Singapore (ISJ) – Scientists of Singapore Immunology Network have developed a cost-effective and safe vaccine to treat dengue. A single dose of the newly designed vaccine is able to cripple the dengue virus as against the current treatment protocol of several booster injections, which does not provide protection against all four serotypes.
Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Rapid urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquitoes? habitats have accelerated the global spread of dengue, resulting in the number of dengue cases increasing tremendously year after year. Despite the spread and the huge strain on healthcare system in endemic countries, no clinically approved vaccine or antiviral treatment is currently available to treat dengue.
Clinical trials by a team of scientists led by Dr. Katja Fink, Roland Zust, Thavamalar Balakrishnan of Singapore Immunology Network have demonstrated that dengue virus mutants lacking 2?-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2?-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1000 plaque forming units was administered. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it.
The research funded by Novartis Institute for Tropical Diseases, Singapore claims promising results, which can rationally be designed into dengue vaccine.
The vaccine developed from mutations in the 2?-O-methyltransferase (MTase), a viral enzyme that methylates viral RNA as a strategy to escape the host immune system. Non-methylated RNA is recognized as ?foreign? and triggers an interferon response in the cell. The MTase mutant virus is immediately recognized by the host?s immune response and hardly has a chance to spread in the organism, while an immune response is effectively triggered by the initially infected cells. Clinical trials on mice and monkeys show that MTase mutant dengue virus cannot infect Aedes mosquitoes. On the whole, the results indicate, 2?-O-MTase mutant dengue virus is safe and highly immunogenic.
?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 it proves to be safe in humans, it can be a major breakthrough for the dengue vaccine field,? said Dr. Katja Fink, the team leader.
