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.
Keywords: Diarrhea score; Double-layered particle; Maternal antibody; Post purification assembly; Rotavirus; Virus-like particles.
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