Functional Antibody-Dependent Enhancement as an Immune Assessment Platform: Development, Standardization, and Translational Interpretation in Flavivirus Research

Functional antibody-dependent enhancement (ADE) represents a fundamental and con-text-dependent characteristic of antiviral antibody responses, reflecting the dual capacity of antibodies to mediate both neutralization and Fc receptor–dependent enhancement of infection. In flavivirus research, this duality complicates interpretation of conventional serological metrics and limits the reliability of single-parameter correlates of immunity. Over the past decade, functional ADE assays have evolved from specialized mechanistic tools into integrated assessment platforms supporting translational immunology, vaccine evaluation, and immune landscape analysis. These platforms combine Fcγ receptor–relevant target-cell systems, standardized viral inputs, dilution-series–based profiling, quantitative enhancement metrics, and quality-control frameworks to enable reproducible and interpretable functional measurements across cohorts and laboratories. This review synthesizes the development, standardization, and global dissemination of functional ADE platforms and emphasizes their role as immune assessment infrastructures rather than isolated experimental assays. Key design principles governing biological relevance, analytical robustness, and inter-site transferability are discussed, together with their im-plications for contextual interpretation of antibody function in populations with diverse exposure and vaccination histories. Emerging directions integrating functional ADE pro-filing with systems immunology, immunogenomics, and computational modeling are highlighted as pathways toward translational interpretation and preparedness-oriented decision-making. By positioning ADE platforms within broader immune assessment frameworks, this review underscores their value for mechanistic inquiry, vaccine evalua-tion, and population-level surveillance in the absence of definitive correlates of protection.