshop 2010: Progress and plans

    Science.gov (United States)

    The Third Veterinary Immunology Committee (VIC) Toolkit Workshop took place at the Ninth International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan on August 18, 2020. The Workshop built on previous Toolkit Workshops and covered various aspects of reagent development, commercialisation an...

  16. The size of the thymus: an important immunological diagnostic tool?

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth

    2003-01-01

    of the thymus relevant to its function and could measurement of the thymus be a useful immunological diagnostic tool in the investigation of thymic function in humans with a depressed immune system? Conclusion: Studies using the size of the thymus as an immunological diagnostic tool should be encouraged....

  17. 42 CFR 493.837 - Standard; General immunology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80 percent...

  18. Pediatric allergy and immunology at Siriraj Hospital.

    Science.gov (United States)

    Vichyanond, Pakit

    2002-08-01

    Like other parts of the world, prevalence of childhood allergic diseases in Thailand, particularly of asthma and allergic rhinitis, has risen sharply over the past decade. Epidemiologic studies in this country indicated that allergic sensitization (mainly to house dust mites, cockroaches and cat dander) is the major important risk factor for the development of asthma. House dust mites are the most important source of allergens causing sensitization among allergic Thai children. A nationwide survey indicated that house dust mites are ubiquitous in Thai homes. Despite the authors' earlier finding that mite allergen levels in Thailand (mean group-I allergen level of 11 mcg/g dust), exceeded the recommended international threshold level to induce asthmatic symptoms (10 mcg/g dust), mite allergen levels in homes within the Bangkok area are in the modest range (5 mcg/g dust). With mattresses in Thailand being commonly laid on hardwood surfaces, the authors demonstrated that only top-covering of these mattresses with locally produced mite-impermeable membrane, mite allergens could be substantially reduced. Other active research in pediatric allergy in Thailand include complete surveys of outdoor aeroallergens and research in pharmacologic managements of allergic diseases. The Thailand Registry of Primary Immune Deficiency has recently been established to collect data on patients with these disorders and to improve means for diagnosis and treatment for these unfortunate patients. Finally, with a recent approval for board certification in pediatric allergy and immunology, it is expected that the number of specialists in this field will increase to a sufficient level to provide adequate care for allergic/immunologic children in Thailand.

  19. Pediatric allergy and immunology in Spain.

    Science.gov (United States)

    Nieto, Antonio; Mazon, Angel; Martin-Mateos, Maria Anunciacion; Plaza, Ana-Maria; Garde, Jesus; Alonso, Elena; Martorell, Antonio; Boquete, Manuel; Lorente, Felix; Ibero, Marcel; Bone, Javier; Pamies, Rafael; Garcia, Juan Miguel; Echeverria, Luis; Nevot, Santiago; Martinez-Cañavate, Ana; Fernandez-Benitez, Margarita; Garcia-Marcos, Luis

    2011-11-01

    The data of the ISAAC project in Spain show a prevalence of childhood asthma ranging from 7.1% to 15.3%, with regional differences; a higher prevalence, 22.6% to 35.8%, is described for rhinitis, and atopic dermatitis is found in 4.1% to 7.6% of children. The prevalence of food allergy is 3%. All children in Spain have the right to be visited in the National Health System. The medical care at the primary level is provided by pediatricians, who have obtained their titles through a 4-yr medical residency training program. The education on pediatric allergy during that period is not compulsory and thus very variable. There are currently 112 certified European pediatric allergists in Spain, who have obtained the accreditation of the European Union of Medical Specialist for proven skills and experience in pediatric allergy. Future specialists in pediatric allergy should obtain their titles through a specific education program to be developed in one of the four accredited training units on pediatric allergy, after obtaining the title on pediatrics. The Spanish Society of Pediatric Allergy and Clinical Immunology (SEICAP) gathers over 350 pediatric allergists and pediatricians working in this field. SEICAP has a growing activity including yearly congresses, continued education courses, elaboration of technical clinical documents and protocols, education of patients, and collaboration with other scientific societies and associations of patients. The official journal of SEICAP is Allergologia et Immunophatologia, published every 2 months since 1972. The web site of SEICAP, http://www.seicap.es, open since 2004, offers information for professionals and extensive information on pediatric allergic and immunologic disorders for the lay public; the web site is receiving 750 daily visits during 2011. The pediatric allergy units are very active in clinical work, procedures as immunotherapy or induction of oral tolerance in food allergy, contribution to scientific literature, and

  20. The clinical significance of immunological contact urticaria to processed grains

    Directory of Open Access Journals (Sweden)

    Michael Ismail

    2012-01-01

    Full Text Available Contact urticaria, is characterized by an urticarial wheal-and-flare reaction at the site of contact by an allergen. Immunological contact urticaria, while less common than non-immunological contact urticaria, has more potentially serious consequences, and therefore, its recognition and treatment is important. Immunological contact urticaria is a type I hypersensitivity reaction. Potential complications include organ system involvement other than skin and even anaphylaxis and death. A vast majority of immunological contact urticaria is work-related. We will discuss the definition of immunological contact urticaria, the mechanism of the contact urticarial reaction, contact urticaria in the occupational setting, and the role of grains in contact urticaria. Testing and treatment are also briefly discussed.

  1. Advances in asthma, allergy and immunology series 2004: basic and clinical immunology.

    Science.gov (United States)

    Chinen, Javier; Shearer, William T

    2004-08-01

    This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.

  2. Ranitidine as adjuvant treatment in colorectal cancer

    DEFF Research Database (Denmark)

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

    2002-01-01

    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...... in curatively resected patients who received a perioperative blood transfusion (n = 358), but it improved the survival of non-transfused patients (n = 202; hazard ratio (HR) 0.6 (95 per cent confidence interval (c.i.) 0.4 to 0.9), P = 0.02) and of non-transfused patients who did not develop 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...

  3. Adjuvant bisphosphonates in early breast cancer

    DEFF Research Database (Denmark)

    Hadji, P; Coleman, R E; Wilson, C

    2016-01-01

    Bisphosphonates have been studied in randomised trials in early breast cancer to investigate their ability to prevent cancer treatment-induced bone loss (CTIBL) and reduce the risk of disease recurrence and metastasis. Treatment benefits have been reported but bisphosphonates do not currently have...... regulatory approval for either of these potential indications. This consensus paper provides a review of the evidence and offers guidance to breast cancer clinicians on the use of bisphosphonates in early breast cancer. Using the nominal group methodology for consensus, a systematic review of the literature...... was augmented by a workshop held in October 2014 for breast cancer and bone specialists to present and debate the available pre-clinical and clinical evidence for the use of adjuvant bisphosphonates. This was followed by a questionnaire to all members of the writing committee to identify areas of consensus...

  4. A unique role of the cholera toxin A1-DD adjuvant for long-term plasma and memory B cell development.

    Science.gov (United States)

    Bemark, Mats; Bergqvist, Peter; Stensson, Anneli; Holmberg, Anna; Mattsson, Johan; Lycke, Nils Y

    2011-02-01

    Adjuvants have traditionally been appreciated for their immunoenhancing effects, whereas their impact on immunological memory has largely been neglected. In this paper, we have compared three mechanistically distinct adjuvants: aluminum salts (Alum), Ribi (monophosphoryl lipid A), and the cholera toxin A1 fusion protein CTA1-DD. Their influence on long-term memory development was dramatically different. Whereas a single immunization i.p. with 4-hydroxy-3-nitrophenyl acetyl (NP)-chicken γ-globulin and adjuvant stimulated serum anti-NP IgG titers that were comparable at 5 wk, CTA1-DD-adjuvanted responses were maintained for >16 mo with a half-life of anti-NP IgG ∼36 wk, but DD dose-dependent increase in germinal center (GC) size and numbers was found, with >60% of splenic B cell follicles hosting GC at an optimal CTA1-DD dose. Roughly 7% of these GC were NP specific. This GC-promoting effect correlated well with the persistence of long-term plasma cells in the bone marrow and memory B cells in the spleen. CTA1-DD also facilitated increased somatic hypermutation and affinity maturation of NP-specific IgG Abs in a dose-dependent fashion, hence arguing that large GC not only promotes higher Ab titers but also high-quality Ab production. Adoptive transfer of splenic CD80(+), but not CD80(-), B cells, at 1 y after immunization demonstrated functional long-term anti-NP IgG and IgM memory cells. To our knowledge, this is the first report to specifically compare and document that adjuvants can differ considerably in their support of long-term immune responses. Differential effects on the GC reaction appear to be the basis for these differences.

  5. Safety of a proteoliposome from Neisseria meningitides as adjuvant for a house dust mite allergy vaccine.

    Science.gov (United States)

    Ramírez, Wendy; Bourg, Virgilio; Torralba, Damaris; Facenda, Elisa; Tamargo, Beatriz; González, Bárbara O; Sierra, Gustavo; Pérez, Oliver; Perez-Llano, Yordanis; Labrada, Alexis

    2017-12-01

    The proteoliposome (PL) of Neisseria meningitidis serogroup B has been reported as a safe and potent vaccine adjuvant, inducing a TH1-skewed response. The present study describes a pre-clinical safety evaluation of an allergy therapeutic vaccine candidate based on purified allergens from Dermatophagoides siboney house dust mite and PL as adjuvant, both components adsorbed onto aluminum hydroxide gel. Two separate studies of acute toxicity evaluation were performed in mice and rabbits, and two repeat-dose studies were conducted in non-sensitized and allergen-sensitized Balb/c mice, respectively. The study in sensitized mice intends to model a therapeutic setting. Aerosolized allergen challenge was used in both settings to model natural respiratory exposure. In the therapeutic setting, mice were administered with three doses containing 2 μg allergen at weekly intervals [subcutaneous route] and subsequently challenged with aerosolized allergen for 6 consecutive days. Parameters of general toxicity effects were assessed via measures of behavior, body weight, food and water consumption, and macroscopic evaluation of organs. Histological examination of organs and the injection site was performed. Potential immunotoxicity effects at the systemic level were assessed by blood eosinophil counting and serum allergen specific IgE by ELISA The vaccine did not produce general or functional toxic effects of significance, at a dose up to 100 μg allergen per kg body weight. An expected local reaction at the injection site was observed, which could be attributed mostly to the immunological effect of aluminum hydroxide. The models implemented here suggest an acceptable safety profile of this vaccine for testing in clinical trials of allergy immunotherapy.

  6. Involvement of gamma interferon in antibody enhancement by adjuvants.

    Science.gov (United States)

    Odean, M J; Frane, C M; Van derVieren, M; Tomai, M A; Johnson, A G

    1990-02-01

    In a previous study the adjuvant action of a monophosphoryl lipid A, a nontoxic derivative of endotoxic lipopolysaccharide (LPS), was found to be negated by a monoclonal anti-gamma interferon (anti-IFN-gamma) antibody. The present investigation centered on three other adjuvants of diverse microbial origins, testing for their capacity to affect the release of IFN-gamma as an explanation for their antibody-enhancing action. The adjuvant action of each of the three, a wild-type LPS, synthetic poly(A)-poly(U) complexes, and a synthetic muramyl dipeptide, n-acetylmuramyl-L-alanyl-D-glutaminyl-n-butyl ester (murabutide), was transferable by adjuvant-stimulated T cells to normal spleen cells on coculture. Supernatant fluids from these T cells contained increased levels of IFN-gamma. Addition of a monoclonal anti-IFN-gamma antibody to adjuvant-stimulated spleen cell cultures reduced the adjuvant action by approximately one-half. Removal of natural killer cells from spleen cell populations prior to culture with antigen had no effect on the enhancement induced by LPS and monophosphoryl lipid A. It was concluded that the enhancement induced by the adjuvants LPS, poly(A)-poly(U), and murabutide is mediated in part by their action on T cells resulting in release of IFN-gamma suggesting activation of a common transmembrane signal.

  7. Adjuvants for veterinary vaccines--types and modes of action.

    Science.gov (United States)

    Gerdts, Volker

    2015-01-01

    Adjuvants are used to improve the immune response to vaccines. Formulation with adjuvants can result in an earlier onset of immunity, an overall stronger immune response, a specific type of immunity, or a longer duration of immunity to the vaccine. Adjuvants were discovered empirically, and for decades, have been used in both humans and animals without understanding the mechanisms of action. With an improved understanding of the immune system, and in particular the interplay between innate and adaptive immunity, we are now getting better insight into the function of adjuvants. As a result, new adjuvants are being developed that are safe and highly effective for common use in humans and animals, as well as for use in high risk populations such as immunocompromised animals, neonates or very old animals. Furthermore, adjuvants can help to reduce the amount of antigen needed in the vaccine, increase the stability of the vaccine and enable alternatiye administration routes such as needle-free delivery of the vaccine. Here, I will provide an over view of the existing adjuvant technologies for veterinary vaccines and provide an outlook into some of the new technologies in preclinical and clinical development.

  8. AS03- and MF59-Adjuvanted Influenza Vaccines in Children

    Directory of Open Access Journals (Sweden)

    Amanda L. Wilkins

    2017-12-01

    Full Text Available Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03 have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1 AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights

  9. AS03- and MF59-Adjuvanted Influenza Vaccines in Children

    Science.gov (United States)

    Wilkins, Amanda L.; Kazmin, Dmitri; Napolitani, Giorgio; Clutterbuck, Elizabeth A.; Pulendran, Bali; Siegrist, Claire-Anne; Pollard, Andrew J.

    2017-01-01

    Influenza is a major cause of respiratory disease leading to hospitalization in young children. However, seasonal trivalent influenza vaccines (TIVs) have been shown to be ineffective and poorly immunogenic in this population. The development of live-attenuated influenza vaccines and adjuvanted vaccines are important advances in the prevention of influenza in young children. The oil-in-water emulsions MF59 and adjuvant systems 03 (AS03) have been used as adjuvants in both seasonal adjuvanted trivalent influenza vaccines (ATIVs) and pandemic monovalent influenza vaccines. Compared with non-adjuvanted vaccine responses, these vaccines induce a more robust and persistent antibody response for both homologous and heterologous influenza strains in infants and young children. Evidence of a significant improvement in vaccine efficacy with these adjuvanted vaccines resulted in the use of the monovalent (A/H1N1) AS03-adjuvanted vaccine in children in the 2009 influenza pandemic and the licensure of the seasonal MF59 ATIV for children aged 6 months to 2 years in Canada. The mechanism of action of MF59 and AS03 remains unclear. Adjuvants such as MF59 induce proinflammatory cytokines and chemokines, including CXCL10, but independently of type-1 interferon. This proinflammatory response is associated with improved recruitment, activation and maturation of antigen presenting cells at the injection site. In young children MF59 ATIV produced more homogenous and robust transcriptional responses, more similar to adult-like patterns, than did TIV. Early gene signatures characteristic of the innate immune response, which correlated with antibody titers were also identified. Differences were detected when comparing child and adult responses including opposite trends in gene set enrichment at day 3 postvaccination and, unlike adult data, a lack of correlation between magnitude of plasmablast response at day 7 and antibody titers at day 28 in children. These insights show the utility

  10. Adjuvants for vaccines to drugs of abuse and addiction.

    Science.gov (United States)

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. Copyright © 2014. Published by Elsevier Ltd.

  11. Diatoms and diatomaceous earth as novel poultry vaccine adjuvants.

    Science.gov (United States)

    Nazmi, A; Hauck, R; Davis, A; Hildebrand, M; Corbeil, L B; Gallardo, R A

    2017-02-01

    Diatoms are single cell eukaryotic microalgae; their surface possesses a porous nanostructured silica cell wall or frustule. Diatomaceous earth (DE) or diatomite is a natural siliceous sediment of diatoms. Since silica has been proved to have adjuvant capabilities, we propose that diatoms and DE may provide an inexpensive and abundant source of adjuvant readily available to use in livestock vaccines.In a first experiment, the safety of diatoms used as an adjuvant for in-ovo vaccination was investigated. In a second experiment, we assessed the humoral immune response after one in-ovo vaccination with inactivated Newcastle Disease Virus (NDV) and DE as adjuvant followed by 2 subcutaneous boosters on d 21 and 29 of age. In both experiments, results were compared to Freund's incomplete adjuvant and aluminum hydroxide.No detrimental effects on hatchability and chick quality were detected after in-ovo inoculation of diatoms and DE in experiments 1 and 2 respectively. In experiment 2 no humoral responses were detected after the in-ovo vaccination until 29 d of age. Seven d after the second subcutaneous booster an antibody response against NDV was detected in chickens that had received vaccines adjuvanted with Freund's incomplete adjuvant, aluminum hydroxide, and DE. These responses became significantly higher 10 d after the second booster. Finally, 15 d after the second booster, the humoral responses induced by the vaccine with Freund's incomplete adjuvant were statistically higher, followed by comparable responses induced by vaccines containing DE or aluminum hydroxide that were significantly higher than DE+PBS, PBS+INDV and PBS alone. From an applied perspective, we can propose that DE can serve as a potential adjuvant for vaccines against poultry diseases. Published by Oxford University Press on behalf of Poultry Science Association 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Pediatric allergy and immunology in Japan.

    Science.gov (United States)

    Ebisawa, Motohiro; Nishima, Sankei; Ohnishi, Hidenori; Kondo, Naomi

    2013-11-01

    The Japanese Society of Pediatric Allergy and Clinical Immunology (JSPACI) was started in 1966 and currently has 3613 members as of August 1, 2012. The number of pediatricians specializing in allergies who have been certified by the Japanese Society of Allergology is 817. Among these, there are 125 training directors and training facilities for allergy and clinical immunology. The JSPACI first published an asthma guideline specific for children in 2000, and this has been revised every 3 yrs, contributing to better control of pediatric asthma. Food allergy management guidelines were first developed in 2005, which have helped to improve the care of food allergy patients. Among 514 pediatric training programs by the Japanese Society of Pediatrics, there are 312 facilities routinely performing oral food challenges. Among these, there were already 53 facilities performing oral immunotherapy at the end of 2011, treating 1400 cases of food allergy. The prevalence of pediatric allergic diseases has increased in Japan over the past 50 yrs. A number of International Study of Asthma and Allergies in Childhood surveys have been conducted in the past at specific times. The prevalence of wheezing among children aged 13-14 yrs in 2002 was 13.0%. Multi-year surveys found a 1.5- to 2-fold increase every 10 yrs until 2002. However, according to the latest data in 2012, asthma prevalence seems to have slightly decreased in Japan. Food allergy mainly associated with infantile atopic eczema among infants younger than 1 yr of age is the most common form as with other developed countries. The estimated food allergy prevalence based on data from several surveys is 5-10% among infants (0-6 yrs) and 1-2% among schoolchildren (6-15 yrs). A variety of patients suffering from primary deficiency syndrome have been actively analyzed. Previously, antibody defects and well-defined syndromes with immunodeficiency were analyzed, but recent research is focusing on not only acquired immune

  13. Virological and Immunological Aspects of AIDS Pathogenesis

    Directory of Open Access Journals (Sweden)

    Brian Conway

    1994-01-01

    Full Text Available The most common and serious problem associated with long term antiretroviral therapy is waning efficacy over time. To date. a number of studies has suggested an association between drug resistance and clinical deterioration. However. a precise causal relationship has yet to be demonstrated. In a large American clinical trial. resistance to zidovudine (ZDV was predictive of subsequent disease progression if this therapy was continued. Surprisingly. this was also predictive of deterioration if therapy was changed to didanosine (ddl. This suggests that other factors (perhaps virological and immunological which may be present in addition to resistance. were as important (if not more so in predicting clinical outcomes. It is likely that viral load. resistance. viral phenotype and alterations in immune function interact in this regard. Proper· studies may allow us to determine a “threshold” for a composite virological and immunological parameter beyond which disease progression will occur. As more antiretroviral agents become available. we will be in a position to intervene to “improve” laboratory markers and monitor them prospectively. potentially to maintain clinical latency for an indefinite period of time. In the authors' laboratories, a quantitative polymerase chain reaction assay for the evaluation of circulating proviral load has been developed. In an initial study of 70 patients. proviral load/ 106 CD4 cells was clearly associated with the severity of immune disease. with up to 9.6% of cells being infected in subjects with CD4 cell counts below 200/µL. However. large variability in proviral load among individuals with comparable or dissimilar CD4 cell counts precludes the use of this measurement as an individual marker of the severity of immune disease. More recent work evaluated the combined use of proviral load (expressed as a dichotomous variable based on values above or below one copy/a03 CD4 cells and resistance in a prospective

  14. Production and purification of immunologically active core protein p24 from HIV-1 fused to ricin toxin B subunit in E. coli

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    Gómez-Lim Miguel A

    2009-02-01

    Full Text Available Abstract Background Gag protein from HIV-1 is a polyprotein of 55 kDa, which, during viral maturation, is cleaved to release matrix p17, core p24 and nucleocapsid proteins. The p24 antigen contains epitopes that prime helper CD4 T-cells, which have been demonstrated to be protective and it can elicit lymphocyte proliferation. Thus, p24 is likely to be an integral part of any multicomponent HIV vaccine. The availability of an optimal adjuvant and carrier to enhance antiviral responses may accelerate the development of a vaccine candidate against HIV. The aim of this study was to investigate the adjuvant-carrier properties of the B ricin subunit (RTB when fused to p24. Results A fusion between ricin toxin B subunit and p24 HIV (RTB/p24 was expressed in E. coli. Affinity chromatography was used for purification of p24 alone and RTB/p24 from cytosolic fractions. Biological activity of RTB/p24 was determined by ELISA and affinity chromatography using the artificial receptor glycoprotein asialofetuin. Both assays have demonstrated that RTB/p24 is able to interact with complex sugars, suggesting that the chimeric protein retains lectin activity. Also, RTB/p24 was demonstrated to be immunologically active in mice. Two weeks after intraperitoneal inoculation with RTB/p24 without an adjuvant, a strong anti-p24 immune response was detected. The levels of the antibodies were comparable to those found in mice immunized with p24 alone in the presence of Freund adjuvant. RTB/p24 inoculated intranasally in mice, also elicited significant immune responses to p24, although the response was not as strong as that obtained in mice immunized with p24 in the presence of the mucosal adjuvant cholera toxin. Conclusion In this work, we report the expression in E. coli of HIV-1 p24 fused to the subunit B of ricin toxin. The high levels of antibodies obtained after intranasal and intraperitoneal immunization of mice demonstrate the adjuvant-carrier properties of RTB when

  15. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

    DEFF Research Database (Denmark)

    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...... that adjuvant chemotherapy compliance is superior after thoracoscopic lobectomy for NSCLC. Instead, significant predictors of chemotherapy compliance are patient's age, comorbidity, and pathologic N status....

