A milk-based self-assemble rotavirus VP6\u2013ferritin nanoparticle vaccine elicited protection against the viral infection

Zhipeng Li,Deshun Shi,Kongwei Huang,Fengchao Wang,Fuhang Liu,Hong Wang,Kuiqing Cui,Qingyou Liu,Zhaojun Duan

doi:10.1186/s12951-019-0446-6

Abstract

BackgroundRotavirus is the leading cause of severe dehydrating diarrhea in young children and the inner capsid protein VP6 is a potential vaccine candidate that can induce cross-protective immune responses against different Rotavirus strains. The use of ferritin nanoparticles as the scaffold of the antigen can improve the immunogenicity of the subunit vaccines and provide broader protection. We here present a non-live and self-assemble recombinant rotavirus VP6–ferritin (rVP6–ferritin) nanoparticle vaccine.ResultsThe rVP6–ferritin nanoparticles were expressed in E. coli and self-assembled to uniform spherical structure which similar to ferritin, and oral administration of them induced efficient humoral and mucosal immunogenicity in mice. The nanoparticles were further transgenically expressed in the milk of mice, and pup mice breastfed by transgenic rVP6–ferritin mothers had strongly induced immunogenicity and—compared to pups breastfed by wild type mothers—the proportion of rotavirus challenged pups with diarrhea symptoms, the duration and intensity of the diarrhea, and the deleterious effects on overall growth resulting from the diarrhea were all significantly reduced.ConclusionsThese results suggest that this recombinant VP6–ferritin nanoparticle vaccine can efficiently prevent the death and malnutrition induced by the rotavirus infection in infants and is a promising candidate vaccine for rotavirus.

Highlights

Rotavirus is the leading cause of severe dehydrating diarrhea in young children and the inner capsid protein VP6 is a potential vaccine candidate that can induce cross-protective immune responses against different Rotavirus strains
Prokaryotic expression, purification and transmission electron microscopy (TEM) analysis The rFerritin, rVP6 and rVP6–ferritin genes were inserted into pET-32a vector between the NcoI and XhoI sites, and the rVP6 was designed to fused on the N-terminus of ferritin (Fig. 1a)
Further analysis showed that the rVP6–ferritin protein self-assembled to spherical particles (~ 20 nm) as visualized by transmission electron microscopy (TEM), which is similar to the ferritin (Fig. 1c)

Summary

Introduction

Rotavirus is the leading cause of severe dehydrating diarrhea in young children and the inner capsid protein VP6 is a potential vaccine candidate that can induce cross-protective immune responses against different Rotavirus strains. It is exciting that the use of nanotechnology made Nano-vaccines to be effective antigen delivery systems [5] and the highly symmetric and self-assembling ferritin nanocage has presented an attractive target for vaccine development. There has been successful application which fused Nanocages formed by the Helicobacter pylori ferritin protein with peptides derived from HIV-1 proteins (the Tat peptide) and influenza virus proteins (haemagglutinin) to develop vaccines that effectively elicit potent humoral responses and induce the production of broadly neutralizing antibodies against these pathogens [16, 17]

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