Financial Times
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Accessed 23 March 2013
March 21, 2013 8:35 pm

Vaccines: Trial setback fails to damp enthusiasm
By Clive Cookson, Science Editor
http://www.ft.com/cms/s/0/9522528c-870d-11e2-9dd7-00144feabdc0.html#axzz2OQIGNQy2

The Third Global Forum on TB Vaccines will open in Cape Town next week with several hundred researchers and clinicians determined to remain upbeat, despite the setback their field received last month.

The first large clinical trial for 90 years of a new vaccine against tuberculosis, MVA85A, failed to show efficacy when the Lancet published results.

The trial was intended to show MVA85A, developed at Oxford university in a £30m programme over 10 years, would boost the immune response of 2,800 South African babies inoculated with BCG. The Bacille Calmette – Guérin vaccine, introduced in 1921 and based on the bacterium that causes bovine tuberculosis, does not produce a good enough response to stop the TB pandemic.

But Professor McShane insists there is still mileage in MVA85A and says a dozen other vaccine candidates working by different mechanisms are in clinical development globally. “We need new drugs too, but the only way we’re going to tackle this epidemic in the long term is through an effective vaccine,” she says.

The team is not giving up on MVA85A. Samples from the infants in the trial will be analysed for clues about how the immune system reacts to vaccination and infection with the Mycobacterium tuberculosis, the TB germ. Researchers will look to improve the immune response with higher or multiple doses, combining MVA85A with other vaccine, or delivering it into the lungs.

Meanwhile a trial of MVA85A in 1,400 HIV-positive adults, at particular risk of developing TB, is going ahead in South Africa and Senegal with results due in 2015, says Prof McShane. The dozen vaccine candidates at earlier stages of clinical development, and a couple of dozen more in pre-clinical research, span a range of approaches. As with MVA85A, some are based on viruses genetically modified to stimulate the immune system against TB. Some, including BCG, are based on mycobacteria such as the one that causes TB. Some are proteins. For example   GlaxoSmithKline, the UK-based pharmaceutical group, has developed a vaccine, M72/AS01E, based on a combination of proteins and adjuvant (a booster chemical). Crucell of the Netherlands uses Ad35, a harmless adenovirus with antigens from Mycobacterium tuberculosis, to stimulate production of protective antibodies.

Two non-profit international bodies organise funding and logistical support for TB vaccine development: the Tuberculosis Vaccine Initiative in Europe and Aeras, based in the US. According to Ann Ginsberg, head of science at Aeras, it is too early to talk about which approach is likely to be most promising.

Dr Ginsberg is confident the MVA85A setback will not undermine funding for vaccine research, which will need hundreds of millions of dollars over the next few years: “Our funders, organisations like the Gates Foundation, [US] National Institutes of Health and the [UK] Department for International Development, are realistic about what it takes to develop a TB vaccine.”

But other TB experts say the challenge of developing an effective vaccine is so great that available money should be focused more on diagnostics and drug development. They express their reservations in an article due to appear in a forthcoming issue of The Lancet Infectious Diseases.

“Without a clear scientific basis for protective immunity against the disease and a biological marker for this, which we don’t have, it is difficult to know how to make an effective vaccine,” says one of the group, Richard Anthony of the Royal Tropical Institute, Amsterdam. One fundamental problem, he says, is past tuberculosis infection does not offer protection and patients recently treated for TB can become reinfected.

At next week’s Cape Town congress, however, most delegates will see the scientific challenge as a reason for making more rather than less effort. “I see the meeting as a rallying of the troops,” says Dr Ginsberg. “Now is the time to push forward, not pull back.”

Copyright The Financial Times Limited 2013.