DNA Vaccine Co-Expressing Hemagglutinin and IFN-γ Provides Partial Protection to Ferrets against Lethal Challenge with Canine Distemper Virus
Jianjun Zhao,
Yiyang Sun,
Ping Sui,
Hongjun Pan,
Yijun Shi,
Jie Chen,
Hailing Zhang,
Xiaolong Wang,
Rongshan Tao,
Mengjia Liu,
Dongbo Sun,
Jiasan Zheng
Affiliations
Jianjun Zhao
Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Yiyang Sun
Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Ping Sui
Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Hongjun Pan
Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences (CAAS), Changchun 130112, China
Yijun Shi
Yantai Animal Disease Control Center of Shandong Province, Yantai 264000, China
Jie Chen
Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences (CAAS), Changchun 130112, China
Hailing Zhang
Institute of Special Animal and Plant Sciences, Chinese Academy of Agricultural Sciences (CAAS), Changchun 130112, China
Xiaolong Wang
Agricultural Bureau of Shanyang Country, Shangluo 726400, China
Rongshan Tao
The Key Laboratory of Environmental Pollution Monitoring and Disease Control, School of Public Health, Guizhou Medical University, Guiyang 550025, China
Mengjia Liu
Jinan Customs in Shandong Province of the P.R. of China, Jinan 250000, China
Dongbo Sun
Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Jiasan Zheng
Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China
Canine distemper (CD), caused by canine distemper virus (CDV), is a highly contagious and lethal disease in domestic and wild carnivores. Although CDV live-attenuated vaccines have reduced the incidence of CD worldwide, low levels of protection are achieved in the presence of maternal antibodies in juvenile animals. Moreover, live-attenuated CDV vaccines may retain residual virulence in highly susceptible species and cause disease. Here, we generated several CDV DNA vaccine candidates based on the biscistronic vector (pIRES) co-expressing virus wild-type or codon-optimized hemagglutinin (H) and nucleocapsid (N) or ferret interferon (IFN)-γ, as a molecular adjuvant, respectively. Apparently, ferret (Mustela putorius furo)-specific codon optimization increased the expression of CDV H and N proteins. A ferret model of CDV was used to evaluate the protective immune response of the DNA vaccines. The results of the vaccinated ferrets showed that the DNA vaccine co-expressing the genes of codon-optimized H and ferret IFN-γ (poptiH-IRES-IFN) elicited the highest anti-CDV serum-neutralizing antibodies titer (1:14) and cytokine responses (upregulated TNF-α, IL-4, IL-2, and IFN-γ expression) after the third immunization. Following vaccination, the animals were challenged with a lethal CDV 5804Pe/H strain with a dose of 105.0 TCID50. Protective immune responses induced by the DNA vaccine alleviated clinical symptoms and pathological changes in CDV-infected ferrets. However, it cannot completely prevent virus replication and viremia in vivo as well as virus shedding due to the limited neutralizing antibody level, which eventually contributed to a survival rate of 75% (3/4) against CDV infection. Therefore, the improved strategies for the present DNA vaccines should be taken into consideration to develop more protective immunity, which includes increasing antigen expression or alternative delivery routes, such as gene gun injection.
