Intravenous Administration Could Improve TB Vaccine Efficacy

In 2018, approximately 23% of the world population or 1.7 billion individuals were infected with tuberculosis (TB). The Mycobacterium tuberculosis bacteria typically attack the lungs but can also affect any parts of the body and can be fatal if not treated properly. In fact, TB is the leading infectious cause of death globally, claiming 1.5 million lives each year.

Concerningly, the only licensed vaccine, Bacille Calmette-Geurin (BCG), was developed a century ago and has low rates of efficacy in protecting against pulmonary TB.

However, new research led by investigators from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) and published in Nature suggests that minor changes could improve efficacy.

Traditionally, the vaccine is administered to infants intradermally and provides protection from disseminated TB. The new research, conducted in rhesus macaques, suggests that changing the dose and performing a switch in route of administration from intradermal to intravenous could increase efficacy in preventing pulmonary TB infection.

The investigators hypothesized that the intradermal route may not generate enough T cells to elicit strong immune responses in the lungs to effectively protect against TB. The study team posited that administering the BCG vaccine via intravenous or aerosol routes could overcome this hurdle.

For the study, groups of rhesus macaques were assigned to receive the vaccine via intradermal, intravenous, or aerosol routes. From there, the team evaluated immune responses in blood and fluid drawn from the lungs for a 24-week period following vaccination. Results indicate that intravenous vaccination led to the highest durable level of T cells in both the blood and lungs.

The study team continued to follow the animals and 6 months after vaccination they exposed the immunized macaques and a group of unvaccinated macaques to a virulent strain of M tuberculosis by introducing the bacteria directly into the lungs. The investigators continued to follow the animals for a 3-month period, tracking infection and disease development.

After the 3-month period, the team reported that, of the animals vaccinated intravenously, 9 out of 10 were highly protected, with 5 showing no detectable infection in any tissue and 3 with only very low counts of the bacteria in lung tissue.

On the other hand, all unvaccinated animals and animals vaccinated via intradermal or aerosol routes showed signs of significantly greater infection.

Based on these findings, the investigators concluded that intravenous vaccination “conferred an unprecedented degree of protection in an animal model of severe TB and represents a major step forward in the field of TB research,” according to a statement issued by NIAID.

Additionally, the findings support further investigation of the IV BCG administration in clinical trials to determine whether this route improves effectiveness in teens and adults.

According to the authors, future work should also determine the mechanisms that lead to sterilizing immunity after intravenous BCG. If successful, it could lead to developing a vaccine designed to activate the same protective mechanisms triggered by intravenous BCG that could be administered in a way that is safe and adaptable to mass vaccination programs.