The results of the first test of the effectiveness of a vaccine against dengue fever, a sometimes fatal disease endemic in most tropical countries, have led both enthusiasm and disappointment. The vaccine has proven safe, and protected against three of the four virus variants of dengue, or serotypes, but surprisingly it did not provide any protection against the fourth. Scientists are puzzled as to why and think about what this means for the global fight against a serious threat to public health.
"For us, it is encouraging. The technology of vaccine clearly has a biological effect preventing dengue," said Derek Wallace, regional director of clinical development Sanofi Pasteur, the French pharmaceutical company developing the vaccine , which reported the results online today in the Lancet .
other scientists are not so good. "It is true that the vaccine shows protection against three strains, but unfortunately, and this is very disappointing, overall it was not effective, showing no protection for the strain of the most common circulating dengue in Thailand, "said Scott O'Neill, an expert in dengue Monash University, Clayton, Australia.
responsible for public health and affected communities are eager to have a vaccine against dengue fever, because there is no treatment and the disease burden is growing. Transmitted by mosquitoes, the four dengue serotypes infect up to 100 million people, mostly children, around the world each year. Exposure to one serotype generally causes minor illness, and the patient is immune from life to a second infection with the same serotype. But for unknown reasons, subsequent exposure to a second dengue serotype increases the risk of disease progression to severe dengue hemorrhagic fever and sometimes deadly. The World Health Organization estimates that each year about half a million cases of severe dengue require hospitalization, and dengue frequently strikes in homes suddenly plaguing hospitals.
The scientists assumed that a vaccine is just as effective against the four serotypes, fearing that the incomplete protection against someone vaccines could put at risk of serious illness. So for decades, research focused on the development of a vaccine for all four serotypes, and then combining them. But in a case of the assembly being less than the sum of its parts, and these formulations were employed as individual vaccines. Putting together the four vaccines in humans "has met with some interference effect that we do not understand," said Scott Halstead, a senior adviser to the Dengue Vaccine Initiative based in Seoul.
This time, Sanofi Pasteur researchers thought they had solved the problem of the combination. early testing indicated that in humans, the vaccine produced a balanced immune response to all four serotypes. in what was the first test of efficacy of the vaccine, more than 4,000 children in Ratchaburi Province of Thailand were divided into vaccination and control groups. the vaccine has proven quite effective in preventing the disease from three serotypes, reduced rates infection of 55.6% for serotype 1, 75.3% for serotype 3, and 100% for serotype 4 after three injections. But it provided close to zero protection against dengue serotype 2, which is the most widespread in the region and is most responsible for serious diseases worldwide.
"Of course, our desire was to have a vaccine that protects against four (serotypes)," Wallace said. But it is encouraging that so far at least, there is no evidence of a post-vaccination infection with dengue serotype 2 infection results in serious illness.
Wallace suggests that there may be a lag between serotype 2 component of the vaccine and the circulating in Thailand. In an accompanying commentary also appears online at The Lancet , Halstead said another possibility is the problem of interference.
Some understanding of why the serotype 2 component proved ineffective could come from ongoing trials involving 31,000 people in 10 countries. Until these results are available in 2014, Wallace said it would be premature to discuss what comes next with the vaccine. Halstead sees several options. The widespread use of a vaccine that protects against three serotypes may cause fewer cases of dengue haemorrhagic fever and to reduce the overall burden of disease; modeling can be used to study this scenario. Or it may be necessary to reformulate the vaccine to make it effective against dengue serotype 2, which would also require to redo clinical trials. Halstead said, it may be time to reconsider the strategy four vaccines in one. "We may have to think of something dramatic," he said.
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