The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response.

Jacky Flipse,Jolanda M Smit,Cameron P Simmons

doi:10.1371/journal.pntd.0003749

Jacky Flipse, Jolanda M Smit + Show 1 more

Open Access

https://doi.org/10.1371/journal.pntd.0003749

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Abstract

Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.

Highlights

The genus Flavivirus of the family Flaviviridae comprises over 50 closely related viruses, including dengue virus (DENV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), tick-borne encephalitis virus (TBEV), and West Nile virus (WNV) (Fig 1)
Flaviviruses are arthropod-borne pathogens, and transmission occurs by ticks (TBEV) or mosquitoes (e.g., JEV and DENV)
Infection with a flavivirus can cause a wide range of clinically overt symptoms [1,2], potentially resulting in death

Summary

Introduction

The genus Flavivirus of the family Flaviviridae comprises over 50 closely related viruses, including dengue virus (DENV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), tick-borne encephalitis virus (TBEV), and West Nile virus (WNV) (Fig 1). The observation that disease can be more severe during secondary infections severely hampered the development of a vaccine, as it implies the need to simultaneously induce immunity to all four existing DENV serotypes over a prolonged period [16,17]. After a primary DENV infection, individuals are protected against disease upon reinfection with the homologous serotype.

Results

Conclusion