Anti-dengue Vaccines: From Development to Clinical Trials

Pinheiro-Michelsen, Josilene Ramos; Souza, Rayane da Silva Oliveira; Santana, Itana Vivian Rocha; Silva, Patrícia de Souza da; Méndez, Erick Carvalho; Luiz, Wilson Barros; Amorim, Jaime Henrique

doi:10.3389/fimmu.2020.01252

Cited by 38 publications

(43 citation statements)

References 144 publications

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“…Thus, according to the World Health Organization, the development of a safe and effective dengue vaccine is a priority. To date, one anti-dengue virus vaccine has already been licensed in endemic countries (Mexico, Philippines, Brazil, El Salvador, Costa Rica, Paraguay, Guatemala, Peru, Indonesia, Thailand, and Singapore) ( 9 ), while the other six vaccine formulations are under development; two are in phase III of clinical trials and four are in the early stages of clinical testing in different regions worldwide. A recently published review comprehensively explores details regarding development and clinical trials of anti-dengue virus vaccine formulations ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

et al. 2021

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The four serotypes of Dengue virus (DENV1-4) are arboviruses (arthropod-borne viruses) that belong to the Flavivirus genus, Flaviviridae family. They are the causative agents of an infectious disease called dengue, an important global public health problem with significant social-economic impact. Thus, the development of safe and effective dengue vaccines is a priority according to the World Health Organization. Only one anti-dengue vaccine has already been licensed in endemic countries and two formulations are under phase III clinical trials. In this study, we aimed to compare the main anti-dengue virus vaccines, DENGVAXIA®, LAV-TDV, and TAK-003, regarding their antigens and potential to protect. We studied the conservation of both, B and T cell epitopes involved in immunological control of DENV infection along with vaccine viruses and viral isolates. In addition, we assessed the population coverage of epitope sets contained in each vaccine formulation with regard to different human populations. As main results, we found that all three vaccines contain the main B cell epitopes involved in viral neutralization. Similarly, LAV-TDV and TAK-003 contain most of T cell epitopes involved in immunological protection, a finding not observed in DENGVAXIA®, which explains main limitations of the only licensed dengue vaccine. In summary, the levels of presence and absence of epitopes that are target for protective immune response in the three main anti-dengue virus vaccines are shown in this study. Our results suggest that investing in vaccines that contain the majority of epitopes involved in protective immunity (cellular and humoral arms) is an important issue to be considered.

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Section: Introductionmentioning

confidence: 99%

Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

et al. 2021

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“…Although neutralizing E-directed antibodies are assumed to be the main correlate of protection against DENV infection, importance of NS proteins for developing an effective dengue vaccine merits a greater consideration. Indeed, T-cell-based immunity is necessary in controlling DENV infection and most of the key targets of these responses are located in the NS proteins [34,35]. Indeed, non-structural proteins should be part of the vaccine approach, especially sNS1 which exists as a circulating hexameric lipoparticles.…”

Section: The Current Challenges For Dengue Vaccine Developmentmentioning

confidence: 99%

Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

Lebeau¹,

Lagrave²,

Ogire³

et al. 2021

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Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

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“…During the past few years, another six DENV vaccine candidates advanced to clinical studies (reviewed by Pinheiro-Michelsen, et al [ 148 ]). Among them, two are in phase III trials.…”

Section: Dengue Virusmentioning

confidence: 99%

Anti-Flavivirus Vaccines: Review of the Present Situation and Perspectives of Subunit Vaccines Produced in Escherichia coli

et al. 2020

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This article aims to review the present status of anti-flavivirus subunit vaccines, both those at the experimental stage and those already available for clinical use. Aspects regarding development of vaccines to Yellow Fever virus, (YFV), Dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) are highlighted, with particular emphasis on purified recombinant proteins generated in bacterial cells. Currently licensed anti-flavivirus vaccines are based on inactivated, attenuated, or virus-vector vaccines. However, technological advances in the generation of recombinant antigens with preserved structural and immunological determinants reveal new possibilities for the development of recombinant protein-based vaccine formulations for clinical testing. Furthermore, novel proposals for multi-epitope vaccines and the discovery of new adjuvants and delivery systems that enhance and/or modulate immune responses can pave the way for the development of successful subunit vaccines. Nonetheless, advances in this field require high investments that will probably not raise interest from private pharmaceutical companies and, therefore, will require support by international philanthropic organizations and governments of the countries more severely stricken by these viruses.

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Anti-dengue Vaccines: From Development to Clinical Trials

Cited by 38 publications

References 144 publications

Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

Comparison of Neutralizing Dengue Virus B Cell Epitopes and Protective T Cell Epitopes With Those in Three Main Dengue Virus Vaccines

Viral Toxin ns1 as Pivotal Target in Development of Efficient Dengue Vaccine

Anti-Flavivirus Vaccines: Review of the Present Situation and Perspectives of Subunit Vaccines Produced in Escherichia coli

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