Antibody-Dependent Enhancement of Viral Infection: Mechanisms, Therapeutic Strategies, and Vaccine Development

• • Subneutralizing antibody concentrations enhance viral infectivity by up to 3.2-fold in Fcγ receptor-expressing cell lines, underscoring the risk of ADE in vaccine-induced immunity. • • Fc mutations engineered to abrogate Fcγ receptor binding reduced viral load by 89% in a murine challenge model, while maintaining neutralizing activity, providing a viable strategy for therapeutic antibody design. • • The study demonstrates that ADE is mediated via Fcγ receptor and complement pathways, with complement activation contributing to enhanced infection in vitro, highlighting the need for comprehensive evaluation of antibody effector functions. • • A novel assay platform was developed to quantify ADE potential, achieving a sensitivity of 95% and specificity of 92%, enabling high-throughput screening of vaccine candidates for ADE risk.