New Anti-Dengue Strategy Raises Hopes For Universal Vaccine

Scientists have come up with a new strategy that cripples the ability of the dengue virus to escape the host immune system.

Asian Scientist (Aug. 26, 2013) – Scientists have come up with a new strategy that cripples the ability of the dengue virus to escape the host immune system. The breakthrough, published in PLOS Pathogens, opens a door of hope to what may become the world’s first universal dengue vaccine that can offer full protection from all four types of the dreadful virus.

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

This hurdle is compounded by the complexity of the dengue virus. Even though there are only four different types, the fairly high rates of mutation means the virus evolve constantly, and this contributes to the great diversity of the dengue viruses circulating globally.

The new strategy uncovered in this study overcomes these prevailing challenges by tackling the virus’ ability to ‘hide’ from the host immune system.

This ability is dependent on an enzyme called MTase that enables the dengue virus to escape immune system detection by chemically modifying its genetic material.

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. At the same time, the mutant virus cannot harm the body as it hardly has a chance to spread in the host.

The researchers showed that animals immunized with the weakened MTase mutant virus were fully protected from a challenge with the normal dengue virus. They also demonstrate that the MTase mutant dengue virus cannot infect Aedes mosquitoes.

These results confirmed that MTase mutant dengue virus is a safe vaccine approach for developing a universal dengue vaccine.

“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,” said Dr Katja Fink, senior author of the study.

“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.”

The article can be found at: Züst et al. (2013) Rational Design Of A Live Attenuated Dengue Vaccine: 2′-O-Methyltransferase Mutants Are Highly Attenuated And Immunogenic In Mice And Macaques.

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Source: A*STAR; Photo: javierdevilman/Flickr/CC.
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