Toward an effective tuberculosis vaccine

When reports surfaced last week of a former El Paso, Texas, hospital nursery employee testing positive for active tuberculosis, the widespread panic that ensued shed light on the scope of public misunderstanding of the disease. Because it’s impossible to say at what moment she became ill, precautionary screenings are recommended for more than 700 infants who passed through the nursery in the past year. Although such investigations are standard and relatively common, the quantity and vulnerability of the babies requiring testing has sparked outrage. Many people have asked: Shouldn’t a vaccine have prevented this?

While we have vaccines to thank for the decline of global diseases like measles and smallpox, vaccination’s role in the worldwide battle against TB has been comparatively minimal. Smart public-health measures—like the preemptive testing currently underway in El Paso—have helped bring the disease’s toll down from its 19th-century peak, but TB still infects more than 8 million patients each year. The rise of tough-to-treat drug-resistant strains shows that antibiotic treatment isn’t enough to wipe out the historically persistent bug, and many experts agree that an effective vaccine would be key in winning the fight. So, what is it about a TB vaccine that’s had science stymied for over a century?

The effort to develop a TB vaccine dates back to 1882, when a German microbiologist named Dr. Robert Koch identified the Mycobacterium Tuberculosis—the bacteria that causes TB—in infected tissue samples. Thanks to this crucial discovery, scientists finally knew what to target in their efforts to develop a solution. A vaccine was the obvious best-case scenario, and many set off to try to create one. One slightly bungled effort in the 1890s yielded the tuberculin skin test, which didn’t provide any immunity but nonetheless proved to be an innovative diagnostic tool. It is nearly the same test that is widely used today that scans for infection by sparking a red, irritated reaction at the injection site when TB antibodies are present. But being infected with TB is different than being sick with it—some estimate that around one-third of the world is infected with TB bacteria, which can lurk quietly in the body for years without ever activating and causing disease. Up to 95 percent of these people will never develop the illness.  

Many other vaccine development efforts were similarly unsuccessful, except for one. The BCG, or Bacillus Calmette-Guérin vaccine, has been on the market for nearly a century. BCG is the most widely used vaccine in the world, and is given to babies in many countries shortly after birth. However, it is not used in the United States, and some TB specialists—like Dr. Lee Reichman in his 2001 book Timebomb—go so far as to call BCG practically useless. The vaccine offers limited protection against types of TB most common in babies and young children, but does not seem to last past puberty. Most countries with the highest TB rates do indeed vaccinate babies against the disease. Besides being relatively weak, BCG comes with another major disadvantage—it creates a lifelong false-positive skin test. This makes TB tougher to diagnose among the vaccinated, unless their symptoms are severe.

It’s a misconception that global TB rates fell due to vaccines or even antibiotics, which didn’t even appear until TB was already on the decline. Instead, improved health, sanitation, quarantine, and screening measures combined to prevent cases before they ever happened. After a few decades of decreasing numbers of cases, the disease’s 1990s comeback—fueled largely by HIV and other geopolitical catastrophes—reignited research and encouraged researches to revisit the white whale of a safe, affordable vaccine.

Any would-be TB vaccine faces serious roadblocks. For one thing, scientists still don’t fully understand the way that TB hibernates in the body. Among people with latent infections, it is difficult to pinpoint why one person never develops an active disease, why another develops it within a year, and why yet another develops it decades later. This not only makes clinical trials difficult, but it also makes it hard to say whether a patient was protected by the vaccine or simply wouldn’t have developed the disease in the first place. Similarly, there are no biomarkers scientists can look for that flag immunity to TB—the only evidence is whether the person gets it or not. And TB tends to behave differently in animals than in people—vaccines that have seemed promising during initial animal trials have been disappointed in human testing.

Still, several promising vaccine candidates in the development pipeline have the potential to change the TB landscape. They take a few different approaches to the classic challenges that have stumped generations of researchers. Aeras, a TB vaccine research firm in Maryland, is currently spearheading the largest-ever adult TB vaccine trial in several sites in Africa. The vaccine is a two-injection “prime-boost” vaccine given to adolescents and adults to amplify and renew the effects of the BCG they received as children. The trial enrolled 3,500 subjects and will last three years, which statisticians say is long enough to distinguish the inoculated group from those given placebos. According to Dr. Ann Ginsburg, the trial’s Chief Medical Officer, the “prime-boost” strategy would be more effective and more error-proof than a several-month round of prophylactic medication that is sometimes prescribed to infected people to keep active disease at bay.

Another advanced trial being conducted in China takes a slightly different approach—it is a six-shot therapeutic vaccine for people who already have an active case of TB, and is designed to significantly shorten their treatment. While this model wouldn’t do as much as a “prime-boost” to prevent new cases, it could still be a major improvement in TB care. TB treatment is notoriously long and arduous, especially for antibiotic-resistant strains—and a significantly shortened treatment period would make it easier for patients and TB management programs to follow each case through to recovery.

While a vaccine would be the gold standard of advancements in TB, it could be years before any of them hit the market. Advancements in drug development, immunity research, and diagnostic techniques also have great promise in our goal to eventually eradicate the disease for good. Until then, our best defense to keep people healthy lies in smart, efficient public-health policy—as it always has.

Source: The Atlantic