Vaccine delivers an immune double whammy to fight tuberculosis

Vaccination is a hugely important public health intervention, perhaps the biggest in the history of mankind. While many childhood diseases are now effectively controlled by immunisation programs (as long as parents vaccinate their kids), there is still no effective vaccine for other serious infections like adult tuberculosis (TB).

Most adult TB vaccines under development focus on boosting the "adaptive" immune response to generate highly activated immune cells to fight off M. tuberculosis bacteria. New research has now revealed that it's also important to consider how such vaccines impact the "innate" immune response, which exists in a state of constant readiness to repel pathogenic invaders.

In a collaborative effort from the McMaster Immunology Research Centre in Canada, researchers first administered a basic TB shot to set up a foundation level of anti-TB immunity. Then, since tuberculosis-causing bacteria enter the human body via the lungs, the team delivered a second inhaled vaccine designed to boost immune cells at the site of pathogen invasion. Two different inhaled vaccines were used, based on adenovirus or vesicular stomatitis virus (VSV).

While both inhaled vaccines generated similar levels of adaptive immunity, the VSV vaccine was not as good as adenovirus at producing robustly activated, multi-functional innate immunity. This led to a poor anti-bacterial effect, and a lack of protection against M.tb bacteria.

The unique nature of each inhaled vaccine appears to be responsible for this difference in outcome. VSV enters lung cells in a certain way, attaching at different sites, activating different intracellular pathways, expressing different viral products and consequently engaging different parts of the immune system. The two different vaccines programmed the two arms of the immune system differently, and the vaccine that engaged adaptive and innate immunity together did the best job at controlling tuberculosis infection.

This research should help to drive the intelligent design of future vaccines against pathogens like HIV and chlamydia, which enter at similar interfaces where the body meets the outside world.

4 Responses to “Vaccine delivers an immune double whammy to fight tuberculosis”

  1. Sandra Reply | Permalink

    Hi,I have had the vaccination in middle east 15 years prior to my ?accidental exposure to TB during my internship year .My Respiratory OSCE exam was about a fellow with TB from ?Vietnam.It was the medical school mistake to expose me with no warning and no mask to TB.Then later on the School wanted to give me antibiotics for 3 months even though I had no symptoms and clear x -ray .I think my vaccination protected me .now 20 years later I am still free of TB and bless the day I had the vaccination.

    • Kausik Datta Reply | Permalink

      I am glad that you are free of TB, Sandra. However, I am not certain why your school wanted to give you a 3 month antibiotic course. If you have been exposed to TB and don't have any clinical symptoms (i.e. clear CXR), you may still have LTBI (latent TB infection). The standard of care in this situation, to my knowledge, is at least 6-9 months of Isoniazide 300mg daily. Some may be alternatively given Rifampin 600mg for 4 months. This regimen is known to provide more than 90% risk reduction for reactivation of LTBI. Currently, the best way to find out this risk is to do a TB ELISpot assay, which checks if your memory T-cells can recognize TB antigens and respond by releasing interferon-γ.

      I don't know what vaccine you received in the middle east, but I am assuming it was BCG. Unfortunately, the efficacy of BCG in adults is highly variable, possibly because BCG doesn't make good immunological memory.

      Again, I am glad you are doing all right. But if you ever have any respiratory symptom, please don't hesitate to go to your doctor, and let them know of your history.

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