Hope after the setbacks? While in 2023, dengue fever has affected at least 5 million people and caused 5,000 deaths according to the World Health OrganizationAdvances in vaccine development offer hope for significant improvement in the prevention of this disease, which is caused by a mosquito-borne arbovirus and can cause high fever, headache, nausea and vomiting.

Until recently, the short history of anti-dengue vaccination was largely dominated by the setbacks of Dengvaxia, the three-dose injectable vaccine that Sanofi launched in late 2015. Two years later, the French laboratory recognized that severe forms of dengue were emerging may occur after administration of the product.

The mechanism of “enabling antibodies” is the main suspect of this harmful effect. To understand this, we must remember that four serotypes of the dengue virus can infect a human body. An initial 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 a reinfection with a different serotype, it may then happen that the antibodies already present in the body, which are poorly adapted to the newcomer or are present in too few numbers, do not inhibit it and, on the contrary, increase its ability to infect.

If Dengvaxia is injected into a person who has never had dengue fever and is therefore “seronegative”, it would play the role of an initial infection and set the stage for more serious forms in the event of a subsequent infection. But when administered after a first infection, it has a protective effect, emphasizes Xavier de Lamballerie, head of the National Reference Center for Arboviruses: In this case “The vaccine will awaken the immune response that is already there.”

Tests are not reliable enough

Therefore, when the European Medicines Agency approved Dengvaxia in December 2018, it only recommended it for people aged 6 to 45 with a history of dengue infection. A vaccination campaign that takes this indication into account therefore requires comprehensive prior screening. However, the available tests are not reliable enough, the High Authority for Health (HAS) reminded in September 2023 Framework noteand adds that they can generate false positive results because they are also susceptible to other viruses such as Zika or West Nile virus.

“Dengvaxia had the great merit of paving the way, but it is really difficult to use”, remarks Mr. de Lamballerie. That explains why “The vaccine is used very little in practice in France”as already mentioned, in April 2023, an opinion from the Health Risk Monitoring and Anticipation Committee (Covars).

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