After the setbacks, hope? While dengue fever has affected at least 5 million people and caused 5,000 deaths in 2023 according to the World Health Organizationadvances in vaccine development give hope for substantial improvement in the prevention of this disease caused by an arbovirus transmitted by mosquitoes and which can cause high fever, headaches, nausea and vomiting.
Until recently, the short history of anti-dengue vaccination was mainly marked by the setbacks of Dengvaxia, the three-dose injectable vaccine launched by Sanofi at the end of 2015. Two years later, the French laboratory recognized that severe forms of dengue were likely to occur after administration of its product.
The mechanism of “facilitating antibodies” is the main suspect of this deleterious effect. To understand this, we must remember that four serotypes of the dengue virus can infect a human body. A first infection with one of these serotypes triggers the production of antibodies that protect against that particular serotype, but not against the others. In the event of reinfection with another serotype, it may then happen that the antibodies already present in the body, poorly adjusted to the newcomer or too few in number, fail to inhibit it and on the contrary increase its infectious capacity.
If Dengvaxia is injected into a person who has never had dengue fever, said to be “seronegative”, it would thus play the role of a first infection and prepare the ground for serious forms in the event of a subsequent infection. But, if it is administered after a first infection, it proves protective, underlines Xavier de Lamballerie, head of the National Reference Center for Arboviruses: in this case, “the vaccine will awaken the immune response already there”.
Not reliable enough tests
Therefore, when the European Medicines Agency authorized Dengvaxia in December 2018, it only recommended it for people aged 6 to 45 with a history of dengue infection. A vaccination campaign respecting this indication therefore requires extensive prior screening. However, the available tests are not reliable enough, recalled the High Authority of Health (HAS) in September 2023 in a framework noteadding that they can generate false positives because they are also susceptible to other viruses such as Zika or West Nile virus.
“Dengvaxia had the great merit of opening the way, but it is really difficult to use”, notes Mr. de Lamballerie. This explains why “the vaccine is in practice very little used in France”as noted, in April 2023, an opinion from the Health Risk Monitoring and Anticipation Committee (Covars).
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