Immunogenicity of adenovirus-derived porcine parvovirus-like particles displaying B and T cell epitopes of foot-and-mouth disease |
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| Affiliation: | 1. Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing 210014, China;2. Zaozhuang Bureau of Animal Husbandry and Veterinary, Zaozhuang 277102, China;1. Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan, ROC;2. Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC;3. Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, ROC;4. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA;5. Department of Biomedical Sciences, School of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC;6. Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC;1. Swiss Tropical and Public Health Institute, P.O. Box, CH-4002 Basel, Switzerland;2. University of Basel, Basel, Switzerland;3. Institut de Recherché en Elevage pour le Developpement, BP: 433, Farcha, N’Djamena, Chad;4. Centre de Support en Santé International, BP: 972, Moursal, N’Djamena, Chad;5. Institut de Géographie et Durabilité, Faculté des Géosciences et de l’Environnement, Université de Lausanne, Switzerland;6. Clinique Vétérinaire Urbain, Farcha, N’Djamena, Chad;1. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China;2. University of Chinese Academy of Sciences, Beijing 100049, PR China;3. China Institute of Veterinary Drug Control, Beijing 100081, PR China;1. Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, 28130 Madrid, Spain;2. Departament de Ciències Experimentals i de la Salut, Universitat Pompeu-Fabra, 08003 Barcelona, Spain;3. Central Veterinary Institute (CVI), Wageningen UR, 8200 AB Lelystad, The Netherlands;4. Centro de Biología Molecular “Severo Ochoa” (CSIC-UAM), 28049 Madrid, Spain |
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| Abstract: | Virus-like particles (VLPs) vaccines combine many of the advantages of whole-virus vaccines and recombinant subunit vaccines, integrating key features that underlay their immunogenicity, safety and protective potential. We have hypothesized here the effective insertion of the VP1 epitopes (three amino acid residues 21–40, 141–160 and 200–213 in VP1, designated VPe) of foot-and-mouth disease (FMDV) within the external loops of PPV VP2 could be carried out without altering assembly based on structural and antigenic data. To investigate the possibility, development of two recombinant adenovirus rAd-PPV:VP2-FMDV:VPe a or rAd-PPV:VP2-FMDV:VPe b were expressed in HEK-293 cells. Out of the two insertion strategies tested, one of them tolerated an insert of 57 amino acids in one of the four external loops without disrupting the VLPs assembly. Mice were inoculated with the two recombinant adenoviruses, and an immunogenicity study showed that the highest levels of FMDV-specific humoral responses and T cell proliferation could be induced by rAd-PPV:VP2-FMDV:VPe b expressing hybrid PPV:VLPs (FMDV) in the absence of an adjuvant. Then, the protective efficacy of inoculating swine with rAd-PPV:VP2-FMDV:VPe b was tested. All pigs inoculated with rAd-PPV:VP2-FMDV:VPe b were protected from viral challenge, meanwhile the neutralizing antibody titers were significantly higher than those in the group inoculated with swine FMD type O synthetic peptide vaccine. Our results clearly demonstrate the potential usefulness of adenovirus-derived PPV VLPs as a vaccine strategy in prevention of FMDV. |
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| Keywords: | Hybrid virus-like particles Porcine parvovirus Foot and mouth disease virus Molecular mimicry |
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