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Sample records for adjuvants immunologic

  1. House dust extracts contain potent immunological adjuvants

    NARCIS (Netherlands)

    Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

    1987-01-01

    A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably endot

  2. The mode of action of immunological adjuvants.

    Science.gov (United States)

    Allison, A C

    1998-01-01

    Adjuvants augment immune responses to antigens and influence the balance between cell-mediated and humoral responses, as well as the isotypes of antibodies formed. New adjuvant formulations include antigen-carrying vehicles and small molecules with immunomodulating activity. Widely used two-phase vehicles comprise liposomes and microfluidized squalene or squalane emulsions. These are believed to target antigens to antigen-presenting cells, including dendritic cells (DC), follicular dendritic cells (FDC) and B-lymphocytes. Activation of complement generates C3d, which binds CR2 (CD21) on FDC and B-lymphocytes, thereby stimulating the proliferation of the latter and the generation of B-memory. Targeting of antigens to DC may favour cell-mediated immunity. Immunomodulating agents induce the production of cytokine cascades. In a primary cascade at injection sites TNF-alpha, GM-CSF and IL-1 are produced. TNF-alpha promotes migration of DC to lymphoid tissues, while GM-CSF and IL-1 accelerate the maturation of DC into efficient antigen-presenting cells for T-lymphocytes. In a secondary cytokine cascade in draining lymph nodes, DC produce IL-12, which induces Th1 responses with the production of IFN-gamma. The cytokines elicit cell-mediated immune responses and the formation of antibodies of protective isotypes, such as IgG2a in the mouse and IgG1 in humans. Antibodies of these isotypes activate complement and collaborate with antibody-dependent effector cells in protective immune responses.

  3. 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 (psalt, there was also evidence of Th2 cytokine induction. Copyright © 2015 Elsevier B.V. All

  4. [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.

  5. Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens.

    Science.gov (United States)

    Knudsen, Niels Peter H; Olsen, Anja; Buonsanti, Cecilia; Follmann, Frank; Zhang, Yuan; Coler, Rhea N; Fox, Christopher B; Meinke, Andreas; D'Oro, Ugo; Casini, Daniele; Bonci, Alessandra; Billeskov, Rolf; De Gregorio, Ennio; Rappuoli, Rino; Harandi, Ali M; Andersen, Peter; Agger, Else Marie

    2016-01-21

    The majority of vaccine candidates in clinical development are highly purified proteins and peptides relying on adjuvants to enhance and/or direct immune responses. Despite the acknowledged need for novel adjuvants, there are still very few adjuvants in licensed human vaccines. A vast number of adjuvants have been tested pre-clinically using different experimental conditions, rendering it impossible to directly compare their activity. We performed a head-to-head comparison of five different adjuvants Alum, MF59®, GLA-SE, IC31® and CAF01 in mice and combined these with antigens from M. tuberculosis, influenza, and chlamydia to test immune-profiles and efficacy in infection models using standardized protocols. Regardless of antigen, each adjuvant had a unique immunological signature suggesting that the adjuvants have potential for different disease targets. Alum increased antibody titers; MF59® induced strong antibody and IL-5 responses; GLA-SE induced antibodies and Th1; CAF01 showed a mixed Th1/Th17 profile and IC31® induced strong Th1 responses. MF59® and GLA-SE were strong inducers of influenza HI titers while CAF01, GLA-SE and IC31® enhanced protection to TB and chlamydia. Importantly, this is the first extensive attempt to categorize clinical-grade adjuvants based on their immune profiles and protective efficacy to inform a rational development of next generation vaccines for human use.

  6. Aspects of the role of mineral oil as immunological adjuvants in rheumatoid arthritis

    OpenAIRE

    Sverdrup, Berit

    2007-01-01

    Environmental factors are likely contributing factors in the development of Rheumatoid Arthritis (RA), an autoimmune disease, for which etiologic factors are still poorly known. Mineral oils are efficient adjuvants which increase immunological responses and are used in animal immunization and for induction of different experimental autoimmune diseases including arthritis. The relationship between environmental exposure to mineral oil and the risk of developing RA is the ...

  7. Immunological and Antitumor Effects of IL-23 as a Cancer Vaccine Adjuvant1

    OpenAIRE

    Overwijk, Willem W; Karin E de Visser; Tirion, Felicia H.; de Jong, Laurina A.; Pols, Thijs W. H.; van der Velden, Yme U; Boorn, Jasper G. van den; Keller, Anna M.; Buurman, Wim A; Theoret, Marc R.; Blom, Bianca; Restifo, Nicholas P.; Kruisbeek, Ada M.; Kastelein, Robert A.; Haanen, John B. A. G.

    2006-01-01

    The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory cytokine, IL-23, in gp100 peptide vaccine therapy of established murine melanoma. Neither systemic nor local IL-23 alone had any impact on tumor growth or tumor-specific T cell numbers. Upon specific va...

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

    Science.gov (United States)

    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.

  9. Immunologic correlates of protection and potential role for adjuvants to improve influenza vaccines in older adults.

    Science.gov (United States)

    McElhaney, Janet E; Coler, Rhea N; Baldwin, Susan L

    2013-07-01

    The decrease in influenza vaccine efficacy in the elderly is associated with a decline in the stimulation of cell-mediated and cytotoxic T-lymphocyte responses required for clinical protection against influenza, and may be particularly problematic when this population is administered split-virus vaccines that lack conserved viral proteins. Adjuvants, which act through innate immune mechanisms, are known to enhance both humoral and T-cell-mediated responses to influenza vaccines in this population. Adjuvant effects including enhanced antigen presentation, activation and maturation of dendritic cells and production of inflammatory cytokines can drive the desired cell-mediated immune responses. Toll-like receptor ligands comprise one class of adjuvants, which interact with external and internal receptors associated with dendritic cells and other APCs, leading to the regulation and production of important inflammatory cytokines. Potential advances in the production of more effective influenza vaccines for older people include the addition of adjuvants to standard split-virus vaccines and the use of alternate routes of vaccine delivery to augment the response to influenza infection. In this review, the authors discuss the impact of immune senescence on the response to influenza vaccination, the correlates of protection against influenza disease and the progress being made in the design of better influenza vaccines for the population aged 65 years and older.

  10. Mucosally induced immunological tolerance, regulatory T cells and the adjuvant effect by cholera toxin B subunit.

    Science.gov (United States)

    Sun, J-B; Czerkinsky, C; Holmgren, J

    2010-01-01

    Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) ('oral tolerance') is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer the relevant Ag together with, and preferably linked to the non-toxic B subunit protein of cholera toxin (CTB). Oral, nasal or sublingual administration of such Ag/CTB conjugates or gene fusion proteins have been found to induce tolerance with superior efficiency compared with administration of Ag alone, including the suppression of various autoimmune disorders and allergies in animal models. In a proof-of-concept clinical trial in patients with Behcet's disease, this was extended with highly promising results to prevent relapse of autoimmune uveitis. Tolerization by mucosal Ag/CTB administration results in a strong increase in Ag-specific regulatory CD4(+) T cells, apparently via two separate pathways: one using B cells as APCs and leading to a strong expansion of Foxp3(+) Treg cells which can both suppress and mediate apoptotic depletion of effector T cells, and one being B cell-independent and associated with development of Foxp3(-) regulatory T cells that express membrane latency-associated peptide and transforming growth factor (TGF-beta) and/or IL-10. The ability of CTB to dramatically increase mucosal Ag uptake and presentation by different APCs through binding to GM1 ganglioside (which makes most B cells effective APCs irrespective of their Ag specificity), together with CTB-mediated stimulation of TGF-beta and IL-10 production and inhibition of IL-6 formation may explain the dramatic potentiation of oral tolerance by mucosal Ags presented with CTB.

  11. The effects of Fumaderm~ on immunological function and cytokines in a rat model of adjuvant-induced arthritis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Objective To study the therapeutic effect of Fumaderm in Freund's complete adjuvant-induced arthritis(AIA)in Spraque-Dawley rats.Methods Adjuvant-induced arthritis(AIA)was established by intradermal injection of 0.1 mL of Freund's complete adjuvant(CFA)in the palmar surface of the right hindpaw and Fumaderm was delivered by oral gavage for 28 days.After CFA injection,the edema of the hindpaw was determined every two days.On 28 days after CFA injection,the lymphocyte subsets of peripheral blood and the cyt...

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

    Science.gov (United States)

    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. Effect of Zinc gluconate adjuvant therapy on myocardial damage, immunologic function and serum inflammatory factors in children with rotaviral enteritis

    Institute of Scientific and Technical Information of China (English)

    Jun Zhu

    2015-01-01

    Objective:To analyze the effects of Zinc gluconate adjuvant therapy on Rotavirus myocardial injury, immune function and serum inflammatory factors of children with viral enteritis. Methods:A total of 138 Rotavirus viral enteritis children were enrolled as research objects. According to stochastic indicator method, they were divided into control group (n=69 cases) which received clinical routine treatment, and observation group (n=69 cases) which received Zinc gluconate adjuvant therapy, myocardial enzyme spectrum; serum inflammatory cytokines and immune function of the two groups were compared.Results:(1) LDH, CK, CK-MB, cTnⅠ myocardial enzyme indexes of the observation group were significantly lower than that of the control group (P<0.05). (2) serum zinc gluconate auxiliary CD19+CD5+CD1dhi B cells expression level of the observation group were higher than that of the control group, CD11b and CD40-CD40L stimulus molecule expression levels of the observation group were significantly lower than that of the control group (P<0.05). (3) Serum zinc gluconate auxiliary TRF1, TRF2 expression levels of the observation group were significantly higher than that of the control group but IL-12 level was lower than control group (P<0.05).Conclusion:Zinc gluconate adjuvant therapy could help to avoid the heart of the children with rotavirus virus enteritis loss, enhance immune function,reduce level of systemic inflammation.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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 D; 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.

  16. [Influenza vaccine and adjuvant].

    Science.gov (United States)

    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.

  17. Factors that Influence the Immunological Adjuvant Effect of Lactobacillus fermentum PC1 on Specific Immune Responses in Mice to Orally Administered Antigens

    Directory of Open Access Journals (Sweden)

    Meera Esvaran

    2016-07-01

    Full Text Available This study examined the influences of the dosage of the adjuvant, the nature of the antigen and the host genetics on the capacity of L. fermentum PC1 (PC1 to function as an oral adjuvant. BALB/c and DBA/1 mice were vaccinated with either ovalbumin (OVA or Salmonella Typhimurium on days 0 and 14, Mice were also dosed with the PC1 (108 CFU or 1011 CFU per dose per mouse with the antigens (days 0 and 14 and alone (days −1 and 13. The higher PC1 dose elicited a greater specific serum IgG2a response than IgG1 for both antigens and mice strains, indicating a Th1-biased humoral immune response. The Th1 bias was also observed at the cellular level with greater specific IFN-γ levels than IL-4 and IL-10 with both antigen types and mouse strains. With the particulate antigen, the lower dose of PC1 elicited a Th1 bias at the cellular level, but a balanced Th1/Th2 response at the systemic humoral level. With the soluble antigen, a strong Th1-biased response occurred at the cellular level while the systemic humoral response was Th2-biased. In conclusion, PC1 at the higher dose was an excellent Th1 adjuvant, which was unaffected by the nature of the antigen or the host’s genetic background.

  18. Chemokines as Cancer Vaccine Adjuvants

    Directory of Open Access Journals (Sweden)

    Agne Petrosiute

    2013-10-01

    Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

  19. 不同佐剂条件下Aβ多肽B细胞表位疫苗诱导产生抗体的免疫反应特性分析%The Immunological Character of Polypeptide B Cell Epitopes Vaccines of Alzheimer's Disease in Different Adjuvants

    Institute of Scientific and Technical Information of China (English)

    陈鳌; 余云舟; 王文斌; 庞晓斌; 王双; 俞炜源; 孙志伟

    2011-01-01

    generate immune response than Mock group or negative control. Of these,the titer of antibodies produced by the Freund's adjuvant group was highest. The results of dot blotting showed that the sera antibodies could bind to the oligomer of Aβ better than the monomer form. But the antibodies have not binding reaction to the fiber form. Conclusion : All of these adjuvants could enhance the effect of polypeptide vaccine against Alzheimer's disease in mouse model. All of the sera antibodies bind to the oligomer form of Aβ.The immunological character shows that the polypeptide vaccine is potential in clinical trial.

  20. From discovery to licensure, the Adjuvant System story

    Science.gov (United States)

    Garçon, Nathalie; Di Pasquale, Alberta

    2017-01-01

    ABSTRACT Adjuvants are substances added to vaccines to improve their immunogenicity. Used for more than 80 years, aluminum, the first adjuvant in human vaccines, proved insufficient to develop vaccines that could protect against new challenging pathogens such as HIV and malaria. New adjuvants and new combinations of adjuvants (Adjuvant Systems) have opened the door to the delivery of improved and new vaccines against re-emerging and difficult pathogens. Adjuvant Systems concept started through serendipity. The access to new developments in technology, microbiology and immunology have been instrumental for the dicephering of what they do and how they do it. This knowledge opens the door to more rational vaccine design with implications for developing new and better vaccines. PMID:27636098

  1. Computer immunology.

    Science.gov (United States)

    Forrest, Stephanie; Beauchemin, Catherine

    2007-04-01

    This review describes a body of work on computational immune systems that behave analogously to the natural immune system. These artificial immune systems (AIS) simulate the behavior of the natural immune system and in some cases have been used to solve practical engineering problems such as computer security. AIS have several strengths that can complement wet lab immunology. It is easier to conduct simulation experiments and to vary experimental conditions, for example, to rule out hypotheses; it is easier to isolate a single mechanism to test hypotheses about how it functions; agent-based models of the immune system can integrate data from several different experiments into a single in silico experimental system.

  2. 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.

  3. 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".

  4. Unwanted Immunology

    Directory of Open Access Journals (Sweden)

    M.V. Supotnytskyi

    2016-07-01

    Full Text Available The paper considers the role of antigenic imprin­ting phenomena and antibody-dependent enhancement of infection in epidemic, infectious and postvaccinal processes. Based on published experimental data, it is shown that both phenomena are directly related to the laws of development and course of epide­mics, the pathogenesis of infectious diseases and safe use of vaccines. Their ignoring by researchers has led to failures in the design of vaccines against HIV/AIDS, dengue fever, influenza, malaria, hemorrhagic fever and encephalitis. These data show that, without taking into account the two phenomena, the further development of immunology and epidemiology in the direction of breakthrough discoveries in there areas of science are impossible.

  5. Evaluation of immunological responses to recombinant Porin A protein (rPoA) from native strains of Neisseria meningitidis serogroups A and B using OMV as an adjuvant in BALB/c mice.

    Science.gov (United States)

    Afrough, Parviz; Bouzari, Saeid; Mousavi, Seyed Fazlollah; Asadi Karam, Mohammad Reza; Vaziri, Farzam; Fateh, Abolfazl; Behrouzi, Ava; Malekan, Mohammadali; Siadat, Seyed Davar

    2017-09-20

    Neisseria meningitidis is one of the main causes of sepsis and meningitis, which are two serious life-threatening diseases in both children and adolescents. Porin A (porA) from both serogroup A and B were cloned into the pET28a plasmid and expressed in E. coli BL21 (DE3). The protein was expressed in Escherichia coli BL21 (DE3) and confirmed by SDS-PAGE and Western blot analysis. BALB/c mice were subcutaneously injected three times with 25 μg of the recombinant PorA. Specific total IgG antibodies and isotypes were evaluated using ELISA assay. Opsonophagocytic assay (OPA) and Serum Bactericidal assay (SBA) were performed. Results showed that vaccinated mice exhibited higher levels of anti-Porin A (p OMV of strain CSBPI G-245 and complete and incomplete Freund's adjuvant were used. Results demonstrated that Porin A could be a valuable target for the development of immunotherapeutic strategies against N. meningitidis. Copyright © 2017. Published by Elsevier Ltd.

  6. Adjuvants for Animal Vaccines.

    Science.gov (United States)

    Burakova, Yulia; Madera, Rachel; McVey, Scott; Schlup, John R; Shi, Jishu

    2017-06-15

    Vaccines are essential tools for the prevention and control of infectious diseases in animals. One of the most important steps in vaccine development is the selection of a suitable adjuvant. The focus of this review is the adjuvants used in vaccines for animals. We will discuss current commercial adjuvants and experimental formulations with attention to mineral salts, emulsions, bacterial-derived components, saponins, and several other immunoactive compounds. In addition, we will also examine the mechanisms of action for different adjuvants, examples of adjuvant combinations in one vaccine formulation, and challenges in the research and development of veterinary vaccine adjuvants.

  7. Adjuvants for malaria vaccines.

    Science.gov (United States)

    Coler, R N; Carter, D; Friede, M; Reed, S G

    2009-09-01

    There is a renewed enthusiasm about subunit vaccines for malaria coincident with the formation of new alliances and partnerships raising international public awareness, attracting increased resources and the re-focusing of research programs on adjuvant development for infectious disease vaccines. It is generally accepted that subunit vaccines for malaria will require adjuvants to induce protective immune responses, and availability of suitable adjuvants has in the past been a barrier to the development of malaria vaccines. Several novel adjuvants are now in licensed products or in late stage clinical development, while several others are in the earlier development pipeline. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe, and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this minireview, we outline the current state of adjuvant research and development as it pertains to effective malaria vaccines.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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…

  13. Adjuvants for allergy vaccines

    National Research Council Canada - National Science Library

    Moingeon, Philippe

    2012-01-01

    .... Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts...

  14. 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.

  15. 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.

  16. Virtual Immunology: Software for Teaching Basic Immunology

    OpenAIRE

    Berçot', Filipe Faria; Fidalgo Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thaís; Alves,Luiz Anastacio

    2013-01-01

    The authors of this publication are on ResearchGate and have made the full-text available on their profiles. 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 free of charge in Portuguese...

  17. Neisseria lactamica antigens complexed with a novel cationic adjuvant

    OpenAIRE

    Gaspar, Emanuelle B.; Rosetti, Andreza S.; Lincopan, Nilton; De Gaspari, Elizabeth

    2013-01-01

    Colonization of the nasopharynx by non-pathogenic Neisseria species, including N. lactamica, has been suggested to lead to the acquisition of natural immunity against Neisseria meningitidis in young children. The aim of this study was to identify a model complex of antigens and adjuvant for immunological preparation against N. meningitidis B, based on cross reactivity with N. lactamica outer membrane vesicles (OMV) antigens and the (DDA-BF) adjuvant. Complexes of 25 µg of OMV in 0.1 mM of DDA...

  18. Development of a minimal saponin vaccine adjuvant based on QS-21

    Science.gov (United States)

    Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

    2014-07-01

    Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

  19. Vitamins as influenza vaccine adjuvant components.

    Science.gov (United States)

    Quintilio, Wagner; de Freitas, Fábio Alessandro; Rodriguez, Dunia; Kubrusly, Flavia Saldanha; Yourtov, Dimitri; Miyaki, Cosue; de Cerqueira Leite, Luciana Cezar; Raw, Isaias

    2016-10-01

    A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans.

  20. Immunological Effects of Silica and Asbestos

    Institute of Scientific and Technical Information of China (English)

    Takemi Otsuki; Fuminori Hyodoh; Ayako Ueki; Yasumitsu Nishimura; Megumi Maeda; Shuko Murakami; Hiroaki Hayashi; Yoshie Miura; Masayasu Kusaka; Takashi Nakano; Kazuya Fukuoka; Takumi Kishimoto

    2007-01-01

    Silicosis patients (SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis (known as Caplan syndrome), and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occurr in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition,immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cellmediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestosrelated malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.

  1. Modelling Immunological Memory

    CERN Document Server

    Garret, Simon; Walker, Joanne; Wilson, William; Aickelin, Uwe

    2010-01-01

    Accurate immunological models offer the possibility of performing highthroughput experiments in silico that can predict, or at least suggest, in vivo phenomena. In this chapter, we compare various models of immunological memory. We first validate an experimental immunological simulator, developed by the authors, by simulating several theories of immunological memory with known results. We then use the same system to evaluate the predicted effects of a theory of immunological memory. The resulting model has not been explored before in artificial immune systems research, and we compare the simulated in silico output with in vivo measurements. Although the theory appears valid, we suggest that there are a common set of reasons why immunological memory models are a useful support tool; not conclusive in themselves.

  2. Epidemiology of tuberculosis immunology.

    Science.gov (United States)

    Fox, G J; Menzies, D

    2013-01-01

    Immunological impairment plays a major role in the epidemiology of TB. Globally, the most common causes of immunological impairment are malnutrition, diabetes, HIV/AIDS, aging, and smoking. With the notable exception of HIV, each factor leads to relatively mild immunological impairment in individuals. However, as these conditions affect a significant proportion of the population, they contribute substantially to the incidence of TB at a global scale. Understanding immunological impairment is central to understanding the global TB pandemic, and vital to the development of effective disease control strategies.

  3. The immunology of filariasis*

    OpenAIRE

    1981-01-01

    This report summarizes the available information on the immunology of filariasis, and discusses immunodiagnosis and the immunological factors influencing the host—parasite relationship in lymphatic filariasis and onchocerciasis. Several areas that require further research are identified, particularly concerning the development of new serological techniques, and the fractionation of specific antigens. The problems associated with vaccine development are considered and the importance of finding...

  4. Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

    Science.gov (United States)

    2015-09-01

    Mesothelioma after Completion of Multimodality Therapy PRINCIPAL INVESTIGATOR: Dr. Marjorie Zauderer CONTRACTING ORGANIZATION: Sloan-Kettering Cancer ...peptides that are given together with Montanide and GM-CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and...GM- CSF as immunologic adjuvants. This WT1 vaccine was previously tested in a small pilot trial, and shown to be safe and immunogenic. We have

  5. Differential Responses to Adjuvants of Macrophages from Young Virgin, Aging Virgin and Aging Breeder Mice.

    Science.gov (United States)

    1985-12-01

    Rb-Ai.62 483 DIFFERENTIAL RESPONSES TO ADJUVANTS OF MACROPHAGES FROM i/i YOUNG VIRGIN AGIN (U) MINNESOTA UNIV DULUTH DEPT OF MEDICAL MICROBIOLOGY RN...ADDRESS (City, State. an ZI 0EC 18 198E- Dept. of Medical Microbiology & Immunology 800 N. Quincy Street E1 8 Duluth, MN 55812-2487 Arlington, VA 22217-5...Aging Breeder Mice by Pamela R. Petrequin and Arthur G. Johnson Dept. of Medical Microbiology /Immunology University of Minnesota-Duluth School of

  6. The new immunology.

    Science.gov (United States)

    Siminovitch, K A

    1992-03-01

    Among the biomedical sciences, immunology stands out as a discipline in which knowledge emanating from fundamental research has rapidly been transferred to the clinical paradigm, with consequent improvement in human health. Virtually all medical subspecialties have benefitted from diagnostic reagents and technologies provided by basic immunology. In terms of numbers of lives saved, immunologic-based therapeutic strategies, most notably vaccination, rank among the most effective measures ever achieved by medical intervention. Yet, despite immunology's profound impact on medicine and the longstanding recognition of many of the general principles and cellular components involved in immunity, until relatively recently, the operational workings of the immune system eluded precise definition. The abstract nature of the immune system rendered the field intangible or, at the very least, confusing, to the nonimmunologic medical community. However, in recent years, this situation has changed radically, as cell cloning, hybridoma, and recombinant DNA technologies have provided the means to delineate the precise immunologic cellular structures and interactions. The purpose of this review is to highlight a few of the most significant advances in immunology during the past decade, and to show how they have made possible the translation of abstract concepts of classical immunology into tangible, structural information. Striking gains in the understanding of antigen recognition, one of the most fundamental aspects of immunity, are described as an illustrative case.

  7. 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.

  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.

  9. 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.

  10. Evolution of Immunological Thinking

    Directory of Open Access Journals (Sweden)

    Alaín Alonso Remedios

    2016-04-01

    Full Text Available At present, the mechanisms involved in the "decision" of the immune system to promote an essentially effector response or a tolerant response are not fully known. Throughout history, immunological thinking has changed as the available technologies have led to a better understanding of the immune system. For these reasons, the present literature review was conducted to summarize the changes in immunological thinking regarding the fundamental problem of immunology. The concept of horror autotoxicus proposed by Erlich and the meaning of the clonal selection theory for understanding central tolerance were discussed. The two-signal model, Jerne’s contributions and his immune network theory were also addressed. Finally, the danger model and the theory of dominant tolerance were analyzed. The contributions of each theory to understanding how the immune system works were included.

  11. Immunology of methanogenic bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Macario, A.J.L.; Macario, E.C. de (New York State Dept. of Health, Albany, NY (United States). Wadsworth Center for Labs. and Research School of Public Health, Albany, NY (United States))

    1993-01-01

    The purpose of this brief review is to highlight some findings using immunologic methods and antibody probes developed for analysis of methanogens directly in samples from bioreactors, avoiding culture isolation. A considerable diversity of methanogens was revealed by antigenic fingerprinting in bioreactors, larger than previously suspected. It was also found that the number and immunologic characteristics of the methanogenic subpopulations form a pattern distinctive of bioreactor type, feedstocks and operating conditions. This pattern changed in response to perturbations and to temperature shifts. Time course quantitative measurements of methanogenic subpopulations demonstrated that these subpopulations undergo sequential changes during bioreactor operation. Parallel microbiologic, physiologic, and chemical determinations demonstrated the reliability of the immunologic methods and their potential for bioreactor monitoring and for manipulating microprobes (e.g. to exclude a strain from a bioreactor). (author)

  12. Investigation of epididymal immunology

    Institute of Scientific and Technical Information of China (English)

    CHANG Zong-Liang

    2005-01-01

    Immunology is the study of the structure and function of the immune system. The immune system consists of an earlier-stage innate immunity and a later-stage adaptive immunity. The task of the immune system is to efficiently respond to non-self antigens and the invasion of pathogens, thereby protecting the host's homeostasis. This review article discusses the structure and function of the epididymis, including the composition of the epithelial cells of the epididymis and their relationship to the immune system, through the assessment of alterations in the immune cells of the epididymis. The review also shows the anti-inflammatory properties of rat epididymal defensin and the description of the blood-epididymis barrier, immune barrier, epididymitis and pathological mechanisms of infertility in males. Taken together, we see that the epididymis possesses a close link with immunology. Finally, this review discusses the future of studies involving epididymal immunology.

  13. 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 ...

  14. Adjuvants for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe

    2012-10-01

    Allergen-specific immunotherapy is currently performed via either the subcutaneous or sublingual routes as a treatment for type I (IgE dependent) allergies. Aluminum hydroxide or calcium phosphate are broadly used as adjuvants for subcutaneous allergy vaccines, whereas commercial sublingual vaccines rely upon high doses of aqueous allergen extracts in the absence of any immunopotentiator. Adjuvants to be included in the future in products for allergen specific immunotherapy should ideally enhance Th1 and CD4+ regulatory T cell responses. Imunomodulators impacting dendritic or T cell functions to induce IL10, IL12 and IFNγ production are being investigated in preclinical allergy models. Such candidate adjuvants encompass synthetic or biological immunopotentiators such as glucocorticoids, 1,25-dihydroxy vitamin D3, selected probiotic strains (e.g., Lactobacillus and Bifidobacterium species) as well as TLR2 (Pam3CSK4), TLR4 (monophosphoryl lipid A, synthetic lipid A analogs) or TLR9 (CpGs) ligands. Furthermore, the use of vector systems such as mucoadhesive particules, virus-like particles or liposomes are being considered to enhance allergen uptake by tolerogenic antigen presenting cells present in mucosal tissues.

  15. Immunologic lung disease

    Energy Technology Data Exchange (ETDEWEB)

    Harman, E.M.

    1985-07-01

    The term immunologic lung disease comprises a broad spectrum of disease. The authors have covered a few entities in which recent studies have been particularly helpful in elucidating pathophysiology though not in uncovering the inciting cause. Common to all of these entities is the problem of finding appropriate methods of defining disease activity and response to treatment. As exemplified by the improved outlook for Goodpasture's syndrome with elucidation of its underlying immunopathology, it is likely that better understanding of the immunologic basis of sarcoid and interstitial disease may be helpful in planning more effective treatment strategies. 44 references.

  16. RADIOECOLOGY AND ECOLOGICAL IMMUNOLOGY

    Directory of Open Access Journals (Sweden)

    V. M. Shubik

    2009-01-01

    Full Text Available The author's investigations results are presented in comparing with literary materials concerning the application of principles and methods of ecological immunology for solving radioecological questions. The data on characteristic of immunity and health of human population affected with radiation factors of the environment is given as well as animals' population state as the links offood ecological chains.

  17. Immunological Treatments for Autism.

    Science.gov (United States)

    Gupta, Sudhir

    2000-01-01

    This article discusses research findings that indicate immunological abnormalities in children with autism, including the dysregulation of the immune system, and concludes that there are sufficient data to suggest a role of the immune system in the pathogenesis of autism. Various biological therapies are analyzed, including intravenous…

  18. 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...

  19. Cancer Immunology and Immunotherapy.

    Science.gov (United States)

    Sukari, Ammar; Nagasaka, Misako; Al-Hadidi, Ameer; Lum, Lawrence G

    2016-11-01

    Hanahan and Weinberg described six distinct biological properties of cancer cells that enable tumor growth and metastasis. These properties were referred to as the traditional hallmarks of cancer. Recent discoveries further elucidated hallmarks including evasion of immune destruction by tumor cells that disrupt anticancer response pathways. This review discusses cancer immunology and new treatment strategies aimed at restoration of antitumor immune responses.

  20. Immunology's theories of cognition.

    Science.gov (United States)

    Tauber, Alfred I

    2013-01-01

    Contemporary immunology has established its fundamental theory as a biological expression of personal identity, wherein the "immune self" is defended by the immune system. Protection of this agent putatively requires a cognitive capacity by which the self and the foreign are perceived and thereby discriminated; from such information, discernment of the environment is achieved and activation of pathways leading to an immune response may be initiated. This so-called cognitive paradigm embeds such functions as "perception," "recognition," "learning," and "memory" to characterize immune processes, but the conceptual character of such functions has meanings that vary with the particular theory adopted. When different formulations of cognition are considered, immunology's conceptual infrastructure shifts: Extensions of conventional psychological understanding of representational cognition based on a subject-object dichotomy support notions of immune agency; alternatively, formulations of perception that dispense with representations and attendant notions of agency reconfigure the predicate epistemology dominating current immune theory. Reviewing immunological literature of the past five decades, these two understandings of perception--representational and non-representational (considered here from ecological, enactivist, and autopoietic perspectives)--offer competing views of immune cognitive functions. These, in turn, provide competing philosophical understandings of immunology's conceptual foundations, which reflect parallel controversies dominating current debates in philosophy of mind and attendant discussions about personal identity.

