A boost for TB immunity: vaccine trials in South Africa

Most people in Britain of a certain age remember lining up at school for the 'TB test' followed usually by the BCG vaccination against tuberculosis. So successful has been the programme to eradicate TB, once a major scourge in the UK, that today only people thought to be at high risk of infection are offered the jab. But the situation in many developing countries is very different, and Professor Helen McShane of Oxford's Jenner Institute is working on new vaccines that might protect vulnerable populations everywhere.

TB remains a major threat, killing 5,000 people every day worldwide. An added problem is the emergence of strains that are resistant to all available antibiotics. So why is the BCG vaccine not the answer? 'All trials that have been conducted in the developing world show little or no efficacy against pulmonary TB, particulary in young adults, where the burden of disease is greatest', says Professor McShane. 'There are several potential reasons; for example, greater exposure to non-tuberculous mycobacteria may interfere with the efficacy of BCG.'

BCG does confer protection against TB meningitis in children, one of the serious complications of the condition. 'That's the justification for saying we still need it', says Professor McShane, 'but we also need something that works better.' One approach is to develop either a genetically-altered or an attenuated form of the BCG bacterium. But the candidate that so far has proved most promising is a 'booster' vaccine based on a protein subunit from the bacterium that can be added to BCG to improve its efficacy. This strategy is derived from the pioneering work on 'prime-boost' vaccines for malaria, undertaken by the Jenner Institute's Director, Professor Adrian Hill.

Professor McShane, working with the South African TB Vaccine Initiative (SATVI), is currently conducting the world's largest TB vaccination trial in infants, and the first to reach Phase IIb, a test of the efficacy of a trial booster vaccine known as MVA85A. They have recruited 2,797 babies in the Western Cape district who were all vaccinated with BCG at birth and then received either the new vaccine or a placebo at 4–6 months of age. They are being followed for 2–3 years to see whether they develop TB.

Thanks to some earlier EU funding for Professor McShane's work, the local hospital where the trials are based was able to buy a digital X-ray machine, only the second in a country that has the highest rates of TB in the world. When she visited, she found the supervisor of the hospital 'skipping round the room' in delight: the machine is used to examine patients in the trial, but also for all the other patients with complicated TB who come there for treatment.

Another trial of the same vaccine is underway in HIV-positive adults in South Africa and Senegal. Professor McShane is also an HIV physician, and is well aware that half of all deaths in HIV-Aids patients are from TB. Meanwhile she is eagerly awaiting the first results of the double-blind study in infants, due in 2013.