  16. Synthesis and Immunological Comparison of Differently Linked Lipoarabinomannan Oligosaccharide-Monophosphoryl Lipid A Conjugates as Antituberculosis Vaccines.

    Science.gov (United States)

    Wang, Lizhen; Feng, Shaojie; Wang, Subo; Li, Hui; Guo, Zhongwu; Gu, Guofeng

    2017-11-20

    A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. The same tetrasaccharide was also coupled with MPLA at the 1-O-position. Immunological activities of the two synthetic conjugates were evaluated in mice and compared. Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection. It was thus speculated that MPLA conjugates might act via stimulating B1 lymphocytes present in the intrapleural and peritoneal cavities. Moreover, the 6'-N-conjugate afforded antibody titers much higher than those of the 1-O-conjugate. These results revealed not only the self-adjuvant property of MPLA conjugates to elicit robust IgG antibody responses but also the impact of MPLA structure on the immunological activity of its conjugates. It was concluded that LAM oligosaccharide-MPLA conjugates, especially 6'-N-linked, are promising candidates as antituberculosis vaccines worthy of further investigation. Additionally, the 6'-amino derivative of MPLA was proved to be a useful carrier for the development of fully synthetic carbohydrate-based conjugate vaccines.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Comparative Safety of Vaccine Adjuvants: A Summary of Current Evidence and Future Needs.

    Science.gov (United States)

    Petrovsky, Nikolai

    2015-11-01

    Use of highly pure antigens to improve vaccine safety has led to reduced vaccine immunogenicity and efficacy. This has led to the need to use adjuvants to improve vaccine immunogenicity. The ideal adjuvant should maximize vaccine immunogenicity without compromising tolerability or safety. Unfortunately, adjuvant research has lagged behind other vaccine areas such as antigen discovery, with the consequence that only a very limited number of adjuvants based on aluminium salts, monophosphoryl lipid A and oil emulsions are currently approved for human use. Recent strategic initiatives to support adjuvant development by the National Institutes of Health should translate into greater adjuvant choices in the future. Mechanistic studies have been valuable for better understanding of adjuvant action, but mechanisms of adjuvant toxicity are less well understood. The inflammatory or danger-signal model of adjuvant action implies that increased vaccine reactogenicity is the inevitable price for improved immunogenicity. Hence, adjuvant reactogenicity may be avoidable only if it is possible to separate inflammation from adjuvant action. The biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare vaccine adverse reactions, such as narcolepsy, macrophagic myofasciitis or Alzheimer's disease. While existing adjuvants based on aluminium salts have a strong safety record, there are ongoing needs for new adjuvants and more intensive research into adjuvants and their effects.

  19. Update on Gender Equity in Immunology, 2001 to 2016.

    Science.gov (United States)

    Shapiro, Virginia Smith; Kovats, Susan; Parent, Michelle A; Gaffen, Sarah L; Hedrick, Catherine C; Jain, Pooja; Denzin, Lisa K; Raghavan, Malini; Stephens, Robin

    2016-11-15

    In 2001, The American Association of Immunologists Committee on the Status of Women conducted a survey examining the percentage of women faculty members within immunology departments or women in immunology graduate programs across 27 institutions in the United States, comparing it to the percentage of women receiving a Ph.D. Here, we examine the representation of women across these same 27 immunology departments and programs to examine changes in gender equity over the last 15 years. Copyright © 2016 by The American Association of Immunologists, Inc.

  20. The influence of the Internet on immunology education.

    Science.gov (United States)

    Debard, Nathalie; Py, Pascal; Kraehenbuhl, Jean-Pierre; Fuchs, Jonathan

    2005-09-01

    The potential of the Internet as a medium through which to teach basic and applied immunology lies in the ability to illustrate complex concepts in new ways for audiences that are diverse and often geographically dispersed. This article explores two collaborative Internet-based learning projects (also known as e-learning projects) that are under development: Immunology Online, which will present an Internet-based curriculum in basic and clinical immunology to Swiss undergraduate and graduate students across five campuses; and the OCTAVE project, which will offer online training to an international cadre of new investigators, the members of which are carrying out clinical trials of vaccines against HIV infection.

  1. Immunological pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Seung Hoon Lee

    2018-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD and ulcerative colitis (UC. The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17 cells and innate lymphoid cells (ILCs are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

  2. Immunologic methods for monitoring carcinogen exposure

    Science.gov (United States)

    Santella, Regina M.; Perera, Frederica P.; Zhang, Yu J.; Chen, Chen J.; Young, Tie L.

    1993-03-01

    Immunologic methods have been developed for monitoring human exposure to environmental and occupational carcinogens. These methods involve the development of monoclonal and polyclonal antisera which specifically recognize the carcinogens themselves or their DNA or protein adducts. Antisera recognizing the DNA adducts of several polycyclic aromatic hydrocarbon diol epoxides have been used in competitive enzyme-linked immunosorbent assays to monitor adducts in tissue or blood samples. Elevated levels of DNA adducts have been seen in mononuclear cells of smokers and in total white blood cells of foundry and coke oven workers. Environmental exposure to PAH has been measured in individuals living in a highly polluted region of Poland. Antisera recognizing PAH-DNA adducts have also been used in immunohistochemical studies to monitor adducts in specific cells of biopsy samples. The DNA adducts of aflatoxin B1 have been monitored in liver tissue of hepatocellular carcinoma patients in Taiwan. Detectable adducts were seen in 50 - 70% of the patients suggesting that dietary exposure to this carcinogen may be a risk factor for cancer induction. Thus, immunoassays for monitoring exposure to carcinogens are an important tool in epidemiologic studies.

  3. Immunological characteristics of mesenchymal stem cells

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    Cíntia de Vasconcellos Machado

    2013-01-01

    Full Text Available Although bone marrow is the main source, mesenchymal stem cells have already been isolated from various other tissues, such as the liver, pancreas, adipose tissue, peripheral blood and dental pulp. These plastic adherent cells are morphologically similar to fibroblasts and have a high proliferative potential. This special group of cells possesses two essential characteristics: self-renewal and differentiation, with appropriate stimuli, into various cell types. Mesenchymal stem cells are considered immunologically privileged, since they do not express costimulatory molecules, required for complete T cell activation, on their surface. Several studies have shown that these cells exert an immunosuppressive effect on cells from both innate and acquired immunity systems. Mesenchymal stem cells can regulate the immune response in vitro by inhibiting the maturation of dendritic cells, as well as by suppressing the proliferation and function of T and B lymphocytes and natural killer cells. These special properties of mesenchymal stem cells make them a promising strategy in the treatment of immune mediated disorders, such as graft-versus-host disease and autoimmune diseases, as well as in regenerative medicine. The understanding of immune regulation mechanisms of mesenchymal stem cells, and also those involved in the differentiation of these cells in various lineages is primordial for their successful and safe application in different areas of medicine.

  4. Immunological and Psychological Benefits of Aromatherapy Massage

    Science.gov (United States)

    2005-01-01

    This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs), white blood cells (WBCs), neutrophils, peripheral blood lymphocytes (PBLs), CD4+, CD8+ and CD16+ lymphocytes, CD4+/CD8+ ratio, hematocrit, humoral parameters including serum interferon-γ and interleukin-6, salivary secretory immunoglobulin A (IgA). Psychological measures including the State–Trait Anxiety Inventory (STAI) questionnaire and the Self-rating Depression Scale (SDS) between recipients (n = 11) of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P aromatherapy and carrier massage, no difference between the aromatherapy and control massage was observed for STAI and SDS. Aromatherapy, in contrast to control massage, did not significantly reduce RBC count or hematocrit. However, aromatherapy massage showed a significant (P > 0.05) increase in PBLs, possibly due to an increase in CD8+ and CD16+ lymphocytes, which had significantly increased post-treatment (P aromatherapy massage could be beneficial in disease states that require augmentation of CD8+ lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients. PMID:15937558

  5. Immunological and Psychological Benefits of Aromatherapy Massage

    Directory of Open Access Journals (Sweden)

    Hiroko Kuriyama

    2005-01-01

    Full Text Available This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs, white blood cells (WBCs, neutrophils, peripheral blood lymphocytes (PBLs, CD4+, CD8+ and CD16+ lymphocytes, CD4+/CD8+ ratio, hematocrit, humoral parameters including serum interferon-γ and interleukin-6, salivary secretory immunoglobulin A (IgA. Psychological measures including the State–Trait Anxiety Inventory (STAI questionnaire and the Self-rating Depression Scale (SDS between recipients (n = 11 of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P 0.05 increase in PBLs, possibly due to an increase in CD8+ and CD16+ lymphocytes, which had significantly increased post-treatment (P < 0.01. Consequently, the CD4+/CD8+ ratio decreased significantly (P < 0.01. The paucity of such differences after carrier oil massage suggests that aromatherapy massage could be beneficial in disease states that require augmentation of CD8+ lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients.

  6. Contact time periods in immunological synapse

    Science.gov (United States)

    Bush, Daniel R.; Chattopadhyay, Amit K.

    2014-10-01

    This paper resolves the long standing debate as to the proper time scale of the onset of the immunological synapse bond, the noncovalent chemical bond defining the immune pathways involving T cells and antigen presenting cells. Results from our model calculations show to be of the order of seconds instead of minutes. Close to the linearly stable regime, we show that in between the two critical spatial thresholds defined by the integrin:ligand pair (Δ2˜ 40-45 nm) and the T-cell receptor TCR:peptide-major-histocompatibility-complex pMHC bond (Δ1˜ 14-15 nm), grows monotonically with increasing coreceptor bond length separation δ (= Δ2-Δ1˜ 26-30 nm) while decays with Δ1 for fixed Δ2. The nonuniversal δ-dependent power-law structure of the probability density function further explains why only the TCR:pMHC bond is a likely candidate to form a stable synapse.

  7. Louis Pasteur, the father of immunology?

    Directory of Open Access Journals (Sweden)

    Kendall A Smith

    2012-04-01

    Full Text Available Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late 19th century that popularized the germ theory of disease, and that introduced the hope that all infectious diseases could be prevented by prophylactic vaccination, as well as also treated by therapeutic vaccination, if applied soon enough after infection. However, Pasteur was working at the dawn of the appreciation of the microbial world, at a time when the notion of such a thing as an immune system did not exist, certainly not as we know it today, more than 130 years later. Accordingly, why was Pasteur such a genius as to discern how the immune system functions to protect us against invasion by the microbial world when no one had even made the distinction between fungi, bacteria or viruses, and no one had formulated any theories of immunity. A careful reading of Pasteur’s presentations to the Academy of Sciences reveals that Pasteur was entirely mistaken as to how immunity occurs, in that he reasoned, as a good microbiologist would, that appropriately attenuated microbes would deplete the host of vital trace nutrients absolutely required for their viability and growth, and not an active response on the part of the host. Even so, he focused attention on immunity, preparing the ground for others who followed. This review chronicles Pasteur’s remarkable metamorphosis from organic chemist to microbiologist to immunologist, and from basic science to medicine.

  8. [Selected immunologic indicators in malignant bone tumors].

    Science.gov (United States)

    Keleová, A; Huraj, E; Jahnová, E; Janota, S; Nyulassy, S

    1990-02-01

    In patients with the malignant tumor of bone (17 osteosarcomas, 8 Ewing tumors) longterm observations were made, and namely at the beginning of the disease, after the surgical removal of the tumor, during chemotherapy and in the terminal phase of the disease. The observations concentrated on the following selected immunology parameters: active lymphocytes T, lymphocytes T, lymphocytes B, large granular lymphocytes, IgG, IgA, IgM and circulating immune complexes. In non-treated patients prior to diagnosing the disease, reduction of active lymphocytes T was found out while the total lymphocytes T remained unchanged. However, no significant differences were found out between benign and malignant tumors. The surgical removal of the tumor results in the change in imunologic indicators, the increase of active lyphocytes T, lymphocytes T and the decrease in the circulating immune complexes. The change is of temporary nature, the subsequent deterioration is caused by both the progression of the disease and chemotherapy. The values of immunoglobulins and lymphocytes B fluctuated during the whole course of the disease in physiological levels. The observation of active lymphocytes T and lymphocytes T can be used for monitoring of the immunosuppression in cytostatic treatment. The levl of IgG is differentially diagnostically used to distinguish between the tumor and inflammatory processes.

  9. Pediatric allergy and immunology in China.

    Science.gov (United States)

    Wong, Gary W K; Li, Jing; Bao, Yi-Xiao; Wang, Jiu-Yao; Leung, Ting Fan; Li, Luan-Luan; Shao, Jie; Huang, Xin-Yuan; Liu, En-Mei; Shen, Kun-Ling; Chen, Yu-Zhi

    2017-10-19

    Over the past 30 years, China has enjoyed rapid economic development along with urbanization at a massive scale that the world has not experienced before. Such development has also been associated with a rapid rise in the prevalence of allergic disorders. Because of the large childhood population in the country, the burden of childhood allergic disorders has become one of the major challenges in the healthcare system. Among the Chinese centers participating in the International Study of Asthma and Allergies in Childhood, the data clearly showed a continuing rise in the prevalence of asthma, allergic rhinitis, and atopic eczema. However, the discipline of pediatric allergy in mainland China is still in its infancy due to the lack of formal training program and subspecialty certification. Clinicians and researchers are increasingly interested in providing better care for patients with allergies by establishing pediatric allergy centers in different regions of the country. Many of them have also participated in national or international collaborative projects hoping to answer the various research questions related to the discipline of pediatric allergy and immunology. It is our hope that the research findings from China will not only improve the quality of care of affected children within this country but also the millions of patients with allergies worldwide. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  10. Polio, terror and the immunological worldview.

    Science.gov (United States)

    Peckham, Robert

    2016-07-22

    This paper adopts a socio-historical perspective to explore when, how and why the eradication of poliomyelitis has become politicised to the extent that health workers and security personnel are targeted in drive-by shootings. Discussions of the polio crisis in Afghanistan and Pakistan have tended to focus on Taliban suspicions of a US-led public health intervention and the denunciation of 'modernity' by Islamic 'extremists'. In contrast, this paper considers a broader history of indigenous hostility and resistance to colonial immunisation on the subcontinent, suggesting how interconnected public health and political crises today have reactivated the past and created a continuity between events. The paper explores how the biomedical threat posed by polio has become intertwined with military and governmental discourses premised on the 'preemptive strike'. Here, the paper tracks the connections between biological immunity and a postcolonial politics that posits an immunological rationale for politico-military interventions. The paper concludes by reflecting on the consequences for global public health of this entanglement of infectious disease with terror.

  11. Etiology and immunology of infectious bronchitis virus

    Directory of Open Access Journals (Sweden)

    LF Caron

    2010-06-01

    Full Text Available Infectious bronchitis virus (IBV of chickens is currently one of the main diseases associated with respiratory syndrome in domestic poultry, as well as with losses related to egg production. The etiological agent is a coronavirus, which presents structural differences in the field, mainly in the S1 spike protein. The immune response against this virus is complicated by the few similarities among serotypes. Environmental and management factors, as well as the high mutation rate of the virus, render it difficult to control the disease and compromise the efficacy of the available vaccines. Bird immune system capacity to respond to challenges depend on the integrity of the mucosae, as an innate compartment, and on the generation of humoral and cell-mediated adaptive responses, and may affect the health status of breeding stocks in the medium run. Vaccination of day-old chicks in the hatchery on aims at eliciting immune responses, particularly cell-mediated responses that are essential when birds are first challenged. Humoral response (IgY and IgA are also important for virus clearance in subsequent challenges. The presence of antibodies against the S1 spike protein in 3- to 4-week-old birds is important both in broilers and for immunological memory in layers and breeders.

  12. Emerging single-cell technologies in immunology.

    Science.gov (United States)

    Herderschee, Jacobus; Fenwick, Craig; Pantaleo, Giuseppe; Roger, Thierry; Calandra, Thierry

    2015-07-01

    During evolution, the immune system has diversified to protect the host from the extremely wide array of possible pathogens. Until recently, immune responses were dissected by use of global approaches and bulk tools, averaging responses across samples and potentially missing particular contributions of individual cells. This is a strongly limiting factor, considering that initial immune responses are likely to be triggered by a restricted number of cells at the vanguard of host defenses. The development of novel, single-cell technologies is a major innovation offering great promise for basic and translational immunology with the potential to overcome some of the limitations of traditional research tools, such as polychromatic flow cytometry or microscopy-based methods. At the transcriptional level, much progress has been made in the fields of microfluidics and single-cell RNA sequencing. At the protein level, mass cytometry already allows the analysis of twice as many parameters as flow cytometry. In this review, we explore the basis and outcome of immune-cell diversity, how genetically identical cells become functionally different, and the consequences for the exploration of host-immune defense responses. We will highlight the advantages, trade-offs, and potential pitfalls of emerging, single-cell-based technologies and how they provide unprecedented detail of immune responses. © Society for Leukocyte Biology.

  13. Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Martín, Jorge; Menéndez, Tamara; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Niebla, Olivia; López, Carlos; Bernardo, Lídice; Sánchez, Jorge; Romero, Yaremis; Martínez, Rafael; Guzmán, María G; Guillén, Gerardo

    2009-02-11

    The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope protein from dengue 2 virus fused to the carrier protein P64k. This construct completely protected monkeys against viral challenge when the Freund's adjuvant was employed. Therefore, to define suitable formulations for human use, the present work relies on the evaluation of PD5, produced with a high purity and under GMP conditions, when formulated either with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The antibody response to the formulation containing the CPS-A was clearly superior to that of the formulation with OMV. The experiment of in vivo protection supported this evidence, since only the group immunized with PD5 and CPS-A was partially protected upon viral challenge. This is the first study in which the polysaccharide A of N. meningitidis is successfully employed as adjuvant for viral antigens.

  14. Immunological mechanisms in aspirin hypersensitivity. Studies on the immunogenicity of free aspirin.

    Science.gov (United States)

    Cîrstea, M; Suhaciu, G; Cîrje, M; Ciontescu, L

    1976-10-01

    Anti-aspiryl antibodies were produced in rabbits and guinea pigs by inoculation of aspirin incorporated in complete or incomplete Freund's adjuvant. These antibodies were readily detected by passive haemagglutination using rabbit erythrocytes incubated with aspirin at alkaline pH. Aspiryl conjugates with ovalbumin, human gamma-globulin, bovine gamma-globulin and rabbit serum were also prepared by incubating the proteins with aspirin at alkaline pH. Aspiryl conjugates prepared by this technique behaved, immunologically, identically with the conjugates prepared from aspirin chloride. By contrast, the molar absorbance at 305 nm of the conjugates prepared from aspirin was about 25 times lower than the molar absorbance of the conjugates prepared from aspirin chloride. Since the absorbance of salicylic acid is about eight times greater than that of aspirin, the conclusion is drawn that the aspiryl/salicylyl ratio is significantly higher in the conjugates prepared by incubating proteins with aspirin at alkaline pH than in the conjugates prepared from aspirin chloride. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with aspirin- or salicylic acid-treated red cells. Sera giving positive passive haemagglutination with aspirin-treated erythrocytes did not react with erythrocytes treated with salicylic acid or acetic anhydride.

  15. Transcutaneous delivery of CpG-adjuvanted allergen via laser-generated micropores.

    Science.gov (United States)

    Hessenberger, Michael; Weiss, Richard; Weinberger, Esther E; Boehler, Christof; Thalhamer, Josef; Scheiblhofer, Sandra

    2013-07-25

    Two main shortcomings of classical allergen-specific immunotherapy are long treatment duration and low patient compliance. Utilizing the unique immunological features of the skin by transcutaneous application of antigen opens new approaches not only for painless vaccine delivery, but also for allergen-specific immunotherapy. Under certain conditions, however, barrier disruption of the skin favors T helper 2-biased immune responses, which may lead to new sensitizations. In a prophylactic approach, an infra-red laser device was employed, producing an array of micropores of user-defined number, density, and depth on dorsal mouse skin. The grass pollen allergen Phl p 5 was administered by patch with or without the T helper 1-promoting CpG oligodeoxynucleotide 1826 as adjuvant, or was subcutaneously injected. Protection from allergic immune responses was tested by sensitization via injection of allergen adjuvanted with alum, followed by intranasal instillation. In a therapeutic setting, pre-sensitized mice were treated either by the standard method using subcutaneous injection or via laser-generated micropores. Sera were analyzed for IgG antibody subclass distribution by ELISA and for IgE antibodies by a basophil mediator release assay. Cytokine profiles from supernatants of re-stimulated lymphocytes and from bronchoalveolar lavage fluids were assessed by flow cytometry using a bead-based assay. The cellular composition of lavage fluids was determined by flow cytometry. Application of antigen via micropores induced T helper 2-biased immune responses. Addition of CpG balanced the response and prevented from allergic sensitization, i.e. IgE induction, airway inflammation, and expression of T helper 2 cytokines. Therapeutic efficacy of transcutaneous immunotherapy was equal compared to subcutaneous injection, but was superior with respect to suppression of already established IgE responses. Transcutaneous immunotherapy via laser-generated micropores provides an efficient

  16. Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: the BEST study.

