After the setbacks, is there some hope? Dengue fever affected at least five million people and caused 5,000 deaths in 2023 according to the World Health Organization. However, progress in vaccine development is promising for a substantial improvement in preventing this disease transmitted by a mosquito-borne arbovirus that can cause high fever, headaches, nausea and vomiting.

Until recently, the short history of dengue vaccination was mostly marked by the setbacks of Dengvaxia, the three-dose injectable vaccine launched by Sanofi in late 2015. Two years later, the French laboratory acknowledged that severe forms of dengue could occur after administration of its product.

The antibody-dependent enhancement mechanism is the main suspect in this harmful effect. To understand it, we need to know that four serotypes of the dengue virus can infect a human organism. A first infection with one of these serotypes triggers the production of antibodies that protect against that particular serotype but not against the others. If reinfection occurs with another serotype, the antibodies already in the system may be inadequately matched or insufficient in quantity to effectively inhibit the new invader, potentially bolstering its infectious capabilities.

If Dengvaxia is injected into a "seronegative" person who has never had dengue fever, it acts as a first infection, paving the way for severe forms of the disease in the event of subsequent infection. However, if given after an initial infection, it proves protective, head of the French National Reference Centre for Arboviruses Xavier de Lamballerie pointed out. "In this case, the vaccine will reawaken the pre-existing immune response."

Consequently, when the European Medicines Agency authorized Dengvaxia in December 2018, it recommended it only for people aged six to 45 with a history of dengue infection. A vaccination campaign based on this recommendation therefore requires extensive prior screening. However, the tests available are not reliable enough, as highlighted by the French National Health Authority (HAS) in September 2023 in a briefing note, adding that they can generate false positives as they are also sensitive to other viruses such as Zika and West Nile virus.

"Dengvaxia deserves credit for paving the way, but it's really difficult to use," said de Lamballerie. This explains why "the vaccine is very little used in practice in France," as observed in an April 2023 statement by the Committee for Monitoring and Anticipating Health Risks (COVARS).

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