The team of scientists from the U.S. National Institute of Allergy and Infectious Diseases and the University of Pittsburgh School found that delivering a high dose of the vaccine intravenously greatly improves the drug's ability to protect against the deadly disease.
Study researchers noted that the existing vaccine methodology is not reliable and has failed to contain TB, which kills more people than any other infectious disease. The findings of the study show that nine out of 10 monkeys who received the intravenous vaccine were highly protected, while six out of 10 monkeys showed no infection at all.
"The effects are fantastic", Joanne Flynn, professor of microbiology and molecular genetics at the University of Pittsburgh, said in a media release, but cautioned that more research is needed before such a strategy can be tested in humans.
Co-author Dr Joanne Flynn, a microbiologist at the Pitt Center for Vaccine Research, told The New York Times that monkeys who had the vaccine injected into their veins had no lung inflammation and had 100,000 times fewer TB bacteria in their lungs.
9 out of 10 animals vaccinated with IV BCG had been extremely protected; six confirmed no detectable an infection in any tissue examined and three had exclusively very low counts of Mtb micro organism in lung tissue.
Six of these nine monkeys showed no detectable signs of infection after they were exposed to TB bacteria.
Monkeys are extremely susceptible to TB.
According to the study, all of the animals which received the standard human dose had persistent lung inflammation, and the average amount of TB bacteria in their lungs was only slightly less than in the monkeys that received no vaccine at all.
The investigators concluded that IV BCG conferred an unprecedented degree of protection in an animal model of severe TB and "represents a major step forward in the field of TB vaccine research".
The researchers say they eventually hope to test an IV BCG vaccine in humans.
Those given the intravenous vaccine, however, had virtually no TB bacteria in the lungs, and only one monkey in this group developed lung inflammation. "The reason the intravenous route is so effective is because the vaccine travels quickly through the bloodstream to the lungs, the lymph nodes and the spleen, and it primes the T cells before it gets killed", Prof.
Three-dimensional PET-CT scans of lungs showing areas of TB infection and tissue inflammation (red and orange) in macaques challenged with Mtb after vaccination with either ID BCG (top row) or IV BCG (bottom).
Flynn's team found BCG and activated T cells in the lungs of all the intravenously vaccinated animals. Among the other groups, BCG was undetectable in the lung tissue and T cell responses were relatively meager. "Now that said, this is a study in monkeys and whether it can translate down the road into an effective and safe way to deliver the vaccine to literally millions of infants and young children, and perhaps also adolescents and adults, remains to be seen". An intravenous vaccine requires more skill to administer and has a higher risk of infection.
"We are still far from the translation potential of this work", Flynn said.
Additional authors are from the University of Pittsburgh, Massachusetts Institute of Technology, Harvard University, and Vir Biotechnology.
This research was funded, in part, by the NIAID Intramural Research Program and through NIH grants 5U24AI118672 and 2RM1HG006193. The monkeys received the vaccine either intradermally, intravenously, or as an aerosol.