Distinctive Immunological Signatures Define Foot-and-Mouth Disease Virus Persistence in Vaccinated Cattle

Persistent infection with foot-and-mouth disease virus (FMDV) develops in over 50% of infected ruminants, presenting major obstacles to disease control and eradication. To clarify host immune correlates of FMDV persistence, we characterized systemic T- and B-cell responses, as well as mucosal responses in 15 vaccinated cattle following experimental FMDV challenge. The prevalence of FMDV persistence was 53.3%. While peripheral CD4⁺, CD8⁺, and γδ T-cell populations and their respective naïve/memory/effector subpopulations showed comparable frequencies between carriers and noncarriers, carriers exhibited significantly lower frequencies of IFN-γ-producing CD4⁺ and CD8⁺ T lymphocytes during early infection, indicating compromised cell-mediated immune responses essential for viral clearance. During persistent infection, carriers displayed a distinctive immunological profile characterized by significantly reduced peripheral B-cell frequencies and increased secretory IgA (sIgA) levels in oropharyngeal fluid (OPF), with comparable systemic antigen-specific and neutralizing antibody titers across groups throughout the study period. Notably, the combination of peripheral B cell frequencies with OPF sIgA levels demonstrated superior diagnostic specificity for vaccinated carrier identification compared to either indicator alone. Our findings highlight key immune features of FMDV persistence and propose a dual-biomarker approach for detecting asymptomatic carriers.