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.

Jeyanathan M, Damjanovic D, Shaler CR, Lai R, Wortzman M, Yin C, Zganiacz A, Lichty BD, & Xing Z (2013). Differentially imprinted innate immunity by mucosal boost vaccination determines antituberculosis immune protective outcomes, independent of T-cell immunity. Mucosal immunology, 6 (3), 612-25 PMID: 23131783