Parra-González Mariana, Nájera-Maldonado Lucio, Peralta-Cuevas Esperanza, Gutierrez-Onofre Ashley J, Garcia-Atutxa Igor, Villanueva-Flores Francisca
Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada (CICATA), Unidad Morelos del Instituto Politécnico Nacional (IPN), Xochitepec, Mexico.
Computer Science Department, Universidad Católica de Murcia (UCAM), Murcia, Spain.
Front Cell Infect Microbiol. 2025 Jun 16;15:1614805. doi: 10.3389/fcimb.2025.1614805. eCollection 2025.
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.
登革热对全球健康构成的威胁日益严重，前所未有的疫情暴露出当前疫苗策略存在重大局限性。传统的减毒活登革疫苗虽然有一定疗效，但面临着关键障碍，包括血清型失衡和抗体依赖性增强（ADE）。本综述批判性地评估了病毒样颗粒（VLP）疫苗作为一种有前景的替代方案，它提供了更安全、非复制性的平台，能模拟病毒结构且无活病毒复制相关风险。重组表达系统的技术进步提高了VLP的产量、稳定性和可扩展性，解决了其应用障碍。最近的临床前研究表明，四价登革VLP疫苗能诱导针对所有血清型的平衡中和抗体，在动物模型中有效规避ADE。这些发现表明其安全性更高且免疫反应强劲，可能超越减毒活疫苗和基于mRNA的疫苗。我们强调VLP疫苗技术的进步，包括设计用于排除与ADE相关免疫致病成分（prM蛋白）的新型四价颗粒设计、创新的稳定性增强配方技术以及具有成本效益的重组生产平台（酵母和植物系统）。此外，本综述还提出了新的应用策略，如区域生产中心、标准化模块化VLP平台、利用替代终点的适应性临床试验框架以及加强国际协调以实现公平的疫苗分配。整合这些科学创新和实际策略，使登革VLP疫苗成为全球登革热预防的关键下一代解决方案。
