RESUMO
BACKGROUND: Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper cells. In order to improve safety, SIT vaccines are often formulated with allergoids (chemically modified allergens). Interaction between T-cells and allergoids is necessary to influence cellular cytokine expression. There have been few reports on identification the early cellular effects of SIT. METHOD: Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4-shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant, monophosphoryl lipid A (MPL). Fourteen grass-allergic patients served as untreated controls. Using the peripheral blood mononuclear cells of these patients, an optimized lymphocyte transformation test (LTT) was employed to monitor the in vitro proliferative response of T-cells to an allergoid challenge (solubilised Pollinex Quattro) before the first and last injection and then 2 and 20 weeks after the final injection. Control challenges utilised preparations of a similar pollen vaccine without the adjuvant MPL and a tree pollen vaccine with and without MPL. RESULTS: The LTT showed increased LTT stimulation indices (SI) in 17/20 SIT patients when the solublised vaccine preparation was used as a challenge before the last injection and 2 weeks after, in comparison to pre-treatment levels. Twenty weeks after therapy, the SI decreased to baseline level. A vaccine challenge without MPL gave lower SI levels. A challenge of a clinically inappropriate tree allergoid vaccine gave no response, and a nontreated group also showed no response. CONCLUSION: Following a short-course SIT adjuvated with MPL, challenges of allergoids were shown to activate allergen-specific T cells in vitro. There was an additional stimulating effect when the challenge was in combination with MPL. There were no non-specific effects of MPL, shown by the tree allergoid/MPL control. The timing of the response was closely correlated to the treatment course; reactivity fell two weeks after the final injection and 20 weeks later it was at baseline level. Thus an immunological response to SIT was detected after very few injections. This methodology could provide a basis for monitoring the immediate progress of allergy vaccinations.
Assuntos
Hipersensibilidade/terapia , Imunoterapia , Extratos Vegetais/administração & dosagem , Linfócitos T/imunologia , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Alérgenos/administração & dosagem , Alérgenos/imunologia , Alergoides , Artemisia/imunologia , Feminino , Humanos , Hipersensibilidade/imunologia , Lipídeo A/administração & dosagem , Lipídeo A/análogos & derivados , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/imunologia , Poaceae/imunologia , Secale/imunologia , Células Th1/imunologia , Tirosina/químicaRESUMO
BACKGROUND: Sublingual immunotherapy (SLIT) is a relatively new form of treatment for type I allergies and a good safety profile is rapidly being established. Evidence on the efficacy of SLIT is increasing, and the present study provides further supportive data. We describe the results of treatment with a SLIT vaccine formulated with a range of allergen extracts obtained by allergologists in daily clinical practice. METHODS: Adult and child patients (n = 159, 81 males, 78 females) with confirmed type I allergic sensitivities were treated with a standardized SLIT vaccine (ORALVAC) using the sublingual-swallow method. Evaluation of the efficacy of SLIT was based on the consumption of anti-allergic medication and a global assessment. Tolerability assessment was based on the incidence of local or systemic reactions. RESULTS: Medication use was significantly reduced compared with that in previous years (p = 0.023). In a large subgroup of patients treated for pollen sensitivity the significance was stronger (p = 0.016). Global assessment revealed that only 3.5 % of patients showed no change in symptoms after therapy. High tolerability was achieved and no serious or severe adverse effects were observed. CONCLUSION: Over a one-year period, adult and child patients with a variety of type I allergies were treated with a SLIT vaccine that has shown significant efficacy and was well-tolerated with no serious or severe adverse events.
Assuntos
Dessensibilização Imunológica , Hipersensibilidade Imediata/terapia , Administração Sublingual , Adolescente , Adulto , Alérgenos/uso terapêutico , Animais , Antialérgicos/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Feminino , Alemanha , Humanos , Hipersensibilidade Imediata/tratamento farmacológico , Lactente , Masculino , Pessoa de Meia-Idade , Ácaros/imunologia , Pólen/efeitos adversos , Pólen/imunologia , Resultado do TratamentoRESUMO
BACKGROUND: Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. METHODS: An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. RESULTS: Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p < 0.01 in all cases). After therapy, skin prick test reactivity was significantly reduced in both groups and pollen-specific IgG was significantly increased in both groups whereas little change was apparent in pollen-specific IgE. Overall tolerability was similar to results obtained in previous studies in adults. CONCLUSION: Short-term SIT using four injections of grass/rye or tree pollen allergoids adsorbed to L-tyrosine and with MPL adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults.
