A live PRV-vectored bivalent vaccine elicits dual protection against pseudorabies virus and swine acute diarrhea syndrome coronavirus

Swine acute diarrhea syndrome coronavirus (SADS-CoV), an emerging bat-derived coronavirus, causes severe diarrhea and mortality in young hosts and exhibits cross-species transmission potential. However, no licensed vaccines are currently available. In this study, we constructed a recombinant pseudorabies virus (PRV) vaccine strain, designated rPRV-SADS-S, which expresses the full-length spike (S) protein of SADS-CoV. This strain was developed based on the PRV Bartha-K61 backbone. In murine models, rPRV-SADS-S induced robust humoral and cellular immune responses against both PRV and SADS-CoV. Immunized mice exhibited complete clinical protection against lethal challenge with PRV. Notably, maternally transferred antibodies provided protection to neonatal mice against lethal SADS-CoV challenge. Moreover, in porcine models, rPRV-SADS-S provided complete clinical protection against lethal PRV challenge in piglets. Immunization of sows with rPRV-SADS-S conferred specific antibodies and neutralizing antibodies against SADS-CoV in newborn piglets and enabled them to resist SADS-CoV challenge. These results demonstrate that rPRV-SADS-S functions as a dual-target vaccine candidate, effectively mitigating the threats posed by both PRV and SADS-CoV. IMPORTANCE: Throughout history, pandemics have vividly demonstrated the reality of animal coronaviruses spilling over into human populations. This situation urgently necessitates the formulation of proactive countermeasures. Although 9 years have passed since SADS-CoV emerged in swine, there are still no licensed vaccines against this bat-derived coronavirus. To address this critical gap, we utilized the PRV Bartha-K61 vector platform to develop a novel bivalent vaccine. This strategic approach not only provides concurrent protection against PRV, a significant porcine pathogen, but also induces protective immunity against SADS-CoV. Our strategy potentially mitigates zoonotic spillover risks to humans, thereby offering a vital tool for One Health preparedness.