Streptococcus equi subsp.zooepidemicus (SEZ) causes acute death in pigs and severely impacts the pig industry
however, comprehensive records of the clinical signs of SEZ from a bacteriological perspective are lacking. In this study, we found that piglets developed fever and a reduced appetite within 24 hours-post-infection (hpi) with SEZ and that sudden death usually started at 36 hpi. The mortality rate reached 100 % within 48 hpi. The moribund piglets presented prominent gross lesions, including swollen lungs with peripheral consolidation, enlarged and congested spleens, turbid cerebrospinal fluid (CSF), and hemorrhagic lymph nodes. Histopathologic analysis revealed widespread septicemia. The liver and spleen harbored the highest CFU burden in moribund piglets, and more SEZ proliferated in the CSF than in the brain parenchyma, suggesting an adaptation of SEZ in the CSF. By using genetically engineered chimeric McAbs with a porcine Fc region that targets the variant region of SzM (vSzM), we efficiently eliminated the SEZ burden and protected organs from gross pathological lesions in piglets. Collectively, these data provide more details concerning the systemic infection of SEZ and the potential preventive and therapeutic effects of McAbs against SEZ infection.