A potential new dengue vaccine – the first to reach phase 3 clinical testing – has demonstrated that it protects 56% of subjects from the disease, according to research published in The Lancet.

Every year, an estimated 390 million dengue infections occur, with about 96 million people worldwide having clinical symptoms of the disease.

In the past 50 years, the disease burden of dengue fever has increased by 30 times, with 70% of the burden reported as being in the Asia-Pacific region.

Currently, there are no licensed vaccines or specific treatments that prevent dengue infection. The main problem with developing a vaccine capable of preventing dengue is that the disease is caused by four separate dengue viruses, so the vaccine must be able to target all four serotypes.

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Against dengue hemorrhagic fever, the vaccine was reported as having 88.5% efficacy. Against dengue-associated hospitalization, the efficacy was 67%.

The new vaccine, CYD-TDV, had previously been tested in a proof-of-concept efficacy trial, but did not meet its primary outcome – the vaccine was effective in 30.2% of the 4002 Thai children who participated in the trial.

A new phase 3 trial took place across five countries in Asia where dengue is endemic. The study participants were 10,275 healthy children between the ages of 2 and 14. The children were randomized into groups – 6,851 of them received three injections of CYD-TDV, while 3,424 received a placebo. The vaccine and placebo were administered at 0, 6 and 12 months, and the participants were followed for 2 years.

The researchers observed that 117 children in the vaccine group and 133 in the placebo group developed dengue more than 28 days after the final injection. From this, they calculate that the vaccine has an overall protective efficacy of 56.5%.

Against dengue hemorrhagic fever – the most severe version of the disease – the vaccine was reported as having 88.5% efficacy. Against dengue-associated hospitalization, the efficacy was 67%.

The efficacy of the vaccine varies across the four different dengue serotypes. It gives low protection against DENV 2 (35%), for instance, but fares better against DEN V 1 (50%), and gives more than 75% protection against DENV 3 and 4.

Generally, the vaccine was well tolerated, with 647 participants reporting side effects – 402 in the vaccine group and 245 in the placebo group.

“Perhaps the most interesting finding of this trial was that efficacy after at least one dose was almost as high as that after three doses,” writes Prof. Annelies Wilder-Smith from Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, in a linked comment.

“Because three doses 6 months apart is an inconvenient and costly immunization schedule for scale up in national programs,” she elaborates, “the question of whether sufficient efficacy can be achieved with a lower number of doses deserves further assessment.”

Prof. Wilder-Smith emphasizes that reducing half of the annual 96 million clinically apparent dengue infections with a vaccine would have a huge public health benefit. But she warns that, even if CYD-TDV is licensed as a vaccine, much more still needs to be done:

Whether the armamentarium of alternative vaccine candidates presently in the pipeline (including inactivated, live attenuated, chimeric, recombinant, subunit and DNA vaccines) will improve efficacy beyond 56% remains to be established. For the moment, the CYD-TDV vaccine is the best we have; however, with 56% efficacy it will never be a single solution. Continued support for the development of other novel strategies including drugs, improved case management, insecticides, and new approaches to vector control, is needed before effective dengue control becomes a credible prospect.”