Novel recombinant bovine papular stomatitis virus expressing foot-and-mouth disease virus-like particles elicits neutralizing antibodies in cattle

Foot-and-mouth disease (FMD) remains a major burden in endemic regions, where inactivated vaccines are constrained by cost, short duration of immunity, cold-chain dependence and high-containment manufacturing. Here, we engineered a recombinant bovine papular stomatitis virus (rBPSV) expressing the FMD virus (FMDV) A24 Cruzeiro capsid precursor P1-2A together with an attenuated 3C protease (3C ^proL127P ). Infection of ovine foetal turbinate cells resulted in FMDV capsid protein expression and assembly of 25–30 nm icosahedral virus-like particles (VLPs). Intramuscular immunization of two BPSV-seropositive calves with rBPSV (10 ⁷ TCID ₅₀ on days 0, 21 and 35) induced anti-FMDV humoral responses. By day 28, liquid-phase blocking ELISA titres exceeded laboratory-defined protective threshold (≥1.9 log ₁₀ ), and homologous neutralizing titres against A24 Cruzeiro surpassed the threshold associated with protection (≥1.36 log ₁₀ ). Intra-serotypic cross-neutralization was observed against A/Argentina/2001, whereas no neutralization was detected against heterologous serotype O ₁ Campos. Pre-existing anti-BPSV antibodies did not prevent induction of neutralizing responses. These findings establish the first proof of concept that BPSV can serve as a cattle-adapted vector platform for delivery of FMDV VLPs.