New analysis reveal dengue vaccine works differently based on prior infection history
Dengue fever is a mosquito-borne tropical disease caused by the dengue virus. Symptoms typically begin three to fourteen days after infection. This may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin rash. Recovery generally takes two to seven days.
In a small proportion of cases, the disease develops into the life-threatening dengue hemorrhagic fever, resulting in bleeding, low levels of blood platelets and blood plasma leakage, or into dengue shock syndrome, where dangerously low blood pressure occurs.
In a recent report by Sanofi, they provided a comprehensive report showing data on their dengue vaccine that helps to further define the population that would best benefit from its protective value.
At present, the World Health Organisation and the National Regulatory Authorities in the places where the vaccine is allowed to be used are looking into assessing the repercussions for the continued roll-out of the vaccine.
Dengue is a malady that cannot be ignored and is prevalent in countries that are home to more than half of the world’s population. The disease can spread fast in active city centres and can cause serious havoc to lives.
According to World Health Organisation, dengue is seen as “the most important mosquito-borne viral disease in the world”
For WHO, Stopping the spread of dengue is their main concern and their goal is to “reduce mortality and morbidity from dengue by at least 50% and 25%, respectively, by the Year 2020 (using 2010 as the baseline)”.
Scientists have not relented in their efforts over the years to produce a vaccine against dengue. This hasn’t come without its challenges as dengue is a difficult disease. Experts have said that there are four distinct strains of the virus and a person can become infected with each one – a potential of four dengue infections in a lifetime. At the same time, dengue infections behave in an unusual way as well. They further revealed that while the majority of dengue infections pass without noticeable symptoms, some can be debilitating and, in rare cases, deteriorate to become a serious illness.
For the vaccine to be considered efficient, it must address the highly abnormal characteristics of dengue disease.
Because of this complexity, Sanofi says their work to develop a vaccine to reduce the burden of dengue took 20 years of research and scientific evaluation, including a development program with close to 40,000 people from 15 countries over a period of 10 years.
All of these trials were conducted in collaboration with scientific experts and health authorities, and we were transparent with the global health community, including the WHO, each step of the way. Research findings on the vaccine, whether interim or final, were openly shared as soon as they became available.
The procedure for this was very thorough and it followed a long sequence of methodological gatherings at both the country and international levels.
This meeting included the European Medicines Agency, the US Food and Drug Administration and regulators from dengue-endemic countries. During open sessions, these regulators were able to ask Sanofi questions about the clinical data on the vaccine before exchanging technical comments on the vaccine’s file amongst themselves and, finally, concluding that the available data were sufficient to allow countries to move ahead with registrations.
The Strategic Advisory Group of Experts (SAGE) on Immunization, an expert body that advises the WHO, conducted an independent review of the clinical trial data available on the vaccine. Based on the SAGE evaluation, the WHO issued a position on the dengue vaccine in July 2016 to guide countries interested in introducing the vaccine into public vaccination programs to reduce their dengue burden
Today this vaccine, after 20 years of development and testing, has been approved in 19 countries. Two of them – the Philippines and Brazil – have initiated targeted public dengue vaccination programs in areas where the dengue burden is heavy.
Periodic safety reports to regulators, ongoing long-term trial results and experience collected from post-marketing surveillance of the vaccine’s impact continue to be shared regularly. All this knowledge about the vaccine is building an understanding of how best to target dengue for vaccination, both within Sanofi and among other research teams working in this field.
Given the complexity of dengue infection, Sanofi continued to work with the scientific community to assess the long-term effectiveness of the vaccine. One hypothesis to be explored was the possibility of diminishing benefit of the vaccine in people without a prior dengue infection before vaccination. The vaccine trials were run mainly in endemic countries so most of the people had a prior dengue infection. So, in order to look back and examine more closely the vaccine’s performance in people who did not have dengue before being vaccinated, Sanofi had to develop a new test that could distinguish antibodies generated in response to vaccination from those due to natural dengue infection.
Development of the test was a complex process and it took close to a year to validate it, conduct supplementary analyses of the long-term clinical trial data and compile the results. In the interim, results from our long-term follow-up continued to show significantly fewer hospitalizations due to dengue in vaccinated individuals nine years and older compared to those who received placebo.
Kemi Ajumobi with wired reports
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