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Review
. 2015 Jun 11;9(6):e0003749.
doi: 10.1371/journal.pntd.0003749. eCollection 2015.

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

Affiliations
Review

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

Jacky Flipse et al. PLoS Negl Trop Dis. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Close relationship between several flaviviruses (left) and within the species of dengue virus (right).
The phylogenetic tree is based on the amino acid sequence of the envelope glycoproteins. The methodology and National Center for Biotechnology Information (NCBI) IDs of all used genotypes for the flaviviruses and dengue viruses are provided in S1 Dataset. The table denominates the percentage of consensus between the serotypes based on the envelope amino acid sequences. Sequence identities were calculated using the Sequence Identity and Similarity (SIAS) calculator (http://imed.med.ucm.es/Tools/sias.html). Scale bar of 0.1 (flaviviruses) or 10 (dengue virus) denotes 0.1 or 10 (silent) substitutions per amino acid for the flavivirus and dengue sequences, respectively.

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