Dr. Pundi Narasimhan Rangarajan, associate professor, Department of Biochemistry, Indian Institute of Science (IISc), Bangalore, has won this year's Shanti Swarup Bhatnagar award instituted by the Council of Scientific and Industrial Research. He is one of the five recipients from Bangalore among the eleven scientists.

Dr. Rangarajan, who is a doctorate in molecular biology with a specialisation in gene expression and infectious diseases, has been engaged in the research of DNA vaccine for rabies, hepatitis-B and Japanese Encephalitis. In an interview with Nandita Vijay, Dr. Rangarajan provides an overview of the science research scenario. Excerpts:

What are the factors that led you to bag the Shanti Swarup Bhatnagar award for medical sciences?
The award is an honour to my research efforts in rabies and Japanese Encephalitis. The award gives tremendous confidence to my abilities and it will also throw open potential opportunities for newer research initiatives.

Would you elaborate on the DNA rabies initiative?
Several studies have shown that DNA rabies vaccine (DRV) comprising of plasmid DNA encoding rabies virus surface glycoprotein protects mice and non-human primates against rabies virus infection. However, in our laboratory, intramuscular inoculation of DRV failed to confer cent percent protection against rabies virus challenge on mice despite inducing significant levels of virus neutralising antibodies. This prompted us to develop new strategies for improving the potency of DRV and combination of rabies vaccine (CRV) which contains DNA vaccine and a small quantity of cell culture derived inactivated rabies virus vaccine.

The DNA rabies vaccine was one of the successful R&D projects carried out under a broad bilateral agreement signed between IISc and Indian Immunologicals Limited (IIL), Hyderabad, with an annual funding of around Rs 50 lakh provided by the company. Research on DNA vaccines led to the development of a novel strategy of enhancing the potency of a DNA vaccine by the addition of a small quantity of inactivated virus. Patents for this invention were granted from Europe, China, Canada South Africa and India. A paper was also published in the Human Gene Therapy Journal in 2001. The inventors of the vaccine are PN Rangarajan, VA Srinivasan, GS Reddy and Subhabrata Biswas. The vaccine has worked well in mice and cattle. The preclinical toxicology study took place under a department of biotechnology grant at National Institute of Nutrition, Hyderabad.

What is the status of the rabies DNA vac as well as other DNA vaccines being developed elsewhere in the world?
The industrial partner, IIL has prepared a batch of the combination rabies vaccine which has passed all the mandatory tests and conforms to the standards laid down by the Indian Veterinary Pharmacopoeia. The animal trials have been completed and the data has been submitted to the regulatory authorities. Subsequently the human trials will be undertaken. If approved, IIL, which is a wholly owned subsidiary of the National Dairy Development Board, plans to sell it under the brand name Dinarab.

Globally, only two veterinary DNA vaccines have so far been granted regulatory approvals. The US FDA has granted a licence to Fort Dodge, a subsidiary of Wyeth, to market West Nile Innovator DNA, a vaccine to prevent West Nile virus infection in horses. Also, the Canadian Food Inspection Agency (CFIA) has granted licence to Aqua Health Limited, a subsidiary of Novartis, to market APEX-IHN, a DNA vaccine to protect farm-raised salmon fish against infectious haematopoietic necrosis virus. We hope that Dinarab will soon be granted regulatory approval so that it will be the third DNA vaccine in the world and first from Asia. So far, no DNA vaccine has been licensed for use in humans.

Have you been involved in the development of any other vac?
We transferred the recombinant hepatitis B vaccine technology to two companies in Hyderabad - Biological E Limited and Indian Immunologicals Limited. Both these companies have launched the vaccine in the market. Biological E Limited is marketing the vaccine as Bevac, while Indian Immunologicals Limited is marketing it as Elovac-B.

What are the benefits of DNA vac for veterinary health?
The combination vaccine costs lesser than the existing ones in the market. The presence of DNA increases the stability and shelf life of the vaccine. DNA vaccines can be produced more rapidly than conventional vaccines.

Could you tell us about your other research efforts?
At present, our research is focused on an area called virogenomics, wherein we are trying to understand gene expression changes induced in the brain by neurotropic viruses such as Japanese Encephalitis and rabies viruses.

We have identified 60 different genes which are activated in the brain in response to the virus infection. Efforts are underway to understand their function. For example, one of the virus-inducible genes makes RNA which does not make any protein and hence we named it as virus inducible non coding RNA or VINC. Another virus-inducible gene called GARG39/IFIT2 codes for a protein which accumulates in the microtubules of actively
dividing normal and cancer cells. These research activities are being funded by a five-year research grant of Rs 70 lakh from the Department of Science and Technology under the Swarna Jayanthi Fellowship. We have also initiated a research programme on the study of biology of non-conventional yeasts such as Pichia pastoris and this project is being
funded by the Department of Biotechnology.

Can you describe the scene for vac research in the country?
Vaccine research shows promise once an industry partner is identified. It is a labour intensive research and a risky exercise, where recognition does not come easily. The interest among academic institutions is picking up and there are several government and international funding agencies, including Gates Foundation, who are keen to promote the development of vaccines.

What according to you are the trends in DNA vac development?
The trend is that work is going on aggressively and researchers and companies have not given up their interest for developing DNA vaccines. This is despite the fact that even globally DNA vaccines have not yet been commercialised.

What are the problems in vac development?
Careers in vaccine research are a challenge. However, there is no dearth of talent in research but the scientific community needs to motivate students to take on the experiments which could in turn help the commercialisation of a vaccine.