title: Improved characteristics and protective efficacy in an animal model of E. coli-derived recombinant double-layered rotavirus virus-like particles.
abstract: Live rotavirus vaccines that are effective in middle- and high-income countries have been found to be less immunogenic and effective in infants in resource-limited settings. The virus-like particle (VLP) approach is promising for rotavirus vaccine development, but challenges remain for VLP production at large scale. In this study, rotavirus capsid VP2 and VP6 proteins were expressed in Escherichia coli and were assembled with high efficiency into homogeneous single-layered VP6-VLPs or double-layered VP2/6-VLPs (dl2/6-VLPs) through a post-purification assembly process. The dl2/6-VLPs were observed to have better thermal stability and antigenicity. Although the immunogenicity of VP6 trimers, VP6-VLPs and dl2/6-VLPs was comparable, the efficacy of the dl2/6-VLPs to protect against rotavirus-induced diarrhea in pups was significantly higher than that of the trimeric VP6 or the VP6-VLPs when assessed using a mouse maternal antibody model. Taken together, the recombinant dl2/6-VLP antigen, which is highly analogous to rotavirus virion-derived double-layered particles, is a viable candidate for vaccine development and has the potential to be a parenterally administered safe and efficacious rotavirus vaccine.
authors: 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 361005, Fujian, PR China.
authors: Tingdong
authors: T
authors: Li
authors: 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 361005, Fujian, PR China.
authors: Haijun
authors: H
authors: Lin
authors: 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 361005, Fujian, PR China.
authors: Yue
authors: Y
authors: Zhang
authors: 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 361005, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian, PR China.
authors: Min
authors: M
authors: Li
authors: 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 361005, Fujian, PR China.
authors: Daning
authors: D
authors: Wang
authors: 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 361005, Fujian, PR China.
authors: Yaojian
authors: Y
authors: Che
authors: 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 361005, Fujian, PR China.
authors: Yinbin
authors: Y
authors: Zhu
authors: 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 361005, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian, PR China.
authors: Shaowei
authors: S
authors: Li
authors: 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 361005, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian, PR China.
authors: Jun
authors: J
authors: Zhang
authors: 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 361005, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian, PR China. Electronic address: sxge@xmu.edu.cn.
authors: Shengxiang
authors: S
authors: Ge
authors: 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 361005, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian, PR China. Electronic address: qinjian_zhao@xmu.edu.cn.
authors: Qinjian
authors: Q
authors: Zhao
authors: 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 361005, Fujian, PR China; School of Public Health, Xiamen University, Xiamen 361005, Fujian, PR China.
authors: Ningshao
authors: N
authors: Xia
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D004926:Escherichia coli; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology; D012400:Rotavirus Infections / Q000517:prevention & control*; D022243:Rotavirus Vaccines / Q000276:immunology*; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D011994:Recombinant Proteins; D022243:Rotavirus Vaccines; C442545:VP2 protein, Rotavirus; C061332:VP6 protein, Rotavirus; D058425:Vaccines, Virus-Like Particle
keywords: Diarrhea score; Double-layered particle; Maternal antibody; Post purification assembly; Rotavirus; Virus-like particles