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Dengue vaccine: Global development update.

Eakachai Prompetchara1,2,3, Chutitorn Ketloy3,4, Stephen J Thomas5

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The first dengue vaccine (CYD-TDV) has limitations, including lower efficacy in certain groups and increased severe dengue risk in young children. Research continues for improved dengue vaccines, with several candidates in development.

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Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • The first licensed dengue vaccine, CYD-TDV (Dengvaxia®), faces challenges with variable efficacy and safety concerns in specific populations.
  • Efficacy of CYD-TDV is lower for DENV2 and in dengue-naïve individuals, particularly children under 9 years old.
  • A significant concern is the increased risk of hospitalization and severe dengue observed in the youngest recipients (2-5 years).

Purpose of the Study:

  • To review the limitations of the current dengue vaccine, CYD-TDV.
  • To highlight ongoing research and development of novel dengue vaccine candidates.
  • To discuss the challenges in dengue vaccine development.

Main Methods:

  • Review of existing literature on CYD-TDV efficacy and safety.
  • Overview of ongoing clinical trials for new dengue vaccine candidates (Phase III, Phase I-II).
  • Summary of preclinical studies exploring diverse vaccine platforms and strategies.

Main Results:

  • CYD-TDV demonstrates reduced efficacy against DENV2 and in younger, dengue-naïve populations.
  • CYD-TDV is associated with an increased risk of severe dengue and hospitalization in children aged 2-5 years.
  • Multiple new vaccine candidates utilizing various platforms (live-attenuated, inactivated, DNA, viral vector) are under investigation.

Conclusions:

  • The limitations of CYD-TDV necessitate the development of more effective and safer dengue vaccines.
  • Ongoing research is exploring diverse strategies, including live-attenuated vaccines (DENVax, TV003/TV005) and other platforms.
  • Key challenges in dengue vaccine development include the lack of ideal animal models, variable immune responses, and defining protective immunity thresholds.