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HEALTH: Dengue vaccine - still a long way off
11.09.2012 - IRIN

Dengue fever is classed by the World Health Organization (WHO) as a “major international public health concern”. WHO estimates that it infects 50-100 million people a year; it is a leading cause of death among children in Asia and Latin America, and it is now spreading outside its traditional heartlands to Africa and the Middle East.

But dengue is difficult to deal with. There is no cure, only treatment for the symptoms. And although there are effective vaccines against related viruses, like yellow fever and Japanese encephalitis, no one has yet succeeded in making a safe, effective vaccine against dengue.

Now a team of researchers working with the French drug company Sanofi Pasteur has carried out a randomized trial of a possible vaccine, involving more than 4,000 schoolchildren in northern Thailand, and have produced some interesting results. Their vaccine was only partly effective but the team’s findings - reported in the British medical journal, the Lancet - suggest that the development of a useful vaccine is getting closer.

Derek Wallace of Sanofi-Pasteur, one of the authors of the report, hailed their results as an important step. “Our study constitutes the first ever demonstration that a safe and effective dengue vaccine is possible,” he says. “Further trials [of the vaccine] are currently under way in a number of different countries, and we hope that the positive results of this trial will be confirmed by these larger studies.”

The trial took place in Thailand’s Muang District, based at Ratchaburi Regional Hospital, and involved researchers from Bangkok’s Mahidol University. Children aged 4-11 from 35 local schools were enrolled in the trials. Two-thirds of them were given three doses of the vaccine, known as CYD-TDV (a recombinant, live, attenuated tetravalent vaccine, based on yellow fever 17D vaccine strain, produced in Vero cells). The control group received either rabies vaccine or a placebo.

The children were vaccinated three times, at six-monthly intervals, and the researchers looked at the presence of dengue antibodies in their blood, as well as checking all cases of fever, mild or serious, and recording which were due to dengue.

The results were mixed. While the vaccine appears to be safe and well tolerated, it had only a limited effect. It gave useful protection against three strains of the disease, those known as DENV 1, 3 and 4. But although the vaccinated children produced antibodies to DENV 2, they still caught the disease just as often as the children in the control group. And unfortunately DENV 2 is the most common strain of dengue fever in northern Thailand.

Caveats

Scott Halstead of the International Vaccine Institute in Seoul, points out that even these results were made less useful by the fact that they did not test the vaccine on teenagers, who are more likely to get the severe form of the disease. He said: “Results from this vaccine trial provide hard evidence of protection against DENV 1, 3 and 4 mild disease but insufficient data to calculate vaccine efficacy rates for severe disease. Future dengue vaccine trials should provide robust evidence of efficacy against severe disease by selecting populations weighted to assure inclusion of sufficient numbers of at risk children.”

Bill Messer, clinical assistant professor at the Division of Infectious Diseases in the University of North Carolina School of Medicine, is blunter, pointing out that Sanofi Pasteur has been trying to refine the vaccine for the past decade (it started presenting papers on it in about 2001) but that the vaccine still cannot produce a "robust" response.

“This [study] is an encouraging first step, but far from where we need to be. It did not show the vaccine can prevent severe cases. That is an important endpoint [for a dengue vaccine]. You need to show recipient populations protection against severe dengue in order to encourage [vaccination],” he said.

While most dengue patients do not have symptoms or only mild pain and a rash, up to 10 percent develop a lethal “severe” form of the disease (previously known as dengue haemorrhagic fever). Only five children in the study had severe dengue, too few to analyse, a limitation the authors noted was being corrected in ongoing studies with 30,000 adults and children in dengue-endemic countries.

Messer also said the number of people tested thus far in Thailand is insufficient to prove the vaccine will not cause severe dengue. Health experts have expressed concern that complications from a dengue vaccine may result in infection rather than confer protection.

Despite some positive results from the trials, it seems that a dengue vaccine is still a long way off.