A vaccine to beat malaria

Achiever

Chetan Chitnis could not respond to most of the calls and text messages he received following the Rs 50-lakh Infosys awards announcement on October 25 as his Blackberry was switched off. He was attending the first board meeting of Malaria Vaccine Development Programme, a new society that aims to take several malaria vaccines from laboratories to the villages of Orissa and Chhattisgarh where malaria kills thousands die every year.

This is ironic in a sense. The bespectacled malaria researcher has a reason to be in active engagement with companies, outfits and voluntary organisations for spreading malaria vaccines to remote hamlets. His Jaivac-1 – first Indian malaria vaccine – has finally entered the human trial phase after an agonising wait and a second vaccine may be coming next year.

After close to 20 years of intense research at the International Centre for Genetic Engineering and Biotechnology in Delhi, Chitnis and his colleague V S Chauhan developed Jaivac-1 against killer Plasmodium falciparum, which was found safe in animal studies carried out by a Pune-based firm.

The phase-I of human clinical trial began in Bangalore in August. Forty five healthy volunteers are being given the shots over the next few months to see if the vaccine – manufactured by Hyderabad-based Bharat Biotechnology – is safe. If the phase-one trial conducted by Lotus Laboratory is successful, the second phase will begin after a year to test the vaccine’s efficacy in children and adults.

The second vaccine against Plasmodium vivax would possibly go into manufacturing in 2011. “We are currently researching on the adjuvant as the vaccine in its current form is not immunogenic enough and common adjuvants do not work that well,” Chitnis told Deccan Herald.

Development of a vaccine against malaria has always been a big challenge for science. Unlike the vaccines against viral or bacterial diseases, complex life cycle of the parasite inside human and mosquito as well as antigenic diversity makes the development of malaria vaccine a complex affair. Add to it the complexities in undertaking a human trial for malaria vaccine and the task becomes more arduous and challenging. “The human malarial parasite P.falciparum, which appears to have an ancient origin and has evolved in parallel with humans is known to possess a complex arsenal of defence against man and therefore the efforts to generate an effective malaria vaccine have been fraught with obstacles,” said Shobhona Sharma and Sulabha Pathak, biologists at Tata Institute of Fundamental Research, Mumbai in a 2008 review article in the Journal of Vector Borne Diseases.

Ideally malaria vaccines should prevent the infection and if that is not possible at least it should decrease the intensity of infection and help contain malaria transmission. Typically recombinant vaccines are designed targeting specific proteins which the parasite needs to survive and multiply inside the host. Since no single antigen can provide cent per cent protection, the researchers felt the answer lies in a mixture of antigens synthetically put together. Other equally important issues are safety, efficacy, storage, adjuvant, frequency of administration, dose and mode of administrations.

For Jaivac-1, two proteins were combined so that the vaccine can attack two targets simultaneously. While Chitnis and his team was behind one protein, the second one came from ICGEB director Chauhan’s group. “Traditional way of making vaccines is not possible in malaria. We need to use genetic engineering and molecular biology to identify what protein is required for the parasite to survive and then design subunit vaccine targeting that protein,” he said.

But why is a vaccine necessary to deal with malaria? Aren’t drugs sufficient? “No, the medicines are becoming ineffective due to resistance. Chloroquine is already out and resistance is being developed against the most preferred drug artemisinin, which is currently being given in combination. Its only a matter of time before resistance develops against artemisin,” said Chitnis.

Second vaccine in the pipeline

The second vaccine against less virulent but more common P.vivax is also in the pipeline. It targets a specific protein – duffy binding protein – which the parasite requires to invade the red blood cells. Two years back, he showed the efficacy of this protein as a vaccine target in a field study in Papua New Guinea with colleagues from Case Western Reserve University in Cleveland, Ohio. Chitnis has a long association with duffy recognising protein. After finishing his studies at Rice University and the University of California, Barkley he joined the laboratory of Loius Miller – who discovered this protein – in the National Institutes of Health in 1990. The research he started there continued till date.

Son of a space scientist father and an oncologist mother, Chitnis started his career in physics and engineering and shifted to the biological stream much later. Though funding in malaria research was much less than the magnitude of the problem, he did not have a regret.

“The situation improved in the last 10 years with Gates Foundation, Welcome Trust and NIH pumping in more money,” he said. How would he like to spend the award money of Rs 50 lakh? “I have not yet thought of it,” was the honest answer. But possibly a part of it would be spent on yet another family trip to an exotic location like the China trip he undertook last year with his wife and two daughters.