A study by immunologists from St John’s Research Institute (SJRI) has found that Bacille Calmette-Guerin (BCG) revaccination in adults enhanced pro-inflammatory markers of trained immunity along with anti-inflammatory pathways. The study was published in iScience, a peer reviewed scientific journal last month.
BCG is a live attenuated vaccine of Mycobacterium bovis that has been used for tuberculosis (TB) control in the young for more than a century. It is part of vaccination programmes in several TB-endemic countries. In India, BCG is routinely administered to newborns and is the first vaccine administered after birth.
The efficacy of BCG in TB control is variable and wanes with age, prompting several studies to explore adult BCG revaccination. The Indian Council of Medical Research (ICMR) is now conducting large-scale clinical trials to explore if BCG revaccination can be used as a strategy in the fight against TB in India, said Annapurna Vyakarnam, whose Human Immunology Laboratory is based at SJRI.
Immune response
Immunologists from her laboratory, with a history of working on BCG, designed studies to better understand BCG-induced trained immune mechanisms. The latest study involved revaccinating young, healthy, health care workers with BCG and then tracking the capacity of host immune cells from these subjects over time to respond in vitro to a variety of pathogen cues, using advanced immunological platforms. Their findings published in iScience confirmed that post BCG revaccination, monocytes responded more efficiently and robustly to bacterial, fungal, and viral challenges compared to cells from the same subjects measured prior to revaccination.
“Importantly, this enhanced immunity was not observed in subjects who did not receive BCG revaccination. Beyond the phenomenon of boosting immunity, our findings showed that BCG revaccination can programme circulating white blood cells such that the induced immune response is more controlled and balanced in terms of expression of immune factors that drive versus counter inflammation,” Professor Vyakarnam, who is heading the study, told The Hindu.
Beyond TB
“Beyond TB, several studies have hinted at an important second and potentially wider benefit of BCG vaccination to health and immunity. Scientists have been working on the theory that BCG rewires/reprogrammes an important immune cell, namely the monocyte, at the epigenetic level. Monocytes are rapidly deployed as part of a host’s first line of defence. Accumulating evidence suggests that once exposed to BCG, these key immune cells remain actively reprogrammed and ready to rapidly respond not just in the fight against Mycobacterium tuberculosis but also to other infectious organisms, leading to a new paradigm termed “trained innate immunity” in immunology,” she explained.
“The scientists driving this programme believe that the ability of BCG to rewire the immune system by promoting a homeostatically controlled immune response is both scientifically interesting and potentially important since balanced and finely tuned immunity is essential to mitigate the long-term consequences of an exaggerated immune response,” she said.
“We are delighted to be the first on the Indian track probing the deep immune waters of BCG revaccination and hope that further funding will help shed light on the wider mechanistic impact of BCG revaccination on infection and immunity in the young, old, and those with chronic ailments,” she said.
The study is a collaborative effort between SJRI, Leiden University Medical Center, Netherlands and Radbound University, Netherlands. At SJRI, all immunological experiments and analysis, led by Project Scientist Asma Ahmed (lead author), were performed at the Human Immunology Laboratory in collaboration with Professors Mary Dias and George D’Souza.