    Science.gov (United States)

    Potthoff, Karin; Schmidt, Martina E; Wiskemann, Joachim; Hof, Holger; Klassen, Oliver; Habermann, Nina; Beckhove, Philipp; Debus, Juergen; Ulrich, Cornelia M; Steindorf, Karen

    2013-03-28

    Cancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce.Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood.In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy. The BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed. The BEST study is the first randomized controlled trial comparing progressive

  17. Archaeosome Adjuvant Overcomes Tolerance to Tumor-Associated Melanoma Antigens Inducing Protective CD8+ T Cell Responses

    Directory of Open Access Journals (Sweden)

    Lakshmi Krishnan

    2010-01-01

    Full Text Available Vesicles comprised of the ether glycerolipids of the archaeon Methanobrevibacter smithii (archaeosomes are potent adjuvants for evoking CD8+ T cell responses. We therefore explored the ability of archaeosomes to overcome immunologic tolerance to self-antigens. Priming and boosting of mice with archaeosome-antigen evoked comparable CD8+ T cell response and tumor protection to an alternate boosting strategy utilizing live bacterial vectors for antigen delivery. Vaccination with melanoma antigenic peptides TRP181-189 and Gp10025-33 delivered in archaeosomes resulted in IFN-γ producing antigen-specific CD8+ T cells with strong cytolytic capability and protection against subcutaneous B16 melanoma. Targeting responses against multiple antigens afforded prolonged median survival against melanoma challenge. Entrapment of multiple peptides within the same vesicle or admixed formulations were both effective at evoking CD8+ T cells against each antigen. Melanoma-antigen archaeosome formulations also afforded therapeutic protection against established B16 tumors when combined with depletion of T-regulatory cells. Overall, we demonstrate that archaeosome adjuvants constitute an effective choice for formulating cancer vaccines.

  18. An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

    Science.gov (United States)

    Fox, Christopher B; Haensler, Jean

    2013-07-01

    With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

  19. A randomised controlled trial comparing the effect of adjuvant ...

    African Journals Online (AJOL)

    A randomised controlled trial comparing the effect of adjuvant intrathecal 2 mg midazolam to 20 micrograms fentanyl on postoperative pain for patients undergoing lower limb orthopaedic surgery under spinal anaesthesia.

  20. Low-dose rituximab as an adjuvant therapy in pemphigus

    Directory of Open Access Journals (Sweden)

    Jaya Gupta

    2017-01-01

    Conclusion: Our results show that low-dose rituximab is a well-tolerated and beneficial adjuvant therapy in recalcitrant pemphigus which helps reduce both the severity of disease as well as the dose of steroids and immunosuppressants.

  1. Adjuvant therapy for gastric cancer: Current and future directions

    Science.gov (United States)

    Foo, Marcus; Leong, Trevor

    2014-01-01

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies. PMID:25320509

  2. Adjuvant therapy for gastric cancer: current and future directions.

    Science.gov (United States)

    Foo, Marcus; Leong, Trevor

    2014-10-14

    The management of gastric cancer continues to evolve. Whilst surgery alone is effective when tumours present early, a large proportion of patients are diagnosed with loco-regionally advanced disease, resulting in high loco-regional and distant relapse rates, with subsequent poor survival. Early attempts at improving outcomes following resection were disappointing; however, randomized trials have now established either post-operative chemoradiotherapy (INT0116) or peri-operative chemotherapy as standard adjuvant therapies in the Western world. There remain, however, significant differences in the approach to management between the West and East. In Asia, where there is the highest incidence of gastric cancer, extended resection followed by adjuvant chemotherapy represents the standard of care. This review discusses current standard adjuvant therapy in gastric adenocarcinoma, as well as recent and ongoing trials investigating novel (neo)adjuvant approaches, which hope to build on the successes of previous studies.

  3. Immune mechanisms of protection: can adjuvants rise to the challenge?

    Directory of Open Access Journals (Sweden)

    Kappler John W

    2010-04-01

    Full Text Available Abstract For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens.

  4. Activity of glycated chitosan and other adjuvants to PDT vaccines

    Science.gov (United States)

    Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

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

    OpenAIRE

    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...

  6. The Immunology Database and Analysis Portal (ImmPort)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The ImmPort system serves as a long-term, sustainable archive of immunology research data generated by investigators mainly funded through the NIAID/DAIT. The core...

  7. Regulatory effects of Tenebrio molitor Linnaeus on immunological ...

    African Journals Online (AJOL)

    AJL

    2012-04-24

    Apr 24, 2012 ... function of mice and therefore, this insect has the potential of a health food supplement. Key words: Tenebrio molitor Linnaeus, mice, immunoregulation, immunological function. INTRODUCTION. Yellow mealworm beetles Tenebrio molitor Linnaeus. (Tenebrionidae, Coleoptera) are considered scavengers.

  8. FOCIS goes south: advances in translational and clinical immunology.

    Science.gov (United States)

    Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

    2017-09-01

    FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

  9. Chronic Renal Allograft Dysfunction: Risk Factors, Immunology and ...

    African Journals Online (AJOL)

    mediated rejection. Non immunological factors include brain death in the donor, increasing donor age, ischemia-reperfusion injury, calcineurin inhibitor nephrotoxicity, hypertension, diabetes mellitus, hyperlipidemia, chronic obstruction and chronic ...

  10. Tumor Biology and Immunology | Center for Cancer Research

    Science.gov (United States)

    Tumor Biology and Immunology The Comparative Brain Tumor Consortium is collaborating with National Center for Advanced Translational Sciences to complete whole exome sequencing on canine meningioma samples. Results will be published and made publicly available.

  11. Affective immunology: where emotions and the immune response converge.

    Science.gov (United States)

    D'Acquisto, Fulvio

    2017-03-01

    Affect and emotion are defined as "an essential part of the process of an organism's interaction with stimuli." Similar to affect, the immune response is the "tool" the body uses to interact with the external environment. Thanks to the emotional and immunological response, we learn to distinguish between what we like and what we do not like, to counteract a broad range of challenges, and to adjust to the environment we are living in. Recent compelling evidence has shown that the emotional and immunological systems share more than a similarity of functions. This review article will discuss the crosstalk between these two systems and the need for a new scientific area of research called affective immunology. Research in this field will allow a better understanding and appreciation of the immunological basis of mental disorders and the emotional side of immune diseases.

  12. THE IMMUNOLOGICAL CHARACTERISTIC OF RA PATIENTS WITH ANAEMIA

    Directory of Open Access Journals (Sweden)

    A. E. Sizikov

    2014-07-01

    Full Text Available Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

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

    Directory of Open Access Journals (Sweden)

    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

  14. Vaccine Adjuvants: from 1920 to 2015 and Beyond

    Directory of Open Access Journals (Sweden)

    Alberta Di Pasquale

    2015-04-01

    Full Text Available 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.

  15. Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides

    Directory of Open Access Journals (Sweden)

    Robin Mesnage

    2018-01-01

    Full Text Available Commercial formulations of pesticides are invariably not single ingredients. Instead they are cocktails of chemicals, composed of a designated pesticidal “active principle” and “other ingredients,” with the latter collectively also known as “adjuvants.” These include surfactants, antifoaming agents, dyes, etc. Some adjuvants are added to influence the absorption and stability of the active principle and thus promote its pesticidal action. Currently, the health risk assessment of pesticides in the European Union and in the United States focuses almost exclusively on the stated active principle. Nonetheless, adjuvants can also be toxic in their own right with numerous negative health effects having been reported in humans and on the environment. Despite the known toxicity of adjuvants, they are regulated differently from active principles, with their toxic effects being generally ignored. Adjuvants are not subject to an acceptable daily intake, and they are not included in the health risk assessment of dietary exposures to pesticide residues. Here, we illustrate this gap in risk assessment by reference to glyphosate, the most used pesticide active ingredient. We also investigate the case of neonicotinoid insecticides, which are strongly suspected to be involved in bee and bumblebee colony collapse disorder. Authors of studies sometimes use the name of the active principle (for example glyphosate when they are testing a commercial formulation containing multiple (active principle plus adjuvant ingredients. This results in confusion in the scientific literature and within regulatory circles and leads to a misrepresentation of the safety profile of commercial pesticides. Urgent action is needed to lift the veil on the presence of adjuvants in food and human bodily fluids, as well as in the environment (such as in air, water, and soil and to characterize their toxicological properties. This must be accompanied by regulatory precautionary

  16. Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

    DEFF Research Database (Denmark)

    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)....

  17. Non-immunological defence mechanisms of the gut.

    OpenAIRE

    Sarker, S. A.; Gyr, K

    1992-01-01

    Non-immunological defence mechanisms represent an important line of intestinal defence in addition to humoral and cellular immunity. This review summarises the evidence for the role of the non-immunological defence system. Protective factors that have been amply documented are gastric juice, intestinal motility, and intestinal flora. Components of pancreatic juice, lysozyme, and epithelial cell turnover may also be involved. Special attention is given to gastric acid, infection with Helicobac...

  18. Perspectives on psycho-neuro-immunology in oncology

    Directory of Open Access Journals (Sweden)

    Vallath Nandini

    2006-01-01

    Full Text Available Psycho-oncology and psycho-neuro-immunology are both powerful new disciplines. Although a lot of literature exists in both of these fields the evidence is often controversial. This paper gives a brief perspective on the origins of psycho-neuro-immunology and discusses how our current understanding of this subject can be translated into clinical practice in an Indian setting.

  19. IMMUNOLOGICAL CLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIAS

    Directory of Open Access Journals (Sweden)

    Samo Zver

    2002-05-01

    Full Text Available Background. ALL is a malignant blood disease and lymphoblasts have origin in B or T lymphatic cell line. In 1997 established new World Health Organisation classification (WHO classification of malignant haematological diseases realizes the importance of cellular immunological markers (immunophenotype and chromosomal abnormalities (cytogenetics. Based on both findings we may distribute the patients in low, intermediate and high risk groups and the outcome of such distribution is risk adopted ALL treatment strategy. On Clinical department of haematology (CDH we have decided to overview immunophenotype characteristics of all ALL patients during the January 1, 1995–December 31, 2001 period.Methods and results. During the January 1, 1995–December 31, 2001 period on CDH we have treated 44 patients: 22 males and 22 females. With flow cytometer Coulter Epics XL MCS we have performed first primary antibody panel for acute leukemias antigens (CD2, CD7, CD10, CD19, CD34, cCD3, cCD13, cCD22, MPO, TdT, followed by secondary panel. The later have included antigen CD20, CD23, membrane and/or cytoplasmatic immunoglobulins or their light chains monoclonal antibodies for B-ALL and antigen CD3, CD4, CD5 and CD8 monoclonal antibodies for T-ALL subsets. Besides immunophenotyping we have evaluated all ALL patients also morphologically according to FAB classification (French-AmericanBritish classification, which is an old classification based solely on morphology.32/44 (73% patients have had immunophenotypic B-ALL, and 12/44 (27% T-ALL. Subgroups distribution of B-ALL immunophenotype were: pro-B 4/44 (9%, »common«-B 18/44 (41%, pre-B 5/44 (11.5% and mature B 5744 (11.5% and for T-ALL immunophenotype were: pro-T 2/44 (4.5%, pre-T 5/44 (11.5%, cortical-T 4/44 (9% and mature-T 1/44 (2%. Our results are quite comparable with the available data from the literature, despite the fact that newest immunological markers such as CD1a, CD79a and CD22 were not available

  20. Spa adjuvant therapy improves diabetic lower extremity arterial disease.

    Science.gov (United States)

    Qiu, Yongbin; Zhu, Yi; Jia, Wei; Chen, Songhua; Meng, Qingzhou

    2014-08-01

    To investigate the effect of spa adjuvant therapy on diabetic lower extremity arterial disease (LEAD). 128 patients with type II diabetes were separated into three groups according to the degree of lower extremity vascular stenosis. Patients within each group were then randomly divided to receive no treatment (control) or spa adjuvant therapy (treatment). Clinical symptoms, blood pressure and hemodynamic analyses were compared between control and treatment groups by Chi square or t-test. After adjuvant therapy with spa, patients' pain, numbness, and cold sensation were significantly improved compared with control groups (PSpa adjuvant therapy also significantly increased the dorsalis pedis pulse and systolic peak velocity ratio of patients with mild lower extremity vascular stenosis compared with control groups (P0.05). Both in the spa and control groups, there were no significant differences before and after medication for fasting, 2-h postprandial blood glucose and glycosylated hemoglobin (HbA1C) analyses (P>0.05). Spa adjuvant therapy can significantly alleviate lower extremity pain, numbness, and cold sensory symptoms in diabetic LEAD patients with stenosis. Moreover, in LEAD patients with mild stenosis, spa adjuvant therapy also improves the dorsalis pedis pulse and systolic peak velocity ratio, suggesting a potential role for spa therapy as an early intervention strategy to treat the initial stages of disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Immunologic responses of bison to vaccination with Brucella abortus strain RB51: comparison of parenteral to ballistic delivery via compressed pellets or photopolymerized hydrogels.

    Science.gov (United States)

    Olsen, Steven C; Christie, R J; Grainger, D W; Stoffregen, W S

    2006-02-27

    This study compared responses of bison calves to 10(10)CFU of Brucella abortus strain RB51 (SRB51) delivered by parenteral or ballistic methods. Two types of biobullet payloads were evaluated; compacted SRB51 pellets or SRB51 encapsulated in photopolymerized poly(ethylene glycol) hydrogels. Bison were vaccinated with saline, parenteral SRB51 alone, or in combination with Spirovac, or ballistically with compressed SRB51 or hydrogel biobullets. Bison parenterally vaccinated with SRB51 had greater (P<0.05) immunologic responses when compared to control bison. Co-administration of Spirovac as an adjuvant did not influence immunologic responses. As compared to compressed SRB51 biobullets, ballistic vaccination with hydrogel biobullets increased cellular immune responses at some sampling times. Our data suggest that hydrogel formulations of SRB51 may be a superior alternative to compressed SRB51 tablets for ballistic vaccination of bison. Although preliminary, data suggests that immunologic responses of bison to SRB51 hydrogel bullets are similar to responses after parenteral vaccination with SRB51.

  2. Cholera in pregnancy: Clinical and immunological aspects.

    Science.gov (United States)

    Khan, Ashraful I; Chowdhury, Fahima; Leung, Daniel T; Larocque, Regina C; Harris, Jason B; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi

    2015-10-01

    The objective of this study was to examine the clinical and immunological features of cholera in pregnancy. Women of reproductive age presenting to the icddr,b Dhaka hospital with cholera, and enrolled as part of a larger cohort study, were tested for pregnancy on admission. We compared initial clinical features and immune responses of pregnant patients with non-pregnant female patients at days 2, 7 and 21 after infection. Among reproductive age women enrolled between January 2001 and May 2006, 9.7% (14/144) were pregnant. The duration of diarrhoea prior to admission tended to be higher in pregnant compared to non-pregnant patients (p=0.08), but other clinical characteristics did not differ. Antibody responses to cholera toxin B subunit (CtxB), toxin-coregulated pilus A (TcpA), Vibrio cholerae lipopolysaccharide (LPS), and serum vibriocidal antibody responses, were comparable between pregnant and non-pregnant patients. There were no deaths among the pregnant cases or non-pregnant controls, and no adverse foetal outcomes, including stillbirths, during 21 days of follow up of pregnant cases. To our knowledge, this is the first report of immune responses in pregnant women with cholera. We found that pregnant woman early in pregnancy has comparable clinical illness and subsequent immune responses compared to non-pregnant women. These findings suggest that the evaluation of safety and immunogenicity of oral cholera vaccines in pregnancy should be an area of future investigations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. Squalene and squalane emulsions as adjuvants.

    Science.gov (United States)

    Allison, A C

    1999-09-01

    Microfluidized squalene or squalane emulsions are efficient adjuvants, eliciting both humoral and cellular immune responses. Microfluidization stabilizes the emulsions and allows sterilization by terminal filtration. The emulsions are stable for years at ambient temperature and can be frozen. Antigens are added after emulsification so that conformational epitopes are not lost by denaturation and to facilitate manufacture. A Pluronic block copolymer can be added to the squalane or squalene emulsion. Soluble antigens administered in such emulsions generate cytotoxic T lymphocytes able to lyse target cells expressing the antigen in a genetically restricted fashion. Optionally a relatively nontoxic analog of muramyl dipeptide (MDP) or another immunomodulator can be added; however, the dose of MDP must be restricted to avoid systemic side effects in humans. Squalene or squalane emulsions without copolymers or MDP have very little toxicity and elicit potent antibody responses to several antigens in nonhuman primates. They could be used to improve a wide range of vaccines. Squalene or squalane emulsions have been administered in human cancer vaccines, with mild side effects and evidence of efficacy, in terms of both immune responses and antitumor activity. Copyright 1999 Academic Press.

  4. Protective Effects of Simvastatin and Hesperidin against Complete Freund's Adjuvant-Induced Rheumatoid Arthritis in Rats.

    Science.gov (United States)

    Ahmed, Yasmin Moustafa; Messiha, Basim A S; Abo-Saif, Ali Ahmed

    2015-01-01

    Rheumatoid arthritis (RA) is a disabling autoimmune disease for which most current treatments cause massive complications, thereby limiting treatment dose and duration. The anti-arthritic effects of the 3-hydroxy-3-metylglutary-CoA reductase inhibitor, simvastatin, and the natural flavonoid, hesperidin, were investigated against complete Freund's adjuvant-induced RA in rats. A normal control group, an arthritis control group, 2 reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and 2 treatment groups receiving simvastatin (0.5 mg/kg/day) and hesperidin (200 mg/kg/day) were included in the study. Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein (COMP) as specific rheumatoid biomarkers, serum immunoglobulin G (IgG) and antinuclear antibody (ANA) as immunological biomarkers, serum tumor necrosis factor-alpha and interleukin-10 as immunomodulatory cytokines, serum myeloperoxidase (MPO) and C-reactive protein as inflammatory biomarkers, and malondialdehyde (MDA) and glutathione (GSH) as oxidative stress biomarkers were assessed, supported by joint and spleen histopathological study. Simvastatin significantly improved all the measured biomarkers, with MMP-3, COMP, and GSH restored to normal levels. Hesperidin significantly improved all the measured biomarkers, with COMP, IgG, ANA, MPO, MDA and GSH restored to normal levels. Simvastatin and hesperidin may be promising protective agents against RA through immunomodulatory, anti-inflammatory and antioxidant potentials. © 2015 S. Karger AG, Basel.

  5. 21 CFR 866.6010 - Tumor-associated antigen immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tumor-associated antigen immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen immunological Test Systems § 866.6010 Tumor-associated antigen immunological test system. (a) Identification. A...

  6. Immunology knowledge as one of the basic sciences that forms the foundations to developing sound clinicians

    OpenAIRE

    Armson, Anthony J.; Meyer, Amanda J.; Losco, Barrett E; Ardakani, Emad M.; Walker, Bruce F.

    2016-01-01

    Objective: The aim of this study was to (1) generate a valid questionnaire to determine immunology knowledge, (2) compare immunology knowledge across 3 different cohorts of chiropractic students that had already studied immunology, (3) examine the attitudes of chiropractic students to the study of immunology, and (4) examine whether students' attitudes affected their knowledge levels.

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

    Science.gov (United States)

    Savelkoul, Huub F. J.; Ferro, Valerie A.; Strioga, Marius M.; Schijns, Virgil E. J. C.

    2015-01-01

    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. PMID:26344951

  8. Gastric carcinoma: curative resection and adjuvant chemotherapy.

    Science.gov (United States)

    Carrillo Hernández, J F; Ernesto de Obaldía Castillo, G; Ramírez Ortega, C; Frías Mendivil, M; Pardo, M

    1994-01-01

    A retrospective study of gastric adenocarcinoma treated with surgery as curative attempt was performed at the Oncology Service, in the Hospital Regional 20 de Noviembre, ISSSTE. Morbidity and mortality of the surgical procedures were evaluated, the significance of several risk factors and the survival impact of adjuvant chemotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC). In the period from 1975 to 1991 a total of 483 new cases were seen. In only 54 patients (11.2%) was it possible to undertake a curative resection. The patients were assigned to three groups of treatment: surgery alone (14 cases), surgery + 5-FU (19 cases), and surgery + 5-FU+MMC (21 cases). Three different types of surgical techniques are regularly performed in our service for gastric cancer treatment: Billroth II distal gastrectomy, total gastrectomy with Roux-En-Y reconstruction, and esophagogastrectomy with esophagogastrostomy. Surgical morbidity and mortality was low, with 9% of duodenal stump fistulas and 27% with partial stenosis of esophagojejunostomy; the operative mortality was zero. Chemotherapy toxicity was transient and low, no related deaths were recorded. The prognostic factors associated significantly with survival were lymph node status and tumor penetration. The histologic differentiation as well as the tumor location and type of surgery had no significance. The estimated 5-year survival of the patients treated with surgery alone was 62%, while that of the patients treated with surgery plus chemotherapy was 38%. These groups were not comparable, however, because of important differences in their prognostic factors. The groups treated with 5-FU alone or in combination with MMC had no survival difference between them.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Adjuvant radiotherapy for stage I endometrial cancer

    Science.gov (United States)

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. Objectives To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. Selection criteria We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Data collection and analysis Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. Main results We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes. EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2

  10. The Multiscale Systems Immunology project: software for cell-based immunological simulation

    Directory of Open Access Journals (Sweden)

    Kepler Thomas B

    2008-04-01

    Full Text Available Abstract Background Computer simulations are of increasing importance in modeling biological phenomena. Their purpose is to predict behavior and guide future experiments. The aim of this project is to model the early immune response to vaccination by an agent based immune response simulation that incorporates realistic biophysics and intracellular dynamics, and which is sufficiently flexible to accurately model the multi-scale nature and complexity of the immune system, while maintaining the high performance critical to scientific computing. Results The Multiscale Systems Immunology (MSI simulation framework is an object-oriented, modular simulation framework written in C++ and Python. The software implements a modular design that allows for flexible configuration of components and initialization of parameters, thus allowing simulations to be run that model processes occurring over different temporal and spatial scales. Conclusion MSI addresses the need for a flexible and high-performing agent based model of the immune system.

  11. Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating.