  1. 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.

  2. 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…

  3. 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.

  4. 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

  5. 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.

  6. Sleep after vaccination boosts immunological memory.

    Science.gov (United States)

    Lange, Tanja; Dimitrov, Stoyan; Bollinger, Thomas; Diekelmann, Susanne; Born, Jan

    2011-07-01

    Sleep regulates immune functions. We asked whether sleep can influence immunological memory formation. Twenty-seven healthy men were vaccinated against hepatitis A three times, at weeks 0, 8, and 16 with conditions of sleep versus wakefulness in the following night. Sleep was recorded polysomnographically, and hormone levels were assessed throughout the night. Vaccination-induced Th cell and Ab responses were repeatedly monitored for 1 y. Compared with the wake condition, sleep after vaccination doubled the frequency of Ag-specific Th cells and increased the fraction of Th1 cytokine-producing cells in this population. Moreover, sleep markedly increased Ag-specific IgG1. The effects were followed up for 1 y and were associated with high sleep slow-wave activity during the postvaccination night as well as with accompanying levels of immunoregulatory hormones (i.e., increased growth hormone and prolactin but decreased cortisol release). Our findings provide novel evidence that sleep promotes human Th1 immune responses, implicating a critical role for slow-wave sleep in this process. The proinflammatory milieu induced during this sleep stage apparently acts as adjuvant that facilitates the transfer of antigenic information from APCs to Ag-specific Th cells. Like the nervous system, the immune system takes advantage of the offline conditions during sleep to foster adaptive immune responses resulting in improved immunological memory.

  7. 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

  8. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  9. Cosmos-1989 immunology studies

    Science.gov (United States)

    Sonnenfeld, Gerald

    1991-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.

  10. 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...

  11. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  12. 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.

  13. Modulation of primary immune response by different vaccine adjuvants

    Directory of Open Access Journals (Sweden)

    Annalisa Ciabattini

    2016-10-01

    Full Text Available Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Since the primary immune response can influence the overall quality of the response generated, here we investigate early biomarkers of adjuvanticity after primary immunization with four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w Squalene, but not aluminum hydroxide (Alum or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed towards a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w Squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w Squalene or CpG adjuvants. Tested adjuvants promoted the germinal centre reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime-boost vaccine immunization protocols.

  14. Islet transplantation: immunological perspectives.

    Science.gov (United States)

    Inverardi, Luca; Kenyon, Norma S; Ricordi, Camillo

    2003-10-01

    Clinical trials of islet transplantation are showing remarkable success, but they require administration of chronic immunosuppression, and are underscoring the large gap that exists between the number of human donors available and the number of patients that could benefit from the procedure. Recent progress has been made in the definition of key immunological mechanisms that are involved in determining islet transplant outcome. Clinical and preclinical studies, and studies in small animal model systems, will all eventually contribute to the definition of efficient and safe protocols for islet transplantation. If the use of xenografts is successful, it might represent a solution to the shortage of human organs.

  15. The immunological synapse

    DEFF Research Database (Denmark)

    Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten

    2003-01-01

    . A distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning...... IS formation, appearance, and cessation. In addition, proposed functions of the IS are discussed. The process of IS formation occurs in a sequential manner, initially causing a remarkable large-scale redistribution of a number of integral membrane and cytosolic proteins. At the T cell/APC interface...

  16. Immunology in Africa.

    Science.gov (United States)

    Cose, Stephen; Bagaya, Bernard; Nerima, Barbara; Joloba, Moses; Kambugu, Andrew; Tweyongyere, Robert; Dunne, David W; Mbidde, Edward; Kaleebu, Pontiano; Elliott, Alison M

    2015-12-01

    Africa is a continent with a large burden of both infectious and non-communicable diseases. If we are to move forward as a continent, we need to equip our growing cadre of exceptional young scientists with the skills needed to tackle the diseases endemic to this continent. For this, immunology is among the key disciplines. Africans should be empowered to study and understand the diseases that affect them, and to perform their cutting-edge research in their country of origin. This requires a multifaceted approach, with buy-in from funders, overseas partners and perhaps, most important of all, African governments themselves.

  17. Mathematics in modern immunology.

    Science.gov (United States)

    Castro, Mario; Lythe, Grant; Molina-París, Carmen; Ribeiro, Ruy M

    2016-04-01

    Mathematical and statistical methods enable multidisciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. We collect a representative sample of studies in T-cell biology that illustrate the benefits of modelling-experimental collaborations and that have proven valuable or even groundbreaking. We conclude that it is possible to find excellent examples of synergy between mathematical modelling and experiment in immunology, which have brought significant insight that would not be available without these collaborations, but that much remains to be discovered.

  18. Kinetics Modeling of Cancer Immunology.

    Science.gov (United States)

    1986-05-09

    CANCER IMMUNOLOGY -1 DTICS ELECTED SEP 9 8 UNITED STATES NAVAL ACADEMY ANNAPOLIS, MARYLAND V ,1986 %,e docment ha le approved for public A." I and sale...1986 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED KINETICS MODELING OF CANCER IMMUNOLOGY Final: 1985/1986 6. PERFORMING ORG. REPORT...137 (1986) "Kinetics Modeling of Cancer Immunology " A Trident Scholar Project Report by Midn I/C Scott Helmers, Class of 1986 United States Naval

  19. Broadening the translational immunology landscape.

    Science.gov (United States)

    Peakman, M

    2012-12-01

    It is just over 5 years since Clinical and Experimental Immunology came under the direction of a new team of Editors and made a concerted effort to refresh its approach to promoting clinical and applied immunology through its pages. There were two major objectives: to foster papers in a field which, at the time, we loosely termed 'translational immunology'; and to create a forum for the presentation and discussion of immunology that is relevant to clinicians operating in this space. So, how are we doing with these endeavours? This brief paper aims to summarize some of the key learning points and successes and highlight areas in which translational gaps remain.

  20. 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.

  1. 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...

  2. 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.

  3. Immunological effects of vasectomy.

    Science.gov (United States)

    Sotolongo, J R

    1982-06-01

    It is only recently that the adverse effects of vasectomy have become the subject of numerous scientific and at times speculative articles in medical and in lay periodicals. In this review of the literature on the immunological effects of vasectomy, attention is directed to the following: immunological response; cellular immunity; effects on testes and epididymis, and systemic effects of sperm autoantibodies. In 1970, 50% of vasectomized men were found to have circulating spermatozoal antibodies. A more recent survey provides confirmation for this finding and presents an incidence of only 2% of agglutinating antibodies and 0% of immobilizing antibodies in a fertile control population. Some recent and convincing studies have shown sperm agglutinating and immobilizing antibodies to remain either at the same titer level or actually to increase 5-12 years postoperatively. Titers range from 2 to 2048 among different patients. The highest incidence of titers is 1 year after vasectomy, but titers can be found as early as 6 months or as late as 20 years postoperatively. The wide range in titers can be explained in terms of technical problems in immune assays, since only immunoglobulins and not those antibodies part of immune complex systems can be measured. Since sperm antigens are in abundant supply in vasectomized men because of the continuous resorption of spermatozoa after vasectomy, possibly undetectable antibody titers actually reflect high levels of antisperm antibodies circulating in the form of immune complexes. Also it may be possible that the variety in measured titers of autoantibodies, as well as the nonuniversal (70%) antibody response in a vasectomized population, is a variable dependent on genetic content and, therefore, an individual characteristic. The fact that hormonal reponse takes place rather readily after vasectomy makes at least some degree of cellular response a necessary occurrence. Studies by Alexander and Anderson, which show delayed

  4. Neisseria lactamica antigens complexed with a novel cationic adjuvant.

    Science.gov (United States)

    Gaspar, Emanuelle B; Rosetti, Andreza S; Lincopan, Nilton; De Gaspari, Elizabeth

    2013-03-01

    Colonization of the nasopharynx by non-pathogenic Neisseria species, including N. lactamica, has been suggested to lead to the acquisition of natural immunity against Neisseria meningitidis in young children. The aim of this study was to identify a model complex of antigens and adjuvant for immunological preparation against N. meningitidis B, based on cross reactivity with N. lactamica outer membrane vesicles (OMV) antigens and the (DDA-BF) adjuvant. Complexes of 25 µg of OMV in 0.1 mM of DDA-BF were colloidally stable, exhibiting a mean diameter and charge optimal for antigen presentation. Immunogenicity tests for these complexes were performed in mice. A single dose of OMV/DDA-BF was sufficient to induce a (DTH) response, while the same result was achieved only after two doses of OMV/alum. In addition, to achieve total IgG levels that are similar to a single immunization with OMV/DDA-BF, it was necessary to give the mice a second dose of OMV/alum. Moreover, the antibodies induced from a single immunization with OMV/DDA-BF had an intermediate avidity, but antibodies with a similar avidity were only induced by OMV/alum after two immunizations. The use of this novel cationic adjuvant for the first time with a N. lactamica OMV preparation revealed good potential for future vaccine design.

  5. 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...

  6. 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.

  7. 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.

  8. Immunological Detection of Arbutin

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The relative molecular mass of Arbutin is small.Both fluorolabeling and radiolabeling may affect its properties and functions.Therefore, the immunoassay of Arbutin was studied.Arbutin was coupled to bovine serum albumin to get the Arbutin-BSA conjugate with high molar ratio of Arbutin to BSA.Two rabbits were injected with the conjugate to develop the anti-Arbutin serum.Ammonium sulfate precipitation and affinity chromatography were used to purify the antibody.Double agar diffusion test and enzyme-linked immunosorbent assay (ELISA) were adopted to identify the antibody titer.The results demonstrated that the purity and activity of the antibody are high.The method proposed is satisfactory for the immunological detection of Arbutin.

  9. Light and immune systems: activation of immunological activities

    Science.gov (United States)

    Huang, Zheng; Liu, Hong; Chen, Wei R.

    2006-02-01

    Light has been used to treat diseases for hundreds of years. Convenient and powerful light sources such as lasers make photomedicine a major branch in diseases treatment and detection. Originally, light was often used for local treatment, using photomechanical, photochemical, photothermal reactions and photomodulation as the major mechanisms. More and more investigators have become interested in the systemic effects of light, particularly in its effects on immune systems. Much work has been done to activate and/or enhance the host immune system to combat cancer, either using light as a direct tool or as an adjuvant method. Light has long been used for assisting disease detection and diagnosis. Advances in light technology have made photo-diagnostics ever more precise spatially and temporally. Many techniques facilitate observation of bio-molecule interactions and other biological processes at the cellular level, hence providing opportunities to detect and monitor immune activities. This manuscript will review recent photo-immunological research in treatment of cancer. The recent development of combination therapies involving lasers will be presented. Specifically, the results of cancer treatment using laser photothermal interaction, either with or without additional immunological stimulation will be discussed. The immunological effects of photodynamic therapy (PDT), and of its combination with immunotherapy in cancer treatment will also be discussed. Much interest has been recently concentrated in the immunological responses after laser treatment. Such responses at cellular and molecular levels will be discussed. The effect of these treatment modalities on the distant metastases also showed promise of light induced antitumor immunity. The combination therapy and induced immunological responses appear to be the key for long-term control of tumors.

  10. How to define green adjuvants.

    Science.gov (United States)

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  11. 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.

  12. Noncoding RNAs in Cancer Immunology.

    Science.gov (United States)

    Li, Qian; Liu, Qiang

    2016-01-01

    Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity.

  13. Immunologic endocrine disorders.

    Science.gov (United States)

    Michels, Aaron W; Eisenbarth, George S

    2010-02-01

    Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA-like molecules determining tissue-specific targeting that, with the loss of tolerance, leads to organ-specific autoimmunity. Disorders such as type 1A diabetes, Graves disease, Hashimoto thyroiditis, Addison disease, and many others result from autoimmune-mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in patients with type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. Although therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  14. Immunological Effect of Subunit Influenza Vaccine Entrapped by Liposomes

    Institute of Scientific and Technical Information of China (English)

    SHUI-HUA ZHANG; JIA-XU LIANG; SHU-YAN DAI; XIAO-LIN QIU; YAN-RONG YI; YUN PAN

    2009-01-01

    Objective To elevate the immunological effect of subunit influenza vaccine in infants and aged people (over 60) using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. Methods Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and ELISA. Results Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/c mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine (mean size: 4.5-5.5 μm, entrapment efficiency: 30%-40%) significantly increased the immunological effect of subunit influenza vaccine. Conclusion The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.

  15. Experimental autoimmune orchitis as a model of immunological male infertility.

    Science.gov (United States)

    Naito, Munekazu; Terayama, Hayato; Hirai, Shuichi; Qu, Ning; Lustig, Livia; Itoh, Masahiro

    2012-12-01

    Clinically, 60-75% of male infertility cases are categorized as idiopathic spermatogenic disturbance. In previous studies of this condition, lymphocytic infiltration and immune deposits were present in several testis biopsy specimens, indicating that inflammatory or immunological factors contribute to the occurrence of the lesions. However, there is currently little evidence regarding immunological infertility in men. Previously, we established an immunological infertility model, experimental autoimmune orchitis (EAO), that can be induced in mice by two subcutaneous injections of viable syngeneic testicular germ cells without the use of any adjuvant. In this EAO model, lymphocytes surround the tubuli recti and then induce spermatogenic disturbance. In addition, after the active inflammation stage of this model, the seminiferous epithelium is damaged irreversibly, resembling the histopathology of human male idiopathic spermatogenic disturbance. In the majority of patients with testicular autoimmunity, there is a chronic and asymptomatic development of the inflammatory reaction. Therefore, this disease is very difficult to diagnose at the ongoing stage, and it is possible that the histopathology of idiopathic spermatogenic disturbance in the clinic is reported at the post-active inflammation stage of autoimmune orchitis. In this review, the histopathology of EAO before and after inflammation is discussed, comparing it with human orchitis.

  16. New horizons in adjuvants for vaccine development.

    Science.gov (United States)

    Reed, Steven G; Bertholet, Sylvie; Coler, Rhea N; Friede, Martin

    2009-01-01

    Over the last decade, there has been a flurry of research on adjuvants for vaccines, and several novel adjuvants are now in licensed products or in late stage clinical development. The success of adjuvants in enhancing the immune response to recombinant antigens has led many researchers to re-focus their vaccine development programs. Successful vaccine development requires knowing which adjuvants to use and knowing how to formulate adjuvants and antigens to achieve stable, safe and immunogenic vaccines. For the majority of vaccine researchers this information is not readily available, nor is access to well-characterized adjuvants. In this review, we outline the current state of adjuvant research and development and how formulation parameters can influence the effectiveness of adjuvants.

  17. A Review and Prospect on Herbicide Adjuvants

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

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

  18. 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

  19. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

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

    2001-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

    AIM: To study the immunological protective effect of H pylori vaccine with chitosan as an adjuvant and its mechanism.METHODS: Female BALB/c mice were randomly divided into seven groups and orally immunized respectively with PBS, chitosan solution, chitosan particles, H pylori antigen, H pylori antigen plus cholera toxin (CT), H pylori antigen plus chitosan solution, H pylori antigen plus chitosan particles once a week for four weeks. Four weeks after the last immunization, the mice were challenged twice by alive H pylori (1 × 109 CFU/mL) and sacrificed. Part of the gastric mucosa was embedded in paraffin, cut into sections and assayed with Giemsa staining. Part of the gastric mucosa was used to quantitatively culture H pylori. ELISA was used to detect cytokine level in gastric mucosa and anti- H pylori IgGl, IgG2a levels in serum.RESULTS: In the groups with chitosan as an adjuvant, immunological protection was achieved in 60% mice, which was significantly higher than in groups with H pylori antigen alone and without H pylori antigen (P < 0.05 or 0.001). Before challenge, the level of IFN and IL-12 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in the control group and the group without adjuvant (P < 0.05 or 0.005). After challenge, the level of IFN and IL-12 was significantly higher in the groups with adjuvant than in the groups without adjuvant and antigen (P < 0.05 or 0.001). Before challenge, the level of IL-2 in gastric mucosa was not different among different groups. Afterchallenge the level of IL-2 was significantly higher in the groups with adjuvant than in the control group (P < 0.05 or 0.001). Before challenge, the level of IL-10 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant (P < 0.05 or 0.01). After challenge, the level of IL-10 was not different among different groups. Before challenge, the level of IL-4 in gastric mucosa

  1. 21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

  2. 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.

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

    Science.gov (United States)

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L.; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    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. PMID:22811748

  4. Uncaria tomentosa-Adjuvant Treatment for Breast Cancer: Clinical Trial.

    Science.gov (United States)

    Santos Araújo, Maria do Carmo; Farias, Iria Luiza; Gutierres, Jessie; Dalmora, Sergio L; Flores, Nélia; Farias, Julia; de Cruz, Ivana; Chiesa, Juarez; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa

    2012-01-01

    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.

  5. Immunological techniques in viral hepatitis.

    Science.gov (United States)

    Rehermann, Barbara; Naoumov, Nikolai V

    2007-03-01

    The need to quantitate and monitor immune responses of large patient cohorts with standardized techniques is increasing due to the growing range of treatment options for hepatitis B and hepatitis C, the development of combination therapies, and candidate experimental vaccines for HCV. In addition, advances in immunological techniques have provided new tools for detailed phenotypic and functional analysis of cellular immune responses. At present, there is substantial variation in laboratory protocols, reagents, controls and analysis and presentation of results. Standardization of immunological assays would therefore allow better comparison of results amongst individual laboratories and patient cohorts. The EASL-sponsored and AASLD-endorsed Monothematic Conference on Clinical Immunology in Viral Hepatitis was held at the University College London, United Kingdom, Oct 7-8, 2006 to bring together investigators with research experience in clinical immunology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections for in-depth discussion, critical evaluation and standardization of immunological assays. This report summarizes the information presented and discussed at the conference, but is not intended to represent a consensus statement. Our aim is to highlight topics and issues that were supported by general agreement and those that were controversial, as well as to provide suggestions for future work.

  6. Sarcoidosis: Immunopathogenesis and Immunological Markers

    Directory of Open Access Journals (Sweden)

    Wei Sheng Joshua Loke

    2013-01-01

    Full Text Available Sarcoidosis is a multisystem granulomatous disorder invariably affecting the lungs. It is a disease with noteworthy variations in clinical manifestation and disease outcome and has been described as an “immune paradox” with peripheral anergy despite exaggerated inflammation at disease sites. Despite extensive research, sarcoidosis remains a disease with undetermined aetiology. Current evidence supports the notion that the immune response in sarcoidosis is driven by a putative antigen in a genetically susceptible individual. Unfortunately, there currently exists no reliable biomarker to delineate the disease severity and prognosis. As such, the diagnosis of sarcoidosis remains a vexing clinical challenge. In this review, we outline the immunological features of sarcoidosis, discuss the evidence for and against various candidate etiological agents (infective and noninfective, describe the exhaled breath condensate, a novel method of identifying immunological biomarkers, and suggest other possible immunological biomarkers to better characterise the immunopathogenesis of sarcoidosis.

  7. Mucosal and systemic adjuvant activity of alphavirus replicon particles

    Science.gov (United States)

    Thompson, Joseph M.; Whitmore, Alan C.; Konopka, Jennifer L.; Collier, Martha L.; Richmond, Erin M. B.; Davis, Nancy L.; Staats, Herman F.; Johnston, Robert E.

    2006-03-01

    Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines. vaccine vector | Venezuelan equine encephalitis virus | viral immunology | RNA virus

  8. Immunological Evaluation of Recent MUC1 Glycopeptide Cancer Vaccines

    Directory of Open Access Journals (Sweden)

    Md Kamal Hossain

    2016-07-01

    Full Text Available Aberrantly glycosylated mucin 1 (MUC1 is a recognized tumor-specific antigen on epithelial cell tumors. A wide variety of MUC1 glycopeptide anti-cancer vaccines have been formulated by many research groups. Some researchers have used MUC1 alone as an immunogen whereas other groups used different antigenic carrier proteins such as bovine serum albumin or keyhole limpet hemocyanin for conjugation with MUC1 glycopeptide. A variety of adjuvants have been used with MUC1 glycopeptides to improve their immunogenicity. Fully synthetic multicomponent vaccines have been synthesized by incorporating different T helper cell epitopes and Toll-like receptor agonists. Some vaccine formulations utilized liposomes or nanoparticles as vaccine delivery systems. In this review, we discuss the immunological evaluation of different conjugate or synthetic MUC1 glycopeptide vaccines in different tumor or mouse models that have been published since 2012.

  9. Citizens unite for computational immunology!

    Science.gov (United States)

    Belden, Orrin S; Baker, Sarah Catherine; Baker, Brian M

    2015-07-01

    Recruiting volunteers who can provide computational time, programming expertise, or puzzle-solving talent has emerged as a powerful tool for biomedical research. Recent projects demonstrate the potential for such 'crowdsourcing' efforts in immunology. Tools for developing applications, new funding opportunities, and an eager public make crowdsourcing a serious option for creative solutions for computationally-challenging problems. Expanded uses of crowdsourcing in immunology will allow for more efficient large-scale data collection and analysis. It will also involve, inspire, educate, and engage the public in a variety of meaningful ways. The benefits are real - it is time to jump in!

  10. Immunological aspects of Graves' disease

    NARCIS (Netherlands)

    B.M. van Ouwerkerk (Marcel)

    1986-01-01

    textabstractAssuming an autoimmune interested to know whether apart from restoring the immunologic parameters. Freshly diagnosed hyperthyroid patients with Graves' disease were all similarly treated with MMI 10 mg t.i.d. and when euthyroidism was achieved, with substitution of thyroid hormone. At

  11. Adjuvant radiation therapy compared with cyclic chemotherapy in patients with mammary carcinoma. II. Changes of mitogen responses of blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Strender, L.E.; Blomgren, H.; Wasserman, J.; Petrini, B.; Baral, E. (Karolinska Sjukhuset, Stockholm (Sweden))

    1981-01-01

    Blood lymphocyte reactivity to purified protein derivative of tuberculin (PPD) and phytohaemagglutinin (PHA) was examined in 62 patients with breast carcinoma who received postoperative adjuvant radiation therapy or cyclic chemotherapy with chlorambucil, methotrexate and 5-fluorouracil. Both treatments impaired the immunologic reactivity of blood lymphocytes as measured by PPD and PHA stimulation in vitro. Radiation therapy seemed to cause more profound and protracted suppression of the PPD response than chemotherapy.

  12. Half a century of Dutch transplant immunology

    NARCIS (Netherlands)

    van Rood, Jon J; Claas, Frans H J; Brand, Anneke; Tilanus, Marcel G J; van Kooten, Cees

    2014-01-01

    The sixties have not only witnessed the start of the Dutch Society for Immunology (NvvI), but were also the flourishing beginning of the discipline of transplant immunology. The interest in immunology in the Netherlands had its start in the context of blood transfusions and not for instance in the f

  13. 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

  14. 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 man. The

  15. 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

  16. 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.

  17. Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B.

    Science.gov (United States)

    Kuipers, Kirsten; Diavatopoulos, Dimitri A; van Opzeeland, Fred; Simonetti, Elles; van den Kieboom, Corné H; Kerstholt, Mariska; Borczyk, Malgorzata; van IngenSchenau, D; Brandsma, Eelke T; Netea, Mihai G; de Jonge, Marien I

    2016-11-15

    For many bacterial respiratory infections, development of (severe) disease is preceded by asymptomatic colonization of the upper airways. For Streptococcus pneumoniae, the transition to severe lower respiratory tract infection is associated with an increase in nasopharyngeal colonization density. Insight into how the mucosal immune system restricts colonization may provide new strategies to prevent clinical symptoms. Several studies have provided indirect evidence that the mucosal adjuvant cholera toxin subunit B (CTB) may confer nonspecific protection against respiratory infections. Here, we show that CTB reduces the pneumococcal load in the nasopharynx, which required activation of the caspase-1/11 inflammasome, mucosal T cells, and macrophages. Our findings suggest that CTB-dependent activation of the local innate response synergizes with noncognate T cells to restrict bacterial load. Our study not only provides insight into the immunological components required for containment and clearance of pneumococcal carriage, but also highlights an important yet often understudied aspect of adjuvants.

  18. Adjuvant

    Directory of Open Access Journals (Sweden)

    Ramadan M. Nafae

    2013-07-01

    Conclusion: Adjunctive 7 day course of low dose hydrocortisone IV in patients with CAP hastens clinical recovery and prevents the development of sepsis-related complications with a significant reduction in the duration of mechanical ventilation, duration of IV antibiotics and length of hospital stay with the improvement in hospital outcome and weaning success from mechanical ventilation.

  19. Immunology for the toxicologic pathologist.

    Science.gov (United States)

    Snyder, Paul W

    2012-01-01

    The immune system functions primarily as a defense mechanism to provide protective immunity against microbial pathogens and cancer. The resulting protective responses occur through the complex interaction of tissues, cells, proteins, and molecular pathways that act in concert with other systems (e.g., nervous and endocrine) to provide the host with immunologic responses that cause pathologic processes seen primarily as inflammatory reactions. The pathologic responses can be attributed to either normal responses to infectious organisms and cancer cells, misdirected responses as in the case of hypersensitivity or autoimmune diseases, or deficient responses attributable to deficiencies or defects in components of the immune system. Pathologists need to have a basic understanding of the immune system to not only interpret findings as to their likely pathogenesis, but also to predict when the immune system may be a potential target. This review will be limited to a general overview of the basic immunologic responses and primary components involved.

  20. Mucosal Immunology of HIV Infection

    OpenAIRE

    Xu, Huanbin; Wang, Xiaolei; Veazey, Ronald S.

    2013-01-01

    Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicti...

  1. Immunological impact of Taekwondo competitions.

    Science.gov (United States)

    Lee, Y W; Shin, K W; Paik, I-Y; Jung, W M; Cho, S-Y; Choi, S T; Kim, H D; Kim, J Y

    2012-01-01

    Immunological changes in elite adolescent female athletes during Taekwondo competitions were investigated on-field. 6 female athletes (16.7 ± 0.8 year-old) volunteered and performed 5 bouts of demonstration Taekwondo competitions simulating real tournaments in intensity, duration, and break-time intervals on the same day. Blood samples were taken before, after the competitions and during the recovery, respectively. Immunological changes and oxidative stress in peripheral blood mononuclear cells were evaluated by flow-cytometry. During the competitions, exercise intensity was 92.2 ± 3.8% (86.1~95.7) of the maximal heart rate. Blood lactate increased immediately after the competitions (p=0.0165) and decreased to baseline during recovery. Intracellular reactive oxygen species (ROS) in the peripheral blood increased continuously during recovery (pTaekwondo competitions. Further large-scaled Taekwondo studies on immunologic and apoptotic changes related to oxidative stress should be performed for improving and protecting the health of adolescent athletes. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Cancer immunotherapy and immunological memory.

    Science.gov (United States)

    Murata, Kenji; Tsukahara, Tomohide; Torigoe, Toshihiko

    2016-01-01

      Human immunological memory is the key distinguishing hallmark of the adaptive immune system and plays an important role in the prevention of morbidity and the severity of infection. The differentiation system of T cell memory has been clarified using mouse models. However, the human T cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. We believe that only human studies can elucidate the human immune system. The importance of immunological memory in cancer immunotherapy has been pointed out, and the trafficking properties and long-lasting anti-tumor capacity of memory T cells play a crucial role in the control of malignant tumors. Adoptive cell transfer of less differentiated T cells has consistently demonstrated superior anti-tumor capacity relative to more differentiated T cells. Therefore, a human T cell population with the characteristics of stem cell memory is thought to be attractive for peptide vaccination and adoptive cell transfer. A novel human memory T cell population that we have identified is closer to the naive state than previous memory T cells in the T cell differentiation lineage, and has the characteristics of stem-like chemoresistance. Here we introduce this novel population and describe the fundamentals of immunological memory in cancer immunotherapy.

  3. A prospect on cancer immunology.

    Science.gov (United States)

    Kobayashi, H

    1979-11-01

    There are several factors involved in studying cancer immunology. For convenience, those factors can be consolidated into two. Firstly, no definite tumor-specific or -associated antigen has been ascertained as yet, except for certain types of tumor. Secondly, there is no definite pattern of immune response of the host against weak antigenic tumor cells. Nobody knows as to what is the nature of the tumor-specific antigen even if it exists, and nobody knows the escape mechanism of tumor cells from the immune defence of the host. There have been a number of approaches for cancer immunotherapy, but so far there has been no definite answer as to whether immunotherapy is a promising approach for cancer treatment. In this review, cancer immunology is divided into three separate subjects. The first of these is tumor antigen; the second, the immune response against tumor antigen; and the third, methods of attacking tumor cells by immunological means including how to increase the antigenicity of tumor cells (xenogenization), and how to increase the immune response of the host (immunotherapy).

  4. Novel Adjuvants and Immunomodulators for Veterinary Vaccines

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. Immunological responses of sheep against adult worm extract antigen of Fasciola gigantica

    Directory of Open Access Journals (Sweden)

    S Widjajanti

    1999-06-01

    Full Text Available Immunological responses of sheep against adult worm extract antigen of Fasciola gigantica were evaluated in an effort to identify the protein antigen for the candidate of vaccine. In this study the protein antigen from adult worms was extracted, and the extract antigen was then intramuscularly injected into 4 groups of 5 sheep. Two groups received one injection, these included one group injected only with extract antigen and the other group injected with extract antigen emulsified in Quil A adjuvant. The other two groups received two injections with a two week interval, these included one group injected only with extract antigen and the other group injected with extract antigen emulsified in Quil A adjuvant. Three weeks later all of the sheep were challenged with 300 metacercariae of F. gigantica. The antibody titer was monitored every two weeks by using ELISA and the protein profile from each group was compared by using western blotting. Fifteen weeks after challenged all of the sheep were killed and the liver flukes were collected from the liver and counted. The results showed that the antibody titer was higher in the group which received two injections, and the additional of Quil A adjuvant gave much better protection from the infection of F. gigantica (57% and could avoid the death of the sheep than twice injection of antigen without Quil A adjuvant (37%.

