title: Characterization and protective efficacy in an animal model of a novel truncated rotavirus VP8 subunit parenteral vaccine candidate.
abstract: The cell-attachment protein VP8* of rotavirus is a potential candidate parenteral vaccine. However, the yield of full-length VP8 protein (VP8*, residues 1-231) expressed in Escherichia coli was low, and a truncated VP8 protein (ΔVP8*, residues 65-231) cannot elicit efficient protective immunity in a mouse model. In this study, tow novel truncated VP8 proteins, VP8-1 (residues 26-231) and VP8-2 (residues 51-231), were expressed in E. coli and evaluated for immunogenicity and protective efficacy, compared with VP8* and ΔVP8*. As well as ΔVP8*, the protein VP8-1 and VP8-2 were successfully expressed in high yield and purified in homogeneous dimeric forms, while the protein VP8* was expressed with lower yield and prone to aggregation and degradation in solution. Although the immunogenicity of the protein VP8*, VP8-1, VP8-2 and ΔVP8* was comparable, immunization of VP8* and VP8-1 elicited significantly higher neutralizing antibody titers than that of VP8-2 and ΔVP8* in mice. Furthermore, when assessed using a mouse maternal antibody model, the efficacy of VP8-1 to protect against rotavirus-induced diarrhea in pups was comparable to that of VP8*, both were dramatically higher than that of VP8-2 and ΔVP8*. Taken together, the novel truncated protein VP8-1, with increased yield, improved homogeneity and high protective efficacy, is a viable candidate for further development of a parenterally administrated prophylactic vaccine against rotavirus infection.
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Miaoge
authors.initials: M
authors.lastname: Xue
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Yaojian
authors.initials: Y
authors.lastname: Che
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Mujin
authors.initials: M
authors.lastname: Fang
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361102, Fujian, PR China. Electronic address: litingdong@xmu.edu.cn.
authors.forename: Tingdong
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361102, Fujian, PR China. Electronic address: sxge@xmu.edu.cn.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361102, Fujian, PR China.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003967:Diarrhea / Q000517:prevention & control; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D007112:Immunity, Maternally-Acquired; D007279:Injections, Subcutaneous; D008807:Mice, Inbred BALB C; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016601:RNA-Binding Proteins; D022243:Rotavirus Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus
keywords: Diarrhea score; Maternal antibody; Rotavirus; Subunit vaccine; VP8* protein; Vaccine