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Indian researchers have been able to bring about more than 50-fold improvement in the efficacy of the commonly used TB vaccine — Bacillus Calmette Guerin (BCG) — by giving mice the anti-leprosy drug (clofazimine) for a month along with a dose of the vaccine. The duration of protection lasted till the end of the trial protocol period of 120 days. Results were published on August 29 in The Journal of Infectious Diseases.
“Mice vaccinated with BCG will remain equally protected if just two doses of anti-leprosy drug are given on the day of vaccination and on day seven. This is because the drug has a long half-life of 28 days in mice,” says Prof. Gobardhan Das, the corresponding author of the paper from the Special Centre for Molecular Medicine, Jawaharlal Nehru University, Delhi. To test the efficacy of the novel strategy, the BCG-vaccinated mice that were co-treated with anti-leprosy drugs for a month were exposed to TB bacteria. “At the end of 60 days after infection, the bacterial load was more than 50 times lesser in mice that got the vaccine and the drug compared with mice that got only the vaccine,” says Dhiraj Kumar Singh, a co-author of the paper from JNU.
Long-lasting memory cells
The BCG vaccine efficacy is critically dependent on the generation of long-lasting memory cells called the central memory T (Tcm) cells. The Tcm cells generate effector memory T (Tem) cells that kill the TB bacteria.
Though effective in children, the vaccine’s efficacy diminishes with time, particularly in TB endemic regions. This is because people in TB endemic countries are continuously exposed to TB bacteria. With regular exposure to TB bacteria, Tem cells that fight the bacteria get used up and the pool of Tcm cells that get converted to Tem cells eventually get exhausted, thereby rendering the host vulnerable to TB infection, explains Mr.
If the Tcm cells are much higher in number to start with then they can convert to Tem cells for a longer period and produce a much rapid and stronger response against TB bacteria and protect the individual from TB infection for an extended period. This is precisely what the team led by Prof. Das achieved. The researchers nearly doubled the size of Tcm cell pool by administering anti-leprosy drug (5 mg/kg body weight) to mice already vaccinated with BCG.
“Initially after vaccination both Tcm and Tem cells are produced. Because we don’t want Tem cells, we try to make most of the cells into Tcm cells. This is achieved by administering the anti-leprosy drug on the same day of BCG vaccination. Since the drug blocks the potassium channel of Tem cells, the production of Tem cells is slowed down or inhibited and the cells are pushed to become Tcm cells. This leads to an increase in Tcm pool,” says Prof. Das.