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

Abstract

ABSTRACT 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. 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.