    Science.gov (United States)

    Alshanqiti, Fatimah M; Al-Masaudi, Saad B; Al-Hejin, Ahmed M; Redwan, Elrashdy M

    2017-01-01

    It's known that diphtheria and tetanus are a contagious lethal diseases over the years, they caused by pathogenic microbes corynebacterium diphtheria and Clostridium tetani, respectively. The diseases result from the production of bacterial toxin. Vaccination with bacterial toxoid vaccines adsorbed on particulates adjuvants still are the best way to prevent this epidemic diseases from spread. The particulate vaccines have been shown to be more efficient than soluble one for the induction of the immune responses. Nanoparticles can be engineered to enhance the immune responses. As well known the immune response to inactivate killed and subunit vaccine enhances by alum adjuvants. The adjuvants examined and tested after reducing its size to particle size, thus mimic size of viruses which is considered smallest units can derive the immune system. The major issue is minimizing the adjuvant particles, to gain insight of resulting immunity types and impact on immune response. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into antigen presenting cells.

  12. Clinical laboratory immunology: an indispensable player in laboratory medicine.

    Science.gov (United States)

    Tebo, Anne E; Detrick, Barbara; Hamilton, Robert G; Khanolkar, Aaruni; O'Gorman, Maurice R G; Schmitz, John L; Abraham, Roshini S

    2014-10-01

    Clinical laboratory immunology affects practically every aspect of medicine. Accordingly, appropriately trained, board-certified clinical laboratory immunologists are key contributors to the diagnosis and management of patients with various immune-mediated conditions. This review highlights the availability of postdoctoral level training programs for clinical laboratory immunology and identifies possible career tracks. Fundamental elements for doctoral level clinical laboratory immunologists are identified and the critical components of diagnostic immunology training as well as career opportunities in and out of academia are described. Relative to other disciplines in laboratory medicine, little emphasis has been given to clinical laboratory immunology in medical, graduate, and postgraduate training. Formal postgraduate fellowship programs and board certification examinations are available, yet there remains a significant lack of awareness in the medical education community about the value and necessity of training in this field. It is anticipated that sharing this knowledge will increase awareness of the discipline of clinical laboratory immunology at the postdoctoral level with implications for the practice of laboratory medicine. Copyright© by the American Society for Clinical Pathology.

  13. Chella David: a lifetime contribution in translational immunology.

    Science.gov (United States)

    Gershwin, M Eric; Shoenfeld, Yehuda

    2011-09-01

    Immunology, like most scientific disciplines, is filled with buzz words. One such buzz word or term has been coined "translational immunology". Indeed, translational research is amongst the most popular expressions used to justify the use of basic research in the hopes that such research will lead to solutions to clinical problems. In fact, no such justification is needed and some of the most important observations in clinical medicine have been derived from basic science; basic science that had no idea at its time of its usefulness in clinical medicine. This special issue is devoted to Chella David. Chella's contributions in immunology have been legion. Before inbred mice became popular, long before multi-million dollar companies were developed to develop such models, Chella David was hard at the bench studying the genetics of the murine immune system and the importance of such mouse models in autoimmune diseases. Importantly, Dr. David provided animals without strings, without the burdens of MTAs, that now impede research. Chella has been generous with his time, with his reagents, and has been a caring and devoted mentor to generations of students. This issue is part of our series to recognize autoimmunologists and dedicated themes that include papers in multiple disciplines of immunology, but especially are focused on cutting-edge applications that will improve clinical therapeutics. Chella David, at age 75, is an athlete in immunology and still keeps going with the same enthusiasm as manifest as a young post-doc. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Immunogenicity of trivalent influenza vaccines in patients with chronic kidney disease undergoing hemodialysis: MF59-adjuvanted versus non-adjuvanted vaccines.

    Science.gov (United States)

    Noh, Ji Yun; Song, Joon Young; Choi, Won Suk; Lee, Jacob; Seo, Yu Bin; Kwon, Young Joo; Ko, Gang Jee; Cha, Dae Ryong; Kang, Young Sun; Lee, Young-Ki; Cheong, Hee Jin; Kim, Woo Joo

    2016-11-01

    Patients with chronic kidney disease (CKD) are at an increased risk of morbidity and mortality from influenza. However, the immunogenicity of influenza vaccine is known to be attenuated in these patients. In this study, the immunogenicity of MF59-adjuvanted and non-adjuvanted trivalent influenza vaccines was compared in CKD patients undergoing hemodialysis (HD). During 2013-2014, 179 CKD patients undergoing HD participated in the study. The patients were randomized into either MF59-adjuvanted vaccine group or non-adjuvanted vaccine group and were immunized with the respective vaccine. Sera were collected prior to vaccination and at 1 month (88 patients in MF59-adjuvanted vaccine group and 86 patients in non-adjuvanted vaccine group) and 6 months post vaccination. Levels of hemagglutination inhibition antibodies were measured. The seroconversion rate of all 3 vaccine strains at 1 month post-vaccination was significantly higher in the MF59-adjuvanted group than in the non-adjuvanted group (47.7% vs. 17.4%, A/H1N1; 42.0% vs. 16.3%, A/H3N2; 31.8% vs. 7.0%, B, P vaccination, the fold increase in geometric mean titer from pre-vaccination for A/H1N1, A/H3N2 and B viruses was significantly greater in the MF59-adjuvanted group than in the non-adjuvanted group. In elderly patients (≥65 years), the seroconversion rate at 1 month post-vaccination against influenza B strain was higher in the MF59-adjuvanted group than in the non-adjuvanted group (33.3% vs. 7.1%, P = 0.03). The MF59-adjuvanted influenza vaccine showed better immunogenicity than the non-adjuvanted influenza vaccine in CKD patients undergoing HD.

  15. Designing CAF-adjuvanted dry powder vaccines: Spray drying preserves the adjuvant activity of CAF01

    DEFF Research Database (Denmark)

    Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis

    2013-01-01

    remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6′-dibehenate (TDB) via...... spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol....... Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process...

  16. Integrating and mining diverse data in human immunological studies.

    Science.gov (United States)

    Siebert, Janet C; Wagner, Brandie D; Juarez-Colunga, Elizabeth

    2014-01-01

    Bioanalysts and immunologists can interrogate the immune system with a variety of high-throughput technologies such as gene expression, multiplex bead arrays and flow cytometry. Conceptually, these assays support systems immunology studies, in which phenomena can be measured and correlated across biological compartments. First, however, the resulting high-dimensional data must be combined in a consistent fashion that supports analysis of the data as an integrated whole. Next, analytical methods must be applied to the hundreds or thousands of readouts. We recommend the use of a four-part analytical pipeline, consisting of data integration, hypothesis generation, prediction and hypothesis testing, and validation. We describe a variety of established methods appropriate for these integrated datasets, and highlight their application to human immunological studies. Our goal is to provide bioanalysts, immunologists and data analysts with a valuable perspective with which to approach the multiassay high-dimensional datasets generated by contemporary immunological studies.

  17. The role of adjuvant therapy in uterine leiomyosarcoma.

    Science.gov (United States)

    Ducie, Jennifer A; Leitao, Mario M

    2016-01-01

    Uterine leiomyosarcoma (uLMS) is a rare mesenchymal tumor of the gynecologic tract. Although diagnosed in only 1-3% of patients with uterine cancer, uLMS accounts for the majority of uterine cancer-related deaths. The standard of care for patients with uLMS includes total hysterectomy and bilateral salpingo-oophorectomy (BSO). There are no standard recommendations regarding adjuvant or palliative therapy. Many cytotoxic and targeted agents have been studied in clinical trials in an effort to identify an effective therapy that may alter the natural history of this disease. Unfortunately, as of now, there are no adjuvant therapy regimens that improve overall survival in this patient population. There is, therefore, an unmet need to identify a novel therapy that will improve the survival of women diagnosed with this aggressive disease. Here we summarize the existing literature on adjuvant therapy in uLMS, specifically highlighting advances made in the last 5 years.

  18. A Common Platform for Antibiotic Dereplication and Adjuvant Discovery.

    Science.gov (United States)

    Cox, Georgina; Sieron, Arthur; King, Andrew M; De Pascale, Gianfranco; Pawlowski, Andrew C; Koteva, Kalinka; Wright, Gerard D

    2017-01-19

    Solving the antibiotic resistance crisis requires the discovery of new antimicrobial drugs and the preservation of existing ones. The discovery of inhibitors of antibiotic resistance, antibiotic adjuvants, is a proven example of the latter. A major difficulty in identifying new antibiotics is the frequent rediscovery of known compounds, necessitating laborious "dereplication" to identify novel chemical entities. We have developed an antibiotic resistance platform (ARP) that can be used for both the identification of antibiotic adjuvants and for antibiotic dereplication. The ARP is a cell-based array of mechanistically distinct individual resistance elements in an identical genetic background. In dereplication mode, we demonstrate the rapid identification, and thus discrimination, of common antibiotics. In adjuvant discovery mode, we show that the ARP can be harnessed in screens to identify inhibitors of resistance. The ARP is therefore a powerful tool that has broad application in confronting the resistance crisis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Immunomodulatory adjuvant therapy in severe community-acquired pneumonia.

    Science.gov (United States)

    Morton, Ben; Pennington, Shaun Harry; Gordon, Stephen B

    2014-10-01

    Severe pneumonia has a high mortality (38.2%) despite evidence-based therapy. Rising rates of antimicrobial resistance increase the urgency to develop new treatment strategies. Multiple adjuvant therapies for pneumonia have been investigated but none are currently licensed. Profound immune dysregulation occurs in patients with severe infection. An initial hyper-inflammatory response is followed by a secondary hypo-inflammatory response with 'immune-paralysis'. There is focus on the development of immunostimulatory agents to improve host ability to combat primary infection and reduce secondary infections. Successful treatments must be targeted to immune response; promising biomarkers exist but have not yet reached common bedside practice. We explore evidence for adjuvant therapies in community-acquired pneumonia. We highlight novel potential treatment strategies using a broad-based search strategy to include publications in pneumonia and severe sepsis. We explore reasons for the failure to develop effective adjuvant therapies and highlight the need for targeted therapy specific to immune activity.

  20. Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine.

    Science.gov (United States)

    Clausi, Amber L; Morin, Andrea; Carpenter, John F; Randolph, Theodore W

    2009-01-01

    The mechanism(s) of the enhancement of the immune response by addition of aluminum salt adjuvants to parenterally administered protein-based vaccines is still the subject of debate. It has been hypothesized, however, that destabilization of the antigen structure on the surface of the adjuvant may be important for eliciting immune response. Also, it has been suggested that immune response to adjuvanted vaccines is reduced if the adjuvant particles become aggregated before administration because of processing steps such as freeze-drying. In this study, we tested these hypotheses and examined the immune response in a murine model to various liquid, freeze-dried, and spray freeze-dried formulations of a model vaccine, bovine intestinal alkaline phosphatase adsorbed on aluminum hydroxide. Enzymatic activity of the alkaline phosphatase was used as a sensitive indicator of intact native antigen structure. By manipulating the secondary drying temperature during lyophilization, vaccines were produced with varying levels of alkaline phosphatase enzymatic activity and varying degrees of adjuvant aggregation, as assessed by particle size distribution. Anti-alkaline phosphatase titers observed in immunized mice were independent of both the antigen's retained enzymatic activity and the vaccine formulation's mean particle diameter. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

  1. Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment

    Directory of Open Access Journals (Sweden)

    Sabita Kumari

    2017-07-01

    Full Text Available Objective The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery. Materials and methods A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality. Results The study analyzed the patients who were treated between January 2012 and June 2015. Among 705 patients with carcinoma of the tongue treated primarily with wide local excision and neck dissection, 383 received adjuvant treatment. A total of 215 patients received radiation, and 168 received concurrent radio-chemotherapy. Of 378 patients, 78 developed hypothyroidism during follow-up: 27 patients received concurrent radio-chemotherapy, and the remaining 51 received only radiation. Lower neck received 40–48 Gy in 2 patients, 50 Gy in 74 patients, and 60–70 Gy and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months. Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the oral tongue. The minimum period to develop hypothyroidism was 3 months in this study. Gender and adjuvant treatment were not found to be significant for the incidence of hypothyroidism. Conclusions A significant number of patients with carcinoma of the tongue who receive adjuvant treatment will develop hypothyroidism, hence frequent monitoring of thyroid function is advised during follow-up.

  2. Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Agbahiwe, Harold C.; Wharam, Moody [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Batra, Sachin [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cohen, Kenneth [Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: sterezak@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

    2013-02-01

    Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

  3. Non-immunological defence mechanisms of the gut.

    Science.gov (United States)

    Sarker, S A; Gyr, K

    1992-01-01

    Non-immunological defence mechanisms represent an important line of intestinal defence in addition to humoral and cellular immunity. This review summarises the evidence for the role of the non-immunological defence system. Protective factors that have been amply documented are gastric juice, intestinal motility, and intestinal flora. Components of pancreatic juice, lysozyme, and epithelial cell turnover may also be involved. Special attention is given to gastric acid, infection with Helicobacter pylori, and hypochlorhydria and their association with infectious diarrhoea. Epidemic hypochlorhydria is discussed since this increases sensitivity to intestinal infections in third world countries. PMID:1644343

  4. Immunology and Immunodiagnosis of Cystic Echinococcosis: An Update

    Directory of Open Access Journals (Sweden)

    Wenbao Zhang

    2012-01-01

    Full Text Available Cystic echinococcosis (CE is a cosmopolitan zoonosis caused by the larval cystic stage of the dog tapeworm Echinococcus granulosus. This complex multicellular pathogen produces various antigens which modulate the host immune response and promote parasite survival and development. The recent application of modern molecular and immunological approaches has revealed novel insights on the nature of the immune responses generated during the course of a hydatid infection, although many aspects of the Echinococcus-host interplay remain unexplored. This paper summarizes recent developments in our understanding of the immunology and diagnosis of echinococcosis, indicates areas where information is lacking, and suggests possible new strategies to improve serodiagnosis for practical application.

  5. Immunologic competence in adults following thymic irradiation in infancy

    Energy Technology Data Exchange (ETDEWEB)

    Ammann, A.J.; Wara, W.M.; Wara, D.W.; Phillips, T.L.

    1977-07-01

    Removal of, or irradiation to, the thymus during the neonatal period in man has resulted in no reported adverse effects on cellular immunity, although thymectomy in neonatal experimental animals is known to produce profound immunological disturbances. Adverse effects in humans may not be recognized until several decades have passed. The immunological capabilities of 7 adults with histories of thymic irradiation as infants were evaluated; normal tests results indicated intact immune systems in all cases. The 3 women tested, however, had abnormal clinical histories, including 2 with multiple tumors and 1 with chronic mucocutaneous candidiasis.

  6. Cardiac monitoring during adjuvant trastuzumab therapy: Guideline adherence in clinical practice

    NARCIS (Netherlands)

    Visser, A.; Ven, E.M.W. van de; Ruczynski, L.I.; Blaisse, R.J.; Halteren, H.K. van; Aben, K.K.H.; Laarhoven, H.W.M. van

    2016-01-01

    BACKGROUND: Cardiotoxicity is an important adverse effect of adjuvant breast cancer treatment with trastuzumab and three monthly left ventricular ejection fraction (LVEF) monitoring is considered mandatory. The purpose of this study was to gain insight into LVEF monitoring during adjuvant

  7. Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer

    Directory of Open Access Journals (Sweden)

    Wojciech Krajewski

    2014-03-01

    Full Text Available Bladder cancer (BCA is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines – IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

  8. [Genetic and immunologic determinants of intravesical BCG therapy in non-muscle-invasive urothelial bladder cancer].

    Science.gov (United States)

    Krajewski, Wojciech; Kołodziej, Anna; Dembowski, Janusz; Zdrojowy, Romuald

    2014-03-20

    Bladder cancer (BCA) is one of the most common cancers. In 2010 in Poland, 6296 people developed bladder cancer and 3110 people died of it. Immunotherapy with BCG (Bacillus Calmette-Guérin) is by far the most effective adjuvant therapy. Noninfiltrating muscle membrane changes, that is, stages Ta, Tis and T1 qualify for BCG immunotherapy. BCG immunotherapy comprises series of bladder instillations, containing attenuated strain of Mycobacterium bovis. The effectiveness of immunotherapy in non-invasive bladder cancer is 70% 5-year survival without recurrence of the tumor. The treatment leads to a reduction of the residual tumor mass, but also to the delay and/or prevention of relapse, disease progression and ultimately death. Cytokines, as key mediators of immune response, play an important role in the pathogenesis of bladder cancer, which occurrence is stimulated by the inflammatory process. BCG immunotherapy provokes an intensive immunological response by the increase of cytokine production. Genetic variants determine inter-individual differences in the incidence of this cancer, as well as the response to the therapy. This is evidenced by the presence of differences in genetic variants of cytokines correlated with the varied risk of bladder cancer incidence. It is believed that concentrations of particular cytokines in urine after installation of BCG may indicate response to the therapy. Increased levels of Th1 cytokines - IFN-γ, IL-2 and TNF-α are correlated with longer survival time without recurrence, whereas high levels of Th2 cytokines such as IL-10, predict unsuccessful BCG therapy.

  9. Comparison of Biological and Immunological Characterization of Lipopolysaccharides From Brucella abortus RB51 and S19.

    Science.gov (United States)

    Kianmehr, Zahra; Kaboudanian Ardestani, Sussan; Soleimanjahi, Hoorieh; Fotouhi, Fatemeh; Alamian, Saeed; Ahmadian, Shahin

    2015-11-01

    Brucella abortus RB51 is a rough stable mutant strain, which has been widely used as a live vaccine for prevention of brucellosis in cattle instead of B. abortus strain S19. B. abortus lipopolysaccharide (LPS) has unique properties in comparison to other bacterial LPS. In the current study, two types of LPS, smooth (S-LPS) and rough (R-LPS) were purified from B. abortus S19 and RB51, respectively. The aim of this study was to evaluate biological and immunological properties of purified LPS as an immunogenical determinant. Primarily, S19 and RB51 LPS were extracted and purified by two different modifications of the phenol water method. The final purity of LPS was determined by chemical analysis (2-keto-3-deoxyoctonate (KDO), glycan, phosphate and protein content) and different staining methods, following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). C57BL/6 mice were immunized subcutaneously three times at biweekly intervals with the same amount of purified LPSs. The humoral immunity was evaluated by measuring specific IgG levels and also different cytokine levels, such as IFN-γ, TNF-α, IL-4 and IL-10, were determined for assessing T-cell immune response. Biochemical analysis data and SDS-PAGE profile showed that the chemical nature of S19 LPS is different from RB51 LPS. Both S and R-LPS induce an immune response. T-cell immune response induced by both S and R-LPS had almost the same pattern whereas S19 LPS elicited humoral immunity, which was higher than RB51 LPS. Purified LPS can be considered as a safe adjuvant and can be used as a component in prophylactic and therapeutic vaccines targeting infectious disease, cancer and allergies.

  10. Tweaking Innate Immunity: The Promise of Innate Immunologicals as Anti-Infectives

    Directory of Open Access Journals (Sweden)

    Kenneth L Rosenthal

    2006-01-01

    Full Text Available New and exciting insights into the importance of the innate immune system are revolutionizing our understanding of immune defense against infections, pathogenesis, and the treatment and prevention of infectious diseases. The innate immune system uses multiple families of germline-encoded pattern recognition receptors (PRRs to detect infection and trigger a variety of antimicrobial defense mechanisms. PRRs are evolutionarily highly conserved and serve to detect infection by recognizing pathogen-associated molecular patterns that are unique to microorganisms and essential for their survival. Toll-like receptors (TLRs are transmembrane signalling receptors that activate gene expression programs that result in the production of proinflammatory cytokines and chemokines, type I interferons and antimicrobial factors. Furthermore, TLR activation facilitates and guides activation of adaptive immune responses through the activation of dendritic cells. TLRs are localized on the cell surface and in endosomal/lysosomal compartments, where they detect bacterial and viral infections. In contrast, nucleotide-binding oligomerization domain proteins and RNA helicases are located in the cell cytoplasm, where they serve as intracellular PRRs to detect cytoplasmic infections, particularly viruses. Due to their ability to enhance innate immune responses, novel strategies to use ligands, synthetic agonists or antagonists of PRRs (also known as 'innate immunologicals' can be used as stand-alone agents to provide immediate protection or treatment against bacterial, viral or parasitic infections. Furthermore, the newly appreciated importance of innate immunity in initiating and shaping adaptive immune responses is contributing to our understanding of vaccine adjuvants and promises to lead to improved next-generation vaccines.

  11. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

    OpenAIRE

    Kataoka, Kosuke; Fujihashi, Kohtaro

    2009-01-01

    In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal ...

  12. Towards understanding the mechanism underlying the strong adjuvant activity of aluminum salt nanoparticles

    OpenAIRE

    Ruwona, Tinashe B.; Xu, Haiyue; Li, Xu; Taylor, Amber; Shi, Yan-chun; Cui, Zhengrong

    2016-01-01

    Aluminum salts such as aluminum oxyhydroxide and aluminum hydroxyphosphate are commonly used human vaccine adjuvants. In an effort to improve the adjuvant activity of aluminum salts, we previously showed that the adjuvant activity of aluminum oxyhydroxide nanoparticles is significantly more potent than that of aluminum oxyhydroxide microparticles. The present study was designed to i) understand the mechanism underlying the potent adjuvant activity of aluminum oxyhydroxide nanoparticles, relat...

  13. Comparative safety of vaccine adjuvants: a summary of current evidence and future needs

    OpenAIRE

    Petrovsky, Nikolai

    2015-01-01

    Improved use of highly pure antigens to improve vaccine safety has led to reduced vaccine immunogenicity and efficacy. This has led to the need to use adjuvants to improve vaccine immunogenicity. The ideal adjuvant should maximize vaccine immunogenicity without compromising tolerability or safety or posing undue risk. Unfortunately, adjuvant research has lagged behind other vaccine areas such as antigen discovery, with the consequence that only a very limited number of adjuvants based on alum...

