title: Immunogenicity and protective efficacy of rotavirus VP8* fused to cholera toxin B subunit in a mouse model.
abstract: In attempts to develop recombinant subunit vaccines against rotavirus disease, it was previously shown that the N-terminal truncated VP8* protein, VP8-1 (aa26-231), is a good vaccine candidate when used for immunization in combination with Freund's adjuvant. However, this protein stimulated only weak immune response when aluminum hydroxide was used as an adjuvant. In this study, the nontoxic B subunit of cholera toxin (CTB) was employed as intra-molecular adjuvant to improve the immunogenicity of VP8-1. Both, the N-terminal and C-terminal fusion proteins, were purified to homogeneity, at which stage they formed pentamers, and showed significantly higher immunogenicity and protective efficacy than a VP8-1/aluminum hydroxide mixture in a mouse model. Compared to VP8-1-CTB, CTB-VP8-1 showed higher binding activity to both, GM1 and the conformation sensitive neutralizing monoclonal antibodies specific to VP8. More importantly, CTB-VP8-1 elicited higher titers of neutralizing antibodies and conferred higher protective efficacy than VP8-1-CTB. Therefore, the protein CTB-VP8-1, with enhanced immunogenicity and immunoprotectivity, could be considered as a viable candidate for further development of an alternative, replication-incompetent, parenterally administered vaccine against rotavirus disease.
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Miaoge
authors.initials: M
authors.lastname: Xue
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Linqi
authors.initials: L
authors.lastname: Yu
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Lianzhi
authors.initials: L
authors.lastname: Jia
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Yijian
authors.initials: Y
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Tingdong
authors.initials: T
authors.lastname: Li
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ge
authors.affiliation: a State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics , National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science and School of Public Health, Xiamen University , Xiamen , China.
authors.forename: Ningshao
authors.initials: N
authors.lastname: Xia
mesh_terms: D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002772:Cholera Toxin / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D008807:Mice, Inbred BALB C; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D012400:Rotavirus Infections / Q000517:prevention & control; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D022243:Rotavirus Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; C079234:NS35 protein, rotavirus; D002772:Cholera Toxin
keywords: VP8-1 protein; cholera toxin B subunit; diarrhea; neutralizing antibody; rotavirus vaccine