Neutralizing Antibodies vs. Viruses: Interacting Mechanisms and Escape Tactics
Hao Lu, Yichen Liu, Yue Song, Longxin Chen, Limeng Zhang, Runting Li, Xiaoning Nie, Guoqiang Zhu, Xueyan Ding, Linqing Wang
Abstract
Virus-neutralizing antibodies (VNAs) serve as critical components of host immune defense, countering viral infections by specifically recognizing epitopes on viral surface antigens to block viral entry and replication. This review elucidates the functional mechanisms of VNAs, with a focus on the dynamic interactions between the Fab region and viral epitopes, including steric hindrance and conformational locking, as well as the effector functions mediated by the Fc segment. Furthermore, we dissect diverse viral evasion strategies against neutralization that have emerged in recent studies, encompassing antigenic drift/shift, glycan shielding, epitope occlusion, antibody-dependent enhancement, and mutation accumulation under population immune pressure. Integrating structural biology insights with clinical evidence, we analyze challenges in developing broadly neutralizing antibodies and highlight innovative technological approaches. Our synthesis aims to establish a theoretical framework for the rational design and clinical translation of next-generation VNAs, thereby advancing novel strategies for antiviral therapeutics development.