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Design and immunogenicity analysis of the combined vaccine against zoonotic hepatitis E and foot-and-mouth disease
Affiliation:1. Department of Gastroenterology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, China;2. College of Basic Medicine, Shanghai University of Medicine & Health Sciences, Shanghai, China;1. Department of Epidemiology and Biostatistics, School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, Shaanxi 710061, China;2. Department of Obstetrics, Northwest Women''s and Children''s Hospital, Xi''an, Shaanxi 710061, China;3. Melbourne Sexual Health Centre, Alfred Health, Melbourne, Australia;4. Central Clinical School, Faculty of Medicine, Monash University, Melbourne, Australia;5. School of Public Health and Preventive Medicine, Faculty of Medicine, Monash University, Melbourne, Australia;1. Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu 210014, China;2. National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu 210014, China;3. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China;4. Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base, Ministry of Science and Technology Nanjing, Jiangsu 210014, China;5. Shandong Provincial Center for Animal Disease Control and Prevention, Jinan, Shandong 250022, China;1. The Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China;2. National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China;3. The Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China;4. Jiangsu Provincial Research Center for Bioactive Product Processing Technology, Jiangnan University, Wuxi 214122, China;5. China Agricultural Veterinary Biological Science and Technology Co., Ltd, Lanzhou 730046, China;1. Servicio Nacional de Sanidad y Calidad Agroalimentaria (SENASA), Talcahuano 1660, CP 1640 Martínez, Argentina;2. Centro de Virología Animal, Instituto de Ciencia y Tecnología Dr. César Milstein, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Saladillo 2468, CP 1440 Buenos Aires, Argentina;3. Biogénesis Bagó S.A., Ruta Panamericana Km 38.2, CP 1619 Garín, Argentina
Abstract:AimDesign and immunogenicity assessment of the combined vaccine candidate against zoonotic hepatitis E virus (HEV) and foot-and-mouth disease virus (FMDV).MethodsUsing the molecular cloning technology, we produced and purified 9 HEV ORF2-truncated proteins (HEV genotype 4). Then, we compared their thermal stability, antigenicity, and immunogenicity to select the best HEV immunogen. Next, we used the adjuvant Montanide ISA-206 to prepare different formulations of HEV vaccine alone, FMDV vaccine alone and HEV-FMDV combined vaccine. The formulations were injected into mice and the induced humoral immune responses were monitored up 12 weeks post-immunization.ResultsThe HEV p222 protein could self-assemble into VLPs (∼34 nm) and showed higher stability and better antigenicity/immunogenicity than the other HEV antigens, thus it was selected as the best HEV immunogen. Mice immunization with the FMDV vaccine alone induced high FMDV-specific antibody titers in a dose-dependent manner; the HEV p222 protein also induced high levels of anti-HEV antibodies but in a dose-independent manner. The HEV-FMDV combination induced anti-FMDV antibody titers 7–16-fold higher than the titers induced by the FMDV vaccine alone, and HEV-specific antibody titers 2.4-fold higher than those induced by the HEV p222 antigen alone.ConclusionHerein, we proposed a new approach for the control of zoonotic HEV infection through its control in its main host (pig). We also designed the first HEV-FMDV combined vaccine and the preliminary analyses revealed a synergistic effect on the immunogenicity of both HEV and FMDV antigens.
Keywords:Hepatitis E virus  Foot-and-mouth disease virus  Combined vaccine  Immunogenicity  Zoonosis
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