Dengue disease burden, the complex four-serotype biology, the development of Dengvaxia (CYD-TDV), the critical issue of pre-existing immunity, and current WHO guidance.
Dengue is a mosquito-borne viral infection caused by the dengue virus (DENV), which has four distinct serotypes (DENV-1, DENV-2, DENV-3, DENV-4). Infection with one serotype provides lifelong immunity to that serotype but only temporary immunity to the others.
The critical challenge with dengue is that subsequent infection with a different serotype increases the risk of severe dengue (dengue hemorrhagic fever/dengue shock syndrome) due to antibody-dependent enhancement (ADE).
Dengvaxia, developed by Sanofi Pasteur, was the first dengue vaccine to receive regulatory approval. However, its rollout revealed critical issues that reshaped dengue vaccine development.
The CYD-TDV trial revealed a critical finding: seronegative individuals (those with no prior dengue infection at vaccination) had a higher risk of severe dengue if they later became infected with dengue. This was due to vaccine-induced antibodies that waned over time, leaving vaccinated seronegative individuals with sub-optimal immunity that could paradoxically enhance disease severity upon natural infection.
The Philippines launched a large-scale school-based vaccination program in 2016, immunizing ~830,000 children. When the safety signal emerged in 2017, the program was suspended. Subsequent investigations and litigation followed, significantly impacting public trust in dengue vaccines.