T Cell and Interferon Expression in Tonsils After Sublingual Immunotherapy and/or Nasal Live Attenuated Influenza Vaccine
试验速览
- 阶段
- 3 期
- 入组人数
- 180
- 试验地点
- 8
- 主要终点
- Expressions of interferon and T cell and closely related cytokines and transcription factors in tonsils.
研究概览
简要总结
Hypotheses
- Immunotherapy induces tolerogenic effects to allergens in T cell regulation in tonsils.
- Influenza vaccination induces a strong interferon response and decreases Th2 response in tonsils.
- Influenza vaccination as an adjuvant on immunotherapy induces a better response to immunotherapy.
详细描述
Background: Tonsils are the primary nasopharyngeal lymphoid tissue and constitute the first contact point of the immune system to allergens and infectious agents. A peripheral T cell repertoire exists in tonsils, and tonsils have an active role for inducing and maintaining peripheral tolerance to allergens. Intralymphatic immunotherapy is a promising alternative for a subcutaneous or sublingual immunotherapy. More data is needed on the interaction between the peripheral (tonsillar) T cell response and specific allergen exposure and impact of respiratory virus infections on tolerance induction. Objective: To study the effects of sublingual grass pollen immunotherapy and/or nasal live attenuated influenza vaccine on tonsillar T cell and interferon (IFN) expression. In addition, we collect material on the investigation of role of tissues in immune tolerance and chronicity in allergic diseases.
Patients: Human tonsil samples will be obtained from less than 30-year-old routine tonsillectomy patients after sublingual grass immunotherapy (n=30), nasal live attenuated influenza vaccine (n=30 for atopic; and n=30 for non-atopic) and immunotherapy+influenza vaccine intervention (n=30). Controls without age limit or intervention (n=580) will also be recruited. Of these, age and atopy-matched controls will be selected as comparator groups for each intervention trial (n=30 for atopic; and n=30 for non-atopic). Control group will also be used for investigation of role of tissues in immune tolerance and chronicity in allergic diseases, immunomodulatory effects of respiratory viruses main focus being on human bocavirus and human rhinovirus infections, and in the search of new respiratory viruses.
Design: Study intervention products will be administered openly but the immunology outcomes will be analysed blindly.
Main outcomes: Gene expressions of IFN and T cell related genes will be the main outcomes and compared between intervention groups and correlated with the number of allergen extract doses or time from nasal influenza vaccination. Systemic immunologic outcomes (in peripheral blood mononuclear cells, blood RNA expression profiles, antibodies and cytokines in serum) will also be studied. The analyses include immunogenetics, virology, bacteriology and sensitization status. Clinical symptom scores will be recorded during the next 12 months from the screening visit.
Anticipated results: We expect that our tonsil approach will offer a new in vivo model for the understanding immune tolerance induction and will give new insights to the immunologic mechanisms in lymphoid tissue level. We hope to demonstrate that the immunologic effects of sublingual pollen immunotherapy can be modified with a nasal live attenuated influenza vaccine and thereby it should give basis for other add-on treatments aiming for more effective immunotherapy. The influenza virus vaccine is expected to promote Th1 cell expression over Th2 cell expression. Since the immunologic outcomes will be correlated to clinical efficacy during next influenza and pollen seasons, we hope to understand the clinical significance of the immunologic outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •elective tonsillectomy with or without adenotomy according to clinical indication
- •age >4 and <30 years
- •written informed consent from the study subject or his/her guardian
- •Fluenz® will be used for ages >4 and <30 years, i.e. off-label use of ages >18 and <30 years
排除标准
- •systemic anti-inflammatory medication within prior 4 weeks
- •systemic diseases affecting the immune system e.g. autoimmune diseases, immune complex diseases or immune deficiency diseases other than allergy, asthma or atopic dermatitis
- •malignancy, depression, psychiatric illness or medication; planned vaccination during the study period (vaccinations should not be given during study period)
- •forced expiratory volume in 1 second (FEV1) is under 80% of normal value or asthma is in a bad balance for those patients who would participate in the immunotherapy
- •sublingual grass pollen will not be given for children under the age of 5
- •additional exclusion criteria for Grazax® include hypersensitivity to any of the excipients (gelatin [fish source], mannitol, sodium hydroxide), inflammatory conditions in the oral cavity with severe symptoms such as oral lichen planus with ulcerations or severe oral mycosis, patients with uncontrolled or severe asthma (in adults: FEV1 < 70% of predicted value after adequate pharmacologic treatment, in children: FEV1 < 80% of predicted value after adequate pharmacologic treatment)
- •addition exclusion criteria for Fluenz® include hypersensitivity to the active substances, to any of the excipients (sucrose, dibasic potassium phosphate, monobasic potassium phosphate, gelatin [porcine, Type A], arginine hydrochloride, monosodium glutamate monohydrate, gentamicin [a possible trace residue], eggs or to egg proteins [e.g. ovalbumin] and children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection
结局指标
主要结局
Expressions of interferon and T cell and closely related cytokines and transcription factors in tonsils.
时间窗: Up to 3 years
Expressions of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2 and Tbet will be analyzed by quantitative real-time PCR.
次要结局
未报告次要终点
研究者
Tuomas Jartti
Dr
Turku University Hospital