Oral levamisole as a route-decoupled adjunct to intramuscular foot-and-mouth disease vaccination: a two-species evaluation.

Introduction: Foot-and-mouth disease (FMD) control still depends largely on inactivated vaccines; however, improving vaccine efficacy without reformulating existing vaccines remains an important practical challenge. Methods: We assessed oral levamisole as an independently administered adjunct alongside, but separately from, a conventional intramuscular bivalent FMD vaccine in mice and FMD-seronegative swine. Serotype-specific immune responses were assessed using structural protein (SP) ELISA and virus-neutralization (VN) assays. IgA-associated responses were examined in mouse serum and saliva and in swine serum, while cytokine-related gene transcription was profiled in porcine peripheral blood mononuclear cells. Murine post-challenge outcomes and porcine safety were also evaluated. Results: Oral levamisole increased antibody and neutralizing responses against FMD virus (FMDV) serotypes O and A in both species. In mice, adjunct treatment improved post-challenge survival (5/5 [100%] with vaccine + levamisole vs. 2/5 [40%] with vaccine alone; log-rank Discussion: These findings support oral levamisole as a practical route-decoupled adjunct for enhancing FMD vaccine responsiveness without requiring modification of the injectable vaccine formulation.