  14. Medical Devices; Immunology and Microbiology Devices; Classification of the Aquaporin-4 Autoantibody Immunological Test System. Final order.

    Science.gov (United States)

    2017-10-30

    The Food and Drug Administration (FDA or we) is classifying the Aquaporin-4 autoantibody immunological test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the Aquaporin-4 autoantibody immunological test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  15. Medical Devices; Immunology and Microbiology Devices; Classification of the Zinc Transporter 8 Autoantibody Immunological Test System. Final order.

    Science.gov (United States)

    2017-10-24

    The Food and Drug Administration (FDA or we) is classifying the zinc transporter 8 autoantibody immunological test system into class II (special controls). The special controls that apply to the device type are identified in this order and will be part of the codified language for the zinc transporter 8 autoantibody immunological test system's classification. We are taking this action because we have determined that classifying the device into class II (special controls) will provide a reasonable assurance of safety and effectiveness of the device. We believe this action will also enhance patients' access to beneficial innovative devices, in part by reducing regulatory burdens.

  16. Clinical and Immunological Effects in Patients with Advanced Non-Small Cell Lung-Cancer after Vaccination with Dendritic Cells Exposed to an Allogeneic Tumor Cell Lysate*

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Kvistborg, Pia; Zocca, Mai-Britt

    2013-01-01

    vaccinations. Seven patients remained in stable disease (SD) three months after the first vac- cination. After ten vaccinations (six months), four patients still showed SD and continued vaccinations on a monthly basis. These four patients received a total of 12, 16, 26 and 35 vaccinations, respectively. Five......Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac®, Dandrit Biotech, Copenhagen, Denmark). Imiquimod cream, proleukin...... and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFN EliSpot. Secondary objec- tives were overall survival, response and quality of life (QoL). Results: Twenty-two patients initiated the vaccination program consisting of ten...

  17. PsychoNeuroImmunology Research Society's Norman Cousins Award.

    Science.gov (United States)

    2015-01-01

    Dr. Rainer H. Straub, University Hospital, Regensburg, Germany, is the recipient of the 2015 Norman Cousins Award and will present the memorial lecture at the PsychoNeuroImmunology Research Society (PNIRS) meeting, June 3–6, Seattle, WA. The Norman Cousins award is the highest honor bestowed by the PNIRS and recognizes sustained and outstanding research contributions in psychoneuroimmunology.

  18. Microglia and CNS Interleukin-1: Beyond Immunological Concepts

    Directory of Open Access Journals (Sweden)

    Xiaoyu Liu

    2018-01-01

    Full Text Available Activation of microglia and expression of the inflammatory cytokine interleukin-1 (IL-1 in the CNS have become almost synonymous with neuroinflammation. In numerous studies, increased CNS IL-1 expression and altered microglial morphology have been used as hallmarks of CNS inflammation. A central concept of how CNS IL-1 and microglia influence functions of the nervous system was derived from the notion initially generated in the peripheral immune system: IL-1 stimulates monocyte/macrophage (the peripheral counterparts of microglia to amplify inflammation. It is increasingly clear, however, CNS IL-1 acts on other targets in the CNS and microglia participates in many neural functions that are not related to immunological activities. Further, CNS exhibits immunological privilege (although not as absolute as previously thought, rendering amplification of inflammation within CNS under stringent control. This review will analyze current literature to evaluate the contribution of immunological and non-immunological aspects of microglia/IL-1 interaction in the CNS to gain insights for how these aspects might affect health and disease in the nervous tissue.

  19. A New Immunologic Method for Detection of Occult Breast Cancer

    Science.gov (United States)

    1999-09-01

    in Workshop on Melanoma Monoclonal Antibodies, NIH. 1981 Workshop on ELISA, Cordia Laboratories, Culver City, invited Faculty. 1982 Invited Faculty...for Workshop on Practical Aspects of ELISA, Cordia Laboratories. 1983 Invited Faculty for Workshop on Melanoma Immunology, European Soc for

  20. Immunologic factors in patients with chronic polypoid sinusitis ...

    African Journals Online (AJOL)

    Immunologic factors in patients with chronic polypoid sinusitis. S Nikakhlagh, M Ghafourian-Boroujerdnia, N Saki, M.R Soltan-Moradi, F Rahim. Abstract. Nasal polyposis is the benign protrusion of soft tissue into the nasal cavity, with multifactorial origin. This study is designed to examine the suggested role of IgE and CD4 ...

  1. Baseline values of immunologic parameters in the lizard Salvator ...

    African Journals Online (AJOL)

    ... related differences in the immune parameters analyzed. Having established baseline values for these four widely-used immunologic biomarkers, ongoing studies will seek to optimize the use of the S. merianae model in future research. Keywords: Biomarkers, Immune system, Reptilian, Salvator merianae, Sentinel model ...

  2. Immunologic and haematologic effects of methanolic stem bark ...

    African Journals Online (AJOL)

    The study was aimed at evaluating the weight, haematologic and immunologic effects of crude methanolic stem bark extract of Azadihiracta indica stem bark on vaccinated chickens experimentally challenged with the velogenic Newcastle disease virus. One hundred day old cockerels were randomly divided into four equal ...

  3. 21 CFR 866.5880 - Transferrin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Transferrin immunological test system. 866.5880 Section 866.5880 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... disorders, such as iron deficiency anemia. (b) Classification. Class II (performance standards). ...

  4. 21 CFR 866.5715 - Plasminogen immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plasminogen immunological test system. 866.5715 Section 866.5715 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES.... Measurement of plasminogen levels may aid in the diagnosis of fibrinolytic (blood-clotting) disorders. (b...

  5. Egyptian Journal of Pediatric Allergy and Immunology (The): Journal ...

    African Journals Online (AJOL)

    Publisher. Contact: Professor Ihab Z. El-Hakim. Email ihab.elhakim@gmail.com. Phone +201111224974. Fax … +202 33045060. Children's Hospital, Ain Shams University, Ramses Street, Abbassiya, Cairo 11566, Egypt. The Egyptian Society of Pediatric Allergy and Immunology ...

  6. Effect of traditional herbs on immunological and virological markers ...

    African Journals Online (AJOL)

    There were no significant changes in the amount of virus in blood of patients on PT or CMC. The findings suggest that traditional herbs improve clinical and immunological status and hence they have a role to play in the management of HIV/AIDS patients and add value to standard CMC. The Zimbabwe Science News ...

  7. Peptide modification in T cell immunology - from molecule to animal

    NARCIS (Netherlands)

    Haan, Ellen Christine de

    2003-01-01

    Chemical knowledge can be applied in the field of immunology. It provides a better understanding of how a peptide interacts with proteins and cells of the immune system. However, it is not possible to predict the outcome of peptide administration in an animal. Peptides are used in experimental

  8. Allergy-immunology glossary | El-Sayed | Egyptian Journal of ...

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 12, No 2 (2014) >. Log in or Register to get access to full text downloads.

  9. Allergy-immunology glossary | El-Sayed | Egyptian Journal of ...

    African Journals Online (AJOL)

    Egyptian Journal of Pediatric Allergy and Immunology (The). Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 2 (2017) >. Log in or Register to get access to full text downloads.

  10. Big Data Analytics in Immunology: A Knowledge-Based Approach

    Directory of Open Access Journals (Sweden)

    Guang Lan Zhang

    2014-01-01

    Full Text Available With the vast amount of immunological data available, immunology research is entering the big data era. These data vary in granularity, quality, and complexity and are stored in various formats, including publications, technical reports, and databases. The challenge is to make the transition from data to actionable knowledge and wisdom and bridge the knowledge gap and application gap. We report a knowledge-based approach based on a framework called KB-builder that facilitates data mining by enabling fast development and deployment of web-accessible immunological data knowledge warehouses. Immunological knowledge discovery relies heavily on both the availability of accurate, up-to-date, and well-organized data and the proper analytics tools. We propose the use of knowledge-based approaches by developing knowledgebases combining well-annotated data with specialized analytical tools and integrating them into analytical workflow. A set of well-defined workflow types with rich summarization and visualization capacity facilitates the transformation from data to critical information and knowledge. By using KB-builder, we enabled streamlining of normally time-consuming processes of database development. The knowledgebases built using KB-builder will speed up rational vaccine design by providing accurate and well-annotated data coupled with tailored computational analysis tools and workflow.

  11. Immunological Adaptations to Pregnancy in Women with Type 1 Diabetes

    NARCIS (Netherlands)

    Groen, Bart; van der Wijk, Anne-Eva; van den Berg, Paul P.; Lefrandt, Joop D.; van den Berg, Gerrit; Sollie, Krystina M.; de Vos, Paul; Links, Thera P.; Faas, Marijke M.

    2015-01-01

    Despite adequate glycemic control, pregnancy outcome of women with type 1 diabetes (T1D) is still unfavorable as compared to healthy women. In a rat-model of T1D under normoglycemic conditions, adverse pregnancy outcome was also observed, which was associated with aberrant immunological adaptations

  12. Immunological Response to Antiretroviral Therapy in HIV-1 Infected ...

    African Journals Online (AJOL)

    Objective: To describe the immunological response to ART in HIV-1 infected ART naïve patients in relation to age, sex, baseline CD4+ T cell counts and generic ART regimens at Muhimbili Nation Hospital, in Dar es Salaam, Tanzania. Methods: Retrospective analysis of data from patients enrolled in the pilot ART program ...

  13. Polish scientists in fish immunology: a short history : review

    NARCIS (Netherlands)

    Muiswinkel, van W.B.; Pilarczyk, A.

    2015-01-01

    This review describes the role played by Polish scientists in the field of fish immunology and vaccination starting around 1900. In the early days, most publications were dealing with a description of relevant cells and organs in fish. Functional studies (phagocytosis, antibody response) came later

  14. Big data analytics in immunology: a knowledge-based approach.

    Science.gov (United States)

    Zhang, Guang Lan; Sun, Jing; Chitkushev, Lou; Brusic, Vladimir

    2014-01-01

    With the vast amount of immunological data available, immunology research is entering the big data era. These data vary in granularity, quality, and complexity and are stored in various formats, including publications, technical reports, and databases. The challenge is to make the transition from data to actionable knowledge and wisdom and bridge the knowledge gap and application gap. We report a knowledge-based approach based on a framework called KB-builder that facilitates data mining by enabling fast development and deployment of web-accessible immunological data knowledge warehouses. Immunological knowledge discovery relies heavily on both the availability of accurate, up-to-date, and well-organized data and the proper analytics tools. We propose the use of knowledge-based approaches by developing knowledgebases combining well-annotated data with specialized analytical tools and integrating them into analytical workflow. A set of well-defined workflow types with rich summarization and visualization capacity facilitates the transformation from data to critical information and knowledge. By using KB-builder, we enabled streamlining of normally time-consuming processes of database development. The knowledgebases built using KB-builder will speed up rational vaccine design by providing accurate and well-annotated data coupled with tailored computational analysis tools and workflow.

  15. Prevalence of immunological failure and durability of first line ...

    African Journals Online (AJOL)

    This a crossectional retrospective follow up study was conducted to determine the prevalence of immunological treatment failure and risk factors associated to it among patients on ARV therapy at Bugando Medical Centre. Method: A crossectional Retrospective study was conducted among all patients on ART from 2005 ...

  16. Immunological challenges during pregnancy : preeclampsia and egg donation

    NARCIS (Netherlands)

    Hoorn, Marie-Louise van der

    2012-01-01

    Human pregnancy is an interesting immunological paradox. The fetus is a semi-allograft, carrying paternal and maternal genes but is not rejected by the maternal immune system. The placenta is a key player in maintaining the pregnancy, since this fetus-derived organ is in direct contact with the

  17. A Prospective Cohort Study of Immunologic and Virologic Outcomes ...

    African Journals Online (AJOL)

    ... and 116(81.1%) and 97(79.3%); p=0.10 respectively. Co-infection has limited impact on immunologic and virologic outcomes, but may be an important cause of hepatotoxicity. KeyWords: HIV/AIDS, Hepatitis virus Co-Infection,HAART Accepted as poster at 14th International Congress on Infectious Diseases, Miami Florida ...

  18. Effect of surgical and immunological castration on haematological ...

    African Journals Online (AJOL)

    Welfare concerns are growing regarding surgical castration (SC) in pets, necessitating the need for non-surgical alternatives. Administration of vaccines against gonadotropins releasing hormone (GnRH) have been reported as alternative to SC. This study determined the effect of surgical and immunological castrations (IC) ...

  19. CHARGE syndrome : a review of the immunological aspects

    NARCIS (Netherlands)

    Wong, Monica T. Y.; Scholvinck, Elisabeth H.; Lambeck, Annechien J. A.; van Ravenswaaij-Arts, Conny M. A.

    2015-01-01

    CHARGE syndrome is caused by a dominant variant in the CHD7 gene. Multiple organ systems can be affected because of haploinsufficiency of CHD7 during embryonic development. CHARGE syndrome shares many clinical features with the 22q11.2 deletion syndrome. Immunological abnormalities have been

  20. Immunologic mapping of glycomes: implications for cancer diagnosis and therapy

    DEFF Research Database (Denmark)

    Zhou, Dapeng; Levery, Steven B; Hsu, Fong-Fu

    2011-01-01

    Cancer associated glycoconjugates are important biomarkers, as exemplified by globo-H, CA125, CA15.3 and CA27.29. However, the exact chemical structures of many such biomarkers remain unknown because of technological limitations. In this article, we propose the "immunologic mapping" of cancer gly...

  1. Immunological cross-reactivity of venoms from some Egyptian ...

    African Journals Online (AJOL)

    The immunological cross-reactivity among the Elapidae, Viperidae and Buthidae venoms was detected in dot blot and western blot assays and quantified in ELISA as percentage of absorbance of heterologous versus homologous reaction. Mutual cross-reactivity between the Elapidae and Viperidae venoms was ...

  2. Advances in basic and clinical immunology in 2010.

    Science.gov (United States)

    Chinen, Javier; Shearer, William T

    2011-02-01

    Reports in basic and clinical immunology in 2010 reflected the use of state-of-the-art genetic and immunologic tools to characterize the pathogenesis of immunologic diseases and the development of novel therapies directed to these conditions. B-cell biology has been explained in greater detail, significantly with lessons from the genetic defects found in the humoral immunodeficiencies. Therapeutic mAbs are given for an increasing number of indications, such as anti-CD20 antibodies or rituximab, which was initially developed for non-Hodgkin lymphomas and is currently used in diverse autoimmune and inflammatory disorders. The report of an infant with severe combined immunodeficiency (SCID) in Massachusetts detected by means of newborn screening and successfully treated with hematopoietic stem cell transplantation validated recent efforts toward newborn screening for SCID. Improvement of survival outcomes for patients with primary immunodeficiencies treated with hematopoietic stem cell transplantation was demonstrated in a large European cohort, with significant appreciation of the type of donor graft, particularly the use of HLA-matched unrelated donors for patients with non-SCID. Progress in cellular mechanisms of drug hypersensitivity included the characterization of nitroso-modified drug metabolites as potent T-cell activators and the identification of the relocation of plasmacytoid dendritic cells from blood to skin as a potential risk factor for reactivation of viral disease. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  3. Veterinary Immunology Committee Toolkit Workshop 2010: progress and plans.

    Science.gov (United States)

    Entrican, Gary; Lunney, Joan K

    2012-07-15

    The 3rd Veterinary Immunology Committee (VIC) Toolkit Workshop took place at the 9th International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan on 18th August 2010. The Workshop built on previous Toolkit Workshops and covered various aspects of reagent development, commercialization and provision to the veterinary immunology research community. The emphasis was on open communication about current progress and future plans to avoid duplication of effort and to update priorities for reagent development. There were presentations on the major reagent development and networking projects such as the BBSRC/RERAD Immunological Toolbox (2004-2009), US Veterinary Immune Reagent Network (VIRN 2006-2010) that has just received renewal funding for 2010-2014, and EU Network for Animal Diseases Infectiology Research Facilities project (NADIR 2009-2013). There were also presentations and discussions on the use of reagents for assay development, particularly multiplexing, and how these new technologies will underpin basic research developments. Mechanisms for improved information exchange, especially though websites with VIC playing a central role, were identified. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Regulation of immunological and inflammatory functions by biotin.

    Science.gov (United States)

    Kuroishi, Toshinobu

    2015-12-01

    Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear protein involved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.

  5. 21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test system. 866.5500 Section 866.5500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... other allergic respiratory disorders. (b) Classification. Class II (performance standards). ...

  6. The immunological response of South African Bulinus natalensis ...

    African Journals Online (AJOL)

    Foot muscle antigens of the diploid Bulinus natalensis from Lake Sibayi showed complete immunological correspondence with antiserum prepared from foot muscle tissues of the diploid B. tropicus. On the other hand, strong “non-identity” reactions occurred when B. natalensis antigens were tested with the antiserum ...

  7. Effect of Allium cepa and Allium sativum on some immunological ...

    African Journals Online (AJOL)

    Extracts of some spices have been reported to play a contributory role in enhancing immune function. We evaluated and compared the effect(s) of single and combined oral administration of fresh aqueous onion (Allium cepa) and garlic (Allium sativum) extracts at different concentrations on some immunological ...

  8. Immunological studies on the mechanism of resistance in ...

    African Journals Online (AJOL)

    The aim of this study was to investigate the possibility of using laboratory rodents as models for immunological studies of onchocerciasis. Living adult Onchocerca (O.) armillata and O. volvulus were surgically transplanted into the peritoneal cavities of rats, after initial immunizations or transplantations, in order to investigate ...

  9. Prevalence of clinical, immunological and irological failure among ...

    African Journals Online (AJOL)

    Background: There is increasing evidence that the current clinical and immunological monitoring tools are not sufficient to identify early enough patients who are failing on treatment. Development of resistance to the limited treatment options for children and premature switching are the dangers. The objective of this study ...

  10. Immunological and Virological Response to HAART in HIV-1 ...

    African Journals Online (AJOL)

    Background: Among the countries highly endemic for viral hepatitis, Nigeria is found. Information on how triple infected persons (HIV, HBV, and HCV) fare on HAART in the country is lacking. Laboratory based investigation was carried out to assess the virological and immunological parameters of HIV-1 infected patients ...

  11. Highlights of the 8th International Veterinary Immunology Symposium

    Science.gov (United States)

    Veterinary immunologists have expanded understanding of the immune systems for our companion animals and developed new vaccines and therapeutics. This manuscript summarizes the highlights of the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto,...

  12. Possible immunological basis for recurrent spontaneous abortion: a ...

    African Journals Online (AJOL)

    Possible immunological basis for recurrent spontaneous abortion: a review. A. G. Tumbo-Oeri, C. A. Omwandho, J. M. Muchiri. Abstract. (East African Medical Journal 2001: 78 (11): 586-589). Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics.

  13. Prevalence and predictors of Immunological failure among HIV ...

    African Journals Online (AJOL)

    This study aimed at assessing the magnitude and factors associated with immunological failure among HIV infected patients on HAART. Methods: A cross sectional study was conducted at Bugando Medical centre HIV care and treatment centre between February-July 2011, involving HIV-infected patients on first line ART ...

  14. Immunological Characterization of Dutch Sesame Seed-Allergic Patients

    NARCIS (Netherlands)

    Teodorowicz, Malgorzata; Terlouw, Rozine J.; Jansen, Ad; Savelkoul, Huub F.J.; Ruinemans-Koerts, Janneke

    2016-01-01

    Background: Sesame seed is an allergen of growing importance worldwide. However, knowledge of the clinically relevant sesame allergen and its cross-reactivity with homologous allergens is limited. The aim of this study was the immunological characterization of Dutch sesame seed-allergic patients

  15. Delta inulin: a novel, immunologically active, stable packing structure comprising β-d-[2 → 1] poly(fructo-furanosyl) α-d-glucose polymers

    Science.gov (United States)

    Cooper, Peter D; Petrovsky, Nikolai

    2011-01-01

    We report a novel isoform of β-d-[2 → 1] poly(fructo-furanosyl) α-d-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37–48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity. PMID:21147758

  16. Ready-to-use colloidal adjuvant systems for intranasal immunization.

    Science.gov (United States)

    Lee, Jeong-Jun; Shim, Aeri; Lee, Song Yi; Kwon, Bo-Eun; Kim, Seong Ryeol; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2016-04-01

    Adjuvant systems based on oil-in-water (o/w) microemulsions (MEs) for vaccination via intranasal administration were prepared and evaluated. A ready-to-use blank ME system composed of mineral oil (oil), Labrasol (surfactant), Tween 80 (cosurfactant), and water was prepared and blended with antigen (Ag) solution prior to use. The o/w ME system developed exhibited nano-size droplets within the tested range of Ag concentrations and dilution factors. The maintenance of primary, secondary, and tertiary structural stability of ovalbumin (OVA) in ME, compared with OVA in solution, was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence intensity measurements, respectively. The uptake efficiency in RAW 264.7 cells, evaluated by flow cytometry, of OVA in the ME group was significantly higher than that of the OVA solution group (p<0.05). In an intranasal immunization study with OVA ME in mice, elevated adjuvant effects in terms of mucosal immunization and Th1-dominant cell-mediated immune responses were identified. Given the convenience of use (simply mixing with Ag solution prior to use) and the adjuvant effects after intranasal immunization, the new o/w ME may be a practical and efficient adjuvant system for intranasal vaccination. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Tailorable Trimethyl chitosans as adjuvant for intranasal immunization

    NARCIS (Netherlands)

    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

  18. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky

    2012-01-01

    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...

  19. Evaluation of the LTK63 adjuvant effect on cellular immune ...

    African Journals Online (AJOL)

    Background: A lot of pathogens enter the body via the nasal route. The construction of non-toxic mutants of heat labile Escherichia coli enterotoxin (LT), which is a potent mucosal adjuvant, represents a major breakthrough for the development of mucosal vaccines. Objective: This study was undertaken to critically evaluate ...

