DNA vaccine targeting betacoronavirus spike protein blocks neuroinvasion and neuroinflammation in swine via dual antiviral-immunomodulatory action
Huabo Yu,
Junchao Shi,
Guoce Fu,
Zezhao Cao,
Ruizhao Qiu,
Tianqi Zhao,
Jing Zhang,
Yungang Lan,
Jiyu Guan,
Kui Zhao,
Feng Gao,
Wenqi He,
Zi Li
Affiliations
Huabo Yu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Junchao Shi
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Guoce Fu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Zezhao Cao
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Ruizhao Qiu
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Tianqi Zhao
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Jing Zhang
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Yungang Lan
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Jiyu Guan
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Kui Zhao
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Feng Gao
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Wenqi He
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Zi Li
State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University
Abstract Porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic betacoronavirus, causes fatal neurological disease in piglets, yet no licensed vaccines exist. Here, we developed a DNA vaccine encoding the receptor-binding domain (RBD) of PHEV spike protein fused to IgG1 Fc, adjuvanted with GEL01 (RBD + GEL01). Immunization in mice and piglets elicited robust neutralizing antibodies (titers up to 1:446 and 1:147, respectively) and Th1-biased cellular immunity. The vaccine restricted viral neuroinvasion, reducing brain viral loads by >90% and confining PHEV to discrete olfactory and cortical regions. Vaccinated animals exhibited preserved motor coordination, cognitive function, and minimal neuropathology. Transcriptomic analysis revealed suppression of proinflammatory mediators (e.g., Cxcl2, Saa3) and enhanced neural repair pathways, highlighting dual virological control and immunomodulatory mechanisms. As the first DNA vaccine against PHEV, the RBD + GEL01 candidate offers scalable protection against neurotropic coronaviruses by dual antiviral-immunomodulatory strategy, underscoring its potential to mitigate economic and zoonotic risks.
