Mycobacterium tuberculosis Bacteria the Cause of TB | NIAID

Tuberculosis (TB) is an airborne bacterium that infects the lungs and can be fatal if left untreated. Therefore, HIV-infected people who are infected with Mycobacterium tuberculosis are particularly susceptible to develop TB disease due to their weakened immune system, and in countries with high TB and HIV prevalence co-infection is common. 35% of HIV-related deaths in 2015 were caused by TB.(1) There is a vaccine for TB, the BCG (bacille Calmette-Guerin); however, it has some limitations because immunocompromised people cannot receive it. The BCG is nearly a century old, and there is a global effort to find a new, updated version. The Desmond Tutu HIV Foundation (DTHF), along with the South African Tuberculosis Vaccine Initiative (SATVI) are trialing a few different variations of vaccines in the search for increased efficacy.
The BCG is a live vaccine, which means that it contains a weakened strain of Mycobacterium bovis, a bacterium related to Mycobacterium tuberculosis, that a healthy person can fight off easily. Vaccination with BCG is like a practice run, and following vaccination, the patient’s immune system can now identify TB if they are infected and stop it from developing to the disease stage. BCG is given to millions of children globally and saves more than 50,000 lives every year because it protects against severe forms of TB. However, immunocompromised people (such as HIV-infected people) are unable to receive this vaccine as their immune system is not strong enough to effectively control and eliminate the BCG vaccine. As TB remains the leading killer of people with HIV, there is a great need for a more inclusive vaccine.
There are two different ways that a person can be affected by TB: Infection and disease. TB infection is the presence of the tuberculosis bacterium in the patient’s body. TB disease is when the patient begins exhibiting symptoms. Thomas Scriba, an associate professor at SATVI, explains that Mycobacterium tuberculosis infects many more people than get the disease. “The estimate in South Africa’s adult population is that 80% show signs of carrying the bacterium in their body but that doesn’t mean that they will get the disease. Around 5-10% with evidence of infection will develop the disease over their lifetime.”

Latent TB (TB infection) vs TB Disease | AidsInfo

SATVI is currently testing two different vaccination approaches: the first one aims to find an alternative to the BCG vaccine by developing attenuated live vaccines and the second is to find “booster vaccines” that can be given after BCG to improve the immune response that BCG provides. The ongoing clinical trials are designed to test the efficacy of these new vaccines (i.e. how well these immunisations work). The human immune response to Mycobacterium tuberculosis is very complex, and it’s difficult to know how best to prevent infection. This is why there are many ongoing trials looking at different approaches to TB immunisation. It is also unethical to not provide a BCG vaccine during clinical trials which makes finding a novel vaccine challenging.
One of the efficacy trials is a multi-site trial for the M72 vaccine run by GSK. This trial is expected to report results in 2019. This vaccine is designed to protect adults from TB disease, which the BCG vaccine is not effectively able to do. It uses a new mechanism of action against TB that scientists hope will be effective in adults.
The other trial, called 040, is testing a new concept; protecting against Mycobacterium tuberculosis infection. Trial 040 works on the rationale that if a vaccine can stop infection, then the disease can never develop. There are three branches to this adolescent trial: revaccination with the BCG vaccine, a new vaccine called H4:IC31, and a placebo. This trial is ongoing at SATVI and DTHF, and results are expected early next year.

Tuberculosis – causes, symptoms, diagnosis, treatment & pathology | Osmosis

New TB vaccines are designed to be safe enough to give to HIV-infected people. There have been many attempts to create a vaccine that is safe for use in immunocompromised people in the past. For example, the MVA85A vaccine which was recently tested in South Africa. Unfortunately, this vaccine was found not to be successful.  
Scriba emphasises the need for a better tuberculosis vaccine. “The current decline in the TB incidence globally and in our country is insufficient to reach the kind of targets that the WHO have set.” It is important to emphasise that there is a big need for a better vaccine. Tuberculosis is often diagnosed after the patient has already infected other people. “A TB vaccine that actually does better than BCG would be a major improvement on what is possible at the moment.”
Written by Caroline Reid