  20. Adjuvant chemotherapy for stage I non-seminomatous testicular ...

    African Journals Online (AJOL)

    chemotherapy regimen consisted of 2 cycles of cisplatin, etoposide and bleomycin. Each cycle of chemotherapy lasted 3 days. There have been no relapses at a median follow-up of. 31 months (range 12 - 53 months). Acute and late toxicity have been modest. We have found adjuvant chemotherapy to be effective after ...

  1. Effect of adjuvant therapies on recurrence in aneurysmal bone cysts.

    Science.gov (United States)

    Keçeci, Burçin; Küçük, Levent; Isayev, Alovsat; Sabah, Dündar

    2014-01-01

    The aim of this study was to define the effective factors such as surgical method, age and cavity filling materials on local recurrence in the treatment of aneurysmal bone cysts. The study included 85 patients (mean age: 17.9 years) that received surgical treatment for primary aneurysmal bone cyst. Nine were treated with cyst excision and 76 with intralesional curettage. The intralesional curettage group was divided into 3 subgroups according to adjuvant therapies applied; the first group received no additional adjuvant therapy, the second group received additional high-speed burr and the third group received additional high-speed burr and alcohol/phenol adjuvant treatments. Bone graft or bone cement was used to fill in the cavity. Mean follow-up period was 107.5 months. Groups were analyzed statistically in terms of local recurrence. Onset of cyst in ages under 10 and 20 years were considered a negative prognostic factor and analyzed statistically. Local recurrence occurred in 10 (11.8%) patients. Mean duration between the initial operation and recurrence was 10 months. There was no significant difference in terms of local recurrence among the surgical treatment groups, adjuvant therapy groups, age groups and bone graft and bone cement groups. Careful curettage of the entire cyst wall remains the most important step in the intralesional treatment of aneurysmal bone cyst.

  2. Lipopolysaccharide contamination in intradermal DNA vaccination : toxic impurity or adjuvant?

    NARCIS (Netherlands)

    Berg, J.H. van den; Quaak, S.G.L.; Beijnen, J.H.; Hennink, W.E.; Storm, G.; Schumacher, T.N.; Haanen, J.B.A.G.; Nuijen, B.

    Purpose: Lipopolysaccharides (LPS) are known both as potential adjuvants for vaccines and as toxic impurity in pharmaceutical preparations. The aim of this study was to assess the role of LPS in intradermal DNA vaccination administered by DNA tattooing. Method: Micewere vaccinated with a model DNA

  3. Effects of pH and adjuvants on clethodim photodegradation

    Energy Technology Data Exchange (ETDEWEB)

    Falb, L.N.; Bridges, D.C.; Smith, A.E. Jr. (Univ. of Georgia, Griffin (USA))

    1990-03-01

    Physical degradation of clethodim (2-(1-(((3-chloro-2-propenyl)oxy)imino)propyl)-5-(2-(ethylthio)propyl)cyclohexane-1,3-dione) occurred in aqueous solution by acid catalysis and photocatalysis in in vitro experiments as assayed by HPLC. Clethodim degradation increased as acidity increased, being further accelerated under UV light with a half-life of 2.4, 2.6, and 3.2 h at pH 5, 6, and 7, respectively. Fewer degradation products were formed under UV plus adjuvant treatments, but the rate of photodegradation was increased by 2- to 7-fold over the UV control. The degradation rate in sunlight plus adjuvant treatments was enhanced by 7- to 27-fold over the sunlight control. The photodegradation rates in the presence of adjuvants followed the sequence LI700 > Dash > Agrioil > XE1167 > CC15943 > control. In summary, clethodim degradation was catalyzed by acid, the rate being accelerated in light (probably a different mechanism), and was further enhanced by the addition of adjuvants to the light treatment.

  4. Dexmedetomidine: An Adjuvant Making Large Inroads into Clinical ...

    African Journals Online (AJOL)

    stroke volume, on rate reducing drugs such as beta blockers, digitalis etc., and ..... Role in Cancer Pain. Dexmedetomidine has been studied as an adjuvant in intractable cancer pain and has been found to benefit in reduction of pain refractory to multiple treatment ... newer α‑2 adrenergic receptor blocker dexmedetomidine.

  5. Effects of 5-fluorouracil adjuvant treatment of colon cancer

    NARCIS (Netherlands)

    Kelder, Wendy; Hospers, Geke A. P.; Plukker, John T. M.

    Since the late 1980s and early 1990s, 5-fluorouracil-based chemotherapy has been the standard adjuvant treatment for Stage III colon cancer. After the initial introduction of 5-fluorouracil in standard treatment protocols, several changes have been made based on results of randomized studies on

  6. Efficacy of Killed Adjuvanted FMD Vaccine Developed with ...

    African Journals Online (AJOL)

    In this study the potency of killed Foot and Mouth Disease (FMD) vaccines serotypes SAT1 (Nig 1/98) and SAT 2 (Nig 2/97) virus isolates, formulated with montanide ISA 206 adjuvant was determined in guinea pigs and cattle by antibody assay using Complement Fixation and Serum Neutralization tests. The antibody titres ...

  7. A randomised controlled trial comparing the effect of adjuvant ...

    African Journals Online (AJOL)

    Abstract. Background: Intrathecal adjuvants are added to local anaesthetics to improve the quality of neuraxial blockade and prolong the ... Methods: A total of 40 patients undergoing lower limb orthopaedic surgery under spinal anaesthesia were randomized to two ... ciceptive stimuli, and the discovery of opioid receptors in.

  8. Latex proteins from Calotropis procera: Toxicity and immunological tolerance revisited.

    Science.gov (United States)

    Bezerra, Camila F; Mota, Érika F; Silva, Ana Claudia M; Tomé, Adriana R; Silva, Maria Z R; de Brito, Daniel; Porfírio, Camila T M N; Oliveira, Ariclécio C; Lima-Filho, José V; Ramos, Márcio V

    2017-08-25

    Many thousands of plants are disseminated worldwide in traditional and folk medicines based on the belief that their leaves, roots, seeds, bark or secretions, when adequately handled, can treat, alleviate or ameliorate numerous disease symptoms. Calotropis procera (Apocynaceae) is a popular medicinal plant and the claims of this shrub's phytomedicinal properties have been scientifically validated. In this study, further prospects towards the in vivo toxicity and oral immunological tolerance of phytomodulatory proteins isolated from the latex of C. procera are reported. Acute toxicity was determined in mice by oral and intraperitoneal administration of latex proteins (LP) and was followed behavioral, hematological and histological analyses. Oral immunological tolerance to LP was assessed by intraperitoneal immunization in mice that had received LP orally before. Animals given 5000 mg/kg orally exhibited only discrete behavioral alterations and augmentation of monocytes. Death was not notified 14 days after exposure. However, all animals receiving LP 150 mg/kg by i.p. died in 1 h. Death (20%) was documented when LP (75 mg/kg) was given in the peritoneum and signs of harmful effects were observed in the survivors (80%). Oral immunological tolerance was observed in animals previously given LP orally, when they were further immunized/challenged with peritoneal exposure to different doses of LP. This was confirmed by the lowering of IgE and IgG in the serum, IL-4 and IFN-γ in spleen homogenates and the absence of anaphylaxis signs. It is therefore concluded that LP exhibited quite discrete adverse effects when orally administrated at higher concentrations and this route of administration did not stimulate adverse immunological reactions. Instead it was observed immunological tolerance. The present study contributes very important information concerning the safe use of C. procera as a phytotherapeutic agent. Copyright © 2017. Published by Elsevier B.V.

  9. Immunological Characterization of Dutch Sesame Seed-Allergic Patients.

    Science.gov (United States)

    Teodorowicz, Malgorzata; Terlouw, Rozine J; Jansen, Ad; Savelkoul, Huub F J; Ruinemans-Koerts, Janneke

    2016-01-01

    Sesame seed is an allergen of growing importance worldwide. However, knowledge of the clinically relevant sesame allergen and its cross-reactivity with homologous allergens is limited. The aim of this study was the immunological characterization of Dutch sesame seed-allergic patients and evaluation of cross-reactivity between sesame seed, tree nut and pollen allergens using different sources of allergen extracts. Six patients with a medical history of sesame seed allergy were included, i.e. 5 with an anaphylactic reaction and 1 with an oral allergy syndrome (OAS). The immunological background of the sesame seed and tree nut IgE sensitization was characterized with Western blotting and a basophil activation test (BAT). The major sesame allergen was identified by nanoLC-MS/MS. Cross-reactivity was measured using an immuno-inhibition assay with the Phadia ImmunoCAP system. Oleosin was identified as the major allergen for the 5 patients with an anaphylactic reaction to sesame seed, but no cross-reactivity between sesame and tree nut proteins was observed. For the patient with OAS, IgE specific to oleosin was not detected but cross-reactivity between sesame seed and tree nut proteins was observed. The BAT and ImmunoCAP inhibition test added value to the clinical and immunological characterization of sesame seed-sensitized patients, distinguishing relevant and non-relevant sensitizations. Our immunological approach enabled us to fully characterize the sensitization pattern of 6 sesame seed-allergic patients. The different protein composition of commercially available allergen extracts influences the outcomes of the immunological assays and thus also the diagnosis to a large extent. © 2016 S. Karger AG, Basel.

  10. System Consolidation During Sleep - A Common Principle Underlying Psychological and Immunological Memory Formation

    NARCIS (Netherlands)

    Westermann, Jürgen; Lange, Tanja; Textor, Johannes; Born, Jan

    2015-01-01

    Sleep benefits the consolidation of psychological memory, and there are hints that sleep likewise supports immunological memory formation. Comparing psychological and immunological domains, we make the case for active system consolidation that is similarly established in both domains and partly

  11. System consolidation during sleep - a common principle underlying psychological and immunological memory formation

    NARCIS (Netherlands)

    Westermann, J.; Lange, T.; Textor, J.C.; Born, J. van den

    2015-01-01

    Sleep benefits the consolidation of psychological memory, and there are hints that sleep likewise supports immunological memory formation. Comparing psychological and immunological domains, we make the case for active system consolidation that is similarly established in both domains and partly

  12. Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging

    DEFF Research Database (Denmark)

    Hofmann, B; Bygbjerg, Ib Christian; Dickmeiss, E

    1989-01-01

    The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total...

  13. Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices.

    Science.gov (United States)

    Switalla, S; Lauenstein, L; Prenzler, F; Knothe, S; Förster, C; Fieguth, H-G; Pfennig, O; Schaumann, F; Martin, C; Guzman, C A; Ebensen, T; Müller, M; Hohlfeld, J M; Krug, N; Braun, A; Sewald, K

    2010-08-01

    Prediction of lung innate immune responses is critical for developing new drugs. Well-established immune modulators like lipopolysaccharides (LPS) can elicit a wide range of immunological effects. They are involved in acute lung diseases such as infections or chronic airway diseases such as COPD. LPS has a strong adjuvant activity, but its pyrogenicity has precluded therapeutic use. The bacterial lipopeptide MALP-2 and its synthetic derivative BPPcysMPEG are better tolerated. We have compared the effects of LPS and BPPcysMPEG on the innate immune response in human precision-cut lung slices. Cytokine responses were quantified by ELISA, Luminex, and Meso Scale Discovery technology. The initial response to LPS and BPPcysMPEG was marked by coordinated and significant release of the mediators IL-1β, MIP-1β, and IL-10 in viable PCLS. Stimulation of lung tissue with BPPcysMPEG, however, induced a differential response. While LPS upregulated IFN-γ, BPPcysMPEG did not. This traces back to their signaling pathways via TLR4 and TLR2/6. The calculated exposure doses selected for LPS covered ranges occurring in clinical studies with human beings. Correlation of obtained data with data from human BAL fluid after segmental provocation with endotoxin showed highly comparable effects, resulting in a coefficient of correlation >0.9. Furthermore, we were interested in modulating the response to LPS. Using dexamethasone as an immunosuppressive drug for anti-inflammatory therapy, we found a significant reduction of GM-CSF, IL-1β, and IFN-γ. The PCLS-model offers the unique opportunity to test the efficacy and toxicity of biological agents intended for use by inhalation in a complex setting in humans. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. Recombinant Hepatitis B Vaccine Adjuvanted With AS04 in Dialysis Patients: A Prospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Fabrizio Fabrizi

    2015-11-01

    Full Text Available Background/Aims: Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination, including to hepatitis B vaccine. A recombinant HB vaccine containing a new adjuvant system AS04 (HBV-AS04 has been recently developed; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis. All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospectively included. Methods: Patients received four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle at months 0,1,2, and 3. Anti-HB surface antibody concentrations were measured at intervals of 1, 2, 3, 4, and 12 months. Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine. Results: 102 patients were enrolled and 91 completed the study. At completion of the vaccination schedule, using per-protocol analysis, 76 of 91 (84% had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations (GMCs of 385.25 mIU/mL. The sero-protection rate at month 12 was 84% (48/57 with lower GMCs (62.74 mIU/mL, PPConclusions: HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present. Prospective studies with HBV-AS04 on larger study groups and with longer follow-ups are under way.

  15. 21 CFR 866.6030 - AFP-L3% immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AFP-L3% immunological test system. 866.6030... Systems § 866.6030 AFP-L3% immunological test system. (a) Identification. An AFP-L3% immunological test... measure, by immunochemical techniques, AFP and AFP-L3 subfraction in human serum. The device is intended...

  16. Reproductive immunology update: the 52nd annual meeting of the American Society of Reproductive Medicine.

    Science.gov (United States)

    Kauma, S W

    1997-02-01

    The American Society of Reproductive Medicine meeting (formerly the American Fertility Society) was held in Boston, Massachusetts, USA, on November 2-6, 1996. Numerous abstracts concerning original research in reproductive immunology were presented at the meeting. In addition, seminars and round table discussions were held on the topics of hormonal immunocontraception, immunologic testing in reproduction, antiphospholipid syndrome, endometriosis, and immunologic infertility.

  17. Immunology for rheumatology residents: working toward a Canadian national curriculum consensus.

    Science.gov (United States)

    Chow, Shirley L; Herman-Kideckel, Sari; Mahendira, Dharini; McDonald-Blumer, Heather

    2015-01-01

    Immunologic mechanisms play an integral role in understanding the pathogenesis and management of rheumatic conditions. Currently, there is limited access to formal instruction in immunology for rheumatology trainees across Canada. The aims of this study were (1) to describe current immunology curricula among adult rheumatology training programs across Canada and (2) to compare the perceived learning needs of rheumatology trainees from the perspective of program directors and trainees to help develop a focused nationwide immunology curriculum. Rheumatology trainees and program directors from adult rheumatology programs across Canada completed an online questionnaire and were asked to rank a comprehensive list of immunology topics. A modified Delphi approach was implemented to obtain consensus on immunology topics. Only 42% of program directors and 31% of trainees felt the current method of teaching immunology was effective. Results illustrate concordance between program directors and trainees for the highest-ranked immunology topics including innate immunity, adaptive immunity, and cells and tissues of the immune system. However, there was discordance among other topics, such as diagnostic laboratory immunology and therapeutics. There is a need to improve immunology teaching in rheumatology training programs. Results show high concordance between the basic immunology topics. This study provides the groundwork for development of future immunology curricula.

  18. Mucosal Immunization with Liposome-Nucleic Acid Adjuvants Generates Effective Humoral and Cellular Immunity

    Science.gov (United States)

    Henderson, Angela; Propst, Katie; Kedl, Ross; Dow, Steven

    2012-01-01

    Development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. We previously reported that cationic liposomes complexed with non-coding plasmid DNA (CLDC) were effective parenteral vaccine adjuvants. However, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. To address these questions, antibody and T cell responses were assessed in mice following intranasal immunization with CLDC-adjuvanted vaccines. The effects of CLDC adjuvant on antigen uptake, trafficking, and cytokine responses in the airways and draining lymph nodes were also assessed. We found that mucosal immunization with CLDC-adjuvanted vaccines effectively generated potent mucosal IgA antibody responses, as well as systemic IgG responses. Notably, mucosal immunization with CLDC adjuvant was very effective in generating strong and sustained antigen-specific CD8+ T cell responses in the airways of mice. Mucosal administration of CLDC vaccines also induced efficient uptake of antigen by DCs within the mediastinal lymph nodes. Finally, a killed bacterial vaccine adjuvanted with CLDC induced significant protection from lethal pulmonary challenge with Burkholderia pseudomallei. These findings suggest that liposome-nucleic acid adjuvants represent a promising new class of mucosal adjuvants for non-replicating vaccines, with notable efficiency at eliciting both humoral and cellular immune responses following intranasal administration. PMID:21600950

  19. Dendritic cell-targeting DNA-based mucosal adjuvants for the development of mucosal vaccines

    Science.gov (United States)

    Kataoka, Kosuke; Fujihashi, Kohtaro

    2009-01-01

    In order to establish effective mucosal immunity against various mucosal pathogens, vaccines must be delivered via the mucosal route and contain effective adjuvant(s). Since mucosal adjuvants can simply mix with the antigen, it is relatively easy to adapt them for different types of vaccine development. Even in simple admixture vaccines, the adjuvant itself must be prepared without any complications. Thus, CpG oligodeoxynucleotides or plasmids encoding certain cDNA(s) would be potent mucosal adjuvant candidates when compared with other substances that can be used as mucosal adjuvants. The strategy of a DNA-based mucosal adjuvant facilitates the targeting of mucosal dendritic cells, and thus is an effective and safe approach. It would also provide great flexibility for the development of effective vaccines for various mucosal pathogens. PMID:19722892

  20. [Status and suggestions for adjuvant standard for Chinese materia medica processing in China].

    Science.gov (United States)

    Yang, Chun-Yu; Cao, Hui; Wang, Xiao-Tao; Tu, Jia-Sheng; Qian, Zhong-Zhi; Yu, Zhi-Ling; Shang, Yue; Zhang, Bao-Xian

    2017-04-01

    In this paper, the status of adjuvant standard for Chinese materia medica processing in the Chinese Pharmacopoeia 2015 edition, the National Specification of Chinese Materia Medica Processing, and the 29 provincial specification of Chinese materia medica was summarized, and the the status including general requirements, specific requirements, and quality standard in the three grade official specifications was collected and analyzed according to the "medicine-adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper also introduced the research situation of adjuvant standard for Chinese materia medica processing in China; In addition, analyzed and discussed the problems existing in the standard system of adjuvant for Chinese materia medica processing, such as lack of general requirements, low level of standard, inconsistent standard references, and lack of research on the standard, and provided suggestions for the further establishment of the national standards system of adjuvant for Chinese materia medica processing. Copyright© by the Chinese Pharmaceutical Association.

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

    Science.gov (United States)

    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 understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants. PMID:25692535

  2. A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

    Science.gov (United States)

    Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

    2016-02-03

    New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    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 understood. Current explanations for the mode of action of aluminum hydroxide-based adjuvants include, among others, the repository effect, pro-phagocytic effect, and activation of the pro-inflammatory NLRP3 pathway. These collectively galvanize innate as well as acquired immune responses and activate the complement system. Factors that have a profound influence on responses evoked by aluminum hydroxide-based adjuvant applications include adsorption rate, strength of the adsorption, size and uniformity of aluminum hydroxide particles, dosage of adjuvant, and the nature of antigens. Although vaccines containing aluminum hydroxide-based adjuvants are beneficial, sometimes they cause adverse reactions. Further, these vaccines cannot be stored frozen. Until recently, aluminum hydroxide-based adjuvants were known to preferentially prime Th2-type immune responses. However, results of more recent studies show that depending on the vaccination route, aluminum hydroxide-based adjuvants can enhance both Th1 as well as Th2 cellular responses. Advances in systems biology have opened up new avenues for studying mechanisms of aluminum hydroxide-based adjuvants. These will assist in scaling new frontiers in aluminum hydroxide-based adjuvant research that include improvement of formulations, use of nanoparticles of aluminum hydroxide and development of composite adjuvants.

  4. Long term effectiveness of adjuvanted influenza A(H1N1)pdm09 vaccine in children.

    Science.gov (United States)

    Örtqvist, Åke; Bennet, Rutger; Hamrin, Johan; Rinder, Malin Ryd; Lindblad, Hans; Öhd, Joanna Nederby; Eriksson, Margareta

    2015-05-21

    Immunological studies have indicated that the effectiveness of AS03 adjuvanted monovalent influenza A(H1N1)pdm09 vaccine (Pandemrix) may be of longer duration than what is seen for non-adjuvanted seasonal influenza vaccines. Sixty-nine percent of children 6 months-18 years of age in Stockholm County received at least one dose of Pandemrix during the 2009 pandemic. We studied the effectiveness of the vaccine during the influenza seasons 2010-2011 and 2012-2013 in children hospitalized with virologically confirmed influenza. The season 2011-2012 was not included, since influenza A(H3N2) was the predominant circulating strain. In a retrospective case-control study using a modified test-negative design we compared the percentage vaccinated with Pandemrix among children diagnosed with influenza A(H1N1)pdm09 (cases), with that of those diagnosed with influenza A(H3N2) or influenza B (controls) during the two seasons. We excluded children born after July 1, 2009, since only children who were 6 months of age or older received the pandemic vaccine in October-December 2009. During the 2010-2011 season, 3/16 (19%) of children diagnosed with influenza A(H1N1)pdm09, vs. 32/41 (78%) of those with influenza A(H3N2) or influenza B had been vaccinated with Pandemrix in 2009. The odds ratio, after adjustment for sex, age and underlying diseases, for becoming a case when vaccinated with Pandemrix was 0.083 (95%CI 0.014, 0.36), corresponding to a VE of 91.7%. During the season 2012-2013, there was no difference between the two groups; 59% of children diagnosed with influenza A(H3N2)/B and 60% of those with influenza A(H1N1)pdm09 had been vaccinated with Pandemrix in 2009. The AS03 adjuvanted monovalent influenza A(H1N1) pdm09 vaccine (Pandemrix) was effective in preventing hospital admission for influenza A(H1N1)pdm09 in children during at least two seasons. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

    Science.gov (United States)

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

    2012-01-01

    Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

  6. Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.

