A new strategy decreases the ability of dengue virus to escape the host immune system has been discovered by A*STAR’s Singapore Immunology Network (SIgN). This strategy opens a door to the world’s first universal dengue vaccine candidate that can give full protection from all four serotypes of the dreadful virus.

The research done in collaboration with Singapore’s Novartis Institute of Tropical Diseases (NITD) and Beijing Institute of Microbiology and Epidemiology and supported by Singapore STOP Dengue Translational and Clinical Research (TCR) Program grant.

Early studies have shown that a weakened virus generate protective immune response offers the best hope for an effective vaccine. However, over the years of vaccine development, scientists have learnt that the path to finding a virus of appropriate strength is fraught with challenges.

Even though there are only four different serotypes, the fairly high rates of mutation means the virus evolve constantly, and this contributes to the great diversity of the dengue viruses circulating globally.

In some cases, the immune response developed following infection by one of the four dengue viruses appears to increase the risk of severe dengue when the same individual is infected with any of the remaining three viruses.

With nearly half the world’s population at risk of dengue infection and an estimated 400 million people getting infected each year, the need for a safe and long-lasting vaccine has never been greater.

The new strategy overcomes the prevailing challenges of vaccine development by tackling the virus’ ability to ‘hide’ from the host immune system.

Dengue virus requires the enzyme called MTase (also known as 2’-O-methyltransferase) to chemically modify its genetic material to escape detection.

In this study, the researchers discovered that by introducing a genetic mutation to deactivate the MTase enzyme of the virus, initial cells infected by the weakened MTase mutant virus is immediately recognized as foreign. As a result, the desired outcome of a strong protective immune response is triggered yet at the same time the mutant virus hardly has a chance to spread in the host.

The researchers went on to demonstrate that the MTase mutant dengue virus cannot infect Aedes mosquitoes. This means that the mutated virus is unable to replicate in the mosquito, and will not be able to spread through mosquitoes into our natural environment.

The results confirmed that MTase mutant dengue virus is potentially a safe vaccine approach for developing a universal dengue vaccine that protects from all four serotypes.

Katja Fink from SIgN said, “There is still no clinically approved vaccine or specific treatment available for dengue, so we are very encouraged by the positive results with this novel vaccine strategy.”

“Our next step will be to work on a vaccine formulation that will confer full protection from all four serotypes with a single injection. If this proves to be safe in humans, it can be a major breakthrough for the dengue vaccine field,” Fink added.