Thursday, March 30

Kolkata researchers develop molecule for TB vaccine

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A team of researchers from the city has zeroed in on a protein which could be used as a vaccine against tuberculosis (TB), a deadly disease that takes an estimated two lives every five minutes in India.

The six-member team from the Indian Institute of Chemical Biology (IICB) and the Bose Institute claims to have successfully tweaked the protein to develop a ‘stable and active’ protein-based molecule that will provide immunity against the disease, which can spread through coughing or sneezing.

The research has been published in the American Chemical Society’s ‘Langmuir’ journal.

The breakthrough could prove to be a boon, especially for Kolkata, which has 2% more paediatric TB patients than the national average, while 34% of the children in the state are believed to be susceptible to the disease. A large number of tuberculosis patients get the bacteria through transmission—especially in crowded public places — and not due to malnutrition, which is the principal trigger for TB.

The researchers led by Krishnananda Chattopadhyay, head of IICB’s structural biology and bioinformatics division, started working on the MPT 63 protein—well-known for its anti-TB characteristics —about a year-and-a-half ago. They soon realized that even though it could effectively fight the disease, the protein was unstable and couldn’t be made into a stable formulation in its original form.

To overcome this, they attempted to tag the protein to a nano particle and altered its genetic sequence to give it a structure suitable for a stable vaccine. But it was easier said than done, said Chattopadhyay, who has worked for more than a decade on developing biologics or protein-based drugs.

TB not a slum disease now, it is endemic:

Researcher Krishnananda Chattopadhyay said, “First, we had to ensure that the protein was stabilized so that it would have a shelf-life. Then, we had to ensure it could be targeted. So, we bound the protein with a nanoparticle, which led us into a bigger roadblock.”

“After a series of experiments, we realized that we had to understand what residues were important to keep the protein active,” he explained.

The team — Achinta Sannigrahi, Sayantani Chall, Amrita Kundu and Krishnananda Chattopadhyay from IICB’s structural biology and bioinformatics division and Bose Institute’s Junaid J Jawed and Subrata Majumdar from the department of molecular medicine — genetically changed the sequence to raise the longevity of the protein. It was just the breakthrough that they needed to turn it converted to an active protein, which is still bound to the nanoparticle.

“We had this interesting problem. Binding it with the nanoparticle made it stable, but as a structure it had to be active as well. Genetic engineering provided the solution. This is a cool strategy the drug developers, particularly the formulators could explore in future,” said Chattopadhyay.

It is cavitary pulmonary tuberculosis or TB of the lungs which is most common in Kolkata. But extra-pulmonary TB or TB of the brain, bones, intestine and skin have also been reported in the city. AMRI Hospitals, Salt Lake recently treated a 40-year-old who had TB in his tonsils.

“It’s not just a slum disease any more as it’s now endemic. The bacteria can be easily transmitted through sneeze or coughing, especially in a crowded place. This has been happening very frequently,” said Debashish Saha, consultant at AMRI. But rather than a vaccine, a new TB drug may have been more useful, Saha added.

But protein-based vaccines and drugs would be more effective compared to their small molecule-based counterparts, said Chattopadhyay. “Unfortunately, large pharmaceutical companies-which are typically multinational-are not going to spend their dollars on infectious diseases, including TB. This has to be developed for us and by us, right here in India,” he emphasized.

Source: The Times Of India

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