A Human Pilot Study to Quantify BCG From the BCG Vaccination Site, and to More Fully Characterise the Immune Response to BCG
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 2
- 主要终点
- Quantification of BCG after BCG vaccination
研究概览
简要总结
This is a human pilot study of 16 healthy BCG-naïve volunteers to quantify BCG from the BCG vaccination site. Volunteers will be vaccinated with BCG. The first 8 will go on to have a punch biopsy and suction blister of the vaccination sites at 2 weeks post vaccination (arm A) the second 8 will have a biopsy and blister at 1 or 4 weeks post-vaccination (arm B). Methods of mycobacterial quantification on these tissue samples will then be compared
详细描述
Over the last 3 years, the McShane group in Oxford have established a clinical trial programme to evaluate the safety and immunogenicity of this BCG prime-MVA85A boost vaccination strategy in a series of Phase I studies in the UK.
To date, in Oxford, the safety and immunogenicity of MVA85A (dose 5x10^7 pfu) has been assessed in 14 mycobacterially and BCG naïve individuals, 27 individuals previously vaccinated with BCG and 12 individuals latently infected with M.tb. In all 53 individuals there have been no serious or severe adverse events, and a single vaccination with MVA85A has been highly immunogenic in BCG naïve volunteers, and significantly moreso in BCG primed volunteers. (23) Following the success of the UK studies, 21 healthy individuals (11 BCG naïve, 10 BCG primed) in the Gambia and 24 healthy adults in Cape Town, South Africa (ongoing age de-escalation phase II trial), have now been vaccinated with MVA85A, with no serious or severe adverse events, and a safety and immunogenicity profile comparable to the UK. A study in infants in the Gambia is now underway and the adolescent arm of the age de-escalation studies in Cape Town is now also underway.
Interferon-gamma as a protective correlate and the need to identify other immunological correlates of protection:
In all of the studies to date, (both preclinical and clinical), the main immunological readout has been the ex-vivo interferon-gamma (IFN- ) Elispot assay, used to assess specific T cell responses to tuberculin PPD, purified antigen 85 complex and pools of overlapping 15mer peptides spanning the length of antigen 85A. The secretion of IFN-y from antigen-specific T cells is the best available immunological correlate of protective immunity. The rationale and evidence supporting the use of assays for determining IFN- production as a correlate of protection are substantial, but alone, it may not be sufficient. There is increasing evidence that CD4(+) T cells possess IFN-gamma-independent mechanisms that can limit the growth of an intracellular pathogen and are dominant in secondary responses to M. tuberculosis.
It is clear that new immunological correlates of protection need to be identified, and given the considerable time and cost involved in any Phase III efficacy trial of a new TB vaccine, there is therefore an urgent need to identify protective correlates which will help distinguish between candidates demonstrated to be safe and immunogenic in phase I trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject is willing and able to give informed consent for participation in the study
- •Male or Female, aged 18 to 50 years
- •In good health
- •BCG-naïve
- •Screening elispot negative (less than 17 spot forming cells per million PBMC) for ESAT 6 and CFP 10 peptide pools
- •Resident in or near Oxford for the duration of the study
- •Female patient/subjects of child bearing potential must be willing to ensure that they practice effective contraception use during the study.
- •Subject has clinically acceptable laboratory results from Pre Study Screen
- •Able (in the Investigators opinion) and willing to comply with all study requirements
- •Willing to allow his or her General Practitioner to be notified of participation in the study
排除标准
- •Previous BCG vaccination
- •Female subject who is pregnant, lactating or planning pregnancy during the course of the study
- •Persons suffering from malignant conditions (e.g., lymphoma, leukaemia, Hodgkin's disease or other tumours of the reticulo-endothelial system), primary or secondary immunodeficiencies, HIV infection, or moderate/severe dermatological conditions
- •Administration of chronic (defined as more than 14 days) immunosuppressive drugs or other immune modifying drugs within six months of vaccination. (For corticosteroids, this will mean prednisolone, or equivalent, ≥ 0.5 mg/kg/day. Inhaled and topical steroids are allowed)
- •Any history of severe allergic reaction or anaphylaxis in reaction to vaccination
- •Administration of immunoglobulins or donation of blood products during the study or within the past 12 weeks
- •Suspected or known current drug and/or alcohol abuse (as defined by an alcohol intake of >42 units a week)
- •Any on-going chronic illness requiring hospital specialist supervision
- •Any other significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or may influence the result of the study, or the subject's ability to participate in the study.
- •Subjects who have participated in another research study involving an investigational product in the past 12 weeks
结局指标
主要结局
Quantification of BCG after BCG vaccination
时间窗: 2 or 4 weeks
次要结局
- Immunogenicity of BCG vaccination(2 or 4 weeks)