Journal
VACCINE
Volume 32, Issue 17, Pages 1921-1931Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2014.01.093
Keywords
Rotavirus; Virus-like particles; Double-layered particle; Post purification assembly; Maternal antibody; Diarrhea score
Categories
Funding
- National High-technology 863 project [2014 AA021302]
- Institute Reconstruction Fund [2011FU125Z04]
- Xiamen City Municipal platform fund on viral biotherapeutics [3502Z20131001]
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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 rotavinis 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 (d12/6VLPs) through a post-purification assembly process. The d12/6-VLP5 were observed to have better thermal stability and antigenicity. Although the immunogenicity of VP6 trimers, VP6-VLPs and d12/6-VLPs was comparable, the efficacy of the d12/6-VLP5 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 d12/6-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. (C) 2014 Elsevier Ltd. All rights reserved.
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