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Review
. 2022 May;36(3):325-336.
doi: 10.1007/s40259-022-00531-z. Epub 2022 May 24.

Dengue Vaccines: An Update

Jesús M Torres-Flores  1 , Arturo Reyes-Sandoval  2 , Ma Isabel Salazar  3
Affiliations
Review

Dengue Vaccines: An Update

Jesús M Torres-Flores et al. BioDrugs. 2022 May.

Abstract

Dengue is one of the most prevalent mosquito-borne diseases in the world, affecting an estimated 390 million people each year, according to models. For the last two decades, efforts to develop safe and effective vaccines to prevent dengue virus (DENV) infections have faced several challenges, mostly related to the complexity of conducting long-term studies to evaluate vaccine efficacy and safety to rule out the risk of vaccine-induced DHS/DSS, particularly in children. At least seven DENV vaccines have undergone different phases of clinical trials; however, only three of them (Dengvaxia®, TV003, and TAK-003) have showed promising results, and are addressed in detail in this review in terms of their molecular design, efficacy, and immunogenicity. Safety-related challenges during DENV vaccine development are also discussed.

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Conflict of interest statement

Jesús M. Torres-Flores, Arturo Reyes-Sandoval, and Ma. Isabel Salazar have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Molecular design of the anti-dengue virus (DENV) vaccines in advanced stages of clinical development. A Dengvaxia® is based on a yellow fever backbone in which the pre-membrane (prM) and envelope (E) genes of YFV have been replaced by the homologous genes from each one of the four DENV serotypes [16, 17]. B TV003/TV005 was constructed by a deletion of 30 nucleotides (172–143) in the TL2 stem-loop of the 3′-UTR of DENV-4 and DENV-1 (rDEN4∆30 and rDEN1∆30), DENV-2 and DENV-3 components were constructed from the rDEN4∆30 backbone [21, 22]. C Tak-003/DENVax is based on a live-attenuated DENV-2 strain (PDK-53-V) in which the pre-membrane (prM) and envelope (E) genes of YFV have been replaced by the homologous genes from each one of the four DENV serotypes [27]
Fig. 2
Fig. 2
Overview of the efficacy trials of anti-dengue virus (DENV) vaccines in children in Latin America and Asia. Phase III clinical trials have been conducted for Dengvaxia and DENVax with mixed results. TV003/TV005 is currently undergoing phase III clinical trials. *The seroconversion rates for TV003/TV005 observed in phase II clinical trials are illustrated. **The lower value of the efficacy range depicted corresponds to the efficacy observed during the phase IIb trial conducted in Thailand. ***DENVax was only efficacious against DENV-1 and DENV-2 in seronegative individuals [38, 86]
Fig. 3
Fig. 3
Schematic representation of antibody-dependent enhancement (ADE) in dengue virus (DENV) infection. Low levels of anti-DENV antibodies (< 1:80) against one DENV serotype promote the formation of virus-immune complexes during secondary infections with a heterologous DENV serotype. These virus-immune complexes are internalized into monocytes, macrophages and dendritic cells via the Fcγ receptor, promoting viral release into the cell cytoplasm. Virus-immune complexes modulate innate immune pathways promoting viral replication and release
See this image and copyright information in PMC

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