New Research Suggests Future Applications


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Research suggests the 100-year-old BCG tuberculosis vaccine may provide clues to the development of future vaccines and personalized treatments. Cara Dolan/Stocksy United
  • The vaccine for tuberculosis was originally developed in 1921, and it is still in use today.
  • Researchers recently compared the effects of tuberculosis vaccines in infants against lab studies.
  • The biomarkers they discovered could be used to develop new and more effective vaccines.

Tuberculosis (TB) is an infection caused by the bacteria mycobacterium tuberculosis that most often affects your lungs. According to the World Health Organization, it’s the second-most infectious cause of death worldwide behind COVID-19.

Perhaps what’s most tragic about that statistic is that the vaccine for TB has been around for over one hundred years.

The bacillus Calmette-Guérin (BCG) vaccine — named for its developers, Albert Calmette and Camille Guérin — was first administered in 1921, and it remains the only TB vaccine to this day.

So how does it work, what can we learn from it, and perhaps most importantly, do you need to have it?

The BCG vaccine is what’s called a live attenuated vaccine. This means that it contains a weakened — but crucially, still living — sample of the bacterium that causes TB.

By fighting off this weakened version of the bacteria, your body learns how to identify and defeat it if it ever comes across it again. This is what we generally know as immunity, but it’s not the only method of inducing it.

Dr. Danelle Fisher, FAAP, a pediatrician and the chair of pediatrics at Providence Saint John’s Health Center in Santa Monica, California, told Healthline that there are many types of vaccines that do not use a live pathogen. Examples include:

  • inactivated vaccines containing killed pathogens
  • toxoid vaccines containing inactivated toxins produced by the pathogens
  • subunit vaccines containing just the identifying pieces of a pathogen instead of the whole thing
  • conjugate vaccines containing the sugar-like polysaccharides that coat bacteria to cause an immune response
  • viral vector vaccines containing a harmless modified virus that creates the identifying pieces of a pathogen within your own body
  • mRNA vaccines cause your own cells to produce identifying pieces of a pathogen that your body can learn from

The mRNA vaccines have gotten a lot of attention lately, as many of the vaccinations for COVID-19 used this method.

Dr. Charles Bailey, medical director for infection prevention at Providence St. Joseph Hospital and Providence Mission Hospital in Southern California, told Healthline that live attenuated vaccines like the BCG vaccine are still common.

“Other live attenuated vaccines include those for measles, mumps, rubella, varicella, typhoid (oral), and yellow fever,” Bailey said.

While some live attenuated vaccines are on the CDC’s child and adolescent immunization schedule, BCG isn’t one of them.

Does this mean it’s not effective? Not at all. In fact, there are many effective vaccines that are not routinely administered in the US.

“There may be the potential for excessive vaccination to ‘exhaust’ the immune system,” Bailey said.

“The use of vaccines must be with the expectation of a benefit that exceeds any potential risk of the treatment. While vaccines are relatively safe and certainly prevent many many more negative outcomes than they might cause, they are not completely devoid of risk,” he added.

So it’s important to focus on vaccines that will have the greatest impact. TB is no longer prevalent enough in the US to widely vaccinate against it.

The BCG vaccine is typically only recommended for people in areas where TB is more common, or for healthcare workers who might treat patients with TB. Eight countries, led by India, China, and Indonesia, account for two-thirds of all TB cases.

Even though the BCG vaccine has been around for a long time, our understanding of the human body is always evolving. This presents an opportunity for researchers to examine time-tested treatments through a modern lens.

In a study published in the journal Cell Reports, experts studied blood samples from infants in Guinea-Bissau both before and after receiving the BCG vaccine. These samples were compared to donated cord blood in Boston that was treated with the BCG vaccine in a laboratory setting.

The results were twofold.

First, they were able to detect changes in metabolic markers, specifically certain lipids (fats), in the infant’s blood samples that correlated with an immune response to the BCG vaccine. This had never been demonstrated before and could be used to aid future research into exactly how the BCG vaccine works to protect against TB.

Second, the test results from infants matched the test results from the laboratory work. This means that future vaccine studies could be done in a laboratory with a higher degree of certainty that they would be just as effective in live people.

“This is an interesting finding in that the metabolic markers may end up being a clue to how each individual responds to a vaccine,” Fisher said.

Doctors may one day be able to use these markers to help determine more precisely how different people will react to specific vaccines. It could help drive future vaccine development or further reduce the incidence of adverse reactions, but it’s also important to keep things in perspective and remember that much more research is needed.

“It may be something to investigate and track, [but] as with any preliminary findings, this would need to be validated by repeat studies,” Bailey said.

What the next hundred years of medicine will bring, only time can tell.



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