The Role of the Intestinal Microbiome in Enteric and Systemic Vaccine Immune Responses
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 2
- 主要终点
- Height of serum anti-rotavirus Immunoglobulin A (IgA) response
研究概览
简要总结
The purpose of this study is to evaluate if the intestinal microbiota influences rotavirus vaccine immune responses in healthy adult volunteers.
详细描述
This study will alter the intestinal microbiota in healthy adults using antibiotics and subsequently measure immune reactions to the rotavirus vaccine (Rotarix), the tetanus vaccine and the pneumococcal vaccine (Pneumo23).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination and laboratory tests carried out within 28 days prior to starting antibiotics (day -98). A subject with a clinical abnormality or laboratory parameter outside the reference range may be included if the investigator agrees that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
- •Male between 18 and 35 years of age, inclusive at the time of signing the informed consent
- •Capable of giving written informed consent and able to comply with the requirements and restrictions listed in the informed consent form
- •Normal defecation pattern (defined as ≤3x/ day and ≥3x/week)
排除标准
- •Subject has had a major illness in the past 3 months or any significant chronic medical illness that the investigator would deem unfavorable for enrollment, including inflammatory diseases.
- •Subject with any history of immunodeficiency
- •Subjects with a history of any type of malignancy
- •Subject with a history of thrombocytopenia or bleeding disorder
- •Subject has a past or current gastrointestinal disease which may influence the gut microbiota
- •Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •History of alcoholism and/or drinking more than an average of 5 units of alcohol per day
- •The subject has received an investigational product within three months of day 0 of the current study
研究组 & 干预措施
Control
Control group - subjects will receive no antibiotics
followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine
干预措施: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine (Biological)
Broad-spectrum antibiotics
Subjects will receive 7 days of pre-treatment (days -9 to -3) with:
- Ciprofloxacin 500mg 2dd1
- Vancomycin 250mg 3dd2
- Metronidazole 500mg 3dd1
followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine
干预措施: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine (Biological)
Narrow-spectrum antibiotics
Subjects will receive 7 days of pre-treatment (days -9 to -3) with:
• Vancomycine 250mg 3dd2
followed by Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine
干预措施: Rotavirus vaccine, Tetanus vaccine and Pneumococcal vaccine (Biological)
结局指标
主要结局
Height of serum anti-rotavirus Immunoglobulin A (IgA) response
时间窗: 28 days post-vaccination
Geometric Mean Concentration (GMC)
次要结局
- Time to positivity for serum anti-rotavirus Immunoglobulin A (IgA) and G (IgG) response(day 0 through day 28 post vaccination)
- Change in pre and post-vaccination anti-rotavirus (anti-RV) serum neutralizing antibodies measured by Geometric Mean Concentration (GMC)(28 days post-vaccination)
- Change in pre and post-vaccination anti-RV serum IgG response measured by Geometric Mean Concentration (GMC)(day 0 through day 28 post vaccination)
- Change in serum tetanus toxoid IgG response, measured as pre and post vaccination titer (international units/mL) ratio(day 0 through day 28 post vaccination)
- Change in serum pneumococcal poly-saccharide-specific IgG for all vaccine strains , measure in pre and post vaccination titer (micrograms/mL) ratio(day 0 through day 28 post vaccination)
- Composition of the fecal micro biome before and after antibiotics and between groups measured by the HITChip and bacterial 16S rRNA sequencing(day -9 and day 0 pre vaccination)
研究者
W.J. Wiersinga, MD, PhD
MD, PhD
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)