  6. Adjuvants: Classification, Modus Operandi, and Licensing

    Science.gov (United States)

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID:27274998

  7. 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

  8. Radiation as an immunological adjuvant: current evidence on dose and fractionation

    Directory of Open Access Journals (Sweden)

    Sandra eDemaria

    2012-10-01

    Full Text Available Ionizing radiation to a cancer site has the ability to convert the irradiated tumor in an immunogenic hub. However, radiation is a complex modifier of the tumor microenvironment and, by itself, is seldom sufficient to induce a therapeutically significant anti-tumor immune response, since it can also activate immune suppressive pathways. While several combinations of local radiation and immunotherapy have been shown in pre-clinical models to induce powerful anti-tumor immunity, the optimal strategy to achieve this effect remains to be defined. When used in vivo, radiation effects on tumors depend on the dose per fraction applied, the number of fractions used, and the total dose. Moreover, the interplay of these three variables is contingent upon the tumor setting studied, both in preclinical and clinical applications. To enable repair of the collateral damage to the normal tissue, radiation is usually given in multiple fractions, usually of 2 Gy. Generally, the use of larger fractions is limited to sterotactic applications, whereby optimal immobilization reduces inter and intra-fraction movement and permits a very conformal delivery of dose to the target, with optimal exclusion of normal tissue. Translation of the partnership of radiation and immunotherapy to the clinic requires a careful consideration of the radiation regimens used. To date, little is known on whether different dose/fractionation regimens have a specific impact on the anti-tumor immune response. Most experiments combining the two modalities were conducted with single fractions of radiotherapy. However, there is at least some evidence that when combined with some specific immunotherapy approaches, the ability of radiation to promote anti-tumor immunity is dependent on the dose and fractionation employed. We critically review the available in vitro and in vivo data on this subject and discuss the potential impact of fractionation on the ability of radiation to synergize with immunotherapy.

  9. 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...

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

    Directory of Open Access Journals (Sweden)

    Mogens Helweg Claesson

    2011-01-01

    Full Text Available 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 both the deleterious and beneficial nonspecific effects of immunisation.

  11. Correlating liposomal adjuvant characteristics to in-vivo cell-mediated immunity using a novel Mycobacterium tuberculosis fusion protein: a multivariate analysis study.

    Science.gov (United States)

    Kastner, Elisabeth; Hussain, M Jubair; Bramwell, Vincent W; Christensen, Dennis; Perrie, Yvonne

    2015-03-01

    In this study, we have used a chemometrics-based method to correlate key liposomal adjuvant attributes with in-vivo immune responses based on multivariate analysis. The liposomal adjuvant composed of the cationic lipid dimethyldioctadecylammonium bromide (DDA) and trehalose 6,6-dibehenate (TDB) was modified with 1,2-distearoyl-sn-glycero-3-phosphocholine at a range of mol% ratios, and the main liposomal characteristics (liposome size and zeta potential) was measured along with their immunological performance as an adjuvant for the novel, postexposure fusion tuberculosis vaccine, Ag85B-ESAT-6-Rv2660c (H56 vaccine). Partial least square regression analysis was applied to correlate and cluster liposomal adjuvants particle characteristics with in-vivo derived immunological performances (IgG, IgG1, IgG2b, spleen proliferation, IL-2, IL-5, IL-6, IL-10, IFN-γ). While a range of factors varied in the formulations, decreasing the 1,2-distearoyl-sn-glycero-3-phosphocholine content (and subsequent zeta potential) together built the strongest variables in the model. Enhanced DDA and TDB content (and subsequent zeta potential) stimulated a response skewed towards a cell mediated immunity, with the model identifying correlations with IFN-γ, IL-2 and IL-6. This study demonstrates the application of chemometrics-based correlations and clustering, which can inform liposomal adjuvant design. © 2015 Royal Pharmaceutical Society.

  12. Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis

    Science.gov (United States)

    Wang, Jingbo; Liu, Rui; Liu, Baoxiu; Yang, Yan; Xie, Jun; Zhu, Naishuo

    2017-01-01

    Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in many subjects. Animal and cellular experiments finally validated that the new vaccine simultaneously improves the humoral and cellular immunity of BALB/c mice without side effects. All this results demonstrate that cordycepin could work as adjuvant to hepatitis b vaccine and systems-pharmacology analysis could be used as a new method to select adjuvants. PMID:28317886

  13. Immunology

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    3.1 Autoimmume disease 2006019 The study of inhibitory peptides on T cell activation in rheumatoid arthritis LI Xia(李霞) , Dept Rheumatol & Immunol, People’s Hosp, Peking Univ, Beijing 100044. Natl Med J China 2005;85(24) :1679 -1682. Objective:To study the inhibitory role of altered HA308 -317 peptides in T cell responses in patients with rheumatoid arthritis (RA). Methods :Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA -

  14. IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    5.1 Autoimmune disease2003029 A linkage study of cytotoxic T lymphocyte-associated antigen 4 gene and Graves’ disease in northern Chinese Han ethnic. JIN Ying ( 金迎 ), et al. Dept Endocrinol, 1st Affili Hosp, China Med Univ, Shenyang 110001. Chin J Intern Med 2002; 41 (12): 809-812. Objective: To determine if the cytotoxic T lympho-

  15. IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    3.1 Autoimmune disease2004022 BL-2, IL-6 and their receptors in patients with systemic lupus erythematosus. QIAN Qihong (钱齐宏), et al. Dept Dermatol & Venereol, 1st Affili Hosp, Suzhou Univ, Suzhou 215006. Chin J Dermatol 2003; 36 (12): 696-698.

  16. IMMUNOLOGY

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    5.1 Autoimmune disease2004189 Serum levels of matrix metallopro-teinases-9 in patients with systemic lupus erythemato-sus. YIN Wenhao (殷文浩), et al. Dept Dermatol 2nd Affili Hosp, Med Sch Zhejiang Univ, Hangzhou 310009. Chin J Dermatol 2004;37(2):77-79.Objective: To determine the serum levels of matrix

  17. Adjuvants are Key Factors for the Development of Future Vaccines: Lessons from the Finlay Adjuvant Platform

    Science.gov (United States)

    Pérez, Oliver; Romeu, Belkis; Cabrera, Osmir; González, Elizabeth; Batista-Duharte, Alexander; Labrada, Alexis; Pérez, Rocmira; Reyes, Laura M.; Ramírez, Wendy; Sifontes, Sergio; Fernández, Nelson; Lastre, Miriam

    2013-01-01

    The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs), AFPL (proteoliposome), and AFCo (cochleate), were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed. PMID:24348475

  18. Summary of the primer on tumor immunology and the biological therapy of cancer

    Directory of Open Access Journals (Sweden)

    Margolin Kim

    2009-01-01

    Full Text Available Abstract The International Society for Biological Therapy of Cancer (iSBTc is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1 cytokines in cancer immunology; (2 anti-angiogenic therapy; (3 end stage: immune killing of tumors; (4 blocking T cell checkpoints; (5 approach to identification and therapeutic exploitation of tumor antigens; (6 T regulatory cells; (7 adoptive T cell therapy; (8 immune monitoring of cancer immunotherapy; and (9 immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.

  19. 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.

  20. [Immunological markers of rheumatoid arthritis].

    Science.gov (United States)

    Matuszewska, Agnieszka; Madej, Marta; Wiland, Piotr

    2016-03-25

    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.

  1. 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.

  2. 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.

  3. 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...... suitable biological samples. The methods of the present invention are useful in therapeutic and diagnostic protocols for human, livestock and veterinary and wild life applications, thus the invention further relates to a method for diagnosing an infection in a mammal....

  4. Immunological aspects of cancer chemotherapy.

    Science.gov (United States)

    Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; Kroemer, Guido

    2008-01-01

    Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.

  5. Purinergic signaling at immunological synapses.

    Science.gov (United States)

    Dubyak, G R

    2000-07-01

    The early studies and hypotheses of Geoffrey Burnstock catalyzed intensive characterization of roles for nucleotides and P2 nucleotide receptors in neurotransmission and neuromodulation. These latter analyses have focused on the mechanisms of nucleotide release and action in the microenvironments of nerve endings and synapses. However, studies of various white blood cells, such as monocytes, neutrophils, and lymphocytes, suggest that locally released nucleotides also modulate intercellular signaling at so-called 'immunological synapses'. This communication describes recent findings and speculations regarding nucleotide release and signaling in several key phases of the immune and inflammatory responses.

  6. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    Directory of Open Access Journals (Sweden)

    WONDIM MELKAM

    2015-01-01

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

  7. 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.

  8. Broadened immunity and protective responses with emulsion-adjuvanted H5 COBRA-VLP vaccines.

    Science.gov (United States)

    Allen, James D; Owino, Simon O; Carter, Donald M; Crevar, Corey J; Reese, Valerie A; Fox, Christopher B; Coler, Rhea N; Reed, Steven G; Baldwin, Susan L; Ross, Ted M

    2017-09-12

    A number of challenges for developing a protective pre-pandemic influenza A vaccine exists including predicting the target influenza strain and designing the vaccine for an immunologically naïve population. Manufacturing and supply of the vaccine would also require implementing ways to increase coverage for the largest number of people through dose-sparing methods, while not compromising the potency of the vaccine. Previously, our group described a novel hemagglutinin (HA) for H5N1 influenza derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This report describes a strategy combining a COBRA-based HA vaccine with an oil-in-water emulsion, resulting in a dose-sparing, immunologically broadened, and protective response against multiple H5N1 isolates. Here, we show that an emulsion-based adjuvant enhances the magnitude and breadth of antibody responses with both a wild-type H5HA (H5N1 WT) and the H5N1 COBRA HA VLP vaccines. The H5N1 COBRA HA VLP, combined with an emulsion adjuvant, elicited HAI specific antibodies against a larger panel of H5N1 viruses that resulted in protection against challenge as efficiently as the homologous, matched vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

    Science.gov (United States)

    Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

    2016-10-01

    A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

  10. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

    Science.gov (United States)

    Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

    2016-01-01

    A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours. PMID:27767031

  11. [Adjuvant dermato-cosmetic acne therapy].

    Science.gov (United States)

    Bayerl, Christiane; Degitz, Klaus; Meigel, Eva; Kerscher, Martina

    2010-03-01

    Adjuvant dermato-cosmetic therapy in acne is an essential part of the concept of treating acne after initiation and during maintenance therapy. Those are mechanical peeling, chemical peeling and its combination. It needs supervision by an experienced dermatologist.

  12. 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.

  13. Adjuvants for spraying of fungicides in wheat

    OpenAIRE

    2014-01-01

    The foliar diseases and spike can markedly reduce the yield of wheat. Despite prevailing chemical control in the management of disease, studies with adjuvants to improve the performance of fungicides are still incipient. The aim of this study was to evaluate the effect of adding adjuvants to chemical fungicides to control leaf diseases and spike, as well as on the yield of wheat crop. The experimental design was a randomized block design with 05 treatments: control (no fungicide application i...

  14. Immunology of the gastrointestinal tract and liver

    Energy Technology Data Exchange (ETDEWEB)

    Heyworth, M.F.; Jones, A.L.

    1988-01-01

    This book contains 11 chapters. Some of the chapter titles are: T cells and Other Non-B Lymphocytes; Mucosal Mast Cells and IgE; Genetic Aspects of Gastrointestinal Immunology; Immunological Functions of the Liver; Lymphocyte Migration and Mucosal Immunity; and Immunoglobulin Circulation and Secretion.

  15. The cognitive paradigm and the immunological homunculus.

    Science.gov (United States)

    Cohen, I R

    1992-12-01

    In last month's issue of Immunology Today, Irun Cohen discussed the inadequacies of the clonal selection paradigm and proposed a cognitive paradigm in which preformed internal images guide and restrict the process of clonal activation. Here he clarifies the nature of these internal images, during on concrete examples from the image of infection and the image of self, the immunological homunculus.

  16. 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."

  17. Evolution and conservation of immunological activity.

    Science.gov (United States)

    Vaz, N M

    2006-12-01

    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."

  18. 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.

  19. Immunological treatment of liver tumors

    Institute of Scientific and Technical Information of China (English)

    Maurizio Chiriva-Internati; Fabio Grizzi; Cynthia A Jumper; Everardo Cobos; Paul L Hermonat; Eldo E Frezza

    2005-01-01

    Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored.Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves.Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction,and propose an innovative algorithm.

  20. Molecular imaging applications for immunology.

    Science.gov (United States)

    Hildebrandt, Isabel Junie; Gambhir, Sanjiv Sam

    2004-05-01

    The use of multimodality molecular imaging has recently facilitated the study of molecular and cellular events in living subjects in a noninvasive and repetitive manner to improve the diagnostic capability of traditional assays. The noninvasive imaging modalities utilized for both small animal and human imaging include positron emission tomography (PET), single photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), ultrasound, and computed tomography (CT). Techniques specific to small-animal imaging include bioluminescent imaging (BIm) and fluorescent imaging (FIm). Molecular imaging permits the study of events within cells, the examination of cell trafficking patterns that relate to inflammatory diseases and metastases, and the ability to rapidly screen new drug treatments for distribution and effectiveness. In this paper, we will review the current field of molecular imaging assays (especially those utilizing PET and BIm modalities) and examine how they might impact animal models and human disease in the field of clinical immunology.

  1. 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.

  2. Challenges in early clinical development of adjuvanted vaccines.

    Science.gov (United States)

    Della Cioppa, Giovanni; Jonsdottir, Ingileif; Lewis, David

    2015-06-08

    A three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

  4. Liposomes containing NY‑ESO‑1/tetanus toxoid and adjuvant peptides targeted to human dendritic cells via the Fc receptor for cancer vaccines.

    Science.gov (United States)

    Cruz, Luis J; Rueda, Felix; Simón, Lorena; Cordobilla, Begoña; Albericio, Fernando; Domingo, Joan C

    2014-04-01

    To improve the immunological response against tumors, a vaccine based on nanoliposomes targeted to the Fcg-receptor was developed to enhance the immunogenicity of tumor-associated antigens (TAAs). Using human dendritic cells in vitro, a fragment of the TAA NY-ESO-1 combined with a T-helper peptide from the tetanus toxoid encapsulated in nanoliposomes was evaluated. In addition, peptides Palm-IL-1 and MAP-IFN-g were coadministered as adjuvants to enhance the immunological response. Coadministration of Palm-IL-1 or MAP-IFN-g peptide adjuvants and the hybrid NY-ESO-1-tetanus toxoid (soluble or encapsulated in nanoliposomes without targeting) increased immunogenicity. However, the most potent immunological response was obtained when the peptide adjuvants were encapsulated in liposomes targeted to human dendritic cells via the Fc receptor. This targeted vaccine strategy is a promising tool to activate and deliver antigens to dendritic cells, thus improving immunotherapeutic response in situations in which the immune system is frequently compromised, as in advanced cancers.

  5. Fourth International Conference: Modern Vaccines/Adjuvants Formulation--Impact on Future Development: May 15-17 2013, CHUV, Lausanne, Switzerland.

    Science.gov (United States)

    Tupin, Emmanuel

    2013-09-01

    On the 15-17th of May 2013, about 120 scientists, postdoctoral fellows and professors representing renowned academic institutes and senior scientists and executives from small biotechs, contract research organizations (CROs) and Big Pharma companies, gathered at the Centre Hospitalier Universitaire Vaudois (CHUV) in Lausanne, Switzerland for the 4th international conference on Modern Vaccines and Adjuvants Formulation. Despite this relative small number, the speakers and attendees covered together a very broad field of expertise. Indeed, experts in microbiology, immunology, biochemistry, formulation, virus and nanoparticle characterization, vaccine production, quality control as well as regulatory professionals attended the conference and were able to present their works and discuss new developments within the field of vaccine and adjuvant development, characterization and approval process. This broad diversity was a highpoint of the conference and allowed for a stimulating environment and underlined the complexity of the challenges that the field currently faces in order to develop better or completely new vaccines and adjuvants.

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

    Science.gov (United States)

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

    2016-02-23

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

  7. Birth of the science of immunology.

    Science.gov (United States)

    Schmalstieg, Frank C; Goldman, Armond S

    2010-05-01

    The science of immunology emerged in the last of the 19th and the first of the 20th century. Substantial progress in physics, chemistry and microbiology was essential for its development. Indeed, microorganisms became one of the principal investigative tools of the major founders of that science - Louis Pasteur, Robert Koch, Ilya Ilich Metchnikoff, Paul Ehrlich and Jules Bordet. It is pertinent that these pioneering scientists were born when questioning and exploration were encouraged because of the legacies of the previous century of enlightenment. Mentors greatly aided their development. Their discoveries were shaped by their individual personalities. In turn they developed other contributors to the nascent field. Their discoveries included the types of leukocytes, the roles of neutrophils in inflammation and defence, cellular lysis due to complement, the principles of humoral and cellular immunology, passive and active immunization, tissue antigens, anaphylaxis, anaphylactoid reactions and autoimmunity. Their work formed the basis of modern immunology that developed many decades later. Immunology has enormously impacted our understanding of the pathogenesis, diagnosis and treatment of infections, immune-mediated disorders and inflammation. Burgeoning advances forecast further important clinical applications of immunology. Yet, their applications will be problematic because few physicians sufficiently understand the science. We propose that understanding modern immunology requires a grasp of how that science developed - who made the discoveries, how they were made, their successes and failures, their interactions and debates all reveal the foundation of modern immunology.

  8. 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.

  9. (Neo)adjuvant systemic therapy for melanoma.

    Science.gov (United States)

    van Zeijl, M C T; van den Eertwegh, A J; Haanen, J B; Wouters, M W J M

    2017-03-01

    Surgery still is the cornerstone of treatment for patients with stage II and III melanoma, but despite great efforts to gain or preserve locoregional control with excision of the primary tumour, satellites, intransits, sentinel node biopsy and lymphadenectomy, surgery alone does not seem to improve survival any further. Prognosis for patients with high risk melanoma remains poor with 5-year survival rates of 40 to 80%. Only interferon-2b has been approved as adjuvant therapy since 1995, but clinical integration is low considering the high risk-benefit ratio. In recent years systemic targeted- and immunotherapy have proven to be beneficial in advanced melanoma and could be a promising strategy for (neo)adjuvant treatment of patients with resectable high risk melanomas as well. Randomised, placebo- controlled phase III trials on adjuvant systemic targeted- and immunotherapy are currently being performed using new agents like ipilimumab, pembrolizumab, nivolumab, vemurafenib and dabrafenib plus trametinib. In this article we review the literature on currently known adjuvant therapies and currently ongoing trials of (neo)adjuvant therapies in high risk melanomas.

  10. 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.

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

    Science.gov (United States)

    Tynan, Graham A; Hearnden, Claire H; Oleszycka, Ewa; Lyons, Claire L; Coutts, Graham; O'Connell, Jean; Corrigan, Michelle A; Lynch, Lydia; Campbell, Matthew; Callanan, John J; Mok, Kenneth H; Geoghegan, Justin; O'Farrelly, Cliona; Allan, Stuart M; Roche, Helen M; O'Shea, Donal B; Lavelle, Ed C

    2014-06-01

    Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody responses to a level comparable to Freund's incomplete adjuvant. The endogenous oils were capable of promoting interleukin (IL)-1α-dependent recruitment of neutrophils and M1-like macrophages, while simultaneously diminishing M2-like macrophages. We found that endogenous oils from subcutaneous and omental adipocytes, and from healthy and unhealthy obese individuals, promoted comparable inflammatory responses. Furthermore, we also confirmed that white adipocytes in visceral fat of metabolically unhealthy obese (MUO) individuals are significantly larger than those in metabolically healthy obese individuals. Since adipocyte size is positively correlated with adipocyte death, we propose that endogenous oils have a higher propensity to be released from hypertrophied visceral fat in MUO individuals and that this is the key factor in driving inflammation. In summary, this study shows that adipocytes contain a potent oil adjuvant which drives IL-1α-dependent proinflammatory responses in vivo.

  12. 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.

  13. 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.

  14. 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

  15. IMMUNOLOGICAL STUDY OF SPONGIFORM ENCEPHALOPATHIES

    Directory of Open Access Journals (Sweden)

    J. Meenupriya

    2013-04-01

    Full Text Available Spongiform encephalopathies, categorized as a subclass of neuro-degenerative diseases and commonly known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. Prion diseases are common among cannibalistic communities; further research has revealed that the infected or malformed prion protein (named PrPsc spreads its virulence to the normal, healthy prion protein (named PrPc when people consume infected tissues. Knowing that a small interaction between normal and infected prion protein creates virulence, this relationship can be studied as a simple antigen-antibody interaction to understand the series of events that transform a normal prion protein into a virulent misfolded protein. Thoroughly modeled and validated structures of both PrPsc and PrPc can be effectively used to map the epitopes and thereby screen the antigen-antibody interaction using docking studies for a particular organism of concern. This simple immunological approach is used to understand the vital interaction between the normal and malformed proteins that is involved in the disease-spreading mechanism. Clarification of this mechanism could be used in various immune- and bioinformatics algorithms to map the interaction epitopes, furthering an understanding of these pathologies.

  16. Immunology of the mammary gland

    Directory of Open Access Journals (Sweden)

    Lazarević Miodrag

    2003-01-01

    Full Text Available The mammary gland is an organ of specific structure whose elementary task is to supply offspring with nutritive and other biologically active substances during the first weeks, or, depending on the species, the first months of life. This prolongs the period of close contact between the mother and her young, which is necessary for their regular growth. Most mammal offspring are born with physiological agammaglobulinaemia, because of the specific structure of the placenta, so that they receive the first specific protection against pathogenic microorganisms through colostrum. Furthermore, this gland is in direct contact with the outer environment through the secretary ducts, so that there are great possibilities for the occurrence of infections. It is therefore necessary to secure protective mechanisms which would prevent such infections. It is clear that there is a distinct connection between the immunological system and the mammary gland, and that link is the central topic of this paper. It presents the basic mechanisms of mammary gland defense which are divided into two categories: nonspecific (innate and specific immune response. The mammary gland secretion contains several types of leukocytes, such as lymphocytes, macrophages, and neutrophiles, as well as 2% epithelial cells. On the average, there are 0.2 x 106 somatic cells in one mililiter of milk. Macrophages account for most of these (58%, as well as lymphocytes (28%, while a smaller number of somatic cells (12% are polymorphonuclears (PMN. The paper considers the characteristics and main functions of these cell types.

  17. Instructive selection and immunological theory.

    Science.gov (United States)

    Lederberg, Joshua

    2002-07-01

    The turning point of modern immunological theory was the advent of the clonal selection theory (Burnet, Talmage - 1957). A useful heuristic in the classification of theoretical models was the contrast of 'instructive' with 'selective' models of the acquisition of information by biological systems. The neo-Darwinian synthesis of the 1940s had consolidated biologists' model of evolution based on prior random variation and natural selection, viz. differential fecundity. While evolution in the large was by then pretty well settled, controversy remained about examples of cellular adaptation to chemical challenges, like induced drug-resistance, enzyme formation and the antibody response. While instructive theories have been on the decline, some clear cut examples can be found of molecular imprinting in the abiotic world, leading, e.g. to the production of specific sorbents. Template-driven assembly, as in DNA synthesis, has remained a paradigm of instructive specification. Nevertheless, the classification may break down with more microscopic scrutiny of the processes of molecular fit of substrates with enzymes, of monomers to an elongating polymer chain, as the reactants often traverse a state space from with activated components are appropriately selected. The same process may be 'instructive' from a holistic, 'selective' from an atomic perspective.

  18. Immunology of Yersinia pestis Infection.

    Science.gov (United States)

    Bi, Yujing

    2016-01-01

    As a pathogen of plague, Yersinia pestis caused three massive pandemics in history that killed hundreds of millions of people. Yersinia pestis is highly invasive, causing severe septicemia which, if untreated, is usually fatal to its host. To survive in the host and maintain a persistent infection, Yersinia pestis uses several stratagems to evade the innate and the adaptive immune responses. For example, infections with this organism are biphasic, involving an initial "noninflammatory" phase where bacterial replication occurs initially with little inflammation and following by extensive phagocyte influx, inflammatory cytokine production, and considerable tissue destruction, which is called "proinflammatory" phase. In contrast, the host also utilizes its immune system to eliminate the invading bacteria. Neutrophil and macrophage are the first defense against Yersinia pestis invading through phagocytosis and killing. Other innate immune cells also play different roles, such as dendritic cells which help to generate more T helper cells. After several days post infection, the adaptive immune response begins to provide organism-specific protection and has a long-lasting immunological memory. Thus, with the cooperation and collaboration of innate and acquired immunity, the bacterium may be eliminated from the host. The research of Yersinia pestis and host immune systems provides an important topic to understand pathogen-host interaction and consequently develop effective countermeasures.

  19. The immunological barriers to xenotransplantation.

    Science.gov (United States)

    Vadori, M; Cozzi, E

    2015-10-01

    The availability of cells, tissues and organs from a non-human species such as the pig could, at least in theory, meet the demand of organs necessary for clinical transplantation. At this stage, the important goal of getting over the first year of survival has been reported for both cellular and solid organ xenotransplantation in relevant preclinical primate models. In addition, xenotransplantation is already in the clinic as shown by the broad use of animal-derived medical devices, such as bioprosthetic heart valves and biological materials used for surgical tissue repair. At this stage, however, prior to starting a wide-scale clinical application of xenotransplantation of viable cells and organs, the important obstacle represented by the humoral immune response will need to be overcome. Likewise, the barriers posed by the activation of the innate immune system and coagulative pathway will have to be controlled. As far as xenogeneic nonviable xenografts, increasing evidence suggests that considerable immune reactions, mediated by both innate and adaptive immunity, take place and influence the long-term outcome of xenogeneic materials in patients, possibly precluding the use of bioprosthetic heart valves in young individuals. In this context, the present article provides an overview of current knowledge on the immune processes following xenotransplantation and on the possible therapeutic interventions to overcome the immunological drawbacks involved in xenotransplantation.

  20. Mycophenolate mofetil as adjuvant in pemphigus vulgaris

    Directory of Open Access Journals (Sweden)

    Sarma Nilendu

    2007-01-01

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

  1. Adjuvant chemotherapy in early breast cancer

    DEFF Research Database (Denmark)

    Ejlertsen, Bent

    2016-01-01

    % of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast...... are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials...... adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours...

  2. 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.

  3. Microbiota Influences Vaccine and Mucosal Adjuvant Efficacy

    Science.gov (United States)

    2017-01-01

    A symbiotic relationship between humans and the microbiota is critical for the maintenance of our health, including development of the immune system, enhancement of the epithelial barrier, and acquisition of nutrients. Recent research has shown that the microbiota impacts immune cell development and differentiation. These findings suggest that the microbiota may also influence adjuvant and vaccine efficacy. Indeed, several factors such as malnutrition and poor sanitation, which affect gut microbiota composition, impair the efficacy of vaccines. Although there is little evidence that microbiota alters vaccine efficacy, further understanding of human immune system-microbiota interactions may lead to the effective development of adjuvants and vaccines for the treatment of diseases. PMID:28261017

  4. [Adjuvant chemotherapy for patients with rectal cancer].

    Science.gov (United States)

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  5. Adjuvants and vector systems for allergy vaccines.

    Science.gov (United States)

    Moingeon, Philippe; Lombardi, Vincent; Saint-Lu, Nathalie; Tourdot, Sophie; Bodo, Véronique; Mascarell, Laurent

    2011-05-01

    Allergen-specific immunotherapy represents a curative treatment of type I allergies. Subcutaneous immunotherapy is conducted with allergens adsorbed on aluminum hydroxide or calcium phosphate particles, whereas sublingual immunotherapy relies on high doses of soluble allergen without any immunopotentiator. There is a potential benefit of adjuvants enhancing regulatory and Th1 CD4+T cell responses during specific immunotherapy. Molecules affecting dendritic cells favor the induction of T regulatory cell and Th1 responses and represent valid candidate adjuvants for allergy vaccines. Furthermore, the interest in viruslike particles and mucoadhesive particulate vector systems, which may better address the allergen(s) to tolerogenic antigen-presenting cells, is documented.

  6. Ocular diseases: immunological and molecular mechanisms

    Directory of Open Access Journals (Sweden)

    Jing Song

    2016-05-01

    Full Text Available Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

  7. Multiscale modelling in immunology: a review.

    Science.gov (United States)

    Cappuccio, Antonio; Tieri, Paolo; Castiglione, Filippo

    2016-05-01

    One of the greatest challenges in biomedicine is to get a unified view of observations made from the molecular up to the organism scale. Towards this goal, multiscale models have been highly instrumental in contexts such as the cardiovascular field, angiogenesis, neurosciences and tumour biology. More recently, such models are becoming an increasingly important resource to address immunological questions as well. Systematic mining of the literature in multiscale modelling led us to identify three main fields of immunological applications: host-virus interactions, inflammatory diseases and their treatment and development of multiscale simulation platforms for immunological research and for educational purposes. Here, we review the current developments in these directions, which illustrate that multiscale models can consistently integrate immunological data generated at several scales, and can be used to describe and optimize therapeutic treatments of complex immune diseases.

  8. 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 ca

  9. Half a century of Dutch transplant immunology.

    Science.gov (United States)

    van Rood, Jon J; Claas, Frans H J; Brand, Anneke; Tilanus, Marcel G J; van Kooten, Cees

    2014-12-01

    The sixties have not only witnessed the start of the Dutch Society for Immunology (NvvI), but were also the flourishing beginning of the discipline of transplant immunology. The interest in immunology in the Netherlands had its start in the context of blood transfusions and not for instance in the field of infectious disease, as in many other countries. It began in the 1950-ties thanks to Joghem van Loghem at that time director of the Central Laboratory of Blood Transfusion in Amsterdam. The discoveries of these times have had major impact for transfusion medicine, hematopoietic stem cell transplantation and organ transplantation. In this review we will look back at some early highlights of Dutch transplant immunology and put them in the perspective of some recent developments.

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

    African Journals Online (AJOL)

    1991-02-02

    Feb 2, 1991 ... immunological abnormalities noted were a positive rheumatoid factor (78,9%), positive ... Rheumatoid arthritis (RA) is a systemic disease characterised by the occurrence of articular and ..... treatment. Br Med] 1982; 285: ...

  11. 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

  12. 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

  13. The pluripotent history of immunology. A review

    Directory of Open Access Journals (Sweden)

    Neeraja Sankaran

    2012-09-01

    Full Text Available The historiography of immunology since 1999 is reviewed, in part as a response to claims by historians such as Thomas Söderqvist the field was still immature at the time (Söderqvist & Stillwell 1999. First addressed are the difficulties, past and present, surrounding the disciplinary definition of immunology, which is followed by a commentary on the recent scholarship devoted to the concept of the immune self. The new literature on broad immunological topics is examined and assessed, and specific charges leveled against the paucity of certain types of histories, e.g. biographical and institutional histories, are evaluated. In conclusion, there are compelling indications that the history of immunology has moved past the initial tentative stages identified in the earlier reviews to become a bustling, pluripotent discipline, much like the subject of its scrutiny, and that it continues to develop in many new and exciting directions.

  14. Modeling-Enabled Systems Nutritional Immunology

    Directory of Open Access Journals (Sweden)

    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.