    Science.gov (United States)

    Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis

    2011-05-15

    In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL). Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Comparative study of the effects of aluminum adjuvants and Freund's incomplete adjuvant on the immune response to an Edwardsiella tarda major antigen.

    Science.gov (United States)

    Jiao, Xu-dong; Cheng, Shuang; Hu, Yong-hua; Sun, Li

    2010-02-17

    Edwardsiella tarda is a severe aquaculture pathogen that can infect many different fish species cultured worldwide. Et49 is a major E. tarda antigen with weak immunoprotective potential. In this study, using Et49 as an example vaccine, the adjuvanticity of Freund's incomplete adjuvant (FIA), aluminum hydroxide, and aluminum phosphate adjuvant were evaluated in a Japanese flounder model. The results showed that the presence of FIA, aluminum hydroxide, and aluminum phosphate adjuvant increased the relative percent of survival of Et49-vaccinated fish by 47%, 19%, and 35%, respectively. Fish vaccinated with FIA-adjuvanted Et49 exhibited longer persistence of vaccine at the injection site and more severe intra-abdominal lesions than fish vaccinated with aluminum-adjuvanted Et49. Both aluminum adjuvants and, to a lesser degree, FIA augmented the production of specific serum antibodies, which reached the highest levels at 6 and 7 weeks post-vaccination. Passive immunization of Japanese flounder with sera from fish vaccinated with aluminum- and FIA-adjuvanted Et49 induced no protection against lethal E. tarda challenge. Examination of the transcription profile of immune-related genes showed that vaccination with aluminum-adjuvanted Et49 significantly enhanced the expression of the genes that are associated mainly with humoral immunity, whereas vaccination with FIA-adjuvanted Et49 induced the expression of a much broader spectrum of genes that are likely to be involved in humoral and innate cellular immunity. These results provide new insights to the action mechanisms of FIA and aluminum adjuvants in Japanese flounder and may be useful for the selection of adjuvant for vaccine formulations intended for Japanese flounder. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  8. PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection.

    Science.gov (United States)

    Cayatte, Corinne; Marin, Alexander; Rajani, Gaurav Manohar; Schneider-Ohrum, Kirsten; Snell Bennett, Angie; Marshall, Jason D; Andrianov, Alexander K

    2017-07-03

    PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), which is an attractive vaccine candidate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV comparable to alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and in the upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF-alum formulations, suggesting an inherent immunostimulating activity of the polyphosphazene adjuvant. We defined these immunologically active RSV sF-PCPP formulations as self-assembled water-soluble protein-polymer complexes with distinct physicochemical parameters. The secondary structure and antigenicity of the protein in the complex were fully preserved during the spontaneous aqueous self-assembly process. These findings further advance the concept of polyphosphazene immunoadjuvants as unique dual-functionality adjuvants integrating delivery and immunostimulating modalities in one water-soluble molecule.

  9. Recognition of higher order patterns in proteins: immunologic kernels.

    Directory of Open Access Journals (Sweden)

    Robert D Bremel

    Full Text Available By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximately thirty amino acids each bounded by cathepsin cleavage sites and each comprising B-cell linear epitopes, MHC-I and MHC-II binding peptides. Such "immunologic kernel" peptides comprise all signals necessary for adaptive immunologic cognition, response and recall. The patterns described indicate a higher order spatial integration that forms a symbolic logic coordinating the adaptive immune system.

  10. IMMUNOLOGICAL AND PSYCHOPHYSIOLOGICAL HETEROGENEITY AMONG PATIENTS WITH BRONCHIAL ASTHMA

    Directory of Open Access Journals (Sweden)

    A. V. Smyk

    2008-01-01

    Full Text Available Abstract. Bronchial asthma is a classic psychosomatic disease by immunopathological origin. In present investigation, we studied influence of body-oriented psychotherapeutic methods directed towards clinico-immunological parameters and special psychological features of the patients with bronchial asthma, i.e., decrease in alexithymia, as an important pathogenetic factor of bronchial asthma, and improvement in motor coordination and interhemispheric interactions in motor sphere. We investigated 38 patients (18 men and 20 women, while discriminating those patients who underwent a course of body-oriented psychotherapy, and a group of comparison, who did not undergo similar therapy. When observing conventional standards of randomization according to sex, age, clinical variants, and disease severity, some heterogeneity of these groups was revealed. In general, the people with active life attitude, being ready to work with a psychologist, possessed special features both in psychological and immunological spheres.

  11. [Demodex folliculorum and rosacea: experimental and immunological studies].

    Science.gov (United States)

    Grosshans, E; Dungler, T; Kien, T T; Kremer, M

    1980-09-15

    When the immunological mechanism of the demodectic mange is well-known in dogs, few things are known about the role of Demodex mites in the pathogenesis of rosacea: the purpose of this study is the research of immunological reactions against Demodex antigens in 31 patients (24 papulopustular rosaceas and 7 granulomatous demodectic rosaceas histologically ascertained). Cultures or survival in vitro of human Demodex mites could not be obtained; therefore demodectic cysts of diseased goats (Demodex caprae) were gathered and soluble antigens were extracted by lyophilization. By different immunoserological methods, Demodex specific antibodies could be demonstrated in sera of rosacea (22%), of diseased goats and of rabbits sensitized with small amounts of demodectic antigen. Frequently cross-reactions were observed.

  12. The immunology of tuberculosis: From bench to bedside

    Science.gov (United States)

    DHEDA, Keertan; SCHWANDER, Stephan K.; ZHU, Bingdong; van ZYL-SMIT, Richard N.; ZHANG, Ying

    2017-01-01

    Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug-resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV. PMID:20415982

  13. Immunological and genetic aspects of asthma and allergy

    Directory of Open Access Journals (Sweden)

    Anne-Marie Madore

    2010-08-01

    Full Text Available Anne-Marie Madore, Catherine LapriseUniversité du Québec à Chicoutimi, Département des sciences fondamentales, Saguenay, CanadaAbstract: Prevalence of allergy and allergic asthma are increasing worldwide. More than half of the US population has a positive skin prick test and approximately 10% are asthmatics. Many studies have been conducted to define immunological pathways underlying allergy and asthma development and to identify the main genetic determinants. In the effort to find missing pieces of the puzzle, new genomic approaches and more standardized ones, such as the candidate gene approach, have been used collectively. This article proposes an overview of the actual knowledge about immunological and genetic aspects of allergy and asthma. Special attention has been drawn to the challenges linked to genetic research in complex traits such as asthma and to the contribution of new genomic approaches.Keywords: immune response, allergy, asthma, genetics, genomics

  14. Advances in mechanisms of asthma, allergy, and immunology in 2010.

    Science.gov (United States)

    Broide, David H; Finkelman, Fred; Bochner, Bruce S; Rothenberg, Marc E

    2011-03-01

    2010 was marked by rapid progress in our understanding of the cellular and molecular mechanisms involved in the pathogenesis of allergic inflammation and asthma. Studies published in the Journal of Allergy and Clinical Immunology described advances in our knowledge of cells associated with allergic inflammation (mast cells, eosinophils, dendritic cells, and T cells), as well as IgE, cytokines, receptors, signaling molecules, and pathways. Studies used animal models, as well as human cells and tissues, to advance our understanding of mechanisms of asthma, eosinophilic esophagitis, food allergy, anaphylaxis and immediate hypersensitivity, mast cells and their disorders, atopic dermatitis, nasal polyposis, and hypereosinophilic syndromes. Additional studies provided novel information about the induction and regulation of allergic inflammation and the genetic contribution to allergic inflammation. Critical features of these studies and their potential effects on human atopic disorders are summarized here. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Advances in mechanisms of asthma, allergy, and immunology in 2011.

    Science.gov (United States)

    Boyce, Joshua A; Bochner, Bruce; Finkelman, Fred D; Rothenberg, Marc E

    2012-02-01

    2011 was marked by rapid progress in the identification of basic mechanisms of allergic disease and the translation of these mechanisms into human cell systems. Studies published in the Journal of Allergy and Clinical Immunology this year provided new insights into the molecular determinants of allergenicity, as well as the environmental, cellular, and genetic factors involved in sensitization to allergens. Several articles focused on mechanisms of allergen immunotherapy and the development of novel strategies to achieve tolerance to allergens. Additional studies identified substantial contributions from T(H)17-type cells and cytokines to human disease pathogenesis. Finally, new therapeutic applications of anti-IgE were identified. The highlights of these studies and their potential clinical implications are summarized in this review. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  16. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland.

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    Hanna Nohynek

    Full Text Available BACKGROUND: Narcolepsy is a chronic sleep disorder with strong genetic predisposition causing excessive daytime sleepiness and cataplexy. A sudden increase in childhood narcolepsy was observed in Finland soon after pandemic influenza epidemic and vaccination with ASO3-adjuvanted Pandemrix. No increase was observed in other age groups. METHODS: Retrospective cohort study. From January 1, 2009 to December 31, 2010 we retrospectively followed the cohort of all children living in Finland and born from January 1991 through December 2005. Vaccination data of the whole population was obtained from primary health care databases. All new cases with assigned ICD-10 code of narcolepsy were identified and the medical records reviewed by two experts to classify the diagnosis of narcolepsy according to the Brighton collaboration criteria. Onset of narcolepsy was defined as the first documented contact to health care because of excessive daytime sleepiness. The primary follow-up period was restricted to August 15, 2010, the day before media attention on post-vaccination narcolepsy started. FINDINGS: Vaccination coverage in the cohort was 75%. Of the 67 confirmed cases of narcolepsy, 46 vaccinated and 7 unvaccinated were included in the primary analysis. The incidence of narcolepsy was 9.0 in the vaccinated as compared to 0.7/100,000 person years in the unvaccinated individuals, the rate ratio being 12.7 (95% confidence interval 6.1-30.8. The vaccine-attributable risk of developing narcolepsy was 1:16,000 vaccinated 4 to 19-year-olds (95% confidence interval 1:13,000-1:21,000. CONCLUSIONS: Pandemrix vaccine contributed to the onset of narcolepsy among those 4 to 19 years old during the pandemic influenza in 2009-2010 in Finland. Further studies are needed to determine whether this observation exists in other populations and to elucidate potential underlying immunological mechanism. The role of the adjuvant in particular warrants further research before drawing

  17. Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.

    Science.gov (United States)

    Dwivedi, Varun; Manickam, Cordelia; Dhakal, Santosh; Binjawadagi, Basavaraj; Ouyang, Kang; Hiremath, Jagadish; Khatri, Mahesh; Hague, Jacquelyn Gervay; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-04-15

    Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Immunological Considerations in In Utero Hematopoetic Stem Cell Transplantation (IUHCT

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    Andrea Ivonne Loewendorf

    2015-01-01

    Full Text Available In utero hematopoetic Stem cell transplantation (IUHCT is an attractive approach and a potentially curative surgery for several congenical hematopoetic diseases. In practice, this application has succeeded only in the context of Severe Combined Immunodeficiency Disorders. Here, we review potential immunological hurdles for the long-term establishment of chimerism and discuss relevant models and findings from both postnatal hematopoetic stem cell transplantation and IUHCT.

  19. Applications of High Throughput Sequencing for Immunology and Clinical Diagnostics

    OpenAIRE

    Kim, Hyunsung John

    2014-01-01

    High throughput sequencing methods have fundamentally shifted the manner in which biological experiments are performed. In this dissertation, conventional and novel high throughput sequencing and bioinformatics methods are applied to immunology and diagnostics. In order to study rare subsets of cells, an RNA sequencing method was first optimized for use with minimal levels of RNA and cellular input. The optimized RNA sequencing method was then applied to study the transcriptional differences ...

  20. STUDIES ON IMMUNOLOGICAL DIAGNOSIS AND THERAPY OF PARAGONIMIASIS

    Science.gov (United States)

    Immunological diagnosis as a screening method for paragonimiasis was made; 115,866 individuals were examined intradermal test with V.B.S. Antigen in... paragonimiasis . Positive skin reactors were included of present and past infections, and were not always shown the present status of lung fluke infections...Chemotherapy of paragonimiasis with Bithionol, in which studies on the minimum effective dose of Bithionol and changes of abnormal shadows in chest X

  1. Immunological mechanisms in atopic dermatitis : clinical and experimental studies

    OpenAIRE

    Tengvall Linder, Maria

    1998-01-01

    The aim of the study was to investigate immunological mechanisms in atopic dermatitis. Serum IgE levels are elevated in 80% of atopic dermatitis patients and CD4+ T cells and environmental allergens are known to be of importance in the pathogenesis of the disease. It was therefore of interest to further elucidate the role of these factors in atopic dermatitis. Cyclosporin A (CSA) was used as a tool for exploring the pathogenesis of atopic dermatitis, with emphasis on the...

  2. [Infectious mononucleosis: etiology, immunological variants, methods of correction].

    Science.gov (United States)

    Gordeets, A V; Savina, O G; Beniova, S N; Chernikova, A A

    2011-01-01

    Clinical options of infectious mononucleosis course depending on infecting agent etiology are presented for Epstein-Barr virus (EBV), cytomegalovirus (CMV), mono and mixed forms of the disease. Examined cytokine profiles demonstrate analogous changes of serum cytokines in the acute stage of the disease irrespective of etiological factors. Data show that it is important and useful clinically and immunologically to include immunomodulators--in particular, cycloferon--info a complex therapy of different types of mononucleosis.

  3. Immunoepidemiology--bridging the gap between immunology and epidemiology.

    Science.gov (United States)

    Hellriegel, B

    2001-02-01

    'Immunoepidemiology' combines individual- and population-oriented approaches to create new perspectives. It examines how inter-individual differences in immune responses affect the population dynamics of micro- and macro-parasites to produce the epidemiological patterns of infection observed in heterogeneous host populations. Here, I discuss how research has only just begun to tap the potential of this integrative discipline that incorporates immunology, parasitology, genetics, epidemiology, ecology, mathematical modelling and statistics.

  4. Immunological Blood Parameters in Infected and Noninfected Biliary Peritonitis

    OpenAIRE

    Bilookiy, O. V.; Rohovyy, Yu. Ye.; Bilookiy, V. V.

    2015-01-01

    This work deals with the study of immunological blood parameters in infected and noninfected biliary peritonitis. Materials and methods. 55 patients with infected and noninfected biliary peritonitis were examined. There were 21 men and 34 women at the age of 28-74 years. 14 patients suffered from noninfected biliary peritonitis, 41 patients suffered from infected biliary peritonitis. The control group included 12 practically healthy persons. Results. The development of noninfected biliary per...

  5. Effect of endosulfan on immunological competence of layer birds

    Directory of Open Access Journals (Sweden)

    P. P. Singh

    2016-07-01

    Full Text Available Aim: The present study was aimed to investigate the immunological competence of endosulfan insecticide after limited oral administration in White Leghorn layer chickens. Materials and Methods: A total of 20 White Leghorn birds were given endosulfan in drinking water at 30 ppm/bird/day (no observable effect level dose for a period of 3-months. Immune competence status of layer birds and chicks hatched from endosulfan offered birds were estimated at 15-day interval in layer birds and at monthly interval in chicks using immunological, biochemical parameters, and teratological estimates. Results: There was a significant decrease in levels of total leukocytes count, absolute lymphocyte count, absolute heterophil count, total serum protein, serum albumin, serum globulin, and serum gamma globulin in the birds fed with endosulfan as compared to control. Similarly, immune competence tests such as lymphocyte stimulation test, oxidative burst assay, and enzyme-linked immunosorbent assay tests indicated lower immunity in birds treated with endosulfan as compared to control. Subsequently, chicks produced from endosulfan-treated birds were also examined for immune competence, but no significant difference was observed between chicks of both the groups. Conclusion: The exposure to endosulfan in limited oral dosage was able to exhibit hemo-biochemical and other changes that could be correlated with changes in the immunological profile of layer chickens suggesting cautious usage of endosulfan insecticide in poultry sheds.

  6. Advances in basic and clinical immunology in 2016.

    Science.gov (United States)

    Chinen, Javier; Badran, Yousef R; Geha, Raif S; Chou, Janet S; Fried, Ari J

    2017-10-01

    Advances in basic immunology in 2016 included studies that further characterized the role of different proteins in the differentiation of effector T and B cells, including cytokines and proteins involved in the actin cytoskeleton. Regulation of granule formation and secretion in cytotoxic cells was also further described by examining patients with familial hemophagocytic lymphohistiocytosis. The role of prenylation in patients with mevalonate kinase deficiency leading to inflammation has been established. We reviewed advances in clinical immunology, as well as new approaches of whole-genome sequencing and genes newly reported to be associated with immunodeficiency, such as linker of activation of T cells (LAT); B-cell CLL/lymphoma 11B (BCL11B); RGD, leucine-rich repeat, tropomodulin domain, and proline-rich domain-containing protein (RLTPR); moesin; and Janus kinase 1 (JAK1). Trials of hematopoietic stem cell transplantation and gene therapy for primary immunodeficiency have had relative success; the use of autologous virus-specific cytotoxic T cells has proved effective as well. New medications are being explored, such as pioglitazone, which is under study for its role in enhancing the oxidative burst in patients with chronic granulomatous disease. Development of vaccines for HIV infection continues to provide insight into the immune response against a virus with an extraordinary mutation rate. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  7. Recommended Immunological Assays to Screen for Ricin-Containing Samples

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    Stéphanie Simon

    2015-11-01

    Full Text Available Ricin, a toxin from the plant Ricinus communis, is one of the most toxic biological agents known. Due to its availability, toxicity, ease of production and absence of curative treatments, ricin has been classified by the Centers for Disease Control and Prevention (CDC as category B biological weapon and it is scheduled as a List 1 compound in the Chemical Weapons Convention. An international proficiency test (PT was conducted to evaluate detection and quantification capabilities of 17 expert laboratories. In this exercise one goal was to analyse the laboratories’ capacity to detect and differentiate ricin and the less toxic, but highly homologuous protein R. communis agglutinin (RCA120. Six analytical strategies are presented in this paper based on immunological assays (four immunoenzymatic assays and two immunochromatographic tests. Using these immunological methods “dangerous” samples containing ricin and/or RCA120 were successfully identified. Based on different antibodies used the detection and quantification of ricin and RCA120 was successful. The ricin PT highlighted the performance of different immunological approaches that are exemplarily recommended for highly sensitive and precise quantification of ricin.

  8. Understanding immunology via engineering design: the role of mathematical prototyping.

    Science.gov (United States)

    Klinke, David J; Wang, Qing

    2012-01-01

    A major challenge in immunology is how to translate data into knowledge given the inherent complexity and dynamics of human physiology. Both the physiology and engineering communities have rich histories in applying computational approaches to translate data obtained from complex systems into knowledge of system behavior. However, there are some differences in how disciplines approach problems. By referring to mathematical models as mathematical prototypes, we aim to highlight aspects related to the process (i.e., prototyping) rather than the product (i.e., the model). The objective of this paper is to review how two related engineering concepts, specifically prototyping and "fitness for use," can be applied to overcome the pressing challenge in translating data into improved knowledge of basic immunology that can be used to improve therapies for disease. These concepts are illustrated using two immunology-related examples. The prototypes presented focus on the beta cell mass at the onset of type 1 diabetes and the dynamics of dendritic cells in the lung. This paper is intended to illustrate some of the nuances associated with applying mathematical modeling to improve understanding of the dynamics of disease progression in humans.

  9. Antibiotic adjuvants - A strategy to unlock bacterial resistance to antibiotics.

    Science.gov (United States)

    González-Bello, Concepción

    2017-09-15

    Resistance to available antibiotics in pathogenic bacteria is currently a global challenge since the number of strains that are resistant to multiple types of antibiotics has increased dramatically each year and has spread worldwide. To unlock this problem, the use of an 'antibiotic adjuvant' in combination with an antibiotic is now being exploited. This approach enables us to prolong the lifespan of these life-saving drugs. This digests review provides an overview of the main types of antibiotic adjuvants, the basis of their operation and the remaining issues to be tackled in this field. Particular emphasis is placed on those compounds that are already in clinical development, namely β-lactamase inhibitors. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. The occurrence of fractures after adjuvant treatment of breast cancer

    DEFF Research Database (Denmark)

    Kristensen, Bent; Ejlertsen, Bent; Jensen, Maj-Britt

    2017-01-01

    BACKGROUND: Adjuvant treatment in breast cancer patients especially with aromatase inhibitors (AIs) has adverse effects on bone metabolism resulting in an increased occurrence of fractures. In order to demonstrate this occurrence, long-term follow-up studies are necessary. From several national...... menopause and tamoxifen treatment were associated with a lower occurrence and AI treatment, age and CCI were associated with a higher occurrence of fractures. CONCLUSION: Before advising adjuvant therapy with AIs fragile patients with chronic diseases should receive special attention in order to reduce...... of the analysis. These data were matched with data on all types of fractures from the Danish National Patient Register and vital data from the Danish Civil Registration System. RESULTS: After data cleaning 66,502 patients were available for analysis and 16,360 of these had incurred 20,341 fractures with 13...

  11. Tocotrienols are good adjuvants for developing cancer vaccines

    Directory of Open Access Journals (Sweden)

    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.

  12. Preparation and evaluation of functional foods in adjuvant arthritis

    OpenAIRE

    Al-Okbi, S. Y.; Mohamed, D. A.

    2012-01-01

    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 functio...

  13. Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

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    Mridula Krishnan

    2017-08-01

    Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

  14. External validation of Adjuvant! Online breast cancer prognosis tool. Prioritising recommendations for improvement.

    Directory of Open Access Journals (Sweden)

    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.

