Boosting BCG's anti-TB immunity
9 February 2009
Some 2 billion people are infected with Mycobacterium tuberculosis, the cause of tuberculosis, and 2 million die of it every year. For more than 80 years, the BCG vaccine has provided some protection, but it has many drawbacks, including its inability to protect adults from infection. A new vaccine being developed by Helen McShane, a Senior Research Fellow in Clinical Science at the University of Oxford, has been shown to boost immune responses dramatically in clinical trials in South Africa and The Gambia.
The vaccine, MVA85A, is based on a modified form of vaccinia virus displaying a TB antigen on its surface. It has been designed as a booster vaccine, stimulating a heightened response by re-stimulating the immune response initially generated by a 'priming' vaccine such as BCG. Following successful trials in the UK, the vaccine has undergone clinical trials in Africa to assess its safety and ability to stimulate immune responses.
In both South Africa and The Gambia, MVA85A had no significant side-effects. Most encouragingly, in both settings it generated powerful T-cell immune responses - those thought most likely to protect against M. tuberculosis. Detailed analysis suggests that a wide range of responses is being stimulated.
Moreover, a trial in the UK has shown that the immune boost provided by MVA85A does not depend on the length of time since BCG was given - responses were the same whether it was given weeks or years later.
These highly promising findings support rapid progress towards phase IIb clinical efficacy trials, which would test the ability of MVA85A to protect against infection with TB.
With a £4m award from Technology Transfer and £4m from the Aeras Global TB Vaccine Foundation, Dr McShane has begun a phase IIb clinical trial of the vaccine in South African children. In addition, Isis Innovation Ltd, the technology transfer arm of the University of Oxford, has announced a new joint venture with biopharmaceutical company Emergent BioSolutions Inc. to develop the vaccine.
Image: Helen McShane at the University of Oxford.
References
Brookes RH et al. Safety and immunogenicity of the candidate tuberculosis vaccine MVA85A in West Africa. PLoS ONE 2008;3(8):e2921.
Hawkridge T et al. Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in healthy adults in South Africa. J Infect Dis 2008;198(4):544–52.
Pathan AA et al. Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: different boosting intervals and implications for efficacy trials. PLoS ONE 2007;2(10):e1052.
Beveridge NE et al. Immunisation with BCG and recombinant MVA85A induces long-lasting, polyfunctional Mycobacterium tuberculosis-specific CD4+ memory T lymphocyte populations. Eur J Immunol 2007;37(11):3089–100.