  15. Immunologic, hemodynamic, and adrenal incompetence in cirrhosis

    DEFF Research Database (Denmark)

    Risør, Louise Madeleine; Bendtsen, Flemming; Møller, Søren

    2015-01-01

    dysfunction, but is not responsive to volume expansion. Recent research indicates that development of hepatic nephropathy represents a continuous spectrum of functional and structural dysfunction and may be precipitated by the inherent immunologic, adrenal, and hemodynamic incompetence in cirrhosis. New...... research explores several new markers of renal dysfunction that may replace serum creatinine in the future and give new insight on the hepatic nephropathy. Our understanding of the pathophysiological mechanisms causing the immunologic, adrenal, and hemodynamic incompetence, and the impact on renal...

  16. 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.

  17. Immunology of allergic contact dermatitis.

    Science.gov (United States)

    Tončić, Ružica Jurakić; Lipozenčić, Jasna; Martinac, Ivana; Gregurić, Sanja

    2011-01-01

    Allergic contact dermatitis (ACD) is a T-cell mediated skin inflammation caused by repeated skin exposure to contact allergens. This review summarizes current knowledge on the immunology of ACD. Different phases in ACD are distinguished, i.e. sensitization, elicitation and resolution phases. We discuss contact allergen presentation and the central role of antigen presenting cells during sensitization phase. There is an extremely complex interaction of different kinds of immune cells, such as antigen presenting cells, T, B, NK lymphocytes, keratinocytes (KCs), endothelium, mast cells (MCs) and platelets, and this complex interaction is guided through orchestration of numerous cytokines and chemokines. The role of adaptive immunity has been recognized in contact hypersensitivity but we also discuss the important role of some parts of innate immunity such as natural killer T lymphocytes (NKT) and complement system. Cooperation of innate and adaptive immunity, in this case NK cells and B cells, initiates elicitation phase by complement cascade activation, vasoactive substance release and endothelial activation. KCs are not only innocent bystanders, on the contrary, they are involved in all phases of ACD, from the early phase of initiation through sending "danger" signals and activation of innate immunity, through their role in Langerhans cells (LCs) migration, T-cell trafficking, through the height of the inflammatory phase with direct interactions with epidermotropic T-cells, and finally through the resolution phase with the production of anti-inflammatory cytokines and tolerogenic presentation to effector T-cells. Th-1 and Th-17 cells are the main effector cells responsible for tissue damage. At the end, we point out several subsets of T regulatory cells, which exert down-regulatory function and regulate the magnitude and duration of inflammatory reaction.

  18. 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.

  19. Cancer immunology for the clinician.

    Science.gov (United States)

    Weiner, Louis M

    2015-05-01

    Cancer immunotherapy is coming of age. It has become abundantly clear that immunotherapy-which has been described as treating the body's immune system so the immune system can treat the cancer-can be routinely effective, and may indeed cure advanced cancers. Accordingly, it is important to understand the basic, clinically relevant principles of cancer immunology to better prepare for an increasingly exciting future. The host immune system is the only active enemy faced by a malignant cell population as it develops. So it is helpful to think of the battle between the cancer cell population and the developing cancer as a Darwinian crucible in which only the malignant cells most fit to thrive in the face of active immune system attack are able to survive in the reluctant host. All successful cancers thus have overcome the defenses mounted by host immune systems by actively thwarting the evolution of anticancer immunity. A malignant cell population that has "solved" the riddle of the host immune system need not employ all of these mechanisms in order to survive in a particular host. Hence, it may be that the dominant mechanism or mechanisms of immune evasion in fact represent potential Achilles' heels that can be therapeutically attacked to restore immune control of a cancer. To better understand where opportunities exist for immunotherapy, it is important to first consider how developing cancers overcome host immunity: by overwhelming, hiding from, subverting, shielding from, defending against, and outlasting the host immune response. Clearly, more than one of these mechanisms may be present in any particular patient, but it is likely that many cancer types employ dominant immune defense mechanisms. There can be no doubt that mobilizing the immune system to attack a cancer, remember the enemy, and continually target emerging clones represents an extremely promising path to cancer prevention and cure.

  20. Gaps in knowledge and prospects for research of adjuvanted vaccines.

    Science.gov (United States)

    Seder, Robert; Reed, Steven G; O'Hagan, Derek; Malyala, Padma; D'Oro, Ugo; Laera, Donatello; Abrignani, Sergio; Cerundolo, Vincenzo; Steinman, Lawrence; Bertholet, Sylvie

    2015-06-08

    A panel of researchers working in different areas of adjuvanted vaccines deliberated over the topic, "Gaps in knowledge and prospects for research of adjuvanted vaccines" at, "Enhancing Vaccine Immunity and Value" conference held in July 2014. Several vaccine challenges and applications for new adjuvant technologies were discussed.

  1. Review article: surgical, neo-adjuvant and adjuvant management strategies in biliary tract cancer.

    Science.gov (United States)

    Skipworth, J R A; Olde Damink, S W M; Imber, C; Bridgewater, J; Pereira, S P; Malagó, M

    2011-11-01

    The majority of patients with cholangiocarcinoma present with advanced, irresectable tumours associated with poor prognosis. The incidence and mortality rates associated with cholangiocarcinoma continue to rise, mandating the development of novel strategies for early detection, improved resection and treatment of residual lesions. To review the current evidence base for surgical, adjuvant and neo-adjuvant techniques in the management of cholangiocarcinoma. A search strategy incorporating PubMed/Medline search engines and utilising the key words biliary tract carcinoma; cholangiocarcinoma; management; surgery; chemotherapy; radiotherapy; photodynamic therapy; and radiofrequency ablation, in various combinations, was employed. Data on neo-adjuvant and adjuvant techniques remain limited, and much of the literature concerns palliation of inoperable disease. The only opportunity for long-term survival remains surgical resection with negative pathological margins or liver transplantation, both of which remain possible in only a minority of selected patients. Neo-adjuvant and adjuvant techniques currently provide only limited success in improving survival. The development of novel strategies and treatment techniques is crucial. However, the shortage of randomised controlled trials is compounded by the low feasibility of conducting adequately powered trials in liver surgery, due to the large sample sizes that are required. © 2011 Blackwell Publishing Ltd.

  2. An adjuvanted inactivated murine cytomegalovirus (MCMV) vaccine induces potent and long-term protective immunity against a lethal challenge with virulent MCMV

    Science.gov (United States)

    2014-01-01

    Background Human cytomegalovirus (HCMV) is a ubiquitous pathogen that causes serious problems in immunocompromised or immunologically immature hosts. Vaccination is the preferred approach for prevention of HCMV infection, but so far no approved HCMV vaccine is available. In this study, we assessed the immunogenicity and protective immunity of a formalin-inactivated murine cytomegalovirus vaccine (FI-MCMV) in a mouse model in combination with adjuvants MF59, alum, or chitosan. Methods Specific-pathogen-free BALB/c mice aged 6–8 weeks were immunized twice, 3 weeks apart, with various doses of FI-MCMV (0.25 μg, 1 μg, 4 μg) with or without adjuvant. Mice were challenged with a lethal dose (5 × LD50) of a more virulent mouse salivary gland-passaged MCMV 3 weeks after the second immunization. The protective immunity of the vaccine was evaluated by determining the survival rates, residual spleen and salivary gland viral loads, body weight changes, and serum anti-MCMV IgG titers. Results Immunization with FI-MCMV vaccine induced a high level of specific antibody response. Antigen sparing was achieved by the addition of an adjuvant, which significantly enhanced the humoral response to vaccine antigens with a wide range of doses. The level of live virus detected in the spleen on day 5 and in the salivary glands on day 21 after the lethal challenge was significantly lower in adjuvant-treated groups than in controls. Survival rates in adjuvant-treated groups also increased significantly. Furthermore, these protective immune responses were sustained for at least 6 months following immunization. Conclusions These results show that inactivated MCMV vaccine is effective, and that the adjuvanted FI-MCMV vaccine provides more effective and longer-term protection than the adjuvant-free vaccine. PMID:24720840

  3. Effect of incorporation of the adjuvant Quil A on structure and immune stimulatory capacity of liposomes.

    Science.gov (United States)

    Demana, Patrick H; Fehske, Christian; White, Karen; Rades, Thomas; Hook, Sarah

    2004-10-01

    Liposomes have been widely used as drug delivery systems for many years. However, they are of limited use as delivery systems for subunit vaccines due to their low immunogenicity. Here we examine the effect of incorporating the adjuvant Quil A into liposomes on the type of particles produced, on the ability of the different particles to incorporate antigen and on the ability of the different particles to stimulate murine bone-marrow-derived dendritic cells (DC) and lymphocytes. The incorporation of increasing amounts of Quil A, from 20% to 70% of the total lipid into liposomes, reduces the size of the particles that form in aqueous dispersion and decreases antigen incorporation and uptake by DC. Interestingly, the particles with 20% Quil A were more toxic to cells in culture than the particles containing 70% Quil A, and the 20% particles were also more immunostimulatory. Copyright 2004 Australasian Society for Immunology Inc.

  4. Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies

    Directory of Open Access Journals (Sweden)

    Guadalupe Veronica Suarez

    2015-01-01

    Full Text Available Worldwide, around 14 million individuals are coinfected with both tuberculosis (TB and human immunodeficiency virus (HIV. In coinfected individuals, both pathogens weaken immunological system synergistically through mechanisms that are not fully understood. During both HIV and TB infections, there is a chronic state of inflammation associated to dramatic changes in immune cytokine and endocrine hormone levels. Despite this, the relevance of immunoendocrine interaction on both the orchestration of an effective immune response against both pathogens and the control of the chronic inflammation induced during HIV, TB, or both infections is still controversial. The present study reviews immunoendocrine interactions occurring during HIV and TB infections. We also expose our own findings on immunoendocrine cross talk in HIV-TB coinfection. Finally, we evaluate the use of adrenal hormones and their derivatives in immune-therapy and discuss the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients.

  5. 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.

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

    Science.gov (United States)

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-08

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. [Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer].

    Science.gov (United States)

    Gu, Jin; Chen, Pengju

    2015-10-01

    The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

  8. 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.

  9. Genetic and immunological features of aggressive periodontitis

    Directory of Open Access Journals (Sweden)

    Miguel Angel MUÑOZ

    2010-03-01

    Full Text Available clinicians and researchers due to its rapid progression and its evidences of genetic character. Different theories have tried to explain the individual differences in susceptibility, where genetic and immunological assays have assumed great importance. The purpose of this study was to review the literature in order to comprehend the genetic and immunological features of aggressive periodontitis. Literature review: Articles were examined, specifically the ones dealing with information regarding genetic and/or immunological studies of individuals related to their disease susceptibility. Conclusions: In the presence of dental biofilm, host susceptibility to aggressive periodontitis varies among regions, countries and races. Immune-inflammatory processes that seem to be modified in aggressive periodontitis patients may be transmitted vertically, explaining familial aggregation associated with this disease.

  10. Sensing Danger: Innate Immunology for Intrusion Detection

    CERN Document Server

    Uwe, Aickelin

    2008-01-01

    The immune system provides an ideal metaphor for anomaly detection in general and computer security in particular. Based on this idea, artificial immune systems have been used for a number of years for intrusion detection, unfortunately so far with little success. However, these previous systems were largely based on immunological theory from the 1970s and 1980s and over the last decade our understanding of immunological processes has vastly improved. In this paper we present two new immune inspired algorithms based on the latest immunological discoveries, such as the behaviour of Dendritic Cells. The resultant algorithms are applied to real world intrusion problems and show encouraging results. Overall, we believe there is a bright future for these next generation artificial immune algorithms.

  11. Immunological alterations in hepatitis C virus infection.

    Science.gov (United States)

    Calvaruso, Vincenza; Craxì, Antonio

    2013-12-21

    A higher prevalence of immunological processes has recently been reported in patients with hepatitis C virus (HCV) infection, focusing the attention of physicians and researchers on the close association between HCV and immune disorders. HCV lymphotropism represents the most important step in the pathogenesis of virus-related immunological diseases and experimental, virologic, and clinical evidence has demonstrated a trigger role for HCV both in systemic autoimmune diseases, such as rheumatoid arthritis, Sjögren syndrome, hemolytic anemia and severe thrombocytopenia, and in organ-specific autoimmune diseases, such as autoimmune hepatitis, thyroid disorders and diabetes. This review will outline the principal aspects of such HCV-induced immunological alterations, focusing on the prevalence of these less characterized HCV extrahepatic manifestations.

  12. 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.

  13. 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.

  14. 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....

  15. Cancer immunology and colorectal cancer recurrence.

    Science.gov (United States)

    Vannucci, Luca

    2011-06-01

    The recurrence of a cancer - local or distant (metastasis) - is manifested by the persistence of cancer cells in the organism after the ablation of the primary lesion, an ineffective anticancer immune response, and by the activity of biological/immunological factors that can stimulate and sustain its development. This review focuses on colorectal carcinoma and discusses some aspects of cancer immunology regarding cancer development and its recurrence. It is addressed also to the clinician to provide new insights helpful for designing better therapeutic strategies and patient's follow up. Therapeutic approaches used during and after surgical treatments, found capable of modulating immunity (differently affecting disease outcome), will also be described.

  16. 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...

  17. Current research status of immunology in the genomic era

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    This review updates the current status of immunology research under the influence of genomics,both conceptually and technologically.It particularly highlights the advantages of employing the high-throughput and large-scale technology,the large genomic database,and bioinformatic power in the immunology research.The fast development in the fields of basic immunology,clinical immunology(tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic strategy.We also speculate the future research directions of immunology in the era of genomics and post-genomics.

  18. Current research status of immunology in the genomic era

    Institute of Scientific and Technical Information of China (English)

    LI HaoWen; LI dinZhi; ZHAO GuoPing; WANG Ying

    2009-01-01

    This review updates the current status of immunology research under the influence of genomics, both conceptually and technologically. It particularly highlights the advantages of employing the high-throughput and large-scale technology, the large genomic database, and bioinformatic power in the immunology research. The fast development in the fields of basic immunology, clinical immunology (tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic strategy. We also speculate the future research directions of immunology in the era of genomics and post-genomics.

  19. Effects of oral administration of type Ⅱ collagen on adjuvant arthritis in rat sand its mechanisms

    Institute of Scientific and Technical Information of China (English)

    胡永秀; 赵文明; 钱娴娟; 张力平

    2003-01-01

    Objective To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly.Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN-γ and TNF-α i n articular steep in rats.Results Oral administration of CⅡ was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CⅡ were stronger than those by Tripterygium Polyglycoside. Oral administration of CⅡ inhibi ted antigen-specific immune response, such as DTH and antibody reaction to CⅡ . In addition, the expression of IFN-γ and TNF-α in joints were locally dow nregulated. Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-γ and TNF-α, and the suppression of cell immunity.

  20. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    OpenAIRE

    2015-01-01

    Glucocorticoids (GCs), synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bact...

  1. 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.

  2. Adjuvant and neoadjuvant treatment in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

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

  3. 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

  4. Adjuvant chemotherapy for early-stage cervical cancer.

    Science.gov (United States)

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-04-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  5. 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 subsequent activation of

  6. Pathogen evolution and the immunological niche.

    Science.gov (United States)

    Cobey, Sarah

    2014-07-01

    Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. © 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  7. 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.

  8. Effects of the phosphodiesterase 4 inhibitor RPR 73401 in a model of immunological inflammation.

    Science.gov (United States)

    Ehinger, A M; Gorr, G; Hoppmann, J; Telser, E; Ehinger, B; Kietzmann, M

    2000-03-24

    The study was performed to investigate effects of the phosphodiesterase 4 inhibitor RPR 73401 [N-(3, 5-dichloropyrid-4-yl)-3-cyclopentyl-oxy-4-methoxybenzamid] on an allergic skin reaction. To simulate an immunological inflammation, BALB/c mice were sensitized to dinitrochlorobenzene or toluenediisocyanate. At first, the abdominal skin was shaved and 50 microliter Freund's adjuvant were injected intracutaneously once. Then, the horny layer was removed by adhesive tape stripping and 100 microliter 0.5% dinitrochlorobenzene or 5% toluenediisocyanate were administered on the epidermis for 4 days. After repeated local treatment of the ear skin with 20 microliter 3% RPR 73401 or intraperitoneal administration of 1 and 5 mg/kg RPR 73401, 20 microliter 1% dinitrochlorobenzene or 0.5% toluenediisocyanate were given topically as a challenge. The vehicle controls showed a high increase in ear thickness over 48 h after challenge, whereas RPR 73401 administered on either route reduced this increase significantly. Nevertheless after topical administration, RPR 73401 had a longer lasting effect. These and other results may point to an indication for RPR 73401 in immunological dermatitis.

  9. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  10. 21 CFR 866.5230 - Colostrum immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Colostrum immunological test system. 866.5230... Colostrum immunological test system. (a) Identification. A colostrum immunological test system is a device... colostrum. Colostrum is a substance excreted by the mammary glands during pregnancy and until production...

  11. 21 CFR 866.5340 - Ferritin immunological test system.

    Science.gov (United States)

    2010-04-01

    ...-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340... Ferritin immunological test system. (a) Identification. A ferritin immunological test system is a device...

  12. Preface to the Publication of Cellular & Molecular Immunology

    Institute of Scientific and Technical Information of China (English)

    Wei-Feng Chen; Kuang-Yen Chou

    2004-01-01

    @@ Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and provided insights into creating a better environment for contemporary human existence.

  13. Preface to the Publication of Cellular & Molecular Immunology

    Institute of Scientific and Technical Information of China (English)

    Wei-FengChen; Kuang-YenChou

    2004-01-01

    Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and

  14. 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

  15. Immunogenicity and immunization costs of adjuvanted versus non-adjuvanted hepatitis B vaccine in chronic kidney disease patients.

    Science.gov (United States)

    Vilajeliu, Alba; Sequera, Víctor-Guillermo; García-Basteiro, Alberto L; Sicuri, Elisa; Aldea, Marta; Velasco, César; Bayas, José M

    2016-09-01

    Hepatitis B virus (HBV) vaccination is recommended for all susceptible chronic pre-hemodialysis and hemodialysis patients. This study assessed the immunogenicity of HBV vaccines (adjuvanted and non-adjuvanted) in chronic kidney disease patients vaccinated at the Hospital Clinic of Barcelona (Spain) between January 2007 and July 2012. In addition, the costs for the health system were evaluated accor-ding to the proportion of vaccine responders after receiving either vaccine. Patients receiving 3 doses of hepatitis B adjuvanted vaccine were 3 times more likely to seroconvert than patients immunized with non-adjuvanted vaccines, OR 3.56 (95% CI 1.84-6.85). This resulted in fewer patients requiring a second course of HBV vaccination and fewer outpatient visits, saving more than €9,500 per 100 patients. The higher immunogenicity of the adjuvanted HBV vaccine would counterbalance the lower costs associated with the non-adjuvanted vaccine.

  16. 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.

  17. 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

  18. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

    Science.gov (United States)

    Coler, Rhea N; Bertholet, Sylvie; Moutaftsi, Magdalini; Guderian, Jeff A; Windish, Hillarie Plessner; Baldwin, Susan L; Laughlin, Elsa M; Duthie, Malcolm S; Fox, Christopher B; Carter, Darrick; Friede, Martin; Vedvick, Thomas S; Reed, Steven G

    2011-01-26

    Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR) 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA). We assessed the effects of GLA on murine and human dendritic cells (DC) by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL) on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC). When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative T(H)1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.

  19. Development and characterization of synthetic glucopyranosyl lipid adjuvant system as a vaccine adjuvant.

    Directory of Open Access Journals (Sweden)

    Rhea N Coler

    Full Text Available Innate immune responses to vaccine adjuvants based on lipopolysaccharide (LPS, a component of gram-negative bacterial cell walls, are driven by Toll-like receptor (TLR 4 and adaptor proteins including MyD88 and TRIF, leading to the production of inflammatory cytokines, type I interferons, and chemokines. We report here on the characterization of a synthetic hexaacylated lipid A derivative, denoted as glucopyranosyl lipid adjuvant (GLA. We assessed the effects of GLA on murine and human dendritic cells (DC by combining microarray, mRNA and protein multiplex assays and flow cytometry analyses. We demonstrate that GLA has multifunctional immunomodulatory activity similar to naturally-derived monophosphory lipid A (MPL on murine DC, including the production of inflammatory cytokines, chemokines, DC maturation and antigen-presenting functions. In contrast, hexaacylated GLA was overall more potent on a molar basis than heterogeneous MPL when tested on human DC and peripheral blood mononuclear cells (PBMC. When administered in vivo, GLA enhanced the immunogenicity of co-administered recombinant antigens, producing strong cell-mediated immunity and a qualitative T(H1 response. We conclude that the GLA adjuvant stimulates and directs innate and adaptive immune responses by inducing DC maturation and the concomitant release of pro-inflammatory cytokines and chemokines associated with immune cell trafficking, activities which have important implications for the development of future vaccine adjuvants.

  20. 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.

  1. Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 agonist, promotes potent systemic and mucosal responses to intranasal immunization with HIVgp140.

    Science.gov (United States)

    Arias, Mauricio A; Van Roey, Griet A; Tregoning, John S; Moutaftsi, Magdalini; Coler, Rhea N; Windish, Hillarie P; Reed, Steven G; Carter, Darrick; Shattock, Robin J

    2012-01-01

    Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular immune responses in both the systemic and mucosal compartments. Based on the known immunological linkage between the upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for the induction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 together with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA) and responses were compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatly enhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG and IgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with high numbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cell responses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Our results show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses, both systemically and mucosally.

  2. Glucopyranosyl Lipid Adjuvant (GLA, a Synthetic TLR4 agonist, promotes potent systemic and mucosal responses to intranasal immunization with HIVgp140.

    Directory of Open Access Journals (Sweden)

    Mauricio A Arias

    Full Text Available Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular immune responses in both the systemic and mucosal compartments. Based on the known immunological linkage between the upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for the induction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 together with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA and responses were compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatly enhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG and IgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with high numbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cell responses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Our results show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses, both systemically and mucosally.

  3. 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.

  4. 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.

  5. 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.

  6. Understanding liver immunology using intravital microscopy.

    Science.gov (United States)

    Marques, Pedro Elias; Oliveira, André Gustavo; Chang, Lynne; Paula-Neto, Heitor Affonso; Menezes, Gustavo Batista

    2015-09-01

    The liver has come a long way since it was considered only a metabolic organ attached to the gastrointestinal tract. The simultaneous ascension of immunology and intravital microscopy evidenced the liver as a central axis in the immune system, controlling immune responses to local and systemic agents as well as disease tolerance. The multiple hepatic cell populations are organized in a vascular environment that promotes intimate cellular interactions, including initiation of innate and adaptive immune responses, rapid leukocyte recruitment, pathogen clearance and production of a variety of immune mediators. In this review, we focus on the advances in liver immunology supported by intravital microscopy in diseases such as isquemia/reperfusion, acute liver injury and infections.

  7. 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.

  8. 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.

  9. 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.

  10. 21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

    Science.gov (United States)

    2010-04-01

    ...: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3010 Adjuvant... weight of finished foamed polyethylene. 1,1-Difluoroethane (CAS Reg. No. 75-37-6) For use as a blowing...

  11. Immunological memory within the innate immune system

    OpenAIRE

    Sun, J. C.; Ugolini, S.; Vivier, E

    2014-01-01

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which hav...

  12. Rapid Advancement of Immunology Study in China

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    The world-renowned Cell Press recently released a new informational supplement--Spotlight on Chi- na-to introduce the rapid developments in the basic and clinical researches in immunology in China. The electronic version of the supplement can be viewed or downloaded for free on the website of the Cell Press (http://www. cell. com/spotlightonchina), and the hard copy will be published along with the new issue of Immunity in November.

  13. Proteomics in immunological reactions to drugs

    OpenAIRE

    Ariza, Adriana; Montañez, M. I.; Pérez-Sala, Dolores

    2011-01-01

    Purpose of review: To discuss the avenues that proteomic techniques are opening for the study of the chemical basis and cellular mechanisms of immunological reactions to drugs. Recent findings: Technical developments in recent years are allowing a detailed characterization of drug–protein interactions. In addition, novel metabolic pathways for drug biotransformation are being uncovered and potential targets for protein haptenation are being proposed that may help in the understanding of t...

  14. Louis Pasteur, the Father of Immunology?

    OpenAIRE

    Kendall A Smith

    2012-01-01

    Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late nineteenth 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 ...

  15. 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.

  16. Photothermal effects of immunologically modified carbon nanotubes

    Science.gov (United States)

    Griswold, Ryan T.; Henderson, Brock; Goddard, Jessica; Tan, Yongqiang; Hode, Tomas; Liu, Hong; Nordquist, Robert E.; Chen, Wei R.

    2013-02-01

    Carbon nanotubes have a great potential in the biomedical applications. To use carbon nanotubes in the treatment of cancer, we synthesized an immunologically modified single-walled carbon nanotube (SWNT) using a novel immunomodifier, glycated chitosan (GC), as an effective surfactant for SWNT. This new composition SWNT-GC was stable due to the strong non-covalent binding between SWNT and GC. The structure of SWNT-GC is presented in this report. The photothermal effect of SWNT-GC was investigated under irradiation of a near-infrared laser. SWNT-GC retained the optical properties of SWNT and the immunological properties of GC. Specifically, the SWNT-GC could selectively absorb a 980-nm light and induce desirable thermal effects in tissue culture and in animals. It could also induce tumor cell destruction, controlled by the laser settings and the doses of SWNT and GC. Laser+SWNT-GC treatment could also induce strong expression of heat shock proteins on the surface of tumor cells. This immunologically modified carbon nanotube could be used for selective photothermal interactions in noninvasive tumor treatment.

  17. Advances in cancer immunology and cancer immunotherapy.

    Science.gov (United States)

    Voena, Claudia; Chiarle, Roberto

    2016-02-01

    After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models.

  18. 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.

  19. 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

  20. 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.

  1. 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...

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

    OpenAIRE

    Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He

    2012-01-01

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

  3. 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.

  4. 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.

  5. Studies on Immunological Effect and Immunological Mechanism Avian Encephalomyelitis Oil Emulsion Inactivated Vaccine

    Institute of Scientific and Technical Information of China (English)

    CHENG Zi-qiang; ZHAO Zhen-hua; RI Mudema

    2002-01-01

    Oil emulsion inactivated vaccine was prepared by susceptible embryos, with different strains of AEV. Four groups of normal chickens of 2 - 7 days of age were given injections for immunization, respectively. Another group was used as control. This study was expected to evaluate the immunological effect and discuss the immunological mechanism by means of five different experiments, i.e. the agar-gel precipitin test,the isolation of lymphokine, the isolation, purification and analysis of blood serum IgG, embryo-susceptibility test, and clinical and pathological examination. The results of these experiments indicated that oil emulsion inactivated vaccine is safe and effective. The chickens were normal when inoculated with AE strong virus after immunity at 4 and 37 weeks. Immunological mechanism is that the humoral immunity played an important role and celluar immunity exists, but it is not important in the process of the resistance to AEV.

  6. Advax-adjuvanted recombinant protective antigen provides protection against inhalational anthrax that is further enhanced by addition of murabutide adjuvant.

    Science.gov (United States)

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

    2014-04-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

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

    Science.gov (United States)

    Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita

    2014-01-01

    Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy. PMID:24554695

  8. 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

    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......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...... 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...

  9. 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......BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... curative resection of colorectal cancer and who do not receive perioperative blood transfusion and do not develop postoperative infectious complications....

  10. Cancer immunology: the search for specificity.

    Science.gov (United States)

    Old, L J

    1982-01-01

    The major focus of cancer immunology has shifted away from arguments about the validity of the immunosurveillance theory of cancer to the more basic question of tumor-specific antigens. Despite vast effort aimed at demonstrations of such antigens, their existence in the generality of cancer remains unproved. Serological analysis of 3 tumor types, mouse leukemia and sarcoma and human malignant melanoma, has received the most attention, and a rudimentary classification of the surface antigens expressed by these tumors has begun to emerge. The prime candidates for antigens that can be considered tumor specific are the few instances of Class 1 antigens that have now been serologically defined on mouse and human tumors. These antigens show an absolute restriction to individual tumors and are not demonstrable on any other normal or malignant cell type. Biochemical and genetic characterizations of Class 1 antigens represent an essential next step in an evaluation of the significance of these antigens. The surprising features of the thymus leukemia (TL) antigens of the mouse provide insight into the genetic origin of another key class of tumor antigens, i.e., those with characteristic properties of both differentiation and tumor-specific antigens. In normal mice, TL antigens are restricted to cells in the thymus, and strains differ with regard to expression versus nonexpression of TL antigens. Genetic information for TL is universal in mice, however, as leukemias that develop in mice normally lacking TL are found to express TL. What is clear from the past two decades of research in cancer immunology is that a far more detailed knowledge of surface antigens of tumor cells will be necessary before we can begin to assess the possibility of immunological control of cancer.

  11. 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...... suitable biological samples. The methods of the present invention are useful in therapeutic and diagnostic protocols for human, livestock and veterinary and wild life applications, thus the invention further relates to a method for diagnosing an infection in a mammal....

  12. 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.

  13. 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.

  14. 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.

  15. Development and controversies of adjuvant therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Pancreatic cancer is an aggressive malignancy with a dismal prognosis. Radical surgery provides the only chance for a cure with a 5-year survival rate of 7%-25%. An effective adjuvant therapy is urgently needed to improve the surgical outcome. This review describes the current status of adjuvant therapy for pancreatic cancer, and highlights its controversies. DATA SOURCES:A Medline database search was performed to identify relevant articles using the keywords"pancreatic neoplasm", and"adjuvant therapy". Additional papers were identiifed by a manual search of the references from the key articles. RESULTS:Eight prospective randomized controlled trials (RCTs) on the use of adjuvant chemotherapy and chemoradiation for pancreatic cancer could be identiifed. The results for adjuvant regimens based on systemic 5-lfuorouracil with or without external radiotherapy were conlficting. The recent two RCTs on gemcitabine based regimen gave promising results. CONCLUSIONS:Based on the available data, no standard adjuvant therapy for pancreatic cancer can be established yet. The best adjuvant regimen remains to be determined in large-scale RCTs. Future trials should use a gemcitabine based regimen.

