REVIEW article
Front. Cell. Infect. Microbiol.
Sec. Microbial Vaccines
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1614805
This article is part of the Research TopicInnovative Vaccine Strategies for Enhanced Flavivirus ImmunizationView all 4 articles
Overcoming Dengue Vaccine Challenges Through Next-Generation Virus-like Particle Immunization Strategies
Provisionally accepted
Mariana Parra-González1*Lucio Nájera-Maldonado1Esperanza Peralta-Cuevas1Ashley J Gutierrez-Onofre1
Igor Garcia-Atutxa2
Francisca Villanueva-Flores1- 1Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA), Unidad Morelos del Instituto Politécnico Nacional (IPN),, Xochiepec, Mexico
- 2Catholic University San Antonio of Murcia, Guadalupe, Murcia, Spain
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Dengue fever represents an escalating global health threat, as unprecedented outbreaks expose significant limitations of current vaccine strategies. Conventional live-attenuated dengue vaccines, while partially efficacious, face critical hurdles including serotype imbalances and antibody-dependent enhancement (ADE). This review critically assesses virus-like particle (VLP) vaccines as a promising alternative, providing safer, non-replicating platforms that mimic viral structure without risks associated with live replication. Technological advancements in recombinant expression systems have improved VLP yield, stability, and scalability, addressing deployment obstacles. Recent preclinical studies demonstrate that tetravalent dengue VLP vaccines induce balanced neutralizing antibodies across all serotypes, effectively circumventing ADE in animal models. These findings suggest superior safety and robust immune responses, potentially surpassing live-attenuated and mRNA-based vaccines. We emphasize advancements in VLP vaccine technology, including novel tetravalent particle designs engineered to exclude ADE-related immunopathogenic components (prM protein), innovative stability-enhancing formulation techniques, and cost-effective recombinant production platforms (yeast and plant-based systems). Additionally, this review proposes novel deployment strategies, such as regional manufacturing hubs, standardized modular VLP platforms, adaptive clinical trial frameworks leveraging surrogate endpoints, and strengthened international coordination for equitable vaccine distribution. Integrating these scientific innovations and practical strategies positions dengue VLP vaccines as pivotal next-generation solutions for global dengue prevention.
Keywords: Dengue Virus, virus-like particle, Vaccine, Antibody-dependent enhancement (ADE), Immunity
Received: 19 Apr 2025; Accepted: 22 May 2025.
Copyright: © 2025 Parra-González, Nájera-Maldonado, Peralta-Cuevas, Gutierrez-Onofre, Garcia-Atutxa and Villanueva-Flores. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mariana Parra-González, Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA), Unidad Morelos del Instituto Politécnico Nacional (IPN),, Xochiepec, Mexico
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