Giving TB vaccine intravenously boosts efficacy. Experiments on rhesus macaques show that changing the method of administration of an existing vaccine gives “astonishing” results in the fight against tuberculosis (TB).
Globally, tuberculosis is one of the Top 10 causes of death and the leading cause of death from infection, ranking higher than HIV and AIDS.
About 10 millions people around the world contracted tuberculosis in 2018, according to the World Health Organization (WHO).
Although most of these cases generally occur in Southeast Asia and Africa, drug-resistant tuberculosis is a “public health threat” worldwide.
There is currently only one vaccine, the Calmette-Guérin bacillus (BCG). Health professionals administer the vaccine intradermally; that is, they inject it directly under the skin.
However, with this method of administration, the effectiveness of the vaccine varies considerably from person to person. But, new research suggests that administering the vaccine intravenously could significantly improve its effectiveness.
JoAnne Flynn, Ph.D., who is a professor of microbiology and molecular genetics at the Center for Vaccine Research at the University of Pittsburgh in Pennsylvania, led the new research with Dr. Robert Seder of the National Institute of Allergies and Infectious Diseases (NIAID) in Bethesda, MD.
Flynn and colleagues published their findings in the newspaper Nature.
As the authors explain in their article, prevention and control of TB infection requires immunity to T cells. T cells are white immune cells, also called lymphocytes.
One of the main challenges in creating an effective vaccine is to trigger and maintain a T-cell response in the lungs to control the infection while simultaneously triggering memory cells that can replenish lung tissue.
With a direct injection into the skin, the BCG vaccine does not produce many resident T cells in the lungs, the authors explain.
However, some previous studies on non-human primates have shown that injecting vaccines intravenously makes them more effective.
So the researchers hypothesized that a “high enough dose” of intravenous BCG would do the trick.
They set out to test their hypothesis and find out how to obtain a sufficient number of T cells that could protect against tuberculosis infection in rhesus macaques prone to infection.
The researchers divided the monkeys into six groups: monkeys who did not receive a vaccine, monkeys who received a standard human injection, monkeys who received a higher dose but by the same standard injection route, the monkeys who inhaled the vaccine in the form of a mist. , monkeys who received an injection over the mist and monkeys who received a higher dose of BCG but in a single intravenous injection.
After 6 months, the scientists exposed the monkeys to tuberculosis. As a result, the majority of monkeys developed pulmonary inflammation.
The team examined the signs of infection and the course of the disease among the different groups of macaques.
Of all the groups, those who received the vaccine intravenously had the greatest protection against TB bacteria. There were almost no TB bacteria in the lungs of these monkeys, while monkeys who received the vaccine in the standard manner had almost as many bacteria as those who had not been vaccinated at all.
“The effects are incredible,” says Flynn. “When we compared the lungs of animals receiving the vaccine intravenously with the standard route, we found a 100,000-fold reduction in bacterial load. Nine out of 10 animals had no inflammation in their lungs. “
“The reason why the IV route is so effective […] is that the vaccine travels quickly through the blood to the lungs, lymph nodes and spleen, and it starts T cells before being killed. ”
Flynn and his team found that the T-cell response in the lungs of monkeys who received an intravenous injection was much more active than in the other groups. They also noted that T cells were more numerous in these monkeys, especially in the lobes of the lung parenchyma.
Intravenous administration “induced many more CD4 and CD8 T lymphocyte responses in the blood, spleen, bronchoalveolar lavage and pulmonary lymph nodes,” write the authors.
Before moving to humans, scientists need to perform more tests to assess the safety and convenience of this vaccine.
“We are far from realizing the translation potential of this work,” says Flynn. “But ultimately, we hope to test in humans.”
So far, the study marks a “paradigm shift” in the way we develop tuberculosis vaccines to “prevent latency, active disease and transmission”, conclude the authors in their article.