  16. The role of adjuvant in mediating antigen structure and stability.

    Science.gov (United States)

    Braun, Latoya Jones; Eldridge, Aimee M; Cummiskey, Jessica; Arthur, Kelly K; Wuttke, Deborah S

    2012-04-01

    The purpose of this study was to probe the fate of a model antigen, a cysteine-free mutant of bacteriophage T4 lysozyme, to the level of fine structural detail, as a consequence of its interaction with an aluminum (Al)-containing adjuvant. Fluorescence spectroscopy and differential scanning calorimetry were used to compare the thermal stability of the protein in solution versus adsorbed onto an Al-containing adjuvant. Differences in accessible hydrophobic surface areas were investigated using an extrinsic fluorescence probe, 8-Anilino-1-naphthalenesulfonic acid (ANS). As has been observed with other model antigens, the apparent thermal stability of the protein decreased following adsorption onto the adjuvant. ANS spectra suggested that adsorption onto the adjuvant caused an increase in exposure of hydrophobic regions of the protein. Electrostatic interactions drove the adsorption, and disruption of these interactions with high ionic strength buffers facilitated the collection of two-dimensional (15) N heteronuclear single quantum coherence nuclear magnetic resonance data of protein released from the adjuvant. Although the altered stability of the adsorbed protein suggested changes to the protein's structure, the fine structure of the desorbed protein was nearly identical to the protein's structure in the adjuvant-free formulation. Thus, the adjuvant-induced changes to the protein that were responsible for the reduced thermal stability were not observed upon desorption.

  17. Progress in adjuvant chemotherapy for breast cancer: an overview.

    Science.gov (United States)

    Anampa, Jesus; Makower, Della; Sparano, Joseph A

    2015-01-01

    Breast cancer is the most common cause of cancer and cancer death worldwide. Although most patients present with localized breast cancer and may be rendered disease-free with local therapy, distant recurrence is common and is the primary cause of death from the disease. Adjuvant systemic therapies are effective in reducing the risk of distant and local recurrence, including endocrine therapy, anti-HER2 therapy, and chemotherapy, even in patients at low risk of recurrence. The widespread use of adjuvant systemic therapy has contributed to reduced breast cancer mortality rates. Adjuvant cytotoxic chemotherapy regimens have evolved from single alkylating agents to polychemotherapy regimens incorporating anthracyclines and/or taxanes. This review summarizes key milestones in the evolution of adjuvant systemic therapy in general, and adjuvant chemotherapy in particular. Although adjuvant treatments are routinely guided by predictive factors for endocrine therapy (hormone receptor expression) and anti-HER2 therapy (HER2 overexpression), predicting benefit from chemotherapy has been more challenging. Randomized studies are now in progress utilizing multiparameter gene expression assays that may more accurately select patients most likely to benefit from adjuvant chemotherapy.

  18. 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.

  19. 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.

  20. The influence of iodine on the immunological properties of thyroglobulin and its immunological complexes.

    Science.gov (United States)

    Gardas, A

    1991-01-01

    Several papers described different immunological properties of thyroglobulin (Tg) after iodination. The influence of iodine-iodide solution on the immunological properties of hTg and its immunological complexes with autoantibodies (aAbs) were studied. Human Tg coated to polystyrene plates, incubated for 30 min with iodine-iodide solution at concentration from 1 to 200 microM at pH 9.0 lost its ability to bind aAbs. Preincubation with iodine (2 microM), decreased aAbs binding by 50%. Tg epitope inactivation induced by iodine depended on the buffer pH and the presence of carbonate ions. The binding of rabbit Tg-antibodies to iodine pretreated Tg was only slightly changed. Thyroglobulin preincubation with iodine solutions decreased aAbs binding from all tested sera (67) of patients with autoimmune thyroid disease (AITD). Excess of iodide (0.2 M KJ) or equimolar concentration of diiodotyrosine protects the Tg molecule from iodine induced inactivation. Immunological complexes of Tg with aAbs dissociate at low iodine concentrations. The results suggest that a product of iodine disproportionation reaction induces changes in the Tg molecule and Tg-aAb's complexes leading to complex dissociation or epitope inactivation.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Suzanne Russo

    2012-03-01

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

  4. Immigrants in immunology: the benefits of lax borders.

    Science.gov (United States)

    Stagaman, Keaton; Martinez, Emily S; Guillemin, Karen

    2015-05-01

    The field of immunology has a long history of illuminating fundamental biological processes of critical importance to human health. From an outsider's perspective, the questions are profoundly philosophical and the experimental approaches are elegantly precise. Yet immunology can also appear impenetrable. Here we recount the experience of two graduate students from the fields of ecology and computer science, who have immigrated into immunological terrain attracted by systems-level questions. We argue that such migrations enrich the field of immunology, and that cultural and institutional changes are needed to promote more interdisciplinary explorations.

  5. Immunological response to hepatitis B vaccine in polytransfused thalassemic patients.

    Science.gov (United States)

    Alavian, Seyed-Moayed; Tabatabaei, Seyed-Vahid

    2010-05-01

    Hepatitis B is an important infection in thalassemia patients and prevention by vaccination is needed. Immunological response to hepatitis B vaccine in polytransfused thalassmia patients needs more attention.

  6. Immunological aspects on IDDM in children.

    Science.gov (United States)

    Ludvigsson, J

    1989-01-01

    Diabetes mellitus in childhood is connected to several immunological phenomena which per se do not prove that immunological mechanisms do cause the beta cell destruction, as such mechanisms could be just secondary. However, there is now evidence which strongly supports the autoimmune hypothesis, like the beta-cell destruction in the transplant given from a healthy twin to the diabetic monozygotic co-twin, the effect in newly-diagnosed diabetes of immunosuppression, the passive transfer in experimental animals of an immune process creating diabetes etc. Several facts such as presence of activated T-cells in the insulitis indicate that the cell-mediated immunity is important, while it is still debatable whether humoral factors, and if so which, alone could be responsible for the beta cell destruction. Recently interleukins and other lymphokines have shown to be of great interest as well as the release of free radicals. This knowledge opens new views on the possibility to put an end to or even prevent the beta cell destruction. Rough immunosuppression with cytostatics or cyclosporin has such severe side-effects that such therapy is contra-indicated at least in children. Until more specific therapies are discovered e.g. vaccination with lymphoblasts or blocking the autoantigens with monoclonal antibodies, supportive measures to protect the beta cells may be one practical way.

  7. Bioinformatics for cancer immunology and immunotherapy.

    Science.gov (United States)

    Charoentong, Pornpimol; Angelova, Mihaela; Efremova, Mirjana; Gallasch, Ralf; Hackl, Hubert; Galon, Jerome; Trajanoski, Zlatko

    2012-11-01

    Recent mechanistic insights obtained from preclinical studies and the approval of the first immunotherapies has motivated increasing number of academic investigators and pharmaceutical/biotech companies to further elucidate the role of immunity in tumor pathogenesis and to reconsider the role of immunotherapy. Additionally, technological advances (e.g., next-generation sequencing) are providing unprecedented opportunities to draw a comprehensive picture of the tumor genomics landscape and ultimately enable individualized treatment. However, the increasing complexity of the generated data and the plethora of bioinformatics methods and tools pose considerable challenges to both tumor immunologists and clinical oncologists. In this review, we describe current concepts and future challenges for the management and analysis of data for cancer immunology and immunotherapy. We first highlight publicly available databases with specific focus on cancer immunology including databases for somatic mutations and epitope databases. We then give an overview of the bioinformatics methods for the analysis of next-generation sequencing data (whole-genome and exome sequencing), epitope prediction tools as well as methods for integrative data analysis and network modeling. Mathematical models are powerful tools that can predict and explain important patterns in the genetic and clinical progression of cancer. Therefore, a survey of mathematical models for tumor evolution and tumor-immune cell interaction is included. Finally, we discuss future challenges for individualized immunotherapy and suggest how a combined computational/experimental approaches can lead to new insights into the molecular mechanisms of cancer, improved diagnosis, and prognosis of the disease and pinpoint novel therapeutic targets.

  8. [Clinical and immunological criteria of burn sepsis].

    Science.gov (United States)

    Shlyk, I V; Pivovarova, L P; Krylov, K M; Filippova, O V; Il'ina, V A; Krylov, P K

    2005-01-01

    A hundred and twenty-nine victims aged 16 to 60 years who had skin burns in the area of 15 to 60% of the body surface without severe concomitant somatic disease (SAPS less than 9 scores). The clinical symptoms of a systemic inflammatory response (SIR) and the signs of wound infection were recorded in all the examinees. The victims underwent a comprehensive clinical and laboratory examination, 55 of them were immunologically studied over time (on admission, on days 3 and 10). To reveal the predictive clinical and immunological criteria for sepsis, the examinees were divided into 3 groups. Group 1 comprised 33 burnt persons who were observed to have the symptoms of SIR and the signs of burn wound infections without impaired function of organs and systems. Group 2 included 46 victims with severe sepsis and a good outcome of burn disease. Group 3 consisted of 50 patients who had died from severe sepsis. Analysis of the results of the study has indicated that the count of formed blood elements by calculating the leukocytic intoxication index, the estimation of the level of lysosomal cation proteins in the neutrophilic granulocytes, the detection of populations of T helper cells, cytotoxic lymphocytes, as well as histomorphological and bacteriological findings are early and valid criteria for the development of infectious complications. Their use for the diagnosis and prediction of sepsis permits initiation of its treatment at early stages, without awaiting the appearance of the signs of a septic process.

  9. Uncertainty of measurement: an immunology laboratory perspective.

    Science.gov (United States)

    Beck, Sarah C; Lock, Robert J

    2015-01-01

    'Measurement uncertainty of measured quantity values' (ISO15189) requires that the laboratory shall determine the measurement uncertainty for procedures used to report measured quantity values on patients' samples. Where we have numeric data measurement uncertainty can be expressed as the standard deviation or as the co-efficient of variation. However, in immunology many of the assays are reported either as semi-quantitative (i.e. an antibody titre) or qualitative (positive or negative) results. In the latter context, measuring uncertainty is considerably more difficult. There are, however, strategies which can allow us to minimise uncertainty. A number of parameters can contribute to making measurements uncertain. These include bias, precision, standard uncertainty (expressed as standard deviation or coefficient of variation), sensitivity, specificity, repeatability, reproducibility and verification. Closely linked to these are traceability and standardisation. In this article we explore the challenges presented to immunology with regard to measurement uncertainty. Many of these challenges apply equally to other disciplines working with qualitative or semi-quantitative data.

  10. Immunological and toxinological responses to jellyfish stings.

    Science.gov (United States)

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

    2011-10-01

    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.

  11. The Vaccine Formulation Laboratory: a platform for access to adjuvants.

    Science.gov (United States)

    Collin, Nicolas; Dubois, Patrice M

    2011-07-01

    Adjuvants are increasingly used by the vaccine research and development community, particularly for their ability to enhance immune responses and for their dose-sparing properties. However, they are not readily available to the majority of public sector vaccine research groups, and even those with access to suitable adjuvants may still fail in the development of their vaccines because of lack of knowledge on how to correctly formulate the adjuvants. This shortcoming led the World Health Organization to advocate for the establishment of the Vaccine Formulation Laboratory at the University of Lausanne, Switzerland. The primary mission of the laboratory is to transfer adjuvants and formulation technology free of intellectual property rights to academic institutions, small biotechnology companies and developing countries vaccine manufacturers. In this context, the transfer of an oil-in-water emulsion to Bio Farma, an Indonesian vaccine manufacturer, was initiated to increase domestic pandemic influenza vaccine production capacity as part of the national pandemic influenza preparedness plan.

  12. 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.

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

    African Journals Online (AJOL)

    between adjuvant intrathecal 2 mg midazolam as compared to intrathecal 20 micrograms fentanyl for patients undergoing ... in mental processes, respiratory depression, and other .... nificance level and power of 90%, the required sample.

  14. Editorial: Short-course adjuvant trastuzumab will increase cure rates ...

    African Journals Online (AJOL)

    Editorial: Short-course adjuvant trastuzumab will increase cure rates in patients with human epidermal growth factor receptor 2-positive breast cancer. ... Journal Home > Vol 107, No 8 (2017) >. Log in or Register to get ... from 32 Countries:.

  15. Endometrial adenocarcinoma, adjuvant radiotherapy tailored to prognostic factors.

    Science.gov (United States)

    Meerwaldt, J H; Hoekstra, C J; van Putten, W L; Tjokrowardojo, A J; Koper, P C

    1990-02-01

    The optimal adjuvant radiotherapy for surgically treated endometrial cancer has not yet been defined. We report on 389 patients treated between 1970 and 1985 with adjuvant radiotherapy. The treatment was tailored to the known prognostic factors: myometrial invasion and grade of differentiation of the tumor. Ten-year overall survival was 67%, 10-year relapse-free survival 77%; 23% relapse, of which 21% distant and 6% locoregional relapse. In a multivariate analysis, stage (pT), grade, and myometrial invasion were prognostic factors. The number of locoregional failures was very small (n = 23). This small number, the fact that radiation treatment was tailored to prognostic factors, and the absence of a nontreated control group precluded an analysis of the effect of the adjuvant irradiation. Large randomized studies with a control (no treatment) arm should be performed to determine the value of adjuvant radiotherapy.

  16. Triple negative breast cancer: adjuvant chemotherapy effect on survival

    National Research Council Canada - National Science Library

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    Purpose: The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival.Material/Methods...

  17. Mx bio adjuvant for enhancing immune responses against influenza virus

    Directory of Open Access Journals (Sweden)

    Sina Soleimani

    2015-06-01

    Conclusion: These data revealed that Mx1 as biological adjuvant was able to increase antibody titer and induction memory immune responses against influenza immunization without causing any side effects.

  18. 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)....

  19. 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

  20. Effect of Freund's adjuvant on standard dark and pastel mink.

    Science.gov (United States)

    Tabel, H; Ingram, D G

    1971-04-01

    Following a long series of injections of homologous immunoglobulin in complete and incomplete Freund's adjuvant into mink, a moderate elevation in the level of gammaglobulin in the serum was observed in a few animals. Relatively mild pathological changes also were seen in liver, spleen, lymph nodes, lungs and kidney. It is concluded that the injection of Freund's adjuvant, under the experimental conditions described, produced lesions which were readily distinguishable from the lesions characteristic of aleutian disease of mink.

  1. Molecular and cellular aspects of immunologic tolerance.

    Science.gov (United States)

    Nossal, G J

    1991-12-18

    This review seeks to explain the most exciting recent data concerning the nature of self/non-self discrimination by the immune system in a manner accessible to a biochemical readership. The nature of recognition in the two great lymphocyte families, B cells and T cells, is described with special emphasis on the nature of the ligands recognized by each. The history of the field of immunologic tolerance is surveyed, as are the key experiments on conventional mice which provided a conceptual framework. This suggested that tolerance was essentially due to 'holes' in the recognition repertoires of both the T and B cell populations so that lymphocytes competent to react to self antigens were not part of the immunologic dictionary. There were essentially two ways to achieve this situation. On the one hand, self antigens might 'catch' developing lymphocytes early in their ontogeny and delete the cell, a process of clonal abortion. On the other hand, self antigens might signal lymphocytes (particularly immature cells) in a negative manner, reducing or abolishing their capacity for later responses, without causing death. This process is referred to as clonal anergy. Evidence for both processes exists. Special emphasis is placed on a wave of experimentation beginning in 1988 which imaginatively uses transgenic mouse technology to study tolerance. Transgenic manipulations can produce mice which synthesize foreign antigens in a constitutive and/or inducible manner, sometimes only in specific locations; mice which possess T or B lymphocytes almost all expressing a given receptor of known specificity; and mice which are an immunologic time bomb in that the antigen is present and so too are lymphocytes all endowed with receptors for that antigen. These experiments have vindicated the possibility of both clonal abortion and clonal anergy in both T and B cell populations, the choice of which phenomenon occurs depending on a number of operational circumstances. For T cell tolerance

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

    Science.gov (United States)

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

    2013-05-10

    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 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 parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations.

  3. Incorporation of a synthetic mycobacterial monomycoloyl glycerol analogue stabilizes dimethyldioctadecylammonium liposomes and potentiates their adjuvant effect in vivo.

    Science.gov (United States)

    Nordly, Pernille; Korsholm, Karen Smith; Pedersen, Esra Alici; Khilji, Tayba Sajid; Franzyk, Henrik; Jorgensen, Lene; Nielsen, Hanne Mørck; Agger, Else Marie; Foged, Camilla

    2011-01-01

    The combination of delivery systems such as cationic liposomes and immunopotentiating molecules is a promising approach for the rational design of vaccine adjuvants. In this study, a synthetic analogue of the mycobacterial lipid monomycoloyl glycerol (MMG), referred to as MMG-1, was synthesized and combined with the cationic surfactant dimethyldioctadecylammonium (DDA). The purpose of the study was to provide a thorough pharmaceutical characterization of the resulting DDA/MMG-1 binary system and to evaluate how incorporation of MMG-1 affected the adjuvant activity of DDA liposomes. Thermal analyses demonstrated that MMG-1 was incorporated into the DDA lipid bilayers, and cryo-transmission electron microscopy (TEM) confirmed that liposomes were formed. The particles had a polydisperse size distribution and an average diameter of approximately 400 nm. Evaluation of the colloidal stability indicated that at least 18 mol% MMG-1 was required to stabilize the DDA liposomes as the average particle size remained constant during storage for 6 months. The improved colloidal stability is most likely caused by increased hydration of the lipid bilayer. This was demonstrated by studying Langmuir-Blodgett monolayers of DDA and MMG-1 which revealed an increased surface pressure in the presence of high concentrations of MMG-1 when the DDA/MMG-1 monolayers were fully compressed, indicating an increased interaction with water due to enhanced hydration of the lipid head groups. Finally, immunization of mice with the tuberculosis fusion antigen Ag85B-ESAT-6 and DDA/MMG-1 liposomes induced a strong cell-mediated immune response characterized by a mixed Th1/Th17 profile and secretion of IgG1 and IgG2c antibodies. The Th1/Th17-biased immunostimulatory effect was increased in an MMG-1 concentration-dependent manner with maximal observed effect at 31 mol% MMG-1. Thus, incorporation of 31 mol% MMG-1 into DDA liposomes results in an adjuvant system with favorable physical as well as

  4. Autoimmune/Inflammatory Syndrome Induced by Adjuvants and Thyroid Autoimmunity

    Science.gov (United States)

    Watad, Abdulla; David, Paula; Brown, Stav; Shoenfeld, Yehuda

    2017-01-01

    The autoimmune/inflammatory syndrome induced by adjuvants (ASIA), presented by Shoenfeld and Agmon-Levin in 2011, is an entity that incorporates diverse autoimmune conditions induced by the exposure to various adjuvants. Adjuvants are agents that entail the capability to induce immune reactions. Adjuvants are found in many vaccines and used mainly to increase the response to vaccination in the general population. Silicone has also been reported to be able to induce diverse immune reactions. Clinical cases and series of heterogeneous autoimmune conditions including systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis have been reported to be induced by several adjuvants. However, only a small number of cases of autoimmune thyroid disorder have been included under the umbrella of ASIA syndrome. Indeed, clinical cases of Hashimoto’s thyroiditis and/or subacute thyroiditis were observed after the exposure to vaccines as well as silicone implantation. In our review, we aimed to summarize the current knowledge on ASIA syndrome presented as endocrinopathies, focusing on autoimmune thyroid disorders associated with the various adjuvants. PMID:28167927

  5. 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.

  6. Communicating the role and value of vaccine adjuvants.

    Science.gov (United States)

    Gellin, Bruce G; Salisbury, David M

    2015-06-08

    Despite the inclusion of adjuvants in many routinely used vaccines to improve the immune response, their presence and role are neither clear in product details such as the packaging or in the Summaries of Product Characteristics, nor understood by health professionals or the public. For many vaccines the adjuvant may simply be described as 'Adsorbed' without clarification that the adsorbing onto a material such as aluminium hydroxide adjuvants the antigens. As many future vaccines are likely to be adjuvanted, the presence of adjuvants, either those used in existing vaccines or novel formulations, may raise public and professional concerns unless communication materials are prepared in advance to allay anxieties such as those that have arisen over some present vaccine ingredients such as thiomersal. This raises a dilemma about how active such communications should be: over-promotion of the presence of a new adjuvant may cause unneeded anxieties; under-promotion may raise concerns over concealment of information. Research is needed and appropriate communication materials should be prepared. Copyright © 2015. Published by Elsevier Ltd.

  7. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 6 - Immunology.

    Science.gov (United States)

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed gaps and priorities for FMDV (foot-and-mouth disease virus) research in the field of immunology. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. Improved understanding of FMDV immunology facilitates the development of vaccines, adjuvants and diagnostic tests, and will allow better assessment and prediction of vaccine potency and match, with reduced use of animals, particularly large animals, in experimental studies. Continued characterization of the immune systems of several FMD host species has underpinned substantial advances in knowledge of their interaction with FMDV. Recent studies have shed light on the mechanisms underlying formation of the bovine B- and T-cell response; there is also a greater understanding of the significance of non-neutralizing antibodies during FMDV infection and the interactions of antibody-bound virus with immune cells. This knowledge is directly relevant to vaccine development, as well as understanding protection and cross-protection. Despite ongoing research, significant knowledge gaps remain in the areas of neonatal and mucosal immunity. The impact of maternally derived antibody upon the neonate's ability to respond to FMD vaccination has received some attention, but few firm conclusions can be drawn at this stage, and little is known of the cellular response of young animals in general. The mucosal immune system of FMDV-susceptible species requires continued characterization, especially if the potential of mucosal vaccine-delivery systems is to be realized for FMD immunization.

  8. 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.

  9. 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....

  10. 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....5240 Complement components immunological test system. (a) Identification. A complement components... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids,...

  11. 21 CFR 866.5180 - Fecal calprotectin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fecal calprotectin immunological test system. 866....5180 Fecal calprotectin immunological test system. (a) Identification. A fecal calprotectin... measure, by immunochemical techniques, fecal calprotectin in human stool specimens. The device is...

  12. 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.

  13. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    Directory of Open Access Journals (Sweden)

    Supreet Sethi

    2017-01-01

    Full Text Available HLA (Human Leucocyte Antigen sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection.

  14. Immunological memory within the innate immune system.

    Science.gov (United States)

    Sun, Joseph C; Ugolini, Sophie; Vivier, Eric

    2014-06-17

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which have resided under the umbrella of innate immunity for decades. The surprising longevity and enhanced responses of previously primed NK cells will be discussed in the context of several immunization settings. © 2014 The Authors.

  15. Clinical and immunological responses in ocular demodecosis.

    Science.gov (United States)

    Kim, Jae Hoon; Chun, Yeoun Sook; Kim, Jae Chan

    2011-09-01

    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.

  16. Desensitization: Overcoming the Immunologic Barriers to Transplantation

    Science.gov (United States)

    Choi, Jua; Vo, Ashley; Peng, Alice; Jordan, Stanley C.

    2017-01-01

    HLA (Human Leucocyte Antigen) sensitization is a significant barrier to successful kidney transplantation. It often translates into difficult crossmatch before transplant and increased risk of acute and chronic antibody mediated rejection after transplant. Over the last decade, several immunomodulatory therapies have emerged allowing for increased access to kidney transplantation for the immunologically disadvantaged group of HLA sensitized end stage kidney disease patients. These include IgG inactivating agents, anti-cytokine antibodies, costimulatory molecule blockers, complement inhibitors, and agents targeting plasma cells. In this review, we discuss currently available agents for desensitization and provide a brief analysis of data on novel biologics, which will likely improve desensitization outcomes, and have potential implications in treatment of antibody mediated rejection. PMID:28127571

  17. Immunological parameters in girls with Turner syndrome

    Science.gov (United States)

    Stenberg, Annika E; Sylvén, Lisskulla; Magnusson, Carl GM; Hultcrantz, Malou

    2004-01-01

    Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X), thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency) ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder). Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls. PMID:15563731

  18. Immunological parameters in girls with Turner syndrome

    Directory of Open Access Journals (Sweden)

    Magnusson Carl GM

    2004-11-01

    Full Text Available Abstract Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X, thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder. Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls.

  19. 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.

  20. Myasthenia gravis: a clinical-immunological update.

    Science.gov (United States)

    Binks, Sophie; Vincent, Angela; Palace, Jacqueline

    2016-04-01

    Myasthenia gravis (MG) is the archetypic disorder of both the neuromuscular junction and autoantibody-mediated disease. In most patients, IgG1-dominant antibodies to acetylcholine receptors cause fatigable weakness of skeletal muscles. In the rest, a variable proportion possesses antibodies to muscle-specific tyrosine kinase while the remainder of seronegative MG is being explained through cell-based assays using a receptor-clustering technique and, to a lesser extent, proposed new antigenic targets. The incidence and prevalence of MG are increasing, particularly in the elderly. New treatments are being developed, and results from the randomised controlled trial of thymectomy in non-thymomatous MG, due for release in early 2016, will be of particular clinical value. To help navigate an evidence base of varying quality, practising clinicians may consult new MG guidelines in the fields of pregnancy, ocular and generalised MG (GMG). This review focuses on updates in epidemiology, immunology, therapeutic and clinical aspects of GMG in adults.

  1. Thyroid carcinoma: immunology, irradiation, and lymphocytic infiltration

    Energy Technology Data Exchange (ETDEWEB)

    Shull, J.H.; Sharon, N.; Victor, T.A.; Scanlon, E.F.

    1979-06-01

    Patients undergoing thyroidectomies at Evanston (I11) Hospital, during a six-month period had immunological studies performed preoperatively. No differential could be found between those with carcinoma or benign pathologic findings. T- and B-cell distribution and lymphocytic response to mitogens varied widely. Quantitative immunoglobulins showed slightly increased levels of IgG in patients wih carcinoma and thyroiditis in comparison with those patients with adenomas. Antithyroglobulin antibodies were negative in all patients. Pathology slides from 107 patients with thyroid carcinoma between 1972 and 1978 at Evanston Hospital were reviewed for the presence of thyroiditis, either focal or diffuse. It was found that 50% of all carcinomas had either diffuse or focal thyroiditis. Diffuse thyroiditis was more common in patients with no history of irradiation and papillary carcinoma, and in younger age groups.

  2. 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.

  3. Anterior uveitis and diabetes mellitus: immunological study.

    Science.gov (United States)

    Castagna, I; Famà, F; Salmeri, G

    1995-01-01

    The association between anterior uveitis (AU) and diabetes mellitus (DM) has always been known. The purpose of this study was to estimate the incidence of this association and to consider a possible role of the cell-mediated immune system. During the years 1989-1992, 196 diabetics (66 patients affected by type I DM and 130 by type II DM) were studied. The study of the lymphocytic subsets and the measurement of the circulating immunocomplexes and autoantibodies (ANA, AMA, ADNA, ASMA, APCA) were carried out, and the results were compared with those of a control group. The results underline the correlation between AU and type I DM. Many immunological reactions could play a crucial role: the high levels of CD8 subsets found could be an expression of the unstable lymphocytic equilibrium.

  4. 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.

  5. A Global Approach to Tumor Immunology

    Institute of Scientific and Technical Information of China (English)

    EnaWang; MonicaCPanelli; VladiaMonsurró; FrancescoMMarincola

    2004-01-01

    Biological and clinical advances in the understanding of tumor immunology suggest that immune responsiveness of human tumors is a complex biological phenomenon that could be best studied by a real-time comparison of tumor/host interactions in the tumor microenvironment through a high-throughput discovery-driven approach. This conclusion is derived from our recognition that too many hypotheses or, in other words, no solid single hypothesis exist, based on experimental results, to further drive experimentation in human subjects. Functional genomic studies entertained during the last few years consolidated the belief that in humans the interactions between tumor and immune cells are too complex to be approached exclusively with a hypothesis driven method. We believe that immune cells suit cancer cells in a Yin and Yang balance by opposing and yet mutually depending on each other. Indeed, immune infiltration in tumors may play a dual role modulating in different circumstances cancer cell growth or destruction through a physiological modulation of inflammation. It is reasonable to question what induces inflammation at the tumor site. We hypothesize that inflammation is primarily driven by the phenotype of tumor cells that can modulate theirmicroenvironment through cell-to-cell interactions or the secretion of soluble factors. Thus, in analogy the observation of immune cells within tumors parallels the presence of paramedics, police and firemen at thescene of an accident, which is reactive to and not causative of the occurrence. In this review we will explore this hypothesis by reporting and summarizing most of our recent work in the frame of available literature on the subject. Cellular & Molecular Immunology.

  6. 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

  7. 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.

  8. MS-20, a chemotherapeutical adjuvant, reduces chemo-associated fatigue and appetite loss in cancer patients.

    Science.gov (United States)

    Chi, Kwan-Hwa; Chiou, Tzeon-Jye; Li, Chung-Pin; Chen, Sheng-Yu; Chao, Yee

    2014-01-01

    A small pilot study of the fermented soybean extract MicrSoy-20(MS-20) demonstrated its ability to restore chemotherapy-induced immunosuppression and improve quality of life (QoL). This randomized, cross-over, comparative trial was conducted to confirm the effects of MS-20 on QoL and to understand its underlying mechanism when used in conjunction with chemotherapy. One hundred forty-three patients undergoing cancer chemotherapy were randomly assigned to 2 groups. Group 1 was administered MS-20 for 1 wk followed by 3 wk of concomitant MS-20 plus chemotherapy. Group 2 was administered chemotherapy for 3 wk. QoL was assessed by the EORTC/QLQ-C30 questionnaire and visual analogue scales (VAS). Changes in immunological parameters and antioxidant profiles were also examined. Significant increases were observed in EORTC/QLQ-C30 scores for physical (4.45, P = 0.023) and social (3.99, P = 0.023) functioning in Group 1 patients compared to Group 2 patients. VAS scores for fatigue and appetite loss significantly improved with MS-20 treatment (P MS-20 as an adjuvant to chemotherapy can be effective in improving QoL for cancer patients.

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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)

  11. 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.

  12. Adjuvant radiotherapy for stage I endometrial cancer.

    Science.gov (United States)

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

    2012-04-18

    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. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. 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. 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. 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. 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, 2,965 women; HR 0.99, 95% CI 0.82 to1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95

  13. Virological and Immunological Aspects of AIDS Pathogenesis

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    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. Diet selection in immunologically manipulated mice.

