The efforts to win the war against tuberculosis using an efficacious vaccine candidate (MVA85A) in infants aged 4-6 months have returned a disappointing verdict despite showing great promise in pre-clinical trials. Though it fulfilled the primary objective of safety and despite inducing modest immune responses, the efficacy of the vaccine was just 17.3 per cent, and hence considered insufficient to protect the infants against TB, notes a paper published recently in The Lancet. This is the first vaccine trial to be conducted after the Bacillus Calmette-Guerin (BCG) vaccine was introduced in 1921. The vaccine was given to infants in South Africa who had already received the BCG vaccine. The rationale was to prime the immune system with BCG and then boost it with the candidate vaccine to enhance the protective efficacy of BCG. It will take a while to know the reasons behind its failure. Meanwhile, there is still some hope that the vaccine, which is being tested in HIV positive adults, will be successful. An efficacious and safer vaccine that would replace BCG is urgently required for HIV positive individuals; BCG being a live-attenuated vaccine is “not recommended” for immune-compromised people. While only 5-10 per cent people who are infected with TB develop active disease over their lifetime, the conversion rate dramatically shoots up to 5-10 per cent per year in the case of HIV positive people, notes a 2012 paper in PLoS Pathogens.
There is still optimism as a dozen vaccines are being tested in clinical trials. But these are not designed to prevent infection or rid the body of the bacteria; they are aimed at boosting protection against the disease. There are several other challenges too. Unlike in the case of other pathogens, protection against TB does not lie in neutralising antibodies; it is the cell-mediated immunity that is important. We still do not know the protective antigens that will stimulate protective immune responses. For instance, we know that antigen 85A complex elicits strong immune response, but whether it will translate to protective effect in humans is not known. The AVA85A vaccine is the best example of this — it induced modest immune responses but the protective effect was low. Hence, it will take a while to produce vaccines that are effective. But meanwhile, across the world, every year, nearly 9 million people will develop active TB and about 1.5 million will die. Worse, fighting the killer disease is getting more complicated with the rapid emergence of drug-resistant bacteria. It took WHO’s declaration of TB as a global emergency for the world to shed its indifference and complacency. Now, it is a race against time.