Same-old TB vaccine could get a manyfold boost its effectiveness: US study

India’s campaign to end tuberculosis or TB by 2025 may have just gotten an unexpected, and very welcome, booster shot.

Scientists at the US-based Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), have potentially cracked the problem of how to improve the efficacy of the TB vaccine - Bacillus Calmette Guérin or BCG vaccine - that has been in use in India for over 70 years. The potential fix is simple, too: give the vaccine intravenously or through IV instead of intradermally or by injection into the skin. The scientists have completed the research in rhesus macaque monkeys, though no human trials have been conducted yet. Here’s why breakthrough is especially important in the Indian context. [caption id=“attachment_4911481” align=“alignnone” width=“1280”] Representational Image. Reuters[/caption]

Tuberculosis in India

TB is one of the top ten causes of death worldwide. According to the World Health Organization’s Global Tuberculosis Report 2019, there were 10 million new cases of TB and 1.2 million TB deaths globally in 2018. India accounted for almost 27% of the new cases of TB, and a whopping 36.6% of the deaths! To be sure, India has made some improvements in dealing with the TB epidemic. TB deaths are down to 440,000 in 2018 (from 615,000 in 2000). The number of cases has dropped by 1.8% - to 2.69 million in 2018, compared with 2.74 million in 2017. But there is much more to be done, if India is to achieve its target of TB-Mukt Bharat by 2025. Since 1948, Bacillus Calmette Guérin or BCG vaccine has been continuously used in India to prevent TB. A dose of 0.05 mL of BCG vaccine is administered intradermally, that is, through the skin, to infants under one year of age. Adults are given 0.1 mL of the same vaccine intradermally. Even after the administration of the vaccine on a large scale, new cases of TB have been reported daily. This indicates that though the BCG vaccine is effective against early-childhood forms of TB, its ability to prevent the contagious pulmonary form (mostly seen in adults) is unsatisfactory. To tackle this situation, US scientists started an experiment to see if changing the route of drug delivery could affect the potency of the drug.

A different route: US study

Dr Patricia A. Darrah from the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), US, along with several other scientists conducted a study on non-human primates (Macaca mulatta, commonly known as rhesus monkeys) to find out if changing the route of delivery could improve the effectiveness of the BGC vaccine. The scientists administered BCG vaccine to the rhesus monkeys by three different routes: aerosol, intradermally (through the skin) and intravenously (through the veins). After 24 weeks of BCG vaccination, the scientists collected blood samples and bronchoalveolar lavage (fluid samples from the small airways of the lungs using a machine called a bronchoscope). Next, they analysed these samples to see the immune response of the body to the vaccination. Shortly after this, the rhesus monkeys were exposed to a low dose of TB bacteria, M. tuberculosis.

The improved path

On exposure to M. tuberculosis, the monkeys who were given the medication intravenously showed better immune responses in the body when compared with monkeys who got the vaccine through the skin or through aerosols The intravenous immunization showed increased CD4 and CD8 T cell (fighter cells of the body) responses in the blood, spleen, bronchoalveolar lavage and lung lymph nodes. Intravenous immunization further induced an enormous amount of antigen-responsive T cells across the alveoli, alveolar ducts and respiratory bronchioles (in the lungs), which develop to become immunized cells in the body.

The conclusion

Even after six months, nine out of ten rhesus monkeys who received intravenous BCG vaccination were highly protected from the TB bacteria. After conducting various tests (like PET-CT scan, mycobacterial growth, pathology and granuloma formation), the results showed that six out of the ten monkeys had no detectable levels of infection in them. The scientists thus concluded that intravenous BCG immunization, in contrast to aerosol or intradermal delivery, results in significant and sustained immune responses in the airways, which can fight with TB much more effectively. To be sure, scientists have suggested changing the mechanism of vaccine delivery to IV before, but this is the first time researchers have been able to do this successfully in monkeys. If it works in humans, a simple switch to IV BCG might help India achieve “TB mukt” status in five years, as promised by the campaign. For more on this topic, please read our article on Tuberculosis Prevention. Health articles in Firstpost are written by myUpchar.com, India’s first and biggest resource for verified medical information. At myUpchar, researchers and journalists work with doctors to bring you information on all things health.