BENGALURU : Scientists from the National Centre for Biological Sciences (NCBS)-Tata Institute of Fundamental Research in Bengaluru, in collaboration with several Indian institutes, have developed a dengue DNA vaccine candidate, accomplishing something that had remained a challenge over the years.
The team of scientists achieved the feat by selecting a part of an important viral protein from four different variations of the dengue virus to develop the vaccine candidate as a ‘consensus vaccine’ that could be effective against different dengue viral variants.
The virus that causes dengue has four types with four different viral antigens – essentially proteins causing infection, against which antibodies are created. The researchers selected a part called Envelope protein Domain III from all the four serotypes of the virus. The ED-III is considered as the most important viral protein. In addition, the researchers also selected NS1 protein from the DENV2 viral variation, which is known to cause severe dengue with internal bleeding and drop in blood pressure.
“In the traditional vaccines, the whole envelope protein is used, which can lead to Antibody Dependent Enhancement -- ADE (where the viral antigen binds to less-effective antibodies making the virus more effective),” said Dr Arun Sankaradoss, project lead and scientist at the TIFR-Bengaluru.
Need for collaboration to fight dengue: Experts
“We have used only the domain III of the envelope protein from all four serotypes to avoid ADE. We have added the NS1 protein that is known to generate both T cell and B cell response,” said Dr Arun Sankaradoss. T and B cells are white blood cells that are part of the immune system that can fight the viral antigens.
“We know there are four serotypes of the virus, but what we found was that there were genetic variations within the serotypes. Any sequence with over 6 per cent difference is considered to be a different genotype. The team created a consensus sequence that is the same across genotypes as well,” said Prof Sudhir Krishna, senior author and anchor of the dengue vaccine development programme at NCBS in Bengaluru, and distinguished visiting professor, Indian Institute of Technology, Goa.
Apart from NCBS, the initiative included Indian Institute of Science (IISc), St John’s Medical College in Bengaluru, Kasturba Hospital in Mumbai, All-India Institute of Medical Sciences (AIIMS) Jodhpur, AIIMS Delhi (both worked as clinical and basic science centres), DSGA Delhi, and Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram.
The preprint paper published in MedRxiv titled ‘Immune profile and responses of a novel Dengue DNA vaccine encoding EDIII-NS1 consensus design based on Indo-African sequences’ aims to address key problems existing while developing a vaccine for dengue.
Prof Krishna said this was the team’s third Indo-African manuscript in 2021. The vaccine challenges range all the way from innovation, immunity, clinical trials, safety, and regulation to manufacturing. He said, “There was an urgent need for more collaborations, to bring teams across India to work together, including the Translational Health Science and Technology Institute (THSTI), Rajiv Gandhi Centre for Biotechnology and NIMHANS. This culture is important.” While it is in the public domain with their existing infrastructure built over decades and support systems, the specific project was supported by Narayana Murthy, the co-founder of Infosys.