Heterologous Effects of BCG in Healthy UK Adults
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02380508|
Recruitment Status : Completed
First Posted : March 5, 2015
Last Update Posted : November 30, 2016
|Condition or disease||Intervention/treatment||Phase|
|Tuberculosis||Drug: BCG SSI Other: No vaccination Drug: BCG Sii||Not Applicable|
Since 1927, it has been observed that BCG-vaccinated neonates have lower all-cause mortality rates. This heterologous or non-specific effect within the first 6-12 months of life has been demonstrated in randomised and observational studies in low income countries with high childhood mortality rates. The most consistent effect is reduced neonatal mortality due to fewer cases of neonatal sepsis, respiratory infection and fever. The main limitation of these studies is the risk of confounding inherent in their cross sectional and observational designs. It is essential that we determine the cogency of this effect, as potential BCG replacement vaccines must be non-inferior to BCG in this regard.
There is a plausible rationale that BCG, a replicating mycobacterium, is capable of inducing non-specific innate immunity, which could induce protection against disease and death from non-mycobacterial infections early in life. For example, intravesical BCG is an effective treatment for bladder cancer, an effect presumed to be non-specific and innate. However, our understanding of the immunological mechanisms involved is incomplete. Data is needed from robust experiments to quantify any causal relationship between infant survival and BCG vaccination. Demonstrating an effect of recent BCG vaccination on the growth of common bacterial pathogens involved in neonatal sepsis, using whole blood in an in-vitro human model, would provide evidence to support a randomised controlled trial in infants in TB high burden countries and would impact on public health vaccination scheduling. In addition it would provide us with an in-vitro model by which to assess future BCG replacement vaccines.
Healthy BCG naïve adults in the UK have been selected for this study because of their low baseline level of anti-mycobacterial immunity and therefore reduced ability to suppress BCG growth. Whilst the target population for the heterologous effects of BCG vaccination is infants, the blood volume required in order to optimise the GIA would not be possible to collect from infants. Therefore by undertaking this work in healthy BCG naïve UK adults we can obtain the blood volumes required for this exploratory work in a population of individuals with a similar background mycobacterial exposure to infants in TB high burden, low income countries.
Volunteers in this study will receive BCG vaccination at the standard dose of 2-8x10^5 cfu. BCG SSI containing Mycobacterium bovis strain Danish 1331 is preferred as it is licensed in the UK for vaccination. However BCG SSI can frequently go into short supply globally with impact on UK supply. In the event of this occurring, BCG vaccine supplied by the Sii (Serum institute of India) will be used instead which contains Mycobacterium bovis BCG strain Moscow 361 I and is on the WHO list of prequalified vaccines. The same strain will be used for all volunteers.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||36 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Evaluation of the Heterologous Effects of Bacille Calmette-Guérin (BCG) Vaccination in Healthy UK Adults|
|Study Start Date :||February 2015|
|Actual Primary Completion Date :||November 2016|
|Actual Study Completion Date :||November 2016|
Experimental: Group 1
32 BCG-naïve subjects receiving BCG SSI or BCG Sii at standard dose (2-8x10^5 cfu) via Intradermal route.
Drug: BCG SSI
Other Name: Bacille Calmette-Guérin Statens Serum Institute (BCG SSI)
Drug: BCG Sii
Other Name: Bacille Calmette-Guérin Serum Institute of India
Experimental: Group 2
8-16 control volunteers receiving no vaccination.
Other: No vaccination
- Growth inhibition assays [ Time Frame: Up to Day 84 ]Determine the heterologous effects of BCG vaccination in healthy UK adults using in-vitro Growth Inhibition Assays as a surrogate marker to assess the individuals' capacity to control growth of S. aureus, K. pneumonia, Group B streptococci and E.coli.
- Immune response markers [ Time Frame: Up to Day 84 ]Evaluation of laboratory markers of the immune response that correlate with levels of bacterial growth inhibition identified using the in-vitro GIAs.
- Background levels of S. aureus, K. pneumonia, Group B streptococci and E.coli carriage. [ Time Frame: Up to Day 14 ]Use of bacterial antibody titres, nasal swab culture and faecal culture to determine background levels of S. aureus, K. pneumonia, Group B streptococci and E.coli carriage in subjects in this study.
- Confounding effects of BCG on bacterial growth. [ Time Frame: Up tp Day 14 ]Use of bacterial antibody titres, nasal swab culture and faecal culture to evaluate confounding effects of BCG on the growth of S. aureus, K. pneumonia, Group B streptococci and E.coli.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02380508
|Centre for Clinical Vaccinology and Tropical Medicine , University of Oxford|
|Oxford, Oxfordshire, United Kingdom, OX3 7LE|
|Oxford University Hospitals- John Warin Ward, University of Oxford|
|Oxford, Oxfordshire, United Kingdom, OX3 7LE|
|NIHR Wellcome Trust Clinical Research Facility, University of Birmingham|
|Birmingham, West Midlands, United Kingdom, B15 2TH|
|Study Director:||Helen McShane||University of Oxford|