The mRNA shield against dengue

Researchers in Bengaluru say more than 1,00,000 cases of dengue are diagnosed in India each year. The infected show no symptoms but some end up with high fever, body aches, headache, nausea and rashes. They get better in a week or two while some get severe symptoms and may need hospital care. Some dengue cases can be fatal.

The dengue virus has four distinct serotypes or strains DENV-1, DENV-2, DENV-3, and DENV-4 each of which have different reactions with our antibodies. While the first infection with any of the four dengue serotypes can prevent reinfection by the same serotype for a long period, the second infection by a different serotype can cause severe disease. This is because the cross-protection offered by the first infection acts as a shield against other serotypes only for two to three years and then begins to drop, says Dr Rahul Roy from the Indian Institute of Science and others who conducted a recent study on the evolution of dengue virus serotypes.

Traditional vaccines are made with live attenuated viruses where a virus rendered non-infectious is injected. The downsides are virus variants and people cannot be indefinitely vaccinated. “The process is risky because, over many immunisations, some viruses can actually go back to being infectious,” said Arati Ramesh from the Tata Institute of Genetics and Society (TIGS), Bengaluru.

“The 2023 Nobel Prize in Physiology to Katalin Karikó and Drew Weissman was for modification of Ribonucleic Acid (RNA) that helped Messenger RNA (mRNA) vaccines work better and become stable in the body. The finding will help mRNA vaccines to work better,” said Rajesh Iyer of TIGS. So, are nucleic acid vaccines with DNA or mRNA better than traditional ones? DNA or mRNA can be encapsulated into a fat molecule and delivered to the nucleus where it can make the protein required for an immune response.

Swetha Raghavan from the Dengue Vaccine Programme at the National Centre for Biological Sciences (NCBS), said: “Our attempt is a first mRNA dengue vaccine for India as an alternative to traditional approaches. One can choose specific antigenic regions to overcome the challenges of Antibody-Dependent Enhancement, confer protection across multiple serotypes, incorporate multiple strain information in the vaccine design, and do away with using whole viruses.” She adds, “so far there are three vaccine candidates, Dengvaxia from Sanofi (not approved in India), QDENGA (Tak 003) from Takeda for use in the European Union and one taken up by ILL, Panacea and Serum Institute and all are live attenuated vaccines.” The National Institute of Virology in Pune and IISc in Bengaluru have been approached for trials on monkeys as trials outside India would be expensive. They want the vaccine to be an Indian vaccine with studies in India and industrial support. Swetha says: “We have tried it on mice and it's working well. Monkey trials will be followed by Phase I human trials.”

mRNA vaccines have manufacturing challenges as these vaccines are not stable for a long time. Arati suggests a way out, “We have self-amplifying vaccines that can amp up the volume of the mRNA in the body.” The upside of these vaccines is that mRNA cannot integrate into the genome because of its transient nature. L S Shashidhara, Director of NCBS said: “Our immediate priority is to complete evaluation of safety and immunogenicity of the vaccine candidates and transition into large-scale manufacturing and clinical trials in partnership with industry.”