Old TB vaccine may work better when delivered intravenously

At a Glance Delivering the only approved tuberculosis vaccine intravenously greatly enhanced its ability to protect rhesus monkeys from infection.

The study provides a new model for understanding the mechanisms underlying vaccine protection against tuberculosis.

University of Pittsburgh School of Medicine

Tuberculosis (TB), the world’s leading cause of death from infection, is caused by Mycobacterium tuberculosis bacteria. It’s spread through the air, often through coughing, by people with TB disease of the lungs. Others can breathe in these bacteria and become infected. TB most commonly affects the lungs (pulmonary TB), but it can also spread to other parts of the body, including the kidney, spine, and brain (disseminated TB).

The world’s only licensed TB vaccine, Bacille Calmette-Guerin (BCG), was developed a century ago. Given to infants intradermally (ID), in which the vaccine is placed just under the skin with a needle, it protects them from disseminated TB. However, BCG given this way is far less effective at preventing pulmonary TB, which is the major cause of illness and deaths in teens or adults.

To control TB infection and prevent clinical disease, a vaccine must elicit strong, sustained responses from the immune system’s T cells. The standard ID delivery route may not generate enough of these critical cells in the lung to immediately control infection and protect against pulmonary TB.

To determine if a different dose or route of administration of this vaccine could be more effective at preventing pulmonary TB, a team led by Drs. Robert A. Seder and Mario Roederer at NIH’s National Institute of Allergy and Infectious Diseases (NIAID) and Dr. JoAnne L. Flynn of the University of Pittsburgh carried out a study in rhesus monkeys. The results were published on January 2, 2020, in Nature.

Five groups of monkeys were given the BGC vaccine in different ways: standard ID, higher dose ID, via aerosol to the lungs, a combination standard-dose ID and aerosol, or as an intravenous, or IV, injection. The scientists assessed immune responses in blood and in fluid drawn from the lining of the lungs for a 24-week period following vaccination. IV administration of the BCG vaccine resulted in 10- to 100-fold higher levels of T cells in the lungs compared with the other routes.

Six months after vaccination, the researchers exposed the groups of vaccinated monkeys and a group of unvaccinated monkeys to TB-causing bacteria. They then tracked the infection and disease development over three months. Nine out of 10 animals vaccinated by IV were highly protected; six showed no detectable infection in any tissue tested, and three had only very low counts of M. tuberculosis bacteria in lung tissue. All unvaccinated animals and those immunized via aerosol or ID showed signs of significantly greater infection.

“This study provides a new framework to understand the immune correlates and mechanisms of protection against TB, and should guide the field of TB vaccine research,” Seder says.