    Science.gov (United States)

    Teixeira, Gerlinde; Paschoal, Patrícia Olaya; de Oliveira, Vivian Leite; Pedruzzi, Monique M B; Campos, Sylvia M N; Andrade, Luiz; Nóbrega, Alberto

    2008-01-01

    Diet selection is a complex problem that animals in wildlife have to deal with daily. In their natural environment, these animals meet a great variety of foods some of which they are able and prepared to eat, yet, not all of it is eaten. In addition to the biological factors, some of which we shall discuss deeper in this paper, an important factor in food preference is social contact. Alterations in the physiology of mammals can have profound effects on the choice or preference for certain foods. On the other hand the decline of taste and smell perception in the elderly, the degree of food restriction, the sensorial properties of foods (such as presentation, taste, and smell) can be considered factors that influence feeding behavior leading to aversion. Many species, including man, learn to associate nausea with taste, and as a consequence avoid its specific intake, which has been shown to be persistent. Conditioned taste aversion is a form of associative learning in which animals display an aversion to the taste of a food that has previously been paired with illness. Our group has investigated the pattern of ingestion of foods that are frequently eaten by mice in wildlife and are potentially allergenic to humans in order to study the immunological consequences to these foods such as oral tolerance and inflammatory processes of the gut. We have chosen two seeds, peanuts (Arachis hypogea) and cashew nuts (Anacardium occidentale), as our source of antigens as the first is considered to be one of the most potent food allergens and for the second there seems to be very little allergy in the human setting. We used male and female, normal, adult CBA/J, A/J, C57BL/6 and Balb/c mice 2-3 months old and hybrid (C57Bl/6xBalb/c) F1, (Balb/cxC57Bl/6) F1), (C57Bl/6xDBA2) F1 mice. Food preference appeared to be strain-specific. Animals tolerized to a determined seed, then immunized with its protein extract and re-exposed to the seed in natura alter their feeding pattern. We

  15. 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

  16. Effects of methionine and arginine dietary levels on the immunity of broiler chickens submitted to immunological stimuli

    Directory of Open Access Journals (Sweden)

    LL Rubin

    2007-12-01

    Full Text Available The present study aimed at assessing the effects of methionine and arginine on the immune response of broiler chickens submitted to immunological stimuli. Three methionine concentrations (0.31, 0.51, and 0.66% from 1 to 21 days of age; 0.29, 0.49, and 0.64% from 22 to 42 days of age and 2 arginine concentrations (1.33 and 1.83%; 1.14 and 1.64% for the same life periods were tested. Birds were divided into two groups for immunological stimuli (3x2x2 arrangement. Vaccines against Marek's disease, fowl pox, infectious bronchitis, Freund's Complete Adjuvant, Sheep red blood cells (SRBC, and avian tuberculin were administered to one group as immunological stimuli; the other group did not receive any stimulus. The experiment was carried out with 432 one-day-old male Ross broilers, distributed into 12 treatments with 6 replicates of 6 birds each. Performance data were weekly collected. Anti-SRBC antibodies were collected by hemagglutination test and cell immune response (CIR was measured by tubercularization reaction in one wattle 24 hours after administration of the second tuberculin injection at 42 days of age. The weight difference between the two wattles of each bird (one injected with tuberculin and the other not was the measure of CIR. Arginine levels did not influence either bird performance or immune response. Methionine concentrations higher or lower than usually adopted in broiler production (0.51 and 0.49% equally failed to influence the birds' immune humoral response, but the best CIR was observed at the intermediate methionine level. Vaccines administered on the first day of age impaired bird performance up to the 21st day of age.

  17. Environmental adjuvants, apoptosis and the censorship over autoimmunity.

    Science.gov (United States)

    Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

    2005-11-01

    Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

  18. Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

    Science.gov (United States)

    Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

    2013-11-01

    The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

  19. Nanoparticulate Adjuvants and Delivery Systems for Allergen Immunotherapy

    Directory of Open Access Journals (Sweden)

    Juliana De Souza Rebouças

    2012-01-01

    Full Text Available In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  20. Optimizing Adherence to Adjuvant Imatinib in Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Tetzlaff, Eric D.; Davey, Monica P.

    2013-01-01

    The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients. PMID:25032004

  1. Regulatory considerations on new adjuvants and delivery systems.

    Science.gov (United States)

    Sesardic, D

    2006-04-12

    New and improved vaccines and delivery systems are increasingly being developed for prevention, treatment and diagnosis of human diseases. Prior to their use in humans, all new biological products must undergo pre-clinical evaluation. These pre-clinical studies are important not only to establish the biological properties of the material and to evaluate its possible risk to the public, but also to plan protocols for subsequent clinical trials from which safety and efficacy can be evaluated. For vaccines, evaluation in pre-clinical studies is particularly important as information gained may also contribute to identifying the optimum composition and formulation process and provide an opportunity to develop suitable indicator tests for quality control. Data from pre-clinical and laboratory evaluation studies, which continue during clinical studies, is used to support an application for marketing authorisation. Addition of a new adjuvant and exploration of new delivery systems for vaccines presents challenges to both manufacturers and regulatory authorities. Because no adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine, pre-clinical and appropriate toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/vaccine combination. Current regulatory requirements for the pharmaceutical and pre-clinical safety assessment of vaccines are insufficient and initiatives are in place to develop more specific guidelines for evaluation of adjuvants in vaccines.

  2. Nanoparticulate adjuvants and delivery systems for allergen immunotherapy.

    Science.gov (United States)

    De Souza Rebouças, Juliana; Esparza, Irene; Ferrer, Marta; Sanz, María Luisa; Irache, Juan Manuel; Gamazo, Carlos

    2012-01-01

    In the last decades, significant progress in research and clinics has been made to offer possible innovative therapeutics for the management of allergic diseases. However, current allergen immunotherapy shows limitations concerning the long-term efficacy and safety due to local side effects and risk of anaphylaxis. Thus, effective and safe vaccines with reduced dose of allergen have been developed using adjuvants. Nevertheless, the use of adjuvants still has several disadvantages, which limits its use in human vaccines. In this context, several novel adjuvants for allergen immunotherapy are currently being investigated and developed. Currently, nanoparticles-based allergen-delivery systems have received much interest as potential adjuvants for allergen immunotherapy. It has been demonstrated that the incorporation of allergens into a delivery system plays an important role in the efficacy of allergy vaccines. Several nanoparticles-based delivery systems have been described, including biodegradable and nondegradable polymeric carriers. Therefore, this paper provides an overview of the current adjuvants used for allergen immunotherapy. Furthermore, nanoparticles-based allergen-delivery systems are focused as a novel and promising strategy for allergy vaccines.

  3. 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.

  4. Advances of Tumor Hyperthermia and Tumor Immunology in Translational Medicine

    Institute of Scientific and Technical Information of China (English)

    Hooshang Lahooti

    2015-01-01

    Hyperthermia is another important method in the treatment of tumors, secondary to surgery, radiotherapy, chemotherapy and biotherapy. It has been demonstrated the efifcacy and versatility of hyperthermia in a lot of randomized trials across various primary cancers. Both heat shock proteins (HSPs) and dendritic cells (DCs) are greatly affected by hyperthermia and closely related to the tumor immunology. Nowadays, tumor hyperthermia and tumor immunology have been attached much attention in the field of translational medicine. In this article, the action mechanism and immunological effects of hyperthermia, activation of HSPs and DCs as well as HSP- and DC-based cancer vaccine were reviewed from the perspective of translational medicine.

  5. Advances of Tumor Hyperthermia and Tumor Immunology in Translational Medicine

    Directory of Open Access Journals (Sweden)

    Hooshang Lahooti

    2015-09-01

    Full Text Available Hyperthermia is another important method in the treatment of tumors, secondary to surgery, radiotherapy, chemotherapy and biotherapy. It has been demonstrated the efficacy and versatility of hyperthermia in a lot of randomized trials across various primary cancers. Both heat shock proteins (HSPs and dendritic cells (DCs are greatly affected by hyperthermia and closely related to the tumor immunology. Nowadays, tumor hyperthermia and tumor immunology have been attached much attention in the field of translational medicine. In this article, the action mechanism and immunological effects of hyperthermia, activation of HSPs and DCs as well as HSP- and DC-based cancer vaccine were reviewed from the perspective of translational medicine.

  6. Induction of systemic and mucosal immunity against methicillin-resistant Staphylococcus aureus infection by a novel nanoemulsion adjuvant vaccine

    Directory of Open Access Journals (Sweden)

    Sun HW

    2015-12-01

    Full Text Available HongWu Sun,1,* Chao Wei,1,* BaoShuai Liu,1 HaiMing Jing,1 Qiang Feng,2 YaNan Tong,1 Yun Yang,1 LiuYang Yang,1 QianFei Zuo,1 Yi Zhang,1 QuanMing Zou,1 Hao Zeng1 1National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University of Chinese PLA, 2Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, People’s Republic of China *These authors contributed equally to this work Abstract: The Gram-positive bacterial pathogen methicillin-resistant Staphylococcus aureus (MRSA can cause infections in the bloodstream, endocardial tissue, respiratory tract, culture-confirmed skin, or soft tissue. There are currently no effective vaccines, and none are expected to become available in the near future. An effective vaccine capable of eliciting both systemic and mucosal immune responses is also urgently needed. Here, we reported a novel oil-in-water nanoemulsion adjuvant vaccine containing an MRSA recombination protein antigen, Cremophor EL-35® as a surfactant, and propylene glycol as a co-surfactant. This nanoemulsion vaccine, whose average diameter was 31.34±0.49 nm, demonstrated good protein structure integrity, protein specificity, and good stability at room temperature for 1 year. The intramuscular systemic and nasal mucosal immune responses demonstrated that this nanoemulsion vaccine could improve the specific immune responses of immunoglobulin (IgG and related subclasses, such as IgG1, IgG2a, and IgG2b, as well as IgA, in the serum after Balb/c mice intramuscular immunization and C57 mice nasal immunization. Furthermore, this nanoemulsion vaccine also markedly enhanced the interferon-γ and interleukin-17A cytokine cell immune response, improved the survival ratio, and reduced bacterial colonization. Taken together, our results show that this novel nanoemulsion vaccine has great potential and is a

  7. Liposome-based polymer complex as a novel adjuvant: enhancement of specific antibody production and isotype switch

    Directory of Open Access Journals (Sweden)

    Chen CH

    2012-02-01

    Full Text Available Chia-Hung Chen1,*, Yu-Ling Lin1,*, Yen-Ku Liu1, Pei-Juin He2, Ching-Min Lin1, Yi-Han Chiu2, Chang-Jer Wu3, Tian-Lu Cheng4, Shih-Jen Liu5,6,**, Kuang-Wen Liao1,2,**1Institute of Molecular Medicine and Bioengineering, 2Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, 3Department of Food Science, National Taiwan Ocean University, Keelung, 4Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 5National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, 6Graduate Institute of Immunology, China Medical University, Taichung, Taiwan, , *Chia-Hung Chen and Yu-Ling Lin contributed equally to this work**Kuang-Wen Liao and Shih-Jen Liu contributed equally to this workAbstract: The aim of vaccination is to induce appropriate immunity against pathogens. Antibody-mediated immunity is critical for protection against many virus diseases, although it is becoming more evident that coordinated, multifunctional immune responses lead to the most effective defense. Specific antibody (Ab isotypes are more efficient at protecting against pathogen invasion in different locations in the body. For example, compared to other Ab isotypes, immunoglobulin (Ig A provides more protection at mucosal areas. In this study, we developed a cationic lipopolymer (liposome-polyethylene glycol-polyethyleneimine complex [LPPC] adjuvant that strongly adsorbs antigens or immunomodulators onto its surface to enhance or switch immune responses. The results demonstrate that LPPC enhances uptake ability, surface marker expression, proinflammatory cytokine release, and antigen presentation in mouse phagocytes. In contrast to Freund's adjuvant, LPPC preferentially activates Th1-immunity against antigens in vivo. With lipopolysaccharides or CpG oligodeoxynucleotides, LPPC dramatically enhances the IgA or IgG2A proportion of total Ig, even in hosts that have developed

  8. 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.

  9. 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.

  10. Immunological Response to Biodegradable Magnesium Implants

    Science.gov (United States)

    Pichler, Karin; Fischerauer, Stefan; Ferlic, Peter; Martinelli, Elisabeth; Brezinsek, Hans-Peter; Uggowitzer, Peter J.; Löffler, Jörg F.; Weinberg, Annelie-Martina

    2014-04-01

    The use of biodegradable magnesium implants in pediatric trauma surgery would render surgical interventions for implant removal after tissue healing unnecessary, thereby preventing stress to the children and reducing therapy costs. In this study, we report on the immunological response to biodegradable magnesium implants—as an important aspect in evaluating biocompatibility—tested in a growing rat model. The focus of this study was to investigate the response of the innate immune system to either fast or slow degrading magnesium pins, which were implanted into the femoral bones of 5-week-old rats. The main alloying element of the fast-degrading alloy (ZX50) was Zn, while it was Y in the slow-degrading implant (WZ21). Our results demonstrate that degrading magnesium implants beneficially influence the immune system, especially in the first postoperative weeks but also during tissue healing and early bone remodeling. However, rodents with WZ21 pins showed a slightly decreased phagocytic ability during bone remodeling when the degradation rate reached its maximum. This may be due to the high release rate of the rare earth-element yttrium, which is potentially toxic. From our results we conclude that magnesium implants have a beneficial effect on the innate immune system but that there are some concerns regarding the use of yttrium-alloyed magnesium implants, especially in pediatric patients.

  11. The microbiota: an exercise immunology perspective.

    Science.gov (United States)

    Bermon, Stéphane; Petriz, Bernardo; Kajėnienė, Alma; Prestes, Jonato; Castell, Lindy; Franco, Octavio L

    2015-01-01

    The gut microbiota consists of a cluster of microorganisms that produces several signaling molecules of a hormonal nature which are released into the blood stream and act at distal sites. There is a growing body of evidence indicating that microbiota may be modulated by several environmental conditions, including different exercise stimulus, as well some pathologies. Enriched bacterial diversity has also been associated with improved health status and alterations in immune system, making multiple connections between host and microbiota. Experimental evidence has shown that reduced levels and variations in the bacterial community are associated with health impairments, while increased microbiota diversity improves metabolic profile and immunological responses. So far, very few controlled studies have focused on the interactions between acute or chronic exercise and the gut microbiota. However, some preliminary experimental data obtained from animal studies or probiotics studies show some interesting results at the immune level, indicating that the microbiota also acts like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with exercise. Thus, our review intends to shed some light on the interaction between gut microbiota, exercise and immunomodulation.

  12. Immunological characteristics of mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

  14. 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.

  15. An immunological model for detecting bot activities

    Science.gov (United States)

    Karim, Md E.; Phoha, Vir V.; Sultan, Md A.

    2009-05-01

    We develop a hierarchical immunological model to detect bot activities in a computer network. In the proposed model antibody (detector)-antigen (foreign object) reactions are defined using negative selection based approach and negative systems-properties are defined by various temporal as well as non-temporal systems features. Theory of sequential hypothesis testing has been used in the literature for identifying spatial-temporal correlations among malicious remote hosts and among the bots within a botnet. We use it for combining multiple immunocomputing based decisions too. Negative selection based approach defines a self and helps identifying non-selves. We define non-selves with respect to various systems characteristics and then use different combinations of non-selves to design bot detectors. Each detector operates at the client sites of the network under surveillance. A match with any of the detectors suggests presence of a bot. Preliminary results suggest that the proposed model based solutions can improve the identification of bot activities.

  16. Effects of protein aggregates: an immunologic perspective.

    Science.gov (United States)

    Rosenberg, Amy S

    2006-08-04

    The capacity of protein aggregates to enhance immune responses to the monomeric form of the protein has been known for over a half-century. Despite the clear connection between protein aggregates and antibody mediated adverse events in treatment with early therapeutic protein products such as intravenous immune globulin (IVIG) and human growth hormone, surprisingly little is known about the nature of the aggregate species responsible for such effects. This review focuses on a framework for understanding how aggregate species potentially interact with the immune system to enhance immune responses, garnered from basic immunologic research. Thus, protein antigens presented in a highly arrayed structure, such as might be found in large nondenatured aggregate species, are highly potent in inducing antibody responses even in the absence of T-cell help. Their potency may relate to the ability of multivalent protein species to extensively cross-link B-cell receptor, which (1) activates B cells via Bt kinases to proliferate, and (2) targets protein to class II major histocompatibility complex (MHC)-loading compartments, efficiently eliciting T-cell help for antibody responses. The review further focuses on protein aggregates as they affect an immunogenicity risk assessment, the use of animal models and studies in uncovering effects of protein aggregates, and changes in product manufacture and packaging that may affect generation of protein aggregates.

  17. A primer on cancer immunology and immunotherapy.

    Science.gov (United States)

    Lotze, Michael T; Papamichail, Michael

    2004-03-01

    The role of immunity in cancer has been abundantly demonstrated in murine tumor models as well as in man. Induction of clinically effective antitumor immune responses, based on this information, in patients with cancer however, remains elusive. This is not because tumors lack recognizable antigens [in fact there is evidence that there are thousands of potential novel targets in each tumor cell] but rather due to the fact that the induction of responses is not adequate nor particularly well understood. Tumors seem to be rather effective at limiting immune responses. Many of the molecularly defined antigens that have been detected on tumor cells are derived from self-proteins and as such are subject to tolerizing mechanisms. Such tumors have also developed escape mechanisms capable of evading or suppressing immune responses. Understanding the role of dendritic cells during the effector phase of the immune response and the complex interactions of stromal, immune, and tumor cells in the tumor microenvironment represent the next challenges to be understood for tumor immunology.

  18. 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.

  19. Louis pasteur, the father of immunology?

    Science.gov (United States)

    Smith, Kendall A

    2012-01-01

    Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late nineteenth 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.

  20. Suppression of complete Freund's adjuvant-induced adjuvant arthritis by cobratoxin

    Institute of Scientific and Technical Information of China (English)

    Yan-li LIU; Hai-ming LIN; Rong ZOU; Jun-chao WU; Rong HAN; Laurence N RAYMOND; Paul F REID; Zheng-hong QIN

    2009-01-01

    Aim:Cobratoxin (CTX),the long-chain α-neurotoxin from Thailand cobra venom,has been demonstrated to have analgesic action in rodent pain models.The present study evaluated the anti-inflammatory and anti-nociceptive effects of CTX on adju-vant arthritis (AA) in rats.Methods: Arthritis was induced by injection of complete Freund's adjuvant (CFA) in rats.Paw swelling and hyperalgesia of AA rats were measured at various times after CFA administration.Tumor necrosis factor-a (TNF-α),interleukin-1 (IL-1),interleukin-2 (IL-2) and interleukin-10 (IL-10) levels in serum were determined with ELISA.Histopathological changes in synoviocytes were examined under a microscope.Involvement of the cholinergic system in the effects of CTX was examinedby pretreatment of animals with the α7 nicotinic receptor (α7-nAChR) antagonist methyllycaconitine (MLA).Results: CFA induced marked paw swelling and reduced thresholds of mechanical and cold-induced paw withdrawal.The lev-els of TNF-α,IL-1 and IL-2 in the serum of AA rats were increased,whereas the level of IL-10 was decreased.Histopathologi-cal examination of synoviocytes showed pronounced inflammation and accumulation of collagen.The administration of CTX (17.0 μg/kg,ip) significantly reduced paw swelling and mechanical and thermal hyperalgesia.CTX also reduced the produc-tion ofTNF-α,IL-1,and IL-2 but increased the production of IL-10 and altered pathohistological changes.The analgesic and anti-inflammatory efficacy of CTX was significantly reduced by MLA (3 mg/kg,sc).Conclusion: These results indicate that CTX has a beneficial effect on CFA-induced arthritis by modulating the production of inflammatory cytokines,α7-nAChR appears to mediate the anti-nociceptive and anti-inflammatory actions of CTX.

  1. The immunobiology of aluminium adjuvants: how do they really work?

    Science.gov (United States)

    Exley, Christopher; Siesjö, Peter; Eriksson, Håkan

    2010-03-01

    Aluminium adjuvants potentiate the immune response, thereby ensuring the potency and efficacy of typically sparingly available antigen. Their concomitant critical importance in mass vaccination programmes may have prompted recent intense interest in understanding how they work and their safety. Progress in these areas is stymied, however, by a lack of accessible knowledge pertaining to the bioinorganic chemistry of aluminium adjuvants, and, consequently, the inappropriate application and interpretation of experimental models of their mode of action. The objective herein is, therefore, to identify the many ways that aluminium chemistry contributes to the wide and versatile armoury of its adjuvants, such that future research might be guided towards a fuller understanding of their role in human vaccinations.

  2. Matrix-M adjuvant enhances antibody, cellular and protective immune responses of a Zaire Ebola/Makona virus glycoprotein (GP) nanoparticle vaccine in mice.

    Science.gov (United States)

    Bengtsson, Karin Lövgren; Song, Haifeng; Stertman, Linda; Liu, Ye; Flyer, David C; Massare, Michael J; Xu, Ren-Huan; Zhou, Bin; Lu, Hanxin; Kwilas, Steve A; Hahn, Timothy J; Kpamegan, Eloi; Hooper, Jay; Carrion, Ricardo; Glenn, Gregory; Smith, Gale

    2016-04-01

    Ebola virus (EBOV) causes severe hemorrhagic fever for which there is no approved treatment or preventive vaccine. Immunological correlates of protective immunity against EBOV disease are not well understood. However, non-human primate studies have associated protection of experimental vaccines with binding and neutralizing antibodies to the EBOV glycoprotein (GP) as well as EBOV GP-specific CD4(+) and CD8(+) T cells. In this report a full length, unmodified Zaire EBOV GP gene from the 2014 EBOV Makona strain (EBOV/Mak) was cloned into a baculovirus vector. Recombinant EBOV/Mak GP was produced in Sf9 insect cells as glycosylated trimers and, when purified, formed spherical 30-40 nm particles. In mice, EBOV/Mak GP co-administered with the saponin adjuvant Matrix-M was significantly more immunogenic, as measured by virus neutralization titers and anti-EBOV/Mak GP IgG as compared to immunization with AlPO4 adjuvanted or non-adjuvanted EBOV/Mak GP. Similarly, antigen specific T cells secreting IFN-γ were induced most prominently by EBOV/Mak GP with Matrix-M. Matrix-M also enhanced the frequency of antigen-specific germinal center B cells and follicular helper T (TFH) cells in the spleen in a dose-dependent manner. Immunization with EBOV/Mak GP with Matrix-M was 100% protective in a lethal viral challenge murine model; whereas no protection was observed with the AlPO4 adjuvant and only 10% (1/10) mice were protected in the EBOV/Mak GP antigen alone group. Matrix-M adjuvanted vaccine induced a rapid onset of specific IgG and neutralizing antibodies, increased frequency of multifunctional CD4+ and CD8(+) T cells, specific TFH cells, germinal center B cells, and persistence of EBOV GP-specific plasma B cells in the bone marrow. Taken together, the addition of Matrix-M adjuvant to the EBOV/Mak GP nanoparticles enhanced both B and T-cell immune stimulation which may be critical for an Ebola subunit vaccine with broad and long lasting protective immunity.

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. Immunologic and clinical outcomes of children on HAART: A ...

    African Journals Online (AJOL)

    Immunologic and clinical outcomes of children on HAART: A retrospective cohort analysis at ... Ethiopian Journal of Health Sciences ... Therefor, early diagnosis and treatment of HIV/AIDS and treatment monitoring should be strengthened.

  8. Evaluation of HIV therapeutic agents on immunological, lipid and ...

    African Journals Online (AJOL)

    Evaluation of HIV therapeutic agents on immunological, lipid and lipoprotein indices in Ghanaian HIV-1 infected patients. ... lipid and lipoprotein changes as well as the atherogenic indices of Ghanaian HIV-1 infected patients. ... Article Metrics.

  9. Aluminium: a natural adjuvant in Leishmania transmission via sand flies?

    Science.gov (United States)

    Maingon, Rhayza; Khela, Amandeep; Sampson, Christopher; Ward, Richard; Walker, Karen; Exley, Christopher

    2008-11-01

    Genetically identical Leishmania chagasi/infantum parasites cause both atypical cutaneous leishmaniasis and visceral leishmaniasis. In this report we have tested the first part of a hypothesis that states that the form of this disease that is manifested depends upon the adjuvant-like activity of aluminium of dietary origin accumulated in the salivary gland of the sand fly vector. In sand flies fed aluminium-supplemented sucrose we have used histochemistry to qualitatively identify aluminium in their salivary glands and graphite furnace atomic absorption spectrometry to quantify the aluminium content of dissected salivary glands. Aluminium may be acting as a natural adjuvant in some forms of leishmaniasis.

  10. Advances of Tumor Hyperthermia and Tumor Immunology in Translational Medicine

    OpenAIRE

    Hooshang Lahooti

    2015-01-01

    Hyperthermia is another important method in the treatment of tumors, secondary to surgery, radiotherapy, chemotherapy and biotherapy. It has been demonstrated the efficacy and versatility of hyperthermia in a lot of randomized trials across various primary cancers. Both heat shock proteins (HSPs) and dendritic cells (DCs) are greatly affected by hyperthermia and closely related to the tumor immunology. Nowadays, tumor hyperthermia and tumor immunology have been attached much attention in the ...

  11. Remembrance of immunology past: conversations with Herman Eisen.

    Science.gov (United States)

    Eisen, Herman N; Schlesinger, Sondra

    2015-01-01

    Herman Eisen and Sondra Schlesinger spent several days together in September 2007 in Woods Hole, Massachusetts, talking about immunology, focusing on his remembrances of the field over the more than 60 years of his involvement. This article is an abridged version of those discussions (the full version is available on the Annual Reviews website). It is both an oral history and a written memory of some important but selected areas of immunology.

  12. 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.

  13. 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...

  14. 21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-macroglobulin immunological test system. 866.5620 Section 866.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5620 Alpha-2-macroglobulin immunological...

  15. 21 CFR 866.5420 - Alpha-1-glycoproteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-glycoproteins immunological test system. 866.5420 Section 866.5420 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5420 Alpha-1-glycoproteins immunological...

  16. 21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866.5400 Section 866.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. ...

  17. 21 CFR 866.5130 - Alpha-1-antitrypsin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antitrypsin immunological test system. 866.5130 Section 866.5130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5130 Alpha-1-antitrypsin immunological test...

  18. 21 CFR 866.5425 - Alpha-2-glycoproteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-glycoproteins immunological test system. 866.5425 Section 866.5425 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5425 Alpha-2-glycoproteins immunological...

  19. 21 CFR 866.5370 - Cohn fraction V immuno-logical test system.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5370 Cohn fraction V immuno-logical test system. (a) Identification. A Cohn fraction V immunological... (disease of the stomach and small intestine), rheumatoid arthritis, and viral hepatitis. (b)...

  20. A Global Approach to Tumor Immunology

    Institute of Scientific and Technical Information of China (English)

    Ena Wang; Monica C Panelli; Vladia Monsurró; Francesco M Marincola

    2004-01-01

    Biological and clinical advances in the understanding of tumor immunology suggest that immune responsiveness of human tumors is a complex biological phenomenon that could be best studied by a real-time comparison of tumor/host interactions in the tumor microenvironment through a high-throughput discovery-driven approach. This conclusion is derived from our recognition that too many hypotheses or, in other words, no solid single hypothesis exist, based on experimental results, to further drive experimentation in human subjects. Functional genomic studies entertained during the last few years consolidated the belief that in humans the interactions between tumor and immune cells are too complex to be approached exclusively with a hypothesis driven method. We believe that immune cells suit cancer cells in a Yin and Yang balance by opposing and yet mutually depending on each other. Indeed, immune infiltration in tumors may play a dual role modulating in different circumstances cancer cell growth or destruction through a physiological modulation of inflammation. It is reasonable to question what induces inflammation at the tumor site. We hypothesize that inflammation is primarily driven by the phenotype of tumor cells that can modulate their microenvironment through cell-to-cell interactions or the secretion of soluble factors. Thus, in analogy the observation of immune cells within tumors parallels the presence of paramedics, police and firemen at the scene of an accident, which is reactive to and not causative of the occurrence. In this review we will explore this hypothesis by reporting and summarizing most of our recent work in the frame of available literature on the subject.

  1. A highlight of recent advances in immunology

    Institute of Scientific and Technical Information of China (English)

    ZHENG DeXian

    2011-01-01

    To celebrate the 60th anniversary of SCIENCE CHINA,six research groups of overseas and domestic Chinese immunologists published a series of review articles (SCIENCE CHINA Life Sciences,2010,53(2):157-158),which highlighted recent advances and their contributions to immunology.Wang YaYa in Prof.Cheng GenHong's group,who discovered the function of TNF receptor-associated factor (TRAF) and other signal molecules in Toll-like receptor (TLR) mediated signaling pathway and innate immunity [1],reviewed TRAF-mediated regulation of immune and inflammatory responses [2].TRAF family consists of six mammalian members (TRAF1,TRAF2,TRAF3,TRAF4,TRAF5,and TRAF6) and participates in signal transduction of a large number of receptor families such as TNF receptor family (TNFR) and TLR-interleukin-1 receptor (TLR-IL-1R)family.Upon receptor-mediated activation,TRAFs are directly or indirectly recruited to the intracellular domains of these receptors and subsequently combine with other signaling molecules to activate the inhibitor of IκB kinase (IKK) complex,TRAF family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1) and the inducible Iκ B kinase (IKK-i),ultimately leading to activation of transcription factors,such as NF-κB,interferon-regulatory factor (IRF),to induce immune or inflammatory responses.In the past few years,immunologists have demonstrated the central role of TRAFs in inflammation,innate immunity.

  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. Immunologic features of Cornelia de Lange syndrome.

    Science.gov (United States)

    Jyonouchi, Soma; Orange, Jordan; Sullivan, Kathleen E; Krantz, Ian; Deardorff, Matthew

    2013-08-01

    Cornelia de Lange syndrome (CdLS) is a genetic syndrome with multisystem abnormalities. Infections are a significant cause of morbidity and mortality. The goals of our study were to identify the frequency and types of infections in CdLS and to determine if underlying immunodeficiency contributes to the clinical spectrum of this syndrome. We assessed infectious histories in 45 patients with CdLS and evaluated conventional immunologic screening tests in 27 patients. Among these 27 subjects, additional phenotypic enumeration of T-cell subsets, expression of activation markers in T cells, and production of cytokines in response to T-cell stimulants were studied in 12 CdLS subjects compared with 12 normal case control subjects. Recurrent infections were reported at high frequency in CdLS patients and included chronic ear infections (53%), chronic viral respiratory infections (46%), pneumonia (42%), sinus infections (33%), oral candidiasis (13%), sepsis (6%), and bacterial skin infections (4%). Full immune evaluation in 27 subjects led to identification of 9 cases of antibody deficiency syndrome in patients with severe forms of CdLS. Subjects with CdLS had decreased percentages of T regulatory cells and T follicular helper cells compared with normal control subjects (P < .05). This study identified for the first time a high frequency of antibody deficiency in CdLS subjects, indicating a critical need for screening and management of immunodeficiency in CdLS patients with a history of well-documented severe or recurrent infections. Furthermore, our results indicate that impaired T-cell populations may be associated with antibody deficiency in CdLS.