Assuntos
Adjuvantes Imunológicos , Alérgenos/imunologia , Dessensibilização Imunológica , Lipídeo A/análogos & derivados , Lipídeo A/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/terapia , Adolescente , Especificidade de Anticorpos , Criança , Dessensibilização Imunológica/efeitos adversos , Edema/etiologia , Eritema/etiologia , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Poaceae , Rinite Alérgica Sazonal/imunologia , Secale , ÁrvoresRESUMO
Background: Specific immunotherapy (SIT) with pollen allergoids formulated with the Th1-inducing adjuvant 3-deacylated monophosphoryl lipid A (MPL® adjuvant, Corixa) has shown good efficacy and tolerability in the treatment of pollen allergies in adults. The aim of this study was to evaluate this treatment in children and adolescents aged 6-17 years old who were sensitive to grass/rye or tree pollens. Methods: An open, multicenter study was performed using 90 children and adolescents. The patients received four subcutaneous injections of grass/rye (n = 64) or tree pollen allergoids (n = 26) adsorbed to L-tyrosine and containing MPL® adjuvant. Efficacy was measured by symptom and medication scoring, skin prick test reactivity and IgG/IgE antibody responses. Tolerability was monitored by recording adverse events. Results: Both grass/rye and tree pollen treatment groups showed significant reductions in symptom scores and anti-allergic medication use compared with the previous pollen seasons (p < 0.01 in all cases). After therapy, skin prick test reactivity was significantly reduced in both groups and pollen-specific IgG was significantly increased in both groups whereas little change was apparent in pollen-specific IgE. Overall tolerability was similar to results obtained in previous studies in adults. Conclusion: Short-term SIT using four injections of grass/rye or tree pollen allergoids adsorbed to L-tyrosine and with MPL® adjuvant was shown to be effective with good tolerability. The treatment compared favorably with previous studies in adults (AU)
Antecedentes: La inmunoterapia específica (ITe) formulada con el adyuvante Th1 inductor 3-deacylated monophosphoryl lipid A (adyuvante MPL, Corixa), ha mostrado una buena eficacia y tolerabilidad en el tratamiento de las enfermedades alérgicas inducidas por pólenes en adultos. El objetivo de este estudio consiste en valorar el tratamiento en niños y adolescentes, 6-17 años, sensibles al polen de gramíneas o árboles. Métodos: Se llevó a cabo un estudio abierto multicéntrico en 90 niños y adolescentes. Los pacientes recibieron 4 dosis por vía subcutánea de alergoides de polen de gramíneas (n = 64) o árboles (n = 26) adsorbidos en L-tirosina y conteniendo el adyuvante MPL. La eficacia se valoró por una puntuación que recogía la evolución de los síntomas y de la necesidad de medicación, reactividad al Prick Test y respuesta IgE e IgG. La tolerabilidad se valoró por el registro de reacciones adversas. Resultados: Ambos grupos de tratamiento, polen de gramíneas y de árboles, mostraron una reducción significativa en las puntuaciones relativas a síntomas y medicación frente a la alergia, cuando se comparan frente a las puntuaciones de la estación anterior (p < 0,01 en todos los casos). Después de la terapia, la reactividad al Prick Test disminuyó de forma significativa en ambos grupos y los niveles en IgG específica al polen aumentó también de forma significa. La tolerabilidad global se mostró semejante a los resultados previos obtenidos en adultos. Conclusión: La ITe de corta pauta de administración, 4 dosis de alergoides de polen de gramíneas o polen de árboles, adsorbidos en L-Tirosina y con MPL como adyuvante, se mostró eficaz con una buena tolerancia, comparables de forma favorable con estudios previos en adultos (AU)
Assuntos
Criança , Adolescente , Masculino , Feminino , Humanos , Dessensibilização Imunológica , Adjuvantes Imunológicos , Secale , Pólen , Especificidade de Anticorpos , Alérgenos , Imunoglobulina E , Imunoglobulina G , Lipídeo A , Edema , Eritema , Poaceae , Árvores , Rinite Alérgica SazonalRESUMO
BACKGROUND: A short-term immunotherapy vaccine for the treatment of pollen allergy has been developed utilising L-tyrosine adsorbed allergoids. The reduced number of injections could provide advantages over long-term therapy schedules. This would improve compliance and support application of specific immunotherapy (SIT) to a greater extent. We report a multicenter study to evaluate the efficacy and safety of this treatment in a clinical practice setting. METHODS: Patients (n = 1808) with a diagnosis of sensitivities to various pollens and symptoms of allergic asthma and/or allergic rhinitis and/or allergic conjunctivitis were selected. The vaccine formulation was made up according to individual sensitivities and contained L-tyrosine adsorbed allergoids. The patients were treated with a 3-injection initial course followed by a 3-injection maintenance course. Efficacy was measured by consumption of symptomatic anti-allergic medication compared with that in the previous season and by physician assessment using a 5-point scale. All adverse events were recorded. RESULTS: Efficacy was demonstrated by a considerable decrease in regular and frequent use of medication compared with that in the previous season (p < 0.001). In addition, in 80 % of the patients, the physician's assessment was either "good" or "very good". These outcomes were unaffected by the closeness of the treatment course to the onset of the pollen season. Tolerability was good and most local and systemic reactions were mild. CONCLUSIONS: The treatment of pollen-allergic patients with a short-term SIT using a 6-injection pollen allergoid/L-tyrosine vaccine in a clinical practice setting provided a high level of efficacy with a low incidence of mainly mild adverse events.
