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Is Dengvaxia a useful vaccine for dengue endemic areas?

BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l5710 (Published 03 October 2019) Cite this as: BMJ 2019;367:l5710
  1. Duane J Gubler, cofounder, Pediatric Dengue Vaccine Initiative; chair, Global Dengue and Aedes-Transmitted Diseases Consortium (GDAC)1,
  2. Scott B Halstead, founder, Pediatric Dengue Vaccine Initiative2
  1. 1Singapore and St George, Utah, USA
  2. 2Bethesda, MD, USA
  1. Correspondence to: D J Gubler duane.gubler{at}duke-nus.edu.sg, S B Halstead halsteads{at}erols.com

An effective dengue vaccine that provides balanced protection is still elusive, and Duane J Gubler argues that some partially effective vaccines offer overall benefit—but Scott B Halstead says that this would need a completely new serotesting regimen to avert serious harm

Yes—Duane J Gubler

The global spread of epidemic dengue over the past 50 years underscores the critical need for a vaccine. The goal has been a vaccine that provides balanced protection against all four dengue virus serotypes to protect against the severe disease facilitated by antibody dependent enhancement (ADE)—where antibodies, instead of inactivating a virus, facilitate viral entry into host cells. Unfortunately, an effective tetravalent vaccine has been an elusive goal.

There are currently three lead candidate dengue vaccines. Dengvaxia, manufactured by Sanofi Pasteur, has been licensed, but it has variable efficacy against the four dengue serotypes and an overall efficacy of only 56%.1 The other two lead candidate vaccines, developed by CDC/Takeda (TAK-003)2 and NIH/Merck (TV003/TV005),3 are still in phase III efficacy trials. At this stage it is uncertain whether either of these vaccines will provide balanced tetravalent protection. The issue is whether we can safely use Dengvaxia or other partially effective vaccines to help control dengue.

Mitigating risk

The answer is yes, but it is complicated and involves the pathogenesis and immunology of dengue infections in humans, neither of which is fully understood. ADE has been considered the principal pathogenetic mechanism of vascular leakage and dengue haemorrhagic fever.4 The main argument against using Dengvaxia is that it increases the risk of severe disease in people who were dengue seronegative at the time of vaccination.5 However, there are good reasons for using Dengvaxia or other …

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