The Influence of BCG Vaccine as a Booster TDaP-IPV Vaccination: an Explorative Study
试验速览
- 阶段
- 4 期
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- T-cell response to TDaP-IPV
研究概览
简要总结
This study has three purposes:
To investigate whether the immune response to pertussis is increased when TDaP-IPV is given together with BCG vaccine, compared to when it is given alone.
To investigate whether BCG vaccination modulates the immune response to non vaccine target antigens (i.e., antigens/pathogens not used in the vaccine itself).
To investigate whether TDaP-IPV vaccination modulates the immune response to non vaccine target antigens.
详细描述
Rationale: The Bacillus Calmette-Guerin (BCG) vaccine not only protects against Mycobacterium tuberculosis, but has also been shown to reduce morbidity and mortality caused by non-related infections. This effect is likely due to non-specific immunomodulatory effects, at least in part on the innate immune system. Additionally, BCG has been shown to improve immunogenicity of other vaccinations. In contrast, whilst the diphtheria-tetanus-pertussis (DTP) combination vaccine protects against infection with Bordetella pertussis, Clostridium tetani and Corynebacterium diphtheria, it has also been associated with increased mortality due to unrelated infections, particularly in girls in high-mortality countries.
Although widespread DTP vaccination has initially reduced pertussis mortality, the disease has persisted and recently resurged in a number of countries with highly vaccinated populations, including the Netherlands. This has been partially attributed to the switch from a whole-cell vaccine (which is still being used in low-income countries) to a more defined acellular pertussis vaccine, which only protects for a limited period (5-8 years). Strategies to improve the efficacy of pertussis vaccination are therefore urgently required.
As the BCG vaccine has already been used to improve the immunogenicity of other vaccines, the investigators hypothesize that BCG vaccination before or at the same time of DTP vaccination increases the immunogenicity of the DTP vaccine in terms of antibody and T-cell responses to pertussis. Moreover, the investigators aim to assess the effect of DTP vaccination on the known long-term beneficial non-specific effects of BCG on non-mycobacterial infections.
Objective: To examine the effect of BCG as an adjuvant on DTP vaccination, and to investigate the non-specific training effects of BCG and DTP, alone and in combination, on the innate immune system.
Study population: Healthy adult volunteers.
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
- 18 Years 至 55 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •healthy females
排除标准
- •systemic medication use other than oral contraceptive drugs
- •history of disease resulting in immunodeficiency
- •previous vaccination with BCG
- •pregnancy
- •allergy to neomycin or polymyxin
- •known previous allergic reaction to vaccination with diphteria, tetanus, pertussis or polio vaccines
- •One of following phenomena after previous vaccination with pertussis containing antigens: Fever >40 °C within 48 hours after vaccination, hypotonous-hyporesponsiveness episode within 48 hours after vaccination, convulsions with or without fever within 3 days after vaccination
研究组 & 干预措施
BCG
Subjects are vaccinated with BCG vaccine (SSI) alone, 0,1ml intradermal
干预措施: BCG vaccine (SSI) (Biological)
BCG+TDaP-IPV
Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously
干预措施: BCG vaccine (SSI) (Biological)
BCG+TDaP-IPV
Subjects are vaccinated with BCG vaccine (SSI) (0.1ml intradermal) and TDaP-IPV vaccine Boostrix Polio (0.5ml intramuscular) simultaneously
干预措施: TDaP-IPV vaccine (Biological)
TDaP-IPV
Subjects are vaccinated with TDaP-IPV vaccine (Boostrix Polio) vaccine alone, 0,5ml intramuscular
干预措施: TDaP-IPV vaccine (Biological)
结局指标
主要结局
T-cell response to TDaP-IPV
时间窗: 1 year
T-cell responses will be measured by FACS
PBMC cytokine response to pertussis related antigens
时间窗: 1 year
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
B-cell phenotype analysis
时间窗: 1 year
pertussis specific B-cells will be analyzed by FACS
Antibody response to TDaP-IPV
时间窗: 1 year
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Antibody response to TDaP-IPV
时间窗: 2 weeks
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
Antibody response to TDaP-IPV
时间窗: 3 months
antibody titers to antigens in the TDaP-IPV (PT, FHA, Prn, DT, TT) will be measured.
T-cell response to TDaP-IPV
时间窗: 2 weeks
T-cell responses will be measured by FACS
T-cell response to TDaP-IPV
时间窗: 3 months
T-cell responses will be measured by FACS
PBMC cytokine response to pertussis related antigens
时间窗: 2 weeks
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
PBMC cytokine response to pertussis related antigens
时间窗: 3 months
IL-6, TNF, IL-1b, IL-10, IL-17, IL-22, IFN-g
B-cell phenotype analysis
时间窗: 2 weeks
pertussis specific B-cells will be analyzed by FACS
B-cell phenotype analysis
时间窗: 3 months
pertussis specific B-cells will be analyzed by FACS
次要结局
- PBMC responses to heterologous antigens(1 year)
- Transcriptional profile of PBMCs(3 months)
- Epigenetic markers of monocytes(3 months)
- PBMC responses to heterologous antigens(1 day)
- PBMC responses to heterologous antigens(4 days)
- PBMC responses to heterologous antigens(2 weeks)
- PBMC responses to heterologous antigens(3 months)
- Transcriptional profile of PBMCs(1 day)
- Transcriptional profile of PBMCs(4 days)
- Transcriptional profile of PBMCs(2 weeks)
- Epigenetic markers of monocytes(1 day)
- Epigenetic markers of monocytes(4 days)
- Epigenetic markers of monocytes(2 weeks)