Developing tuberculosis vaccines - challenges and strategies 1

Published on June 30, 2015   25 min

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0:00
Hello. My name is Tom Evans. I am a physician and the chief executive officer of Aeras, a nonprofit biotechnology organization that is dedicated to developing tuberculosis vaccines for the developing world and all of the world. And I'd like to talk to you today about where we are with TB vaccines, noting that it's May of 2015. And this will be a fast-moving field.
0:22
To start with, Mycobacterium tuberculosis is the bacterial cause of this disease. It's important to realize that this bacterium has co-evolved with man sometime over the last 10,000 to 70,000 years. There is still some controversy. And it's very unique in that it is covered with these waxy mycolic acids and glycolipid structures that make it very different from some other bacteria. They give it a protective coating. And they are part of its pathogenesis.
0:48
Now, tuberculosis, why do a vaccine for tuberculosis? Tuberculosis has been mother nature's number one killer over the past two centuries. Over the past two centuries, a billion people, that was with a B, have died from tuberculosis. Last year, tuberculosis was tied with HIV as the leading cause of infectious disease death in the world. A person dies from tuberculosis every 21 seconds. There are 1.5 million deaths per year, somewhere between 9 and 10 million new cases per year. And this is an epidemic that continues unabated throughout the world.
1:25
Unlike some other diseases, although the incidence is highest in Sub-Saharan Africa, especially in the cone of Africa down into South Africa, Botswana, Mozambique area, the burden is highest in India, with the largest number of cases due to their population. The second highest number of cases is in China. And the third highest number of cases is in Indonesia. So the BRICS countries, as well as Sub-Saharan Africa, really bear most of the burden from TB.
1:54
Not only are there millions of cases of tuberculosis every year, there are 650,000 drug-resistant cases of TB in 2013. There are two forms, a multi-drug-resistant form that requires 18 months of therapy, including injectables either two to three times a week or daily, as well as extremely drug-resistant TB that is defined by resistance to the drugs INH and rifampin, any of the fluoroquinolones, such as ciprofloxacin, and at least one of the other injectable drugs, such as amikacin, kanamycin, or capreomycin. This is a very huge burden, both in cost and in death. The mortality from XDR-TB is somewhere between 20% to 70%, depending on what part of the world you look in. The treatment is at least two years. It is highly toxic. And some strains have been found to be untreatable, with some mortality in some regions, such as South Africa, that have reached up to 80%.
2:48
For the longest time, there was sort of a sense that TB was getting under control, especially since in Europe and the US, we were able to control tuberculosis in year-on-year we've seen a decrease in the overall trend. However, worldwide, this has not been the case. And the control community has worked extremely hard to reduce the rate of tuberculosis. And there have been major successes. However, in order to really achieve a tuberculosis-free world, that is less than one per million case by the year 2050 and a rate of 10 per 1,000 by the year 2035, the WHO acknowledged that we will not be able to reach the millennial goals without introduction of new tools, such as a new vaccine or new prophylaxis in the year 2025. So all of us are working as diligently as possible to find these new tools and the new vaccine, so that we can move forward. Before we launch into a review of the tuberculosis vaccine world, it's important to review a couple of aspects about tuberculosis.
3:51
Tuberculosis being a bacterial disease of the lung is diagnosed by culture as the gold standard, that is, a culture is taken of sputum. That sputum is cultured by a variety of different means, sometimes modern means, such as MGIT collection of systems. But they can also be diagnosed by smears by looking for what's called an AFB smear positive stain. They can be diagnosed often by very characteristic x-ray findings, especially cavitary upper lobe lesions. You can also diagnose tuberculosis very accurately and very specifically using PCR techniques, such as the field available GeneXpert.
4:29
In order to understand some of the issues of tuberculosis vaccines, it's important to realize that you could also diagnose Mycobacterium tuberculosis infection. And as I'll go through, this is not the same as disease. Mycobacterium tuberculosis infection is diagnosed by an immunological reaction that shows that the person has likely or has certainly been infected with tuberculosis. The most common way of doing this in the past was using a tuberculin skin test. That's the little bump that's put under your arm and then read out 48 to 72 hours later. It is very sensitive and somewhat specific, but can be interfered with by both BCG and nontuberculous mycobacteria in the environment. These are organisms like TB that live in the soil and water around us. As an alternative over the last many years and decades, there have been a number of approved tests called interferon-gamma release assays. There are a number of these on the market. In the United States, the main one used is the IGRA. There's also a T-SPOT developed in the UK. But these also measure interferon-gamma production when you stimulate all blood taken from the patient and then read out on an ELISA to look for interferon-gamma production. So these will be two of the methodologies we'll be talking about as we go through vaccine development.
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