Researchers from the Texas Biomedical Research Institute claim that by shortening a key ingredient when administering the only approved tuberculosis, long-term protection against the devastating disease in mice was significantly enhanced.
If the discovery continues to be true in nonhuman primates and clinical trials, it has the potential to save millions of lives.
The Bacillus Calmette-Guerin(BCG) vaccine is widely used to inoculate children against TB, but its effectiveness is decreasing throughout the year. Researchers around the world are looking for more powerful vaccines and therapies.
According to Joanne Turner, PhD, Texas Biomeds'' Executive Vice President, Research, and senior paper author, we can reverse BCGs diminishing effectiveness by combining it with a host-directed therapy into one dose. This makes it very beneficial for the clinic.
Decades of research
Turner emphasised that the findings are based on more than 20 years of research. Throughout her career, she has been examining the influence of a molecule, interleukin-10 (IL-10) on TB. While IL-10 typically helps stifle excessive inflammation during infection, however, through numerous studies, Turner and her colleagues have found IL-10 does more harm than good in TB, revealing that it can result in TB infection.
Turner and her colleagues blocked IL-10 at different times during infection late into infection, the first three weeks during infection and have eliminated IL-10 completely. All signs indicate improved TB control and improved survival. In the present study, the team looked at what happens if temporarily blocked IL-10 beforeinfection occurs, at the same time as giving the BCG vaccination.
Host-directed therapy + vaccine
The researchers combined the BCG vaccine with an antibody that blocks IL-10 activity for about one week. This antibody is the host''s choice, and they gave the mixture in one dosage, waiting six weeks until the IL-10 blocker was no longer present, and the BCG protection had been developed. The mice also had significant inflammation and damage in the lungs. Notably, the mice given the vaccine/IL-10 blocker were given levels of several long-term memory immune cells, which are critical for ongoing TB control.
This indicates that the early development of an immune response is critical for managing TB infection in the long run, and that IL-10 hinders the development of that long-term immunity, according to Turner. By briefly blocking IL-10 at the same time as giving the vaccine, it allows the vaccine and the immune system to do their jobs, thus creating those long-lasting memory immune cells.
Collaborators at Texas Biomed are planning to investigate if the combination works in nonhuman primates safely. If those results are promising then the combination may go into human clinical trials. This is especially true of the BCG vaccine that is already widespread use and the IL-10 blocker is being tested against other diseases.
IL-10 had been relegated to TB from experiments, even if it was detected in humans with TB. However, this conclusion was made in the most common strain of research mouse, which is fairly resistant to TB and does not produce much IL-10.
Turner and colleagues worked on a variety of mouse strains, called CBA/J, that is more susceptible to TB. IL-10 knock-out mice for Turner, which required several years of research and since 2011, the mice have been instrumental in proving IL-10. These animals can even form human-like granulomas that form around the bacteria to prevent it from spreading.
We only saw that because we were working in a different mouse strain than the standard laboratory mouse strain, Turner believes. It is gratifying that those knock-out mice we developed are available for other researchers to work with. Diversity in animal models is critical to understand human diseases.