Heterologous Effects of BCG in Healthy UK Adults
Condition: Tuberculosis
MeSH terms: Tuberculosis
Study type: Interventional

Summary: 
      TB038 is a clinical study to assess the non-specific effects of BCG vaccination and gain a
      better understanding of how the body's immune system reacts to BCG and in turn potentially
      prevents infection from other bacteria.
    

Detailed description: 
      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.
    

Intervention name(s): BCG SSI; No vaccination; BCG Sii
Intervention type(s): Drug; Other; Drug
Intervention description(s): Intradermal injection; intradermal injection
Other intervention name(s): Bacille Calmette-Guérin Statens Serum Institute (BCG SSI); Bacille Calmette-Guérin Serum Institute of India
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: BCG study