Platform Vaksin Dengue Generasi Baru untuk Memitigasi Antibody-Dependent Enhancement pada Wisatawan Internasional: Tinjauan Naratif mengenai Virus-Like Particles, Modifikasi Epitop, dan Teknologi mRNA

Abstract

Global population mobility presents a major challenge in travel medicine, particularly in managing Emerging Infectious Diseases (EIDs) in tropical and subtropical regions. Dengue Virus (DENV) infection remains the leading cause of febrile illness in international travelers visiting hyperendemic areas such as Bali, Indonesia. The central immunopathological challenge is Antibody-Dependent Enhancement (ADE), wherein sub-neutralizing cross-reactive
antibodies—particularly against the highly conserved fusion loop (FL) epitope of the Envelope (E) protein—facilitate massive viral entry into Fcγ receptor-bearing cells, causing severe dengue. This phenomenon renders current immunoprophylaxis strategies, including the chimeric live-attenuated CYD-TDV and second-generation TAK-003 vaccines, inadequate for immunologically naïve travelers. This narrative review critically evaluates the biomolecular efficacy and safety profiles of three next-generation vaccine platforms—Virus-Like Particles (VLP), epitope modification, and nucleoside-modified mRNA—in mitigating ADE risk in dengue-naïve travelers. A comprehensive
literature search was conducted via PubMed, ScienceDirect, and WILEY using MeSH terms and Boolean operators, restricted to publications from 2021–2026. Evidence demonstrates that tetravalent VLP vaccines induced high-titer, durable neutralizing antibodies against all four DENV serotypes in 100% of non-human primate subjects without detectable in vitro ADE activity. Epitope-modification approaches utilizing computational in silico exclusion of ADE-inducing domains and NS1-targeting ADCC mechanisms offer high safety profiles. Meanwhile, AFL (Anti-Fusion Loop) mRNA-LNP vaccines demonstrated superior ADE reduction alongside potent CD8+ T-cell stimulation. Among these platforms, VLP technology presents the most promising candidate for traveler immunoprophylaxis in Indonesia, given its solid preclinical data, balanced tetravalent efficacy, and absence of ADE activity.