Role of the sponsor: Employees of MedImmune worked collaboratively with the investigators of RTI Health Solutions in the design of the study, in interpretation HA1077 of the results, and reviewed and contributed to the manuscript. Additional contributions: We would like to thank Complete Healthcare Communications, Inc. (Chadds Ford, PA, USA) for editorial assistance in manuscript preparation. ”
bovis based Bacille Calmette Guérin (BCG) was originally introduced in the 1930s as an oral vaccine against the human pathogen Mycobacterium tuberculosis, the cause of tuberculosis. In the 1960s, most of the world moved towards intradermal vaccination with lyophilized BCG, but some countries, including Brazil, continued to exploit the oral vaccination route  and . BCG, which is still available as a live vaccine, was derived by extensive passage from M. bovis, which naturally infects humans and cattle via the gastrointestinal tract. Live Mycobacteria have the potential to interact strongly with both the innate and adaptive immune system and any vaccine based on them has the potential to be used as a safe clinical probe of Selleck TGF beta inhibitor human responses .
Thus, BCG-based vaccines can potentially provide a safe but effective tool to mimic natural infection and stimulate both innate and acquired immunity under relatively ‘natural’ conditions of gut infection. Further, as BCG is a licensed vaccine many ethical hurdles are consequently reduced for human studies. Immune responses can be both protective and dangerous to the host. For example, many of the symptoms associated with the reactogenicity of vaccines are in fact inappropriately stimulated innate responses. Innate immune responses are difficult to safely monitor in humans as approved methods for stimulating such responses are not generally available and would raise ethical concerns. By delivering oral BCG (which has been given orally to millions of
people with a good record of safety) to healthy volunteers under controlled conditions we aimed to assess if this system had value for monitoring and innate immune activation. The impact of gastrointestinal colonization by BCG was indirectly determined by measuring antigen-specific T-cell and cytokine responses, along with microarray analysis. Further insight was obtained by systematically recording clinical symptoms associated with sequential BCG challenges such as abdominal pain, diarrhoea; upper respiratory tract congestion, secretion; fever and headache. In this way, we sought to build-up an integrated picture of innate and adaptive immune responses at various time points before and after a series of bacterial challenges. We used an oral BCG preparation (BCG Moreau Rio de Janeiro), commercially produced, which has a strong safety record in extensive human testing .