Assuntos
Alérgenos/uso terapêutico , Asma/terapia , Conjuntivite Alérgica/terapia , Dessensibilização Imunológica , Pólen/efeitos adversos , Rinite Alérgica Sazonal/terapia , Adolescente , Adsorção , Adulto , Alérgenos/administração & dosagem , Asma/etiologia , Asma/imunologia , Criança , Conjuntivite Alérgica/etiologia , Conjuntivite Alérgica/imunologia , Dessensibilização Imunológica/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pacientes Desistentes do Tratamento , Poaceae , Rinite Alérgica Sazonal/etiologia , Rinite Alérgica Sazonal/imunologia , Segurança , Resultado do Tratamento , Árvores , TirosinaRESUMO
BACKGROUND: a new range of allergy vaccines has been developed by the introduction of a relatively new Th1-inducing adjuvant known as 3-deacylated monophosphoryl lipid A (MPL). MPL adjuvant is of natural origin, derived from the lipopolysaccharide of Salmonella minnesota R595. This adjuvant is incorporated in a glutaraldehyde-modified pollen extract adsorbed to L-tyrosine (Pollinex Quattro). A major potential benefit provided by MPL adjuvant is the promotion of a Th1 response which enhances the efficacy of allergy vaccination and can consequently allow a reduction in the number of injections required for treatment. The standardisation of Pollinex Quattro tree pollen allergy vaccine is described and we include details of some innovative analytical procedures. METHODS AND RESULTS: an essential feature of the analytical strategy is the assay of the MPL adjuvant using a recently developed HPLC technique. The adjuvant has a complex chemical structure and the analysis is illustrated in detail. We give a full picture of the vaccine standardisation by describing biochemical and immunological characterisation of the allergen extract, together with some brief manufacturing details. CONCLUSIONS: a high overall level of standardisation is illustrated by a number of different tests applied to all stages of vaccine manufacture. Tree pollen allergen potency is measured following the pollen extraction, chemical modification and formulation as a tyrosine adsorbate. Good batch-to-batch reproducibility is shown. The HPLC assay for MPL adjuvant showed high quality resolution which did not vary when measuring raw material or when incorporated in the vaccine and the technically complex assay is shown to be reliable.
Assuntos
Adjuvantes Imunológicos , Alérgenos/uso terapêutico , Lipídeo A/análogos & derivados , Lipídeo A/imunologia , Extratos Vegetais/normas , Pólen/imunologia , Rinite Alérgica Sazonal/prevenção & controle , Células Th1/imunologia , Árvores , Vacinas/normas , Adsorção , Alérgenos/efeitos dos fármacos , Alérgenos/imunologia , Antígenos de Plantas/uso terapêutico , Cromatografia Líquida de Alta Pressão , Reagentes de Ligações Cruzadas/farmacologia , Eletroforese em Gel de Poliacrilamida , Glutaral/farmacologia , Imunoeletroforese Bidimensional , Focalização Isoelétrica , Lipídeo A/química , Estrutura Molecular , Extratos Vegetais/imunologia , Pólen/efeitos dos fármacos , Controle de Qualidade , Reprodutibilidade dos Testes , TirosinaRESUMO
Methods are described for the preparation of pure crystalline samples of the penicilloic and penilloic acids of penicillin G, carbenicillin, cloxacillin, floxacillin, methicillin, penicillin V, and ticarcillin and the penicilloic acids of amoxicillin, ampicillin, phenethicillin, and propicillin. The interaction between the compounds and rabbit antibenzylpenicilloyl antibodies was evaluated by hemagglutination inhibition measurements. A significant correlation was found in this system between the reactivity of penicilloic acids and the corresponding penilloic acids; on average, the penicilloic acids were more reactive on a molar basis by a factor of 11. The results are discussed in terms of the general immunochemistry and side-chain structure of the parent penicillins.
Assuntos
Ácido Penicilânico/síntese química , Animais , Reações Cruzadas , Testes de Inibição da Hemaglutinação , Técnicas In Vitro , Ácido Penicilânico/imunologia , Penicilina G/análogos & derivados , CoelhosRESUMO
Timothy pollen extracts have been reacted with glutaraldehyde under conditions leading to different degrees of aggregation of the product. Aggregation tends to enhance the previously demonstrated effects of glutaraldehyde in that reactivity with human IgE antibody, and ability to induce IgE antibody in the Bordetella pertussis-treated rat, are further reduced. Ability to induce IgG antibody with specificity for unmodified extract is substantially retained in all aggregated products.