BENGALURU: NCBS scientists in collaboration with several institutes have developed a Dengue DNA vaccine candidate. 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 some of the key problems existing with developing a vaccine for dengue.
Prof. Sudhir Krishna, the senior author and anchor of the Dengue vaccine development program at National Centre for Biological Sciences in Bengaluru, and Distinguished visiting professor IIT Goa explained to TNIE that this is our third Indo African manuscript in 2021. The vaccine challenges range all the way from innovation, immunity, clinical trials, safety, and regulation to manufacturing. “We hope to engage in serious dialogue and build new partnerships as we chart our course ahead. I guess we see ourselves as an Indo-African pathogen science and vaccine catalyst within a larger ecosystem,” he said.
The researchers point out that the covid vaccine rollout has brought out some major insights. First, the number of first-time use of major new technology approaches adenoviruses, nucleic acid delivery systems for example, explains Prof Sudhir.
“They have been in the pipeline for some time and crisis often drives change. RNA in the nucleic acid delivery systems has been a major player and DNA, while there are several groups, to the best of my knowledge only the Indian Zydus Cadila has been cleared for human use,” he added.
Another lead researcher of the study Arun Sankaradoss at NCBS explained that there are four issues: immunity, delivery, safety, and manufacturing process with the development of dengue vaccine. Dr.Arun Sankaradoss explained that in the study they focused on the Envelope domain III region of the viral proteins as responses to this segment were reported to circumvent antibody-dependent enhancement (ADE) of Dengue, a challenge to develop vaccines to this disease.
In addition, “we have added the Non-structural protein-1 (NS1) to the vaccine as an additional target for cellular immunity to broaden the immune response generated by this vaccine. Following a large Dengue viral sequencing exercise in India, complemented with data from east Africa, our approach was to generate a consensus-based vaccine to explore tackling the issues of viral diversity and vaccine should work across serotypes and genotypes,” Dr Arun explained.
The study found that vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. “Passive transfer of the immune serum protected AG129 mice [deficient in interferon-α/β and γ receptors] challenged with a virulent DENV strain”. These findings collectively suggest an alternative strategy for dengue vaccine design; and offers a novel vaccine candidate with possible broad-spectrum protection and successful clinical translation, the researchers explained.
The vaccine platform which is DNA based could definitely be a real game-changer, very cheap and easily done in India and Africa with no cold chain issues. It should also be versatile in terms of packing multiple proteins, explains Prof Sudhir.
Also, explaining the need for more such collaborations, Prof Sudhir says, there is definitely a need to bring teams from across India to work together, THSTI, IISc, RGCB, NIMHANS, and so on. This culture is important. While it’s 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.