  4. Contamination of DNase Preparations Confounds Analysis of the Role of DNA in Alum-Adjuvanted Vaccines

    OpenAIRE

    Noges, Laura E.; White, Janice; Cambier, John C.; Kappler, John W.; Marrack, Philippa

    2016-01-01

    Aluminum salt (alum) adjuvants have been used for many years as adjuvants for human vaccines because they are safe and effective. Despite its widespread use, the means by which alum acts as an adjuvant remains poorly understood. Recently, it was shown that injected alum is rapidly coated with host chromatin within mice. Experiments suggested that the host DNA in the coating chromatin contributed to alum’s adjuvant activity. Some of the experiments used commercially purchased DNase and showed ...

  5. 75 FR 66766 - NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development

    Science.gov (United States)

    2010-10-29

    ... discovery, development and clinical evaluation of adjuvants for use with preventive vaccines. NIAID has developed a draft Strategic Plan and Research Agenda for Adjuvant Discovery and Development, which... HUMAN SERVICES NIAID Blue Ribbon Panel Meeting on Adjuvant Discovery and Development Notice is...

  6. 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.

    2010-01-01

    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 v

  7. Postoperative adjuvant chemotherapy in rectal cancer operated for cure

    DEFF Research Database (Denmark)

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

    2012-01-01

    in Dukes´ C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive...

  8. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    Science.gov (United States)

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant.

  9. Teaching adjuvant endocrine breast cancer treatment to medical students

    NARCIS (Netherlands)

    Visser, M. de; Fluit, C.R.M.G.; Timmer-Bonte, J.N.H.; Ottevanger, P.B.; Verhagen, C.A.H.H.V.M.; Klaassen, T.; Laarhoven, H.W.M. van

    2013-01-01

    Background: In undergraduate medical education, students are supposed to acquire knowledge and understanding about the basic principles of adjuvant breast cancer treatment. The best education method in this context is unknown. In this randomised study we assessed the effect of designing a patient ed

  10. Local anesthetis and adjuvants in pediatric regional anesthesia.

    Science.gov (United States)

    Mossetti, Valeria; Vicchio, Noemi; Ivani, Giorgio

    2012-06-01

    The pediatric loco-regional techniques are considered very safe and effective, first of all because they target the therapy directly to the site of surgery, decreasing the risks of intravenous analgesia. The quality of local anesthesia is influenced by structural and biophysical characteristics of local anesthetics drug, dose, site of injection, mixture of local anesthetics and possible addition of a vasoconstrictor or an adjuvant to prolong the analgesic effect. In children, unlike adults, small nerve diameters and short distance between Ranvier nodes permit to use large volumes and low concentrations of local anesthetics. The clinical practice has shown that in pediatric population, effective analgesia is obtained by 1% mepivacaine, 1% lidocaine and 0.25% bupivacaine or better 0.2% ropivacaine, 0.2-0.25% levobupivacaine. In addition, levobupivacaine and ropivacaine have a better profile in terms of safety in comparison to bupivacaine and are the local anesthetics of choice for the daily clinical practice also in children as in adults. Among the adjuvant, clonidine and ketamine showed the best pharmacokinetic and pharmacodynamic profiles of effective and safety, improving and prolonging the action of associated local anesthetics. Therefore, the use of enantiomers, in association with adjuvants as clonidine or ketamine, using the multimodal approach of integrated anesthesia, makes the clinical practice effective and safe in the pediatric operating rooms. This review focuses on the overview of local anesthetics and adjuvants used today in locoregional pediatric anesthesia, with an emphasis on the advantages and disadvantages of each drug.

  11. 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

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

    NARCIS (Netherlands)

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

    2006-01-01

    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 vari

  13. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    Science.gov (United States)

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

  14. Persistent neurocognitive problems after adjuvant chemotherapy for breast cancer

    NARCIS (Netherlands)

    Kreukels, B.P.C.; van Dam, F.S.A.M.; Ridderinkhof, K.R.; Boogerd, W.; Schagen, S.B.

    2008-01-01

    Background: Neurocognitive problems have been observed in a number of women previously treated with adjuvant chemotherapy for breast cancer. The present study aims to combine the results of neuropsychological and electrophysiological techniques collected in patients with breast cancer treated with c

  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...... histopathology. A clinical oncologist, who was blinded to the surgical approach, reviewed all medical oncology charts for types of adjuvant chemotherapy, reasons for not initiating or stopping treatment, number of cycles delivered, and time interval from surgery to initial chemotherapy. RESULTS: During a 6-year...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p

  16. Adjuvant chemotherapy for the perineural invasion of colorectal cancer.

    Science.gov (United States)

    Suzuki, Toshiaki; Suwa, Katsuhito; Ogawa, Masaichi; Eto, Ken; Kawahara, Hidejiro; Fujita, Tetsuji; Ikegami, Masahiro; Yanaga, Katsuhiko

    2015-11-01

    To evaluate the association of perineural invasion (PNI) with outcomes in patients after colorectal resection of colorectal cancer (CRC) and to assess the effect of PNI on the response to adjuvant chemotherapy. Data were retrospectively reviewed for 178 patients with consecutive stages I-III CRC who underwent curative surgery between January 1999 and December 2004. PNI data were examined, and the overall survival (OS) and disease-free survival rates were analyzed. PNI was detected in 36 of 178 patients (20%) and positively correlated with lymphatic invasion (P = 0.020), venous invasion (P = 0.037), and the incidence of metastasis or recurrence (P = 0.029). Five-year disease-free survival was 46% and 68% (P negative prognostic factor of OS; among PNI-positive patients, median OS with adjuvant chemotherapy was almost twofold higher than that without adjuvant chemotherapy (6 versus 2.8 y; P = 0.017). PNI was a poor predictor of survival among patients with stage III CRC, and adjuvant chemotherapy may attenuate the adverse effects of PNI on survival. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Triple negative breast cancer: adjuvant chemotherapy effect on survival.

    Science.gov (United States)

    Steponaviciene, L; Lachej-Mikeroviene, N; Smailyte, G; Aleknavicius, E; Meskauskas, R; Didziapetriene, J

    2011-01-01

    The purpose of this study was to evaluate the overall survival of patients with triple negative breast cancer and the impact of different adjuvant chemotherapy regimens on survival. The study group consisted of 99 breast cancer patients with immunohistochemically confirmed triple negative breast cancer. The impact of various factors as well as the impact of different chemotherapy regimens on survival was evaluated. The overall survival of breast cancer patients was 97.0% (95% CI 90.9-99.0), 84.9% (95% CI 76.1-90.6) and 66.5% (95% CI 55.5-75.3) 10, 30 and 60 months after diagnosis, respectively. Univariate analysis demonstrated that the following were significant risk factors for breast cancer patients survival: patient's age, stage of disease, tumour size, lymph node status, type of surgery and chemotherapy. Better survival was related to younger patients' age, smaller tumour size, lower stage of disease, no lymph nodes involvement. Survival rates were higher among patients who received adjuvant chemotherapy and underwent quadrantectomy. In the multivariate statistical analysis the significant independent prognostic variables influencing survival were lymph node status and adjuvant chemotherapy. Survival rates of the patients, who received adjuvant anthracycline containing chemotherapy were higher, than those in non-anthracycline containing treatment group, but the difference was not statistically significant. Patients who had lymph node status N2-3 and those who did not receive adjuvant chemotherapy showed worse prognosis and survival than other patients. The impact of chemotherapy type (anthracycline containing or non-anthracycline containing) on patients survival was not statistically significant.

  18. 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.

  19. Confirmation studies of Soviet research on immunological effects of microwaves: Russian immunology results.

    Science.gov (United States)

    Grigoriev, Yury G; Grigoriev, Oleg A; Ivanov, Alexander A; Lyaginskaya, Antonina M; Merkulov, Anton V; Shagina, Natalia B; Maltsev, Vyacheslav N; Lévêque, Philippe; Ulanova, Alla M; Osipov, Vyacheslav A; Shafirkin, Alexander V

    2010-12-01

    This paper presents the results of a replication study performed to investigate earlier Soviet studies conducted between 1974 and 1991 that showed immunological and reproductive effects of long-term low-level exposure of rats to radiofrequency (RF) electromagnetic fields. The early studies were used, in part, for developing exposure standards for the USSR population and thus it was necessary to confirm the Russian findings. In the present study, the conditions of RF exposure were made as similar as possible to those in the earlier experiments: Wistar rats were exposed in the far field to 2450 MHz continuous wave RF fields with an incident power density in the cages of 5 W/m² for 7 h/day, 5 days/week for a total of 30 days, resulting in a whole-body SAR of 0.16 W/kg. Effects of the exposure on immunological parameters in the brain and liver of rats were evaluated using the complement fixation test (CFT), as in the original studies, and an additional test, the more modern ELISA test. Our results, using CFT and ELISA, partly confirmed the findings of the early studies and indicated possible effects from non-thermal RF exposure on autoimmune processes. The RF exposure resulted in minor increases in formation of antibodies in brain tissue extract and the exposure did not appear to be pathological. In addition, a study was conducted to replicate a previous Soviet study on effects from the injection of blood serum from RF-exposed rats on pregnancy and foetal and offspring development of rats, using a similar animal model and protocol. Our results showed the same general trends as the earlier study, suggesting possible adverse effects of the blood serum from exposed rats on pregnancy and foetal development of intact rats, however, application of these results in developing exposure standards is limited.

  20. IMMUNOLOGICAL PROCESSES IN CANCER: A LINK BETWEEN INFLAMMATION AND IMMUNITY

    Directory of Open Access Journals (Sweden)

    Vanessa Jacob Victorino

    2014-01-01

    Full Text Available Cancer is a worldwide issue and one of the most relevant death causes in child and adults. There are several causes that can lead to cancer development. It is well known that inflammation is one known hallmark of cancer and it favors tumor cells growth. Several alterations in immunological and inflammatory processes are caused in response to tumor presence and both innate and adaptive immunity have effective mechanism to destroy tumor cells. Nevertheless, distinct tumor types developed mechanisms to evade anti-tumor immunological responses. Here, we revise researches regarding inflammation and immune response during cancer development, as well as cancer signaling pathways and immunotherapy that have been performed in Brazil. The better understanding of the mechanisms regarding cancer and immunological processes is of huge importance and it may support the development of new cancer targets.

  1. Implementation and research of integrated curriculum of immunology

    Institute of Scientific and Technical Information of China (English)

    Guang-jie CHEN; Xiao-yin NIU; Li-hua JIANG; Ye-bin XI; Hai-liang GE

    2015-01-01

    In order to get adapted to the teaching reform in Shanghai Jiao Tong University School of Medicine,and promote the integration of the teaching of basic and clinical medicine for medical students,the integrated curriculum of host defense and immunity integrates medical immunology with the morphological structure and histogenesisof the immune system. In this paper,we focus on the different integration medical immunology curriculum in the world and our unique integrated immunology curriculum. This paper introduces the condition of host defense and immunity both at home and abroad and its status and role in the integrated curriculum system in School of Medicine,and summarizes the contents,experience and improvement measures for the implementation of host defense and immunity.

  2. The role of cytokines in immunological tolerance: potential for therapy.

    Science.gov (United States)

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  3. Breaking Immunological Tolerance through OX40 (CD134

    Directory of Open Access Journals (Sweden)

    Pratima Bansal-Pakala

    2001-01-01

    Full Text Available Immunological tolerance represents a mechanism by which cells of the host remain protected from the immune system. Breaking of immunological tolerance can result in a variety of autoimmune diseases such as rheumatoid arthritis, diabetes, and multiple sclerosis. The reasons for tolerance breaking down and autoimmune processes arising are largely unknown but of obvious interest for therapeutic intervention of these diseases. Although reversal of the tolerant state is generally unwanted, there are instances where this may be of benefit to the host. In particular, one way a cancerous cell escapes being targeted by the immune system is through tolerance mechanisms that in effect turn off the reactivity of T lymphocytes that can respond to tumor-associated peptides. Thus tolerance represents a major obstacle in developing effective immunotherapy against tumors. The molecules that are involved in regulating immunological tolerance are then of interest as they may be great targets for positively or negatively manipulating the tolerance process.

  4. Cellular & Molecular Immunology receives its first Impact Factor

    Institute of Scientific and Technical Information of China (English)

    Zhigang Tian

    2010-01-01

    @@ The 2009 edition of the JCR, in which Cellular (c) Molecular Immunology (CMI) is listed for the first time, reveals an Impact Factor of 2.765, placing CMI 63rd out of 128 in the Immunology subject category. According to ISI's ranking this also places the journal 5th out of 114 journals published in China and 23rd out of 587 journals published in the Asia-Pacific region. This is an excellent first Impact Factor for a young journal like CMI and,together with our publishing partner Nature Publishing Group and the continued support of our readers and authors, we hope to further build on this into the future. We are delighted that CMI can be internationally recognized as important in the field of immunology.

  5. IMMUNOLOGICAL FEATURES IN LIVER CIRRHOSIS INDUCED BY HEPATITIS B VIRUS

    Directory of Open Access Journals (Sweden)

    O. I. Urazova

    2007-01-01

    Full Text Available Abstract. A comparative analysis of immunological data was performed in the patients with HBV-induced liver cirrhosis, and in a group of patients with acute and chronic viral hepatitis B (AVHB, CVHB. Activation of B cell immune compartment (increase in CD22+ lymphocytes and IL4, circulating immune complexes in blood was demonstrated in patients with liver cirrhosis, being also associated with increased numbers of CD16+ lymphocytes and T-cell deficiency. It was revealed that the differences are most expressed upon comparison of immunologic data from the patients with liver cirrhosis, and AVHB followed by clearance of the virus. When comparing these groups, the differences in immunological state between the patients with liver cirrhosis and CVHB did not depend on the phase of viral replication or integration.

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

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth

    2003-01-01

    The report on the influence of seasonal factors on thymic size in early life describes a pattern of ultrasonographically measured thymic growth in Gambian infants including the finding of a smaller thymus in the hungry season. These factors raise a number of important questions: Is the size...... 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....

  7. 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...... glycomes based on specific immune recognition of glycan structures, which can be hypothesized theoretically, produced chemically, and examined biologically by immuno-assays. Immunologic mapping of glycans not only provides a unique perspective on cancer glycomes, but also may lead to the invention...

  8. 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.

  9. The bioinorganic chemistry and associated immunology of chronic beryllium disease.

    Science.gov (United States)

    Scott, Brian L; McCleskey, T Mark; Chaudhary, Anu; Hong-Geller, Elizabeth; Gnanakaran, S

    2008-07-07

    Chronic beryllium disease (CBD) is a debilitating, incurable, and often fatal disease that is caused by the inhalation of beryllium particulates. The growing use of beryllium in the modern world, in products ranging from computers to dental prosthetics (390 tons of beryllium in the US in the year 2000) necessitates a molecular based understanding of the disease in order to prevent and cure CBD. We have investigated the molecular basis of CBD at Los Alamos National Laboratory during the past six years, employing a multidisciplinary approach of bioinorganic chemistry and immunology. The results of this work, including speciation, inhalation and dissolution, and immunology will be discussed.

  10. The bioinorganic chemistry and associated immunology of chronic beryllium disease†

    Science.gov (United States)

    McCleskey, T. Mark; Chaudhary, Anu; Hong-Geller, Elizabeth; Gnanakaran, S.

    2013-01-01

    Chronic beryllium disease (CBD) is a debilitating, incurable, and often fatal disease that is caused by the inhalation of beryllium particulates. The growing use of beryllium in the modern world, in products ranging from computers to dental prosthetics (390 tons of beryllium in the US in the year 2000) necessitates a molecular based understanding of the disease in order to prevent and cure CBD. We have investigated the molecular basis of CBD at Los Alamos National Laboratory during the past six years, employing a multidisciplinary approach of bioinorganic chemistry and immunology. The results of this work, including speciation, inhalation and dissolution, and immunology will be discussed. PMID:18566702

  11. Some scientific and organizational challenges in cancer immunology.

    Science.gov (United States)

    Steinman, Ralph M

    2009-09-01

    This volume provides a small sampling of the rapidly growing science of cancer immunology. Growth in the field includes advances on the requirements for immunization or vaccination and the ways in which immunity can be suppressed or blocked, including active tumor-based mechanisms. I would like to introduce the papers in this volume and then deal with a subject that pervaded many discussions among symposium participants. The subject is the need for a much better supported and organized effort to design optimal studies of immunology in cancer patients so that cancer vaccines can become a major means to prevent and treat this disease.

  12. Adenoids in children: Advances in immunology, diagnosis, and surgery.

    Science.gov (United States)

    Brambilla, Ilaria; Pusateri, Alessandro; Pagella, Fabio; Caimmi, Davide; Caimmi, Silvia; Licari, Amelia; Barberi, Salvatore; Castellazzi, Annamaria M; Marseglia, Gian Luigi

    2014-04-01

    Adenoids are strategically located for mediating local and regional immune functions as they are exposed to antigens from both the outside air and the alimentary tract. Recurrent or chronic respiratory infections can induce histomorphological and functional changes in the adenoidal immunological barrier, sometimes making surgical treatment necessary. Our aim in this review is to summarize the crucial points about not only the immunological histopathology of adenoidal tissue, especially in patients with adenoid hypertrophy, but also the most common and useful diagnostic techniques and surgical options.

  13. Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

    Science.gov (United States)

    Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

    2014-02-01

    The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

  14. Plant Viruses as Nanoparticle-Based Vaccines and Adjuvants

    Directory of Open Access Journals (Sweden)

    Marie-Ève Lebel

    2015-08-01

    Full Text Available Vaccines are considered one of the greatest medical achievements in the battle against infectious diseases. However, the intractability of various diseases such as hepatitis C, HIV/AIDS, malaria, tuberculosis, and cancer poses persistent hurdles given that traditional vaccine-development methods have proven to be ineffective; as such, these challenges have driven the emergence of novel vaccine design approaches. In this regard, much effort has been put into the development of new safe adjuvants and vaccine platforms. Of particular interest, the utilization of plant virus-like nanoparticles and recombinant plant viruses has gained increasing significance as an effective tool in the development of novel vaccines against infectious diseases and cancer. The present review summarizes recent advances in the use of plant viruses as nanoparticle-based vaccines and adjuvants and their mechanism of action. Harnessing plant-virus immunogenic properties will enable the design of novel, safe, and efficacious prophylactic and therapeutic vaccines against disease.

  15. Antifungal adjuvants: Preserving and extending the antifungal arsenal.

    Science.gov (United States)

    Butts, Arielle; Palmer, Glen E; Rogers, P David

    2017-02-17

    As the rates of systemic fungal infections continue to rise and antifungal drug resistance becomes more prevalent, there is an urgent need for new therapeutic options. This issue is exacerbated by the limited number of systemic antifungal drug classes. However, the discovery, development, and approval of novel antifungals is an extensive process that often takes decades. For this reason, there is growing interest and research into the possibility of combining existing therapies with various adjuvants that either enhance activity or overcome existing mechanisms of resistance. Reports of antifungal adjuvants range from plant extracts to repurposed compounds, to synthetic peptides. This approach would potentially prolong the utility of currently approved antifungals and mitigate the ongoing development of resistance.

  16. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs.

    Science.gov (United States)

    Slot, A; Meerwaldt, J H; van Putten, W L; Treurniet-Donker, A D

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma (T3 or T4, positive lymph nodes, positive resection line) received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fractions in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m2) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial.

  17. [Stomach carcinoma. Optimizing therapy by neoadjuvant or adjuvant therapy?].

    Science.gov (United States)

    Rosen, H

    1999-01-01

    Despite the decreasing frequency of gastric cancer in most Western countries prognosis could not be improved by surgery alone in the past. Advanced tumor stage due to late diagnosis is one of the reasons for this observation. Contrary to breast and colorectal cancer, postoperative chemotherapy failed to improve prognosis in gastric cancer. Small number of patients in Western studies, insufficient surgical procedures and the high frequency of locoregional relapse may be attributed for this observation. Intraperitoneal, adjuvant chemotherapy showed a positive impact on survival in Asian studies only, but was also used successfully as a part of a multimodality approach in Western phase II trials. Since neoadjuvant therapy proved to create downstaging of tumor size in some patients with advanced gastric cancer some working groups tried to influence prognosis of potentially resectable tumors by preoperative chemotherapy, surgical resection and postoperative, adjuvant therapy in the recent past. However, the efficacy of this therapeutic approach has to be reconfirmed in a controlled, phase III fashion.

  18. Adjuvant postoperative radiotherapy for gastric carcinoma with poor prognostic signs

    Energy Technology Data Exchange (ETDEWEB)

    Slot, A.; Meerwaldt, J.H.; Treurniet-Donker, A.D. (Dr. Daniel Den Hoed Cancer Center, Rotteram (Netherlands). Department of Radiotherapy); Putten, W.L.J. van (Dr. Daniel Den Hoed Cancer Center, Rotterdam (Netherlands). Department of Statistics)

    1989-12-01

    Fifty-seven patients with poor prognostic factors following resection with curative intent for gastric adenocarcinoma T{sub 3} or T{sub 4}, positive lymph nodes, positive resection line received adjuvant radiotherapy. A dose of 30.0-50.0 Gy was given in 10-25 fraction in one course or with a split of 2 weeks after 15 fractions. This was combined with 5-fluorouracil (5-FU) (375 mg/m{sup 2}) given i.v. as a bolus during the first 4 days of radiation (n = 49). The 5-year survival was 26%; this rate is higher than the figures mentioned in the literature after surgery alone. The only way to prove the role of adjuvant radiotherapy for gastric carcinoma is a prospective randomized trial. (author). 11 refs., 2 figs., 6 tabs.

  19. [How I treat colorectal cancer. I. Prevention and adjuvant treatment].

    Science.gov (United States)

    Bours, V; Jerusalem, G; Fillet, G

    1998-04-01

    Colorectal adenocarcinoma is a major cause of cancer-related morbidity and mortality in Belgium and in other western countries. Prevention implies a modification of alimentation and maybe a chronic uptake of acetylsalicylic acid. Treatment of colorectal cancers is based on surgery and the prognosis is determined by the locoregional or metastatic tumor spread. Complete resection of any Astler Coller stage C colorectal malignant tumor has to be followed by a 5-fluorouracil-based adjuvant chemotherapy. In these protocols, 5-fluorouracil is administered together with folinic acid or levamisole. The administration of an adjuvant chemotherapy could also be considered for stage BII diseases. As rectal cancers are characterized by high local relapse rates, their treatment should associate radiotherapy, given either post-surgery or preferentially pre-surgery, with resection and chemotherapy. Appropriate treatment of colorectal cancers thus requires a concerted multidisciplinary approach.

  20. 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.

  1. German Society for Immunology and Australasian Society for Immunology joint Workshop 3(rd) -4(th) December 2015 - Meeting report.

    Science.gov (United States)

    Kurts, Christian; Gottschalk, Catherine; Bedoui, Sammy; Heinzel, Susanne; Godfrey, Dale; Enders, Anselm

    2016-02-01

    The German Society for Immunology (DGfI) and the Australasian Society for Immunology (ASI) hosted the first DGfI-ASI joint workshop from December 3-4, 2015 in Canberra, Australia. A delegation of 15 distinguished German immunologists discussed the workshop topic "immune regulation in infections and immune mediated diseases" with the aim to establish new German-Australasian collaborations, discuss new concepts in the field of immune regulation and build a scientific network to create more utilizable resources for excellent (trans-border) immunological research. The workshop was associated with the 45(th) Annual Scientific Meeting of the ASI held from Nov 29-Dec 3, 2015, opening up even more opportunities for finding new collaboration partners. A return meeting will be linked to the annual DGfI meeting that will take place in 2017 in Erlangen.

  2. Advances in the research of adjuvants for Chlamydia trachomatis vaccines%沙眼衣原体疫苗佐剂研究进展

    Institute of Scientific and Technical Information of China (English)

    褚福娟; 陈莉莉

    2013-01-01

    沙眼衣原体是感染性致盲和细菌性性传播疾病的主要病原体.接种疫苗是预防和控制沙眼衣原体感染最经济有效的途径.蛋白或多肽疫苗、DNA疫苗和树突状细胞疫苗是具有应用前景的三类沙眼衣原体疫苗.与传统灭活疫苗相比,这三类疫苗往往存在免疫原性弱等缺陷,急需发展新型免疫佐剂来增强其免疫效果,此文对这三类沙眼衣原体疫苗佐剂的研究进展作一综述.%Chlamydia trachomatis (Ct) is the main pathogen of infectious blindness and bacterial sexually transmitted diseases.Vaccination is the most economical and effective way to control Ct infections.There are three types of Ct vaccines with strong application prospects,including protein or polypeptide vaccine,DNA vaccine and dendritic cell vaccine.The immunogenicity of the three types of vaccines is weaker than that of the traditional inactivated vaccines,and development of effective immunologic adjuvants is urgently needed to enhance immune effects.This article reviews the research progress of adjuvants for these three types of vaccines.

  3. Preparation and evaluation of functional foods in adjuvant arthritis

    OpenAIRE

    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...

  4. Adjuvant properties of a simplified C32 monomycolyl glycerol analogue.

    Science.gov (United States)

    Bhowruth, Veemal; Minnikin, David E; Agger, Else Marie; Andersen, Peter; Bramwell, Vincent W; Perrie, Yvonne; Besra, Gurdyal S

    2009-04-01

    A simplified C(32) monomycolyl glycerol (MMG) analogue demonstrated enhanced immunostimulatory activity in a dioctadecyl ammonium bromide (DDA)/Ag85B-ESAT-6 formulation. Elevated levels of IFN-gamma and IL-6 were produced in spleen cells from mice immunised with a C(32) MMG analogue comparable activity to the potent Th1 adjuvant, trehalose 6,6'-di-behenate (TDB).

  5. Adjuvants to local anesthetics: Current understanding and future trends

    Science.gov (United States)

    Swain, Amlan; Nag, Deb Sanjay; Sahu, Seelora; Samaddar, Devi Prasad

    2017-01-01

    Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal

  6. Hypothesis: Silver Nanoparticles as an Adjuvant for Cancertherapy

    Directory of Open Access Journals (Sweden)

    Ramin Mohammadzadeh

    2012-06-01

    Full Text Available Cytotoxic agents are a main part of therapeutic process against the observed tumors, which lead to some unwished damages, due to drug uptake by normal body cells causing various tissue/organ failures associated with formal administration manners. But nowadays the risk is reduced by new target therapy techniques, of which the observed physical nature of micelles and nanosilver particles, governing their special behavior, could help using micelle-coated silver nanoparticles as a novel adjuvant for cancer target therapy.

  7. 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.

  8. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland.

    Directory of Open Access Journals (Sweden)

    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

  9. 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.

  10. Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

    Directory of Open Access Journals (Sweden)

    Ivana Škrnjug

    Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

  11. [Adjuvant chemotherapy in colon cancer. About 119 cases].

    Science.gov (United States)

    Yaich, Asma; Khanfir, Afef; Bayrouti, Mohamed Issam; Frikha, Mounir

    2015-04-01

    colon cancer is a public health problem worldwide and in Tunisia. The prognosis of patients with unresectable colorectal cancer varies according to the stage. The indication for adjuvant chemotherapy is well established in the colon cancer stage III, while it remains a matter of controversy for stage II. The aim of this work is to identify the epidemiological and anatomoclinical assess therapeutic outcomes in terms of overall survival of patients with high-risk stage II and stage III colon cancer treated with surgery and adjuvant chemotherapy. DS: It's a retrospective study based on 119 patients with colon adenocarcinoma from 1996 to 2010. This patients suffering from colon cancer classified stage II and III having them all radical surgery and adjuvant chemotherapy. The average age of our patients was 53 years. The surgery was performed in an emergency situation in 53 patients (44%). Stages II and III, respectively, were observed in 47% and 53% of cases. Three regimens of chemotherapy were used: protocol FUFOL (50%), followed by FOLFOX (34%) and the protocol LV5FU2 (16%). Overall survival of patients all stages combined was 73.4% at 5 years. Stage III of the TNM classification (p = 0.03) and the number of cycles of chemotherapy colon cancer is improving thanks to recent advances that have enabled the integration of new cytogenetic factors in the therapeutic decision.

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

    Science.gov (United States)

    Kobiyama, Kouji; Ishii, Ken J

    2015-09-01

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

  13. A Purified Recombinant Lipopeptide as Adjuvant for Cancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Ying-Chyi Song

    2014-01-01

    Full Text Available Synthetic lipopeptides have been widely used as vaccine adjuvants to enhance immune responses. The present study demonstrated that the tryptic N-terminal fragment of the lipoprotein rlipo-D1E3 (lipo-Nter induces superior antitumor effects compared to a synthetic lipopeptide. The lipo-Nter was purified and formulated with protein or peptide vaccines to determine if lipo-Nter could be used as a novel adjuvant and could induce antitumor immunity in a cervical cancer model. Purified lipo-Nter activated the maturation of bone marrow-derived dendritic cells (BM-DCs, leading to the secretion of TNF-α through TLR2/6 but not TLR1/2. A recombinant mutant HPV16 E7 (rE7m protein was mixed with lipo-Nter to immunize the mice; the anti-E7 antibody titers were increased, and the T helper cells were skewed toward the Th1 fate (increased IL-2 and decreased IL-5 secretion. Single-dose injection of rE7m and lipo-Nter inhibited tumor growth, but the injection of rE7m alone did not. Accordingly, lipo-Nter also enhanced the antitumor immunity of the E7-derived peptide but not the synthetic lipopeptide (Pam3CSK4. We demonstrated that the lipo-Nter of a bacterial-derived recombinant lipoprotein is a novel adjuvant that could be used for the development of a new generation of vaccines.

  14. Adherence to adjuvant endocrine therapy in women with breast cancer.

    Science.gov (United States)

    Danilak, Melanie; Chambers, Carole R

    2013-06-01

    To determine how many breast cancer patients who initiated adjuvant endocrine therapy discontinued early and to evaluate adherence in patients who persisted with therapy. Secondary objectives were to explore possible trends to see if certain factors may correlate to early discontinuation of therapy. A retrospective review of charts and pharmacy dispensing records was conducted, including patients who initiated adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute from 1 January to 31 December, 2006. Out of 346 patients, 81 (22%) discontinued therapy within 2 years. Adherence rates calculated for the 265 patients who remained on therapy beyond 2 years showed that 247 (93%) of these patients had 80% or better adherence. Patients who did not undergo chemotherapy and patients with Cross Cancer Institute follow-up times of less than 1 year were significantly more likely to discontinue therapy early. The majority of patients who were prescribed adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute remained on therapy for at least 2 years and were adherent. Longer follow-up by Cross Cancer Institute practitioners may help decrease discontinuation rates.

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

    Directory of Open Access Journals (Sweden)

    Woditschka Stephan

    2009-01-01

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

  16. 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.

