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, researchers said. (Agencies)
The new strategy uncovered in this study by ASTAR's Singapore Immunology Network (SIgN) 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. 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. Animal models immunized with the weakened MTase mutant virus were fully protected from a challenge with the normal dengue virus. 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. "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," team leader, said Dr Katja Fink, who conducted the study in collaboration with Singapore's Novartis Institute of Tropical Diseases (NITD) and Beijing Institute of Microbiology and Epidemiology.
"We are into the seventh decade of dengue vaccine development, this indeed is an exciting breakthrough that brings us a step closer to an effective vaccine," said associate Professor Leo Yee Sin, head of the Singapore STOP Dengue Translational and Clinical Research (TCR) Programme. The study was published in the Plos Pathogens journal.
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, researchers said.