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Tuberculosis vaccine trial shows disappointing results

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f765 (Published 06 February 2013) Cite this as: BMJ 2013;346:f765
  1. Anne Gulland
  1. 1London

A clinical trial of one of the first tuberculosis vaccines to be developed in nearly 100 years has shown disappointing results in protecting children against the disease.

A paper published by the Lancet showed that the modified vaccinia Ankara virus expressing antigen 85A (MVA85A), the most advanced of 12 candidate vaccines currently in clinical trials, showed an efficacy rate of less than 20%.1

Hopes for the vaccine had been high, as previous small trials had shown that the vaccine generated a good immune response in adults.2

The only available vaccine against tuberculosis, BCG, first used in 1921, has highly variable results. It protects against disseminated tuberculosis in young children, but protection against pulmonary tuberculosis, the commonest form of the disease, is variable. And in countries where the disease is endemic, such as South Africa, where the trial took place, the incidence is high, despite high BCG coverage.

The trial, conducted by a consortium that included Oxford University and the Wellcome Trust, randomised 2794 healthy BCG vaccinated infants aged 4-6 months to receive MVA85A (1399 babies) or placebo (1398) and followed them for 37 months. The aim was to assess the safety, immunogenicity, and efficacy of MVA85A as a booster to BCG against tuberculosis and Mycobacterium tuberculosis infection in infants.

The number of cases of tuberculosis was 39 in the placebo group and 32 in the MVA85A group, giving an efficacy rate of just 17.3%. Helen McShane, professor of vaccinology at Oxford University and one of the researchers who developed the vaccine, told a telephone press conference that the “outcome was not the one we hoped for, nor the one we expected.”

She added, “The level of immune response was not sufficient to give additional protection [to BCG]. We don’t know exactly why it didn’t work as we hoped . . . But this is a step on the road towards a new TB vaccine.”

She added that the study reaffirmed the vaccine’s promising safety profile: there were 257 serious adverse events in the MVA85A group and 258 in the placebo group, none of which was attributed to the vaccine.

The authors said that, although the vaccine had not proved effective in protecting young children, it may have potential among adults or adolescents.

In an editorial accompanying the paper, Christopher Dye, director of health information in the World Health Organization’s Office of HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases, and Paul Fine, professor of communicable disease epidemiology at the London School of Hygiene and Tropical Medicine, wrote that the trial presented a “serious challenge” to those working on tuberculosis vaccines. However, they added that the findings were not a “terminal prognosis” for MVA85A or for any of the other vaccines currently in development.

Richard White, an epidemiologist at the London School of Hygiene and Tropical Medicine, said that the results were disappointing, but he hailed the trial as “historic.”

He said, “This trial result raises many questions, some of which are already being explored in trials. For example, might MVA85A be effective if given to adults? This would be hugely valuable, because the majority of TB disease and deaths are among adults.”

Notes

Cite this as: BMJ 2013;346:f765

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