New study reports the improved efficacy of the tuberculosis vaccine by changing the vaccination method.
The World Health Organization reported that in 2018 a total of 1.5 million died from Tuberculosis (TB) worldwide, making it the leading cause of death from a single infectious agent. The WHO also lists multidrug-resistant TB as a health security threat. Despite these alarming statistics, TB is preventable and treatable with incidence rates falling by about two percent every year. Ending the TB epidemic by the year 2030 is one of the Sustainable Development Goals of the United Nations.
Tuberculosis is caused by the bacteria, Mycobacterium tuberculosis and is spread through the air when people with an active infection cough, sneeze, or speak. People suffering from HIV/AIDS are 19 times more likely to develop an active TB infection. Undernourished people and those who smoke are also at an increased risk of TB infection.
Vaccination against TB bacteria at an early age is one of the primary methods of controlling the infection. Currently, there is only one approved tuberculosis vaccine, the Bacillus Calmette-Guérin (BCG) vaccine. The BCG vaccine is administered at birth as an intradermal injection or an injection in the skin. Some reports indicate that the vaccine may not be very effective in adolescents and adults.
New study, same vaccine
A recent study has shown that changing the route of administration of the tuberculosis vaccine from an intradermal injection to an intravenous method greatly improves the effectiveness of the vaccine in preventing infection in rhesus monkeys that have been exposed to the infectious bacteria. This study was carried out by researchers from the National Institute of Health’s National Institute of Allergy and Infectious Diseases and collaborators from the University Of Pittsburgh School Of Medicine. The results were published in the January 2020 issue of Nature.
The researchers assessed how the dosage and administration route of the BCG vaccine influenced the immune response and protection after exposure to the Mtb bacteria in rhesus macaques. The rhesus monkeys were vaccinated with the BCG vaccine by intradermal, aerosol, or intravenous methods. After a period of six months post-vaccination the monkeys were then challenged with a low dose of a highly pathogenic strain of the Mtb bacteria and their immune responses were studied at a tissue, cellular, and genetic level.
Intravenous BCG vaccination was the most effective
Post-vaccination analysis of the immune response showed that only the intravenous administered BCG vaccine induced an increase in T cells that were specifically responsive to the mycobacterium antigen and a ten-fold increase in T cells overall as compared to the other modes of vaccination. In vitro gene expression experiments revealed higher expression of genes that were protective against TB in the IV vaccinated group. The monkeys were challenged with Mtb bacteria six months after vaccination after which infection and disease progression was monitored by CT scanning of the lungs. The IV vaccinated monkeys showed no increase in cellular activity that would indicate an active infection. They also showed fewer granulomas in their lungs with six out of the ten monkeys in the IV vaccinated group showing no granulomas at all throughout infection. The researchers also found that the Mtb bacteria were rapidly eliminated in the IV vaccinated monkeys as only three in this group showed the presence of very low levels of the bacteria in lung tissue. All other monkeys that were immunized via intradermal or aerosol routes or were unvaccinated showed signs of greater infection.
Overall, the tuberculosis vaccine via the intravenous route showed greater protection through greater and sustained immune response specifically in the lungs. The researchers suggest that this study “represents a major step forward in the field of TB vaccine research.”
Written by Bhavana Achary, Ph.D
Darrah, P.A., Zeppa, J.J., Maiello, P. et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature 577, 95–102 (2020) doi:10.1038/s41586-019-1817-8
Press release retrieved from – https://www.eurekalert.org/pub_releases/2020-01/nioa-cro123019.php
WHO statistics on TB prevalence obtained from – https://www.who.int/news-room/fact-sheets/detail/tuberculosis
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