A research team at Oxford University in the UK is very close to determining the efficacy of their new tuberculosis (TB) vaccine. If current clinical trials are successful, it will be the first new TB vaccine in almost a century.
The urgent need for a new vaccine is emphasised by research showing that extensively drug-resistant (XDR) forms of the disease are rapidly spreading.
Today, most babies in the world are immunized with the old Bacille Calmette-Guerin (BCG) vaccine, first used in 1921. The leader of the Oxford research team, Helen McShane, says it saves children's lives, but beyond infancy its effects are limited.
"We know that when BCG is given at birth, it does work well to protect against tubercular meningitis and the disseminated disease that has spread outside the lungs… What we also know is that BCG is very variable in protecting against lung disease, which is where the burden of the disease is, particularly in adults and adolescents,” she said.
Oxford’s vaccine, known as MVA85A, is designed to boost the effects of BCG. “It's that efficacy against severe disease which is the rationale behind keeping BCG and making it better,” McShane said.
Clinical trials are taking place in South Africa, following 3,000 babies, all of whom received BCG; half of them also received the new booster vaccine. Trials of the vaccine’s effectiveness in adults are taking place in both South Africa and Senegal, with results expected in the first quarter of 2013.
Boosting immune response
The vaccine is designed to stimulate an immune response known as cell-mediated immunity. “This is different from all the vaccines we have licensed today - with the exception of BCG - which work by the production of antibodies,” McShane said.
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“Because TB is very good at hiding within cells, we need T-cells [a kind of white blood cell] to protect against TB. And indeed that’s the reason why HIV-infected people are more susceptible to TB - because HIV damages your T-cells. So the vaccine that we have developed works by boosting the T-cells which are induced by BCG.”
TB is a major cause of death among the HIV-positive. Asked whether this kind of vaccine could prevent TB in people living with HIV, McShane said that it might - but only for those with immune systems strengthened by antiretroviral medications. "I do think that’s going to be crucial for these vaccines to work, [but] I think it would be very hard for it to work in HIV-positive individuals with very low CD4 counts [a measure of immune health].”
After decades of neglect, the world is seeing a flurry of activity around the development of new TB vaccines, reflecting increased interest and funding from donors such as the Bill and Melinda Gates Foundation and the British and Dutch governments. Added pressure comes from the emergence, first, of multi-drug resistant TB, and, more recently, of XDR-TB, which can be nearly impossible to treat.
MVA85A is the front-runner among the vaccines in development, but there are others on the way. Some use virus vectors, like the Oxford vaccine, which uses an adenovirus, from the family of organisms that cause the common cold. Others use peptides, and one, says McShane, is a recombinant form of BCG, modified to express more antigens and to make it safer for use in people living with HIV.
Some researchers are working on improved TB treatments to address the disease’s growing drug resistance, but the process of bringing new drugs to market is slow, and few new treatments have even started clinical trials. Vaccines may be a better bet and, given the market, may be easier to put into production.
The problem is that TB is a disease of poverty: According to the World Health Organization, over 95 percent of cases and deaths are in developing countries, where sufferers often cannot afford treatments. This makes the expensive process of developing new TB medications unattractive to drug companies. Most of the current research is publicly funded.
“It’s been hard to make a convincing market argument for TB drugs,” Ann Ginsberg, vice president of scientific affairs at Aeras, a non-profit organization working on TB vaccines, told PlusNews. “The reality is that the vast majority of companies working on TB drugs do not expect to make any profit from it. They are in it because they think it is the right thing to do. They hope not to lose money in the process, but they don’t expect to make any,” she said.
“But because of global vaccination, you are talking about so many people who would ideally be vaccinated that there’s probably a reasonable profit to be made there.”