Evasion of humoral immune responses by a key mutational region of the S2 subunit in PEDV variants

PEDV variant strains pose a serious threat to piglet health worldwide. Despite the availability of commercial vaccines developed based on classical PEDV strains, they have shown limited efficacy against newly emerging variants. Moreover, variant strains exhibit varying degrees of genomic mutations compared to classical strains, and the regulatory effects of these mutations on viral biology have not been systematically studied. In this study, we identify the 894-993 amino acid (aa) region within the S2 subunit as a key determinant of humoral immune evasion in variants. Mutations in this region were shown to reduce neutralization sensitivity, alter membrane fusion activity, and increase the structural rigidity of the S protein. These findings greatly enhance our understanding of the biological characteristics of PEDV variants and provide a new potential strategy and important theoretical support for viral control and vaccine development.