The most promising candidate vaccine for one of the top killer diseases, tuberculosis, suffered a setback yesterday when researchers reported in The Lancet that it did not induce enough immune protection in infants.
The three-year trial on the most advanced new TB vaccine candidate, MVA85A, was carried out in South Africa among nearly 2,800 babies.
While the phase IIB trial designed to assess how well a vaccine works showed the vaccine to be safe, it also did little to protect infants from TB. The hope now is that further research may find that the vaccine is of benefit to adults.
MVA85A was designed by researchers at the University of Oxford, United Kingdom, to boost the body's immune response to BCG (Bacillus Calmette-Gurin), the only vaccine licensed for TB.
Most countries where the disease is endemic give children BCG, but this does not protect adults from pulmonary TB, the most common and infectious form of the disease, and has limited efficacy in children.
As a result, scientists have been looking for alternatives, as well as new ways to boost the efficacy of BCG. Currently, a dozen candidate TB vaccines are in different stages of clinical trials.
TB kills around 1.4 million people every year and more than 95 per cent of cases and deaths occur in developing countries.
In the study, infants of four to six months in age, previously vaccinated with BCG, received MVA85A.
Unfortunately we saw no significant evidence of increased protection against TB above BCG alone, said Helen McShane, from the University of Oxford, during a teleconference after the study's publication. Obviously that's not the outcome that we hoped for or the one that we expected.
But she added that the primary aim of the trial was safety and we found the vaccine to be safe.
MVA85A has been in tests since 2002 in animals and adults, and small early trials showed that it was well tolerated and stimulated an immune response that the researchers considered powerful enough to protect against TB.
McShane says it is not clear why the vaccine did not work as expected, but added that more research would be done to understand the reason.
In TB vaccine development, we don't know what kind of immune response we really need to get to make an effective vaccine, and that's why trials like this are crucial, McShane tells SciDev.Net. The information we get from the immunology helps us to refine the research line of the vaccine.
Jennifer Cohn, a medical coordinator at international medical charity Mdicins Sans Frontires, says the researchers will need to look at MVA85A's potential to help those with stronger immune systems than infants, such as adolescents or adults.
The lesson that we have learned is that we can't put all the eggs in one basket and we need to invest in all of the other vaccines in the pipeline. [MVA85A] is theoretically an incredibly important vaccine, but we don't have the holy grail by any means yet, Cohn tells SciDev.Net.
This is echoed by Mario Raviglione, director of the WHO's Stop TB Department, who says that the disappointing results point to the need to invest in vaccine research.
The lack of capacity to conduct large clinical trials in most affected countries is considered one of the main obstacles to developing a vaccine.
This study shows that it is possible to conduct a very serious clinical trial with a strong candidate vaccine, he tells SciDev.Net.
Link to study in The Lancet (*free registration required)
The Lancet doi: 10.1016/S0140-6736(13)60177-4 (2013)