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In Animal Study, TB Vaccine Works Far Better With IV Administration

Simple change in dosage and route may improve a century-old vaccine

Changing the dose and route of administration of the tuberculosis vaccine may greatly improve its effectiveness in teens and adults, according to a study conducted in animals and published in Nature.

Tuberculosis (TB) is the leading infectious cause of death globally. The world’s only licensed TB vaccine, Bacille Calmette-Guerin (BCG), was developed a century ago. Given to infants via a needle placed just under the skin, BCG protects babies from a form of the disease called disseminated TB but is far less effective at preventing pulmonary TB, the major cause of illness and deaths, in teens or adults.

Researchers from the National Institute of Allergy and Infectious Diseases and colleagues found that changing the dose and route of administration from intradermal (ID) to intravenous (IV) greatly increases the vaccine’s ability to protect rhesus macaques from infection following exposure to Mycobacterium tuberculosis, which causes TB. The findings support investigation of IV BCG administration in clinical trials to determine whether this route improves its effectiveness in teens and adults.

To control M. tuberculosis infection and prevent clinical disease, a TB vaccine must elicit strong, sustained responses from the immune system’s T cells, specifically in the lungs. However, the ID route of BCG administration may not generate enough of these critical cells in the lungs. The researchers hypothesized that administration of BCG by IV or aerosol (AE) routes would confer substantially better protection from infection and/or disease in rhesus macaques following challenge with virulent M. tuberculosis.

In their study, groups of animals received the BGC vaccine by ID, AE, or IV routes. The scientists assessed immune responses in blood and in fluid drawn from the lungs for a 24-week period following vaccination. IV BCG vaccination resulted in the highest durable levels of T cells in the blood and lungs.

Six months after vaccination, the researchers exposed groups of vaccinated rhesus macaques (immunized via ID, AE, or IV routes) and a group of unvaccinated macaques to a virulent strain of M. tuberculosis by introducing the bacteria directly into the animals’ lungs. They tracked the infection and disease development over three months. Nine out of 10 animals vaccinated with IV BCG 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 ID or AE routes showed signs of significantly greater infection.

Source: National Institutes of Health, January 2, 2020

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