  17. The Quest for an HIV-1 Vaccine Adjuvant: Bacterial Toxins as New Potential Platforms.

    Science.gov (United States)

    Nashar, Toufic O

    2014-06-01

    While tremendous efforts are undergoing towards finding an effective HIV-1 vaccine, the search for an HIV-1 vaccine adjuvant lags behind and is understudied. More recently, however, efforts have focused on testing adjuvant formulations that can boost the immune response and generate broadly neutralizing antibodies to HIV-1 ENV (gp160). Despite this, there remain a number of challenges towards achieving this goal. These include safety of adjuvant formulations; stability of the incorporated antigens; maintenance of ENV immunogenicity; optimal inoculation sites; the effective combination of adjuvants; stability of ENV neutralizing epitopes in some adjuvant formulations; mucosal immunity; and long-term maintenance of the immune response. A new class of adjuvants for HIV-1 proteins is suggested to overcome many of the limitations of some other adjuvants. Type 1 (LT-I) and type 2 (LT-II) human E. coli enterotoxins (HLTs) and their non-toxic B-subunits derivatives are strong systemic and mucosal adjuvants and effective carriers for other proteins and epitopes. Their stable molecular structure in the presence of fused proteins and epitopes, and their ability to target surface receptors on antigen presenting cells make them ideal for the delivery of HIV-1 ENV or HIV other proteins. Importantly, unlike some other adjuvants, HLTs and derivatives have well-defined modes of immune system activation. The challenges in finding optimal HIV-1 vaccine adjuvant formulation and the important properties of HLTs are discussed.

  18. Comparable quality attributes of hepatitis E vaccine antigen with and without adjuvant adsorption-dissolution treatment.

    Science.gov (United States)

    Zhang, Yue; Li, Min; Yang, Fan; Li, Yufang; Zheng, Zizheng; Zhang, Xiao; Lin, Qingshan; Wang, Ying; Li, Shaowei; Xia, Ningshao; Zhang, Jun; Zhao, Qinjian

    2015-01-01

    Most vaccines require adjuvants for antigen stabilization and immune potentiation. Aluminum-based adjuvants are the most widely used adjuvants for human vaccines. Previous reports demonstrated the preservation of antigen conformation and other antigen characteristics after recovery from adjuvanted Hepatitis B and human papillomavirus vaccines. In this study, we used a combination of various physiochemical and immunochemical methods to analyze hepatitis E vaccine antigen quality attributes after recovery from adjuvants. All biochemical and biophysical methods showed similar characteristics of the p239 protein after recovery from adjuvanted vaccine formulation compared to the antigen in solution which never experienced adsorption/desorption process. Most importantly, we demonstrated full preservation of key antigen epitopes post-recovery from adjuvanted vaccine using a panel of murine monoclonal antibodies as exquisite probes. Antigenicity of p239 was probed with a panel of 9 mAbs using competition/blocking ELISA, surface plasmon resonance and sandwich ELISA methods. These multifaceted analyses demonstrated the preservation of antigen key epitopes and comparable protein thermal stability when adsorbed on adjuvants or of the recovered antigen post-dissolution treatment. A better understanding of the antigen conformation in adjuvanted vaccine will enhanced our knowledge of antigen-adjuvant interactions and facilitate an improved process control and development of stable vaccine formulation.

  19. 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.

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

    NARCIS (Netherlands)

    Haan, Ellen Christine de

    2004-01-01

    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 trea

  1. 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

  2. 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

  3. 21 CFR 866.5110 - Antiparietal antibody immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antiparietal antibody immunological test system. 866.5110 Section 866.5110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... cells are those cells located in the stomach that produce a protein that enables vitamin B12 to be...

  4. 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.

  5. 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.

  6. 21 CFR 866.5660 - Multiple autoantibodies immunological test system.

    Science.gov (United States)

    2010-04-01

    .... Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system. 866.5660 Section 866.5660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  7. MISSION OF IMMUNOLOGY%免疫学的使命

    Institute of Scientific and Technical Information of China (English)

    王璞玥; 杜生明

    2012-01-01

    As one of the most important and exciting research areas in life sciences, immunology has been witnessing and driving advances in biological research as well as basic medicine studies. Here we revealed characteristics of immunology, analyzed pivotal roles immunology has been playing in meeting demands of social development, and discussed major breakthroughs Chinese immunologists have achieved in recent years. Further, major efforts and measures are proposed to improve immunology research in China in the future.%免疫学与人类健康密切相关。作为生命科学领域最活跃最前沿的基础学科之一,免疫学见证着生命科学和基础医学的发展和突破。本文分析了现今免疫学的内涵和特点以及在社会发展中的作用,提出了我国免疫学研究人员在今后工作中努力的方向。

  8. A Multi-Agent Immunology Model for Security Computer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper presents a computer immunology model for computersecurity , whose main components are defined as idea of Multi-Agent. It introduces the n at ural immune system on the principle, discusses the idea and characteristics of Mu lti-Agent. It gives a system model, and describes the structure and function of each agent. Also, the communication method between agents is described.

  9. CHARGE syndrome : a review of the immunological aspects

    NARCIS (Netherlands)

    Wong, Monica Ty; Scholvinck, Elisabeth H.; Lambeck, Annechien Ja; van Ravenswaaij-Arts, Conny Ma

    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 describ

  10. 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... vitro coagulation studies classified under § 864.5425 of this chapter or prothrombin time tests...

  11. Cancer vaccines: the perspective of the Cancer Immunology Branch, NCI.

    Science.gov (United States)

    Sogn, J A; Finerty, J F; Heath, A K; Shen, G L; Austin, F C

    1993-08-12

    The Cancer Immunology Branch, NCI, is supporting a great deal of exciting research relevant to cancer vaccine development. The few areas highlighted here are representative of ongoing research opportunities, but further progress depends largely on a continued infusion of investigator-initiated ideas to realize the potential of current research areas and open new ones.

  12. 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

  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. 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.

  15. 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.

  16. 21 CFR 866.5150 - Bence-Jones proteins immunological test system.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866... bone marrow cells), leukemia (cancer of the blood-forming organs), and lymphoma (cancer of the...

  17. [Clinical-immunological and microbiological parallels in chronic generalized parodontitis and peptic ulcer of the stomach].

    Science.gov (United States)

    Orekhova, L Iu; Neĭzberg, D M; Stiuf, I Iu

    2006-01-01

    Clinical, immunological and DNA diagnostic examinations of 101 patients with chronic generalized parodontitis and peptic ulcer have revealed similar features of immunological disorders of gastric and oral mucosa and the role of Helicobacter pylori.

  18. 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.

  19. 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

    2014-01-23

    We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in the 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 (60)Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25kGy). 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.

  20. Experimental investigations on immunology of the parathyroid gland

    Science.gov (United States)

    Lupulescu, A.; Potorac, E.; Pop, A.; Heitmanek, Constanta; Merculiev, Elena; Chisiu, N.; Oprisan, R.; Neacsu, C.

    1968-01-01

    Repeated inoculation of homologous parathyroid tissue in dogs induced isoimmune hypoparathyroidism, with all the characteristic biochemical and histopathological features and the presence of complement fixing antibodies in the serum. Disturbances of calcium and phosphorus metabolism were similar to, but less severe than, those observed in dogs with hypoparathyroidism induced by complete thyro-parathyroidectomy. Injection of rabbits with crude extracts of dog, rat, hog and human parathyroid or with bovine parathormone (PTH), each incorporated in Freund's adjuvant, resulted in the development of complement fixing and precipitating antibodies: these reacted with the corresponding tissue preparations, but did not show cross-reactivity. Antibodies were not detected in the serum of normal dogs or in control dogs inoculated with Freund's adjuvant alone. Study of the parathyroid glands by electron microscopy provided information on the mechanism of PTH secretion and synthesis in normal dogs and in those with hypoparathyroidism. ImagesFIG. 3FIG. 4-8FIG. 9FIG. 10-11 PMID:4968246

  1. Immunological Properties of Hepatitis B Core Antigen Fusion Proteins

    Science.gov (United States)

    Francis, Michael J.; Hastings, Gillian Z.; Brown, Alan L.; Grace, Ken G.; Rowlands, David J.; Brown, Fred; Clarke, Berwyn E.

    1990-04-01

    The immunogenicity of a 19 amino acid peptide from foot-and-mouth disease virus has previously been shown to approach that of the inactivated virus from which it was derived after multimeric particulate presentation as an N-terminal fusion with hepatitis B core antigen. In this report we demonstrate that rhinovirus peptide-hepatitis B core antigen fusion proteins are 10-fold more immunogenic than peptide coupled to keyhole limpet hemocyanin and 100-fold more immunogenic than uncoupled peptide with an added helper T-cell epitope. The fusion proteins can be readily administered without adjuvant or with adjuvants acceptable for human and veterinary application and can elicit a response after nasal or oral dosing. The fusion proteins can also act as T-cell-independent antigens. These properties provide further support for their suitability as presentation systems for "foreign" epitopes in the development of vaccines.

  2. 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...

  3. 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...

  4. 21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Immunoglobulins A, G, M, D, and E immunological... Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification. An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of...

  5. 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.

  6. 21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antichymotrypsin immunological test system. 866.5080 Section 866.5080 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5080 Alpha-1-antichymotrypsin...

  7. 21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inter-alpha trypsin inhibitor immunological test system. 866.5890 Section 866.5890 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5890 Inter-alpha trypsin inhibitor...

  8. Adjuvant Activity of a Novel Metabolizable Lipid Emulsion with Inactivated Viral Vaccines

    Science.gov (United States)

    1980-06-01

    hamsters, sheep, and two species of nonhuman 0 primates which demonstrate the adjuvant activity of a new metabolizable lipid emulsion with marginally...mice, hamsters, sheep, and two species of nonhuman primates . This adjuvant has several 10.000 advantages over other known adjuvant com-cpounds. It is...plaque neutralization method for arboviruses . Proc. Soc. granulomatous reaction was not observed. We Exp. Biol. Med. 125:741-747. closely observed the

  9. Insight into the cellular fate and toxicity of aluminium adjuvants used in clinically approved human vaccinations

    OpenAIRE

    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...

  10. 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).

  11. Characteristics and prognosis of patients with early-stage endometrial cancer who refuse adjuvant radiotherapy.

    Science.gov (United States)

    Koskas, Martin; Huchon, Cyrille; Amant, Frederic

    2016-06-01

    To investigate the risk factors for refusing adjuvant radiotherapy in patients who have undergone surgery for early-stage endometrial cancer, and to compare their survival rates with patients who have undergone adjuvant radiotherapy. Data from the Surveillance, Epidemiology, and End Results database for patients operated on for histologically-proven early-stage endometrioid endometrial cancer, between 1988 and 2012, were screened. Univariate and multivariate logistic regression analyses tested the associations between refusal of adjuvant radiotherapy and demographic, tumoral, and management characteristics. Overall and cancer-related survival rates were compared between 376 patients who refused adjuvant radiotherapy and 752 patients who received adjuvant radiotherapy, matched for demographics (age, race, year of diagnosis, marital status, region), tumoral (grade, FIGO stage, size), and management (lymphadenectomy performed) criteria. 434 of the 16,014 patients (2.7%) who were proposed adjuvant radiotherapy refused this treatment. Older, widowed, divorced, or separated patients, who were recently diagnosed and managed in the Northern plains or Pacific coast (USA), with limited tumoral extension, were more likely to refuse adjuvant radiotherapy. Five-year cancer-related survival was significantly lower in patients who refused adjuvant radiotherapy (88.9% vs. 95.7%, pradiotherapy. Refusing adjuvant radiotherapy increased cancer-related death but probably does not reduce overall survival. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans......Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

  13. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    Science.gov (United States)

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per; Yilmaz, Mette; Falkmer, Ursula; Sorbye, Halfdan

    2015-04-01

    The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU/oxaliplatin. A review of the literature was made identifying 24 randomized controlled trials on adjuvant treatment of rectal cancer based on about 10 000 patients. The trials were subdivided into a number of clinically relevant subgroups. As regards patients treated with preoperative (chemo) radiotherapy, four randomized studies were found where use of adjuvant chemotherapy showed no benefit in survival. Three trials were found in which a subset of patients received preoperative (chemo) radiotherapy. Two of these trials showed a statistically significant benefit of adjuvant chemotherapy. Twenty trials were identified in which the patients did not receive preoperative (chemo) radiotherapy, including five Asian studies in which a statistically significant benefit from adjuvant chemotherapy was reported. Most of the data found did not support the use of postoperative adjuvant chemotherapy for patients already treated with preoperative (chemo) radiotherapy. For patients not treated preoperatively, several studies support the use of single agent 5-FU chemotherapy. Treatment guidelines seem to differ according to if preoperative chemoradiation is considered of importance for use of adjuvant chemotherapy and if adjuvant colon cancer studies are considered transferrable to rectal cancer patients regardless of the molecular differences.

  14. 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

    BACKGROUND AND OBJECTIVES: In stage III colonic cancer, time from surgery to start of adjuvant chemotherapy may influence survival. In this study, we evaluated the effect of timing of adjuvant therapy on survival. METHODS: Database study from the Danish Colorectal Cancer Group's national database....... RESULTS: The final population included 1,827 patients scheduled for adjuvant chemotherapy. Adjuvant therapy started within 4 and 8 weeks improved survival when compared to start later than 8 weeks (HR [95%CI]: 1.7 [1.1-2.6]; P = 0.024 and 1.4 [1.07-1.8]; P = 0.013, respectively), whereas...

  15. Adjuvants and immunostimulants in fish vaccines: current knowledge and future perspectives.

    Science.gov (United States)

    Tafalla, Carolina; Bøgwald, Jarl; Dalmo, Roy A

    2013-12-01

    Vaccination is the most adequate method to control infectious diseases that threaten the aquaculture industry worldwide. Unfortunately, vaccines are usually not able to confer protection on their own; especially those vaccines based on recombinant antigens or inactivated pathogens. Therefore, the use of adjuvants or immunostimulants is often necessary to increase the vaccine efficacy. Traditional adjuvants such as mineral oils are routinely used in different commercial bacterial vaccines available for fish; however, important side effects may occur with this type of adjuvants. A search for alternative molecules or certain combinations of them as adjuvants is desirable in order to increase animal welfare without reducing protection levels. Especially, combinations that may target specific cell responses and thus a specific pathogen, with no or minor side effects, should be explored. Despite this, the oil adjuvants currently used are quite friendlier with respect to side effects compared with the oil adjuvants previously used. The great lack of fish antiviral vaccines also evidences the importance of identifying optimal combinations of a vaccination strategy with the use of a targeting adjuvant, especially for the promising fish antiviral DNA vaccines. In this review, we summarise previous studies performed with both traditional adjuvants as well as the most promising new generation adjuvants such as ligands for Toll receptors or different cytokines, focussing mostly on their protective efficacies, and also on what is known concerning their effects on the fish immune system when delivered in vivo.

  16. Stage IB endometrial cancer. Does lymphadenectomy replace adjuvant radiotherapy?

    Science.gov (United States)

    Bottke, Dirk; Wiegel, Thomas; Kreienberg, Rolf; Kurzeder, Christian; Sauer, Georg

    2007-11-01

    The role of surgical lymph node dissection and adjuvant radiation therapy (RT) in early stage endometrial cancer is no longer clearly defined. The increased appreciation of lymphadenectomy and the absence of survival advantage from adjuvant RT rise controversies how patients should adequately be treated in stage IB endometrial cancer. The aim of this review is to rule out the validity of either treatment option and determine which preference provides the best therapeutic benefit. Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. Based on the available data in the literature, for stage IB grade 1 or 2, the risk of pelvic relapse is considered too low to justify pelvic RT. However, intravaginal RT (IVRT) should be recommended for those >or= 60 years old or with lymphovascular invasion (LVI). For patients with stage IB grade 3 (and IC all grades), the treatment recommendation is mainly based on whether surgical lymph node staging was performed. These patients have--without surgical lymph node staging--a high risk of pelvic recurrence and should therefore primarily undergo relaparotomy for lymphadenectomy or pelvic RT as second choice. If these patients had a surgical lymph node staging, then IVRT alone is a reasonable alternative to pelvic RT. Overall survival may not be the only ideal endpoint for stage IB endometrial cancer since causes of death are mostly other than endometrial cancer. Conventional pelvic RT may be overtreatment in some patients, in particular in those patients with a large number of negative lymph nodes after lymphadenectomy. However, negative surgical staging should not be understood as adjuvant RT can be omitted in all patients.

  17. Treg inducing adjuvants for therapeutic vaccination against chronic inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Chantal eKeijzer

    2013-08-01

    Full Text Available Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation, the observed side effects illustrate the need for more specific interventions. Regulatory T cells (Treg are pivotal controllers of (autoaggressive immune responses, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Especially antigen-specific targeting of Treg would enable tailor made interventions, while obviating negative side effects of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for such interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory site. Heat shock proteins show several of these characteristics.The development of antigen-specific Treg inducing vaccines is a major novel goal in the field of immunotherapy in autoimmune diseases. Progress is hampered by the lack of effective antigens and by the fact that other factors such as dose, route and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to effective induction of Treg. The use of a Treg inducing adjuvant might be required to achieve effective regulatory responses, in the case of ongoing inflammation. Future goals will be the optimization of natural Treg expansion (or the induction of adaptive Treg without loss of their suppressive function or the concomitant induction of non-regulatory T cells. Here, we discuss the potential use of protein/peptide-based vaccines combined with Treg inducing adjuvants for the development of therapeutic vaccines against chronic

  18. Adjuvant Ab Interno Tumor Treatment After Proton Beam Irradiation.

    Science.gov (United States)

    Seibel, Ira; Riechardt, Aline I; Heufelder, Jens; Cordini, Dino; Joussen, Antonia M

    2017-06-01

    This study was performed to show long-term outcomes concerning globe preservation in uveal melanoma patients after proton beam therapy with the main focus on outcomes according to different adjuvant ab interno surgical procedures. Retrospective cohort study. All patients treated with primary proton beam therapy for choroidal or ciliary body melanoma between June 1998 and June 2015 were included. A total of 2499 patients underwent primary proton beam therapy, with local tumor control and globe preservation rates of 95.9% and 94.8% after 5 years, respectively. A total of 110 (4.4%) patients required secondary enucleation. Unresponsive neovascular glaucoma was the leading cause of secondary enucleation in 78 of the 2499 patients (3.1%). The 5-year enucleation-free survival rate was 94.8% in the endoresection group, 94.3% in the endodrainage group, and 93.5% in the comparator group. The log-rank test showed P = .014 (comparator group vs endoresection group) and P = .06 (comparator group vs endodrainage-vitrectomy group). Patients treated with endoresection or endodrainage-vitrectomy developed less radiation retinopathy (30.5% and 37.4% after 5 years, P = .001 and P = .048 [Kaplan-Meier], respectively) and less neovascular glaucoma (11.6% and 21.3% after 5 years, P = .001 and P = .01 [Kaplan-Meier], respectively) compared with the comparator group (52.3% radiation retinopathy and 57.8% neovascular glaucoma after 5 years). This study suggests that in larger tumors the enucleation and neovascular glaucoma rates might be reduced by adjuvant surgical procedures. Although endoresection is the most promising adjuvant treatment option, the endodrainage-vitrectomy is recommended in patients who are ineligible for endoresection. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Beryllium, an adjuvant that promotes gamma interferon production.

    Science.gov (United States)

    Lee, J Y; Atochina, O; King, B; Taylor, L; Elloso, M; Scott, P; Rossman, M D

    2000-07-01

    Beryllium is associated with a human pulmonary granulomatosis characterized by an accumulation of CD4(+) T cells in the lungs and a heightened specific lymphocyte proliferative response to beryllium (Be) with gamma interferon (IFN-gamma) release (i.e., a T helper 1 [Th1] response). While an animal model of Be sensitization is not currently available, Be has exhibited adjuvant effects in animals. The effects of Be on BALB/c mice immunized with soluble leishmanial antigens (SLA) were investigated to determine if Be had adjuvant activity for IFN-gamma production, an indicator of the Th1 response. In this strain of Leishmania-susceptible BALB/c mice, a Th2 response is normally observed after in vivo SLA sensitization and in vitro restimulation with SLA. If interleukin-12 (IL-12) is given during in vivo sensitization with SLA, markedly increased IFN-gamma production and decreased IL-4 production are detected. We show here that when beryllium sulfate (BeSO(4)) was added during in vivo sensitization of BALB/c mice with SLA and IL-12, significantly increased IFN-gamma production and decreased IL-4 production from lymph node and spleen cells were detected upon in vitro SLA restimulation. No specific responses were observed to Be alone. Lymph node and spleen cells from all mice proliferated strongly and comparably upon in vitro restimulation with SLA and with SLA plus Be; no differences were noted among groups of mice that received different immunization regimens. In vivo, when Be was added to SLA and IL-12 for sensitization of BALB/c mice, more effective control of Leishmania infection was achieved. This finding has implications for understanding not only the development of granulomatous reactions but also the potential for developing Be as a vaccine adjuvant.

  20. Caffeine as an opioid analgesic adjuvant in fibromyalgia

    OpenAIRE

    Scott JR; Hassett AL; Brummett CM; Harris RE; Clauw DJ; Harte SE

    2017-01-01

    J Ryan Scott,1 Afton L Hassett,1 Chad M Brummett,1 Richard E Harris,1,2 Daniel J Clauw,1,2 Steven E Harte1,2 1Chronic Pain and Fatigue Research Center, Department of Anesthesiology, 2Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA Background: Caffeine’s properties as an analgesic adjuvant with nonsteroidal anti-inflammatory drugs/acetaminophen are well documented. However, little clinical research has explored ca­ffeine&a...

  1. Radiation Recall Reaction Induced by Adjuvant Trastuzumab (Herceptin

    Directory of Open Access Journals (Sweden)

    Caroline Chung

    2009-01-01

    trastuzumab (Herceptin administration, there has been no published case of radiation recall reaction associated with trastuzumab. This case describes a clinical presentation consistent with a radiation recall reaction following administration of adjuvant trastuzumab after neoadjuvant FEC-D chemotherapy and locoregional radiotherapy for HER2-positive, locally advanced breast cancer in a premenopausal woman. Although the mechanism and etiology of radiation recall dermatitis remain unclear, this case raises further hypotheses regarding a possible drug dose-dependence and possible predisposing risk factor for the development of radiation recall reactions.

  2. Adjuvant chemo-radiation for gastric adenocarcinoma: an institutional experience

    Directory of Open Access Journals (Sweden)

    Ghosn Marwan G

    2010-06-01

    Full Text Available Abstract Background Studies have shown that surgery alone is less than satisfactory in the management of early gastric cancer, with cure rates approaching 40%. The role of adjuvant therapy was indefinite until three large, randomized controlled trials showed the survival benefit of adjuvant therapy over surgery alone. Chemoradiation therapy has been criticized for its high toxicity. Methods 24 patients diagnosed between September 2001 and July 2007 were treated with adjuvant chemoradiation. 18 patients had the classical MacDonald regimen of 4500 cGy of XRT and chemotherapy with 5-fluorouracil (5FU and leucovorin, while chemotherapy consisted of 5FU/Cisplatin for 6 patients. Results This series consisted of non-metastatic patients, 17 females and 7 males with a median age of 62.5 years. 23 patients (96% had a performance status of 0 or 1. The full course of radiation therapy (4500 cGy was completed by 22 patients (91.7%. Only 7 patients (36.8% completed the total planned courses of chemotherapy. 2 local relapses (10%, 2 regional relapses (10% and 2 distant relapses (10% were recorded. Time to progression has not been reached. 9 patients (37.5% died during follow-up with a median overall survival of 75 months. Patients lost a mean of 4 Kgs during radiation therapy. We recorded 6 episodes of febrile neutropenia and the most frequent toxicity was gastro-intestinal in 17 patients (70.8% with 9 (36% patients suffering grade 3 or 4 toxicity and 5 patients (20% suffering from grade 3 or 4 neutropenia. 4 (17% patients required total parenteral nutrition for a mean duration of 20 days. 4 patients suffered septic shock (17% and 1 patient developed a deep venous thrombosis and a pulmonary embolus. Conclusions Adjuvant chemo-radiation for gastric cancer is a standard at our institution and has resulted in few relapses and an interesting median survival. Toxicity rates were serious and this remains a harsh regimen with only 36.8% of patients completing the

  3. [Value of adjuvant physiotherapy in postoperative pain management].

    Science.gov (United States)

    Bullmann, V; Weber, T P; Kienle, B; Schulte, T L

    2008-10-01

    In times of limited financial and human resources the application of adjuvant physiotherapy postoperatively in orthopaedic patients requires reevaluation. In the early postoperative course physiotherapy improves the patients' mobility. However, it is not able to reduce the need for pain medication. It is intended to minimize complications and to mobilize and motivate the patients early. In contrast, massages are of minor importance in the immediate postoperative course and are applied only in a few selected cases. Cryotherapy plays a major role especially after shoulder and knee surgery. On the other hand, transcutaneous electrical nerve stimulation (TENS) and acupuncture are applied only in selected patients after orthopaedic surgery, e.g., after limb amputation.

  4. 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

  5. Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

    Science.gov (United States)

    Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

    2009-07-01

    Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX ( Pproducts by gamma irradiation.

  6. 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.

  7. Stem Cell Niche, the Microenvironment and Immunological Crosstalk

    Institute of Scientific and Technical Information of China (English)

    Law Sujata; S. Chaudhuri

    2008-01-01

    The concept of stem cells, their physiological existence, the intricate anatomical localization, the known and the unknown functions, and their exclusive utility for the purpose of regenerative medicine, are all now encompassed within an emergent question, 'how compatible these cells are immunologically?'Indeed, the medical aspects of stem cells are dependent on a large number of queries based on the basic properties of the cells. It has greatly been emphasized to probe into the basic research on stem cells before any successful therapeutic attempts are made. One of the intricate aspects of the adult stem cells is its immunological behavior in relation to the microenvironmental associates, the stromal ceils in the presence of a suitable target.

  8. Koch Institute Symposium on Cancer Immunology and Immunotherapy.

    Science.gov (United States)

    Drake, Adam; Joshi, Nikhil S; Szeto, Gregory L; Zhu, Eric; Eisen, Herman N; Irvine, Darrell J

    2013-10-01

    The 12(th) annual summer symposium of The Koch Institute for Integrative Cancer Research at MIT was held in Cambridge, MA, on June 14(th), 1023. The symposium entitled "Cancer Immunology and Immunotherapy" focused on recent advances in preclinical research in basic immunology and biomedical engineering, and their clinical application in cancer therapies. The day-long gathering also provided a forum for discussion and potential collaborations between engineers and clinical investigators. The major topics presented include: (i) enhancement of adoptive cell therapy by engineering to improve the ability and functionality of T-cells against tumor cells; (ii) current therapies using protein and antibody therapeutics to modulate endogenous anti-tumor immunity; and (iii) new technologies to identify molecular targets and assess therapeutic efficacy, and devices to control and target drug delivery more effectively and efficiently.

  9. 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.

  10. Pathophysiology and immunological profile of myasthenia gravis and its subgroups.

    Science.gov (United States)

    Romi, Fredrik; Hong, Yu; Gilhus, Nils Erik

    2017-08-03

    Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present. Copyright © 2017. Published by Elsevier Ltd.

  11. 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

  12. Interrupting the transmission of wild polioviruses with vaccines: immunological considerations.

    OpenAIRE

    Ghendon, Y.; Robertson, S. E.

    1994-01-01

    In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of...

  13. Immunological evaluation of rheumatoid arthritis patients treated with itolizumab

    OpenAIRE

    Aira, Lazaro E.; Hernández, Patricia; Prada, Dinorah; Chico, Araceli; Gómez, Jorge A.; González, Zuyén; Fuentes, Karla; Viada, Carmen; Mazorra, Zaima

    2015-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical ...

  14. [Immunological characteristics of the 2-stage method of smallpox vaccination].

    Science.gov (United States)

    Marennikova, S S; Matsevich, G R; Sokolova, A F; Shul'ga, L G; Manenkova, G M

    1977-05-01

    As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained.

  15. 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...

  16. Acute Necrotizing Ulcerative Gingivitis: Microbial and Immunologic Studies

    Science.gov (United States)

    1983-10-01

    34 Odd ii 4n....00p IdaOdifir 0’ block flumber) Periodontal Disease Spirochetes Microbiology Fusobacteria immunology Bacteroides 20. AN3T7RAC~r C4.tft...and serological etudies with ’We 7. nucleatum isolates from patients with ANUG, chronic periodontitis , Juvenile periodontitis , and adults and children...routine periodontal procedures (34-37). Early studies on the histopathology of ANUG lesions reported that the pathological process appears to begin or the

  17. Autoimmune diseases and fungal infections: immunological mechanisms and therapeutic approaches

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jian-zhong

    2009-01-01

    @@ Autoimmune disease represents a breakdown of natural tolerance to autoreactive antigens.Pemphigus and lupus erythematosus are common autoimmune diseases either skin-specific or with predominant skin involvement. During the past decades,much progress has been made in understanding the mechanism of autoimmune diseases and the immunological mechanism in some infectious diseases such as fungal infections. Various novel approaches have been developed in the treatment of these diseases.

  18. Immunologic glycosphingolipidomics and NKT cell development in mouse thymus

    DEFF Research Database (Denmark)

    Li, Yunsen; Thapa, Prakash; Hawke, David

    2009-01-01

    Invariant NKT cells are a hybrid cell type of Natural Killer cells and T cells, whose development is dependent on thymic positive selection mediated by double positive thymocytes through their recognition of natural ligands presented by CD1d, a nonpolymorphic, non-MHC, MHC-like antigen presenting...... for identifying additional ligands for NKT cells. Our results also provide early insights into cellular lipidomics studies, with a specific focus on the important immunological functions of glycosphingolipids....

  19. Immunology and Immunodiagnosis of Cystic Echinococcosis: An Update

    OpenAIRE

    Wenbao Zhang; Hao Wen; Jun Li; Renyong Lin; McManus, Donald P.

    2012-01-01

    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 ...

  20. HPV Infection: Immunological Aspects and Their Utility in Future Therapy

    OpenAIRE

    Efthimios Deligeoroglou; Aikaterini Giannouli; Nikolaos Athanasopoulos; Vasileios Karountzos; Anastasia Vatopoulou; Konstantinos Dimopoulos; George Creatsas

    2013-01-01

    High prevalence and mortality rates of cervical cancer create an imperative need to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves as the key causative factor in cervical malignancies. Understanding the immunological details and the microenvironment of the infection can be a useful tool for the development of novel therapeutic interventions. Chronic infection and progression to carcinogenesis are sustained by immortalization potential of HPV, evasion techniques, ...