  15. Adjuvant trastuzumab: a 10-year overview of its benefit.

    Science.gov (United States)

    Lambertini, Matteo; Pondé, Noam F; Solinas, Cinzia; de Azambuja, Evandro

    2017-01-01

    Anti-HER2 targeted therapy is one of the key advances in the treatment of breast cancer that have occurred in the last 20 years. In the adjuvant setting, the use of trastuzumab has led to prolonged and sustained survival benefit with very little toxicity as also confirmed by the 10-year follow-up results from the pivotal trials. Despite the survival improvement, several key issues are not entirely resolved in this field. These issues have led to multiple research efforts in de-escalating or escalating the standard treatment with chemotherapy and 1 year of adjuvant trastuzumab. Areas covered: In this paper, we present an in depth overview on the state of the art on these key issues of refining decision-making in adjuvant anti-HER2 therapy. Expert commentary: Despite many important research efforts in the field, chemotherapy plus trastuzumab for a total duration of 1 year remains the standard of care. However, recent data showed that besides standard anthracycline- and taxane-based cytotoxic therapy, alternative chemotherapy regimens can now be proposed to patients with small tumors without nodal involvement and to women at high-risk of developing cardiotoxicity. Of note, besides HER2 itself, biomarkers predicting patients who may truly benefit from anti-HER2 agents are still lacking.

  16. Adjuvants for Leishmania vaccines: From Models to Clinical Application

    Directory of Open Access Journals (Sweden)

    Vanitha S. Raman

    2012-06-01

    Full Text Available Two million new cases of leishmaniasis occur every year, with the cutaneous leishmaniasis (CL presentation accounting for approximately two-thirds of all cases. Despite the high incidence rates and geographic expansion of the disease, CL remains a neglected tropical disease without effective intervention strategies. Efforts to address this deficit have given rise to the experimental murine model of CL. By virtue of its simplicity and pliability, the CL model has been used to provide substantial information regarding cellular immunity, as well as in the discovery and evaluation of various vaccine adjuvants. The CL model has facilitated in vivo studies of the mechanism of action of many adjuvants, including the TLR4 agonist MPL, the TLR7/8 agonist Imiquimod, the TLR9 agonist CpG, adenoviral vectors and the immunostimulatory complexes (ISCOM. Together, these studies have helped to unveil the requirement for certain types of immune responses at specific stages of CL disease and provide a basis to aid the design of effective second-generation vaccines for human CL. This review focuses on adjuvants that have been tested in experimental CL, outlining how they have helped advance our understanding of the disease and ultimately, how they have performed when applied within clinical trials against human CL.

  17. Montanide ISA™ 201 adjuvanted FMD vaccine induces improved immune responses and protection in cattle.

    Science.gov (United States)

    Dar, Pervaiz; Kalaivanan, Ramya; Sied, Nuru; Mamo, Bedaso; Kishore, Subodh; Suryanarayana, V V S; Kondabattula, Ganesh

    2013-07-18

    Despite significant advancements in modern vaccinology, inactivated whole virus vaccines for foot-and-mouth disease (FMD) remain the mainstay for prophylactic and emergency uses. Many efforts are currently devoted to improve the immune responses and protective efficacy of these vaccines. Adjuvants, which are often used to potentiate immune responses, provide an excellent mean to improve the efficacy of FMD vaccines. This study aimed to evaluate three oil adjuvants namely: Montanide ISA-201, ISA-206 (SEPPIC, France) and GAHOL (an in-house developed oil-adjuvant) for adjuvant potential in inactivated FMD vaccine. Groups of cattle (n=6) were immunized once intramuscularly with monovalent FMDV 'O' vaccine formulated in these adjuvants, and humoral (serum neutralizing antibody, IgG1 and IgG2) and cellular (lymphoproliferation) responses were measured. Montanide ISA-201 adjuvanted vaccine induced earlier and higher neutralizing antibody responses as compared to the two other adjuvants. All the adjuvants induced mainly serum IgG1 isotype antibody responses against FMDV. However, Montanide ISA-201 induced relatively higher IgG2 responses than the other two adjuvants. Lymphoproliferative responses to recall FMDV antigen were relatively higher with Montanide ISA-201, although not always statistically significant. On homologous FMDV challenge at 30 days post-vaccination, 100% (6/6) of the cattle immunized with Montanide-201 adjuvanted vaccine were protected, which was superior to those immunized with ISA-206 (66.6%, 4/6) or GAHOL adjuvanted vaccine (50%, 3/6). Virus replication following challenge infection, as determined by presence of the viral genome in oropharynx and non-structural protein serology, was lowest with Montanide ISA-201 adjuvant. Collectively, these results indicate that the Montanide ISA-201 adjuvanted FMD vaccine induces enhanced immune responses and protective efficacy in cattle. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. The Effect of Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in Healing after Nipple-Sparing Mastectomy.

    Science.gov (United States)

    Frey, Jordan D; Choi, Mihye; Karp, Nolan S

    2017-01-01

    Nipple-sparing mastectomy is the latest advancement in the treatment of breast cancer. The authors aimed to investigate the effects of neoadjuvant and adjuvant chemotherapy in nipple-sparing mastectomy. Patients undergoing nipple-sparing mastectomy from 2006 to June of 2015 were identified. Results were stratified by presence of neoadjuvant or adjuvant chemotherapy. A total of 840 nipple-sparing mastectomies were performed. Twenty-eight were in those who received neoadjuvant chemotherapy and 93 were in patients receiving adjuvant chemotherapy. Patients receiving both neoadjuvant and adjuvant chemotherapy were included in the neoadjuvant group. Nipple-sparing mastectomies that received neoadjuvant (with or without adjuvant) chemotherapy were compared to those in patients who received adjuvant chemotherapy. Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have explantation (p = 0.0239) and complete nipple-areola complex necrosis (p = 0.0021). Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have implant explantation (p = 0.0015) and complete nipple-areola complex necrosis (p = 0.0004) compared to those with no chemotherapy. Compared to nipple-sparing mastectomies in patients with no chemotherapy, those with adjuvant chemotherapy were more likely to have a hematoma (p = 0.0021). Those that received both neoadjuvant and adjuvant chemotherapy were more likely to have complete nipple-areola complex necrosis compared with both the neoadjuvant chemotherapy-only and adjuvant chemotherapy-only groups (p < 0.0001). Nipple-sparing mastectomy is safe to perform in the setting of neoadjuvant and adjuvant chemotherapy. As a whole, neoadjuvant (with or without adjuvant) chemotherapy increases risk of complications. Therapeutic, III.

  19. Obesity Outweighs Protection Conferred by Adjuvanted Influenza Vaccination.

    Science.gov (United States)

    Karlsson, Erik A; Hertz, Tomer; Johnson, Cydney; Mehle, Andrew; Krammer, Florian; Schultz-Cherry, Stacey

    2016-08-02

    Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health. Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the

  20. Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations.

    Science.gov (United States)

    Tomljenovic, L; Shaw, C A

    2012-02-01

    Immune challenges during early development, including those vaccine-induced, can lead to permanent detrimental alterations of the brain and immune function. Experimental evidence also shows that simultaneous administration of as little as two to three immune adjuvants can overcome genetic resistance to autoimmunity. In some developed countries, by the time children are 4 to 6 years old, they will have received a total of 126 antigenic compounds along with high amounts of aluminum (Al) adjuvants through routine vaccinations. According to the US Food and Drug Administration, safety assessments for vaccines have often not included appropriate toxicity studies because vaccines have not been viewed as inherently toxic. Taken together, these observations raise plausible concerns about the overall safety of current childhood vaccination programs. When assessing adjuvant toxicity in children, several key points ought to be considered: (i) infants and children should not be viewed as "small adults" with regard to toxicological risk as their unique physiology makes them much more vulnerable to toxic insults; (ii) in adult humans Al vaccine adjuvants have been linked to a variety of serious autoimmune and inflammatory conditions (i.e., "ASIA"), yet children are regularly exposed to much higher amounts of Al from vaccines than adults; (iii) it is often assumed that peripheral immune responses do not affect brain function. However, it is now clearly established that there is a bidirectional neuro-immune cross-talk that plays crucial roles in immunoregulation as well as brain function. In turn, perturbations of the neuro-immune axis have been demonstrated in many autoimmune diseases encompassed in "ASIA" and are thought to be driven by a hyperactive immune response; and (iv) the same components of the neuro-immune axis that play key roles in brain development and immune function are heavily targeted by Al adjuvants. In summary, research evidence shows that increasing concerns

  1. Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

    Directory of Open Access Journals (Sweden)

    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.

  2. Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity

    Science.gov (United States)

    Cooper, P. D.; Barclay, T. G.; Ginic-Markovic, M.; Petrovsky, N.

    2014-01-01

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of 60Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25 kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants. PMID:24342245

  3. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    OpenAIRE

    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...

  4. Comparison of immunogenicity of Aluminum salts as adjuvant for recombinant Hepatitis-B vaccine

    OpenAIRE

    Fazeli MR; Abbaspour M; Ghahremani MH; Alimian M; Ilka H; Jamalifar H; Azadi S; Azizi E

    2007-01-01

    Background: Aluminum salts are common adjuvants in human and animal vaccine preparations. The two adjuvants aluminum phosphate and aluminum hydroxide show acceptable immunoadjuvant properties with many antigens. These two salts have different physicochemical characteristics that make each one suitable for certain antigens. The surface antigen of Hepatitis B (HBsAg) has several antigenic epitopes that bind to aluminum adjuvants by a ligand exchange mechanism. Although HBV vaccines using an alu...

  5. Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions

    OpenAIRE

    Watkinson, Allan; Soliakov, Andrei; Ganesan, Ashok; Hirst, Karie; LeButt, Chris; Fleetwood, Kelly; Fusco, Peter C.; Fuerst, Thomas R.; Lakey, Jeremy H.

    2013-01-01

    Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as ...

  6. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations.

    Science.gov (United States)

    Pérez, O; Batista-Duharte, A; González, E; Zayas, C; Balboa, J; Cuello, M; Cabrera, O; Lastre, M; Schijns, V E J C

    2012-08-01

    Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized.

  7. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    . 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......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...

  8. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

    Science.gov (United States)

    Pérez, O.; Batista-Duharte, A.; González, E.; Zayas, C.; Balboa, J.; Cuello, M.; Cabrera, O.; Lastre, M.; Schijns, V.E.J.C.

    2012-01-01

    Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized. PMID:22527130

  9. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

    Directory of Open Access Journals (Sweden)

    O. Pérez

    2012-08-01

    Full Text Available Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS. Ideally, new strategies should combine immune potentiators (IP and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized.

  10. Immunological and biological properties of recombinant Lol p 1.

    Science.gov (United States)

    Boutin, Y; Lamontagne, P; Boulanger, J; Brunet, C; Hébert, J

    1997-03-01

    Current forms of allergy diagnosis and therapies are based on the use of natural allergenic extracts. Despite strong evidence that higher therapeutic efficacy may be achieved with purified allergens, the purification of multiple allergic components from extracts is a fastidious and sometimes an impossible task. However, the use of recombinant allergens may be an alternative to overcome this problem. In this study, we compared the immunological properties of recombinant (r) Lol p 1 with those of the natural protein. We cloned directly the gene encoding Lol p 1 from genomic DNA of ryegrass pollen. This gene was subcloned into the expression vector pMAL-c and expressed as fusion protein. Subsequently, rLol p 1 was cleaved from maltose-binding protein using factor Xa. Using binding inhibition and proliferative assays, we assessed the immunological properties of the recombinant allergens. The capacity of rLol p 1 to trigger basophil histamine release and to elicit a skin reaction was also assessed and compared to those of its natural counterpart. We found that the Lol p 1 gene has no introns since we amplified this gene directly from genomic DNA. We demonstrated that the binding sites of anti-Lol p 1 monoclonal antibody, specific human IgG and IgE antibody are well conserved on rLol p 1 as no difference in the binding inhibition profile was observed when using either natural or recombinant protein. At the T-cell level, rLol p 1 elicited a T-cell response in mice comparable to that observed with the natural protein. In addition, we demonstrated that the biological characteristics of rLol p 1 were comparable to those of the natural counterpart, in that rLol p 1 elicited a skin wheal reaction and induced basophil histamine release in grass-allergic patients only. The data indicate that natural Lol p 1 and rLol p 1 shared identical immunological and biological properties.

  11. Advances in basic and clinical immunology in 2011.

    Science.gov (United States)

    Chinen, Javier; Shearer, William T

    2012-02-01

    Investigations of basic immunologic mechanisms and clinical studies of primary immunodeficiencies were most prevalent in 2011. Significant progress was achieved in the characterization of T(H)17 cell differentiation and associated cytokines in the setting of inflammatory disorders, HIV infection, and immunodysregulation disorders. The role of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) mutations in the pathogenesis of CVID was further described and reported to be likely mediated by impaired TACI expression affecting B-cell function. The frequency of autoimmunity in patients with partial DiGeorge syndrome was estimated at 8.5%, predominantly resulting in blood cytopenias and hypothyroidism. Several reports emphasized the presentation of neoplasias, most often lymphomas, as the first manifestation of several primary immunodeficiencies. Novel strategies for newborn screening of B-cell lymphopenia by measuring immunoglobulin κ chain-deletion recombinant excision circles and for adenosine deaminase deficiency using tandem mass spectrometry were demonstrated to be feasible at a large scale. Progress in the treatment of primary immunodeficiencies included increased success with unrelated HLA-compatible donors for hematopoietic stem cell transplantation and the development of new gene therapy approaches with improved safety features. Induced pluripotent stem cells were developed from patients with primary immunodeficiencies, providing a virtually unlimited resource for pathophysiology and gene correction studies. New findings in several of the uncommon immunodeficiencies, such as the increased susceptibility to severe viral infections caused by defects in the activation of the Toll-like receptor 3 pathway, overall contributed to the understanding of their immunologic basis and provided for the design of effective diagnostic and therapeutic strategies. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published

  12. Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy

    Directory of Open Access Journals (Sweden)

    Santiago Bernal-Macías

    2015-01-01

    Full Text Available Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL. Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl.

  13. Visceral leishmaniasis: immunology and prospects for a vaccine.

    Science.gov (United States)

    Kaye, P M; Aebischer, T

    2011-10-01

    Human visceral leishmaniasis (HVL) is the most severe clinical form of a spectrum of neglected tropical diseases caused by protozoan parasites of the genus Leishmania. Caused mainly by L. donovani and L. infantum/chagasi, HVL accounts for more than 50 000 deaths every year. Drug therapy is available but costly, and resistance against several drug classes has evolved. Here, we review our current understanding of the immunology of HVL and approaches to and the status of vaccine development against this disease. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

  14. Amiodarone-induced severe hepatitis mediated by immunological mechanisms.

    Science.gov (United States)

    Breuer, H W; Bossek, W; Haferland, C; Schmidt, M; Neumann, H; Gruszka, J

    1998-06-01

    A 64-year-old man developed a fulminant hepatitis 4 days after initiation of amiodarone treatment and a total dose of 7.1 g. The direct Coombs test was positive and became negative again soon after stopping treatment. Immediately after stopping treatment the extremely increased parameters of hepatic failure returned to normal again. A rechallenge with 200 mg of amiodarone was accompanied by a positive Coombs test which again became negative after several days. We conclude that the occurrence of an acute hepatitis soon after initiation of amiodarone treatment is mediated by immunological mechanisms. There should be high vigilance with respect to this rare life-threatening adverse drug reaction.

  15. Immunology and Homeopathy. 4. Clinical Studies—Part 1

    Directory of Open Access Journals (Sweden)

    Paolo Bellavite

    2006-01-01

    Full Text Available The evidence-based research of the effectiveness of homeopathic medicines in common immunologic disorders is reviewed. In part 1, we introduce methodological issues of clinical research in homeopathy, and criteria utilized to evaluate the literature. Then 24 studies (12 randomized and 12 non-randomized on common upper respiratory tract infections and otorhinolaryngologic complaints are described. In part 2, the focus will be on allergic diseases and the effectiveness of homeopathy will be globally evaluated and discussed using the criteria of evidence-based medicine.

  16. Serum Leptin Levels in Women with Immunological Recurrent Abortion

    Science.gov (United States)

    Zarei, Saeed; Soltanghoraee, Haleh; Mohammadzadeh, Afsaneh; Arefi, Soheila; Zarnani, Amir Hassan; Idali, Farah; Tavangar, Banafsheh; Savadi Shiraz, Elham; Moshref Behzad, Narges; Jeddi-Tehrani, Mahmood

    2010-01-01

    Introduction Recurrent abortion (RA) may be a consequence of aberrant expression of immunological factors during pregnancy. Although the relative importance of immunological factors in human reproduction remains controversial, substantial evidence suggests that autoantibodies contribute to reproductive failure. Production of such antibodies is under the control of cytokines; and leptin, besides its role in reproductive success, has a profound effect on directing the cytokine profile toward Th1 (cellular) pattern. Therefore, the present study was performed to assess serum leptin levels in women with immunological recurrent abortion. Materials and Methods In this prospective study, 250 women who attended Avicenna Infertility Clinic with RA were screened for known causes of abortion from July to December 2008 in Tehran, Iran. Eighty-one patients with normal karyotypes and hormonal profile with normal ovaries and uterus and no signs of infection were categorized as patients with immunological (IRA, n = 39) or unexplained (URA, n = 42) recurrent abortion based on presence or absence of autoantibodies. After blood sampling, levels of anti-nuclear antibody (ANA), anti-double stranded DNA antibody (anti-dsDNA), lupus anti-coagulant antibody (LACAb), anti-phospholipid antibody (APA), anti-cardiolipin antibody (ACA), anti-thyroglobulin antibody (TgAb), anti-thyroperoxidase antibody (TPOAb) and anti-thrombin III antibody (ATIIIAb) were measured by enzyme-linked immunosorbent assay (ELISA) or chemiluminescent enzyme immunoassay (CLEIA). Results In IRA group, 9 (23.1%), 24 (61.5%), 25(64.1%) and 1 (2.6%) women were above the normal cut-off point for ANA, TgAbs, TPOAbs and AT-III Abs, respectively. IRA patients had normal values of LACAbs, APA and ACA. With normal level of fasting blood sugar (FBS), IRA and URA groups had similar serum leptin levels (23.7 ± 13.2 ng/ml vs. 22.7 ± 12.5 ng/ml, respectively). Serum leptin concentrations showed a positive correlation with weight

  17. Hematology and immunology studies - The second manned Skylab mission

    Science.gov (United States)

    Kimzey, S. L.; Johnson, P. C.; Ritzman, S. E.; Mengel, C. E.

    1976-01-01

    The hematologic and immunologic functions of the Skylab 3 astronauts were monitored during the preflight, inflight, and postflight phases of the mission. Plasma protein profiles showed high consistency in all phases. A transient suppression of lymphocyte responsiveness was observed postflight. A reduction in the circulating blood volume due to drops in both the plasma volume and red cell mass was found. The loss of red cell mass is most likely a suppressed erythrypoiesis. The functional integrity of the circulating red cells did not appear to be compromised in the course of flight.

  18. Immunological disturbance in West and Lennox-Gastaut syndromes

    Directory of Open Access Journals (Sweden)

    Terezinha C. B. Montelli

    1984-06-01

    Full Text Available Cell-mediated and humoral immunity were investigated in 18 patients with West syndrome, 12 with Lennox-Gastaut syndrome and 19 healthy controls. The study included determination of Ô and  peripheral blood lymphocytes, serum levels of IgG, IgA and IgM, skin sensibilization with DNCB, intracutaneous PHA, leucocyte migration inhibition test and lymphocyte blastic transformation in the presence of PHA. Cell-mediated deficiency was detected in 28 children whereas low levels of immunoglobulins were observed only in 6 children. Immunological disturbances were more prominent in children with West syndrome.

  19. Controlling the Immunological Crosstalk during Conception and Pregnancy

    DEFF Research Database (Denmark)

    Lynge Nilsson, Line; Djurisic, Snezana; Hviid, Thomas Vauvert F

    2014-01-01

    of HLA-G expression, have been linked to reproductive failure and pre-eclampsia. Based on recent studies, we speculate that HLA-G might be involved in mechanisms in reproductive immunology even before conception because HLA-G can be detected in the genital tract and in the blood of non-pregnant women......-G in relation to reproduction: from genetics to physiological effects, from pregnancy and pregnancy complications to a short discussion on future possible means of preventative measures and therapy....

  20. Identification of GLA/SE as an effective adjuvant for the induction of robust humoral and cell-mediated immune responses to EBV-gp350 in mice and rabbits.

    Science.gov (United States)

    Heeke, Darren S; Lin, Rui; Rao, Eileen; Woo, Jennifer C; McCarthy, Michael P; Marshall, Jason D

    2016-05-17

    Childhood infection with Epstein-Barr virus (EBV) is often asymptomatic and may result in mild flu-like symptoms, but exposure during adolescence and young adulthood can lead to acute infectious mononucleosis (AIM) with a pathology characterized by swollen lymph nodes, sore throat, and severe fatigue lasting weeks or months. A vaccine targeting the envelope glycoprotein gp350 adjuvanted with aluminum hydroxide complexed with the TLR4 agonist monophosphoryl lipid A (MPLA) achieved a 78% reduction in AIM incidence in a small phase II trial of college-age individuals, but development of this vaccine was halted by the manufacturer. Here, we report the evaluation in mice and rabbits of an EBV-gp350 vaccine combined with an adjuvant composed of the synthetic TLR4 agonist glucopyranosyl lipid A (GLA) integrated into stable emulsion (SE). In mice, GLA/SE-adjuvanted gp350 generated high IgG titers (both IgG1 and IgG2a/c subtypes), elevated EBV-neutralizing antibody titers, and robust poly-functional anti-gp350 CD4(+) T cell responses. In addition, GLA/SE routinely demonstrated superior performance over aluminum hydroxide in all immunological readouts, including induction of durable neutralizing antibody titers out to at least 1 year post-vaccination. Both components of the GLA/SE adjuvant were found to be required to get optimal responses in both arms of the immune response: specifically, SE for neutralizing antibodies and GLA for induction of T cell responses. Furthermore, this vaccine also elicited high neutralizing antibody titers in a second species, rabbit. These promising results suggest that clinical development of a vaccine comprised of EBV-gp350 plus GLA/SE has the potential to prevent AIM in post-adolescents. Copyright © 2016 Elsevier Ltd. All rights reserved.