Oral immunization of mice using transgenic tomato fruit expressing VP1 protein from enterovirus 71.
Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease associated with fatal neurological complications in young children, and several major outbreaks have occurred recently. This study developed an effective antiviral agent by transforming the gene for VP1 protein, a previously defined epitope and also a coat protein of EV71, into tomato plant. VP1 protein was first fused with sorting signals to enable it to be retained in the endoplasmic reticulum of tomato plant, and its expression level increased to 27 microg/g of fresh tomato fruit. Transgenic tomato fruit expressing VP1 protein was then used as an oral vaccine, and the development of VP1-specific fecal IgA and serum IgG were observed in BALB/c mice. Additionally, serum from mice fed transgenic tomato could neutralize the infection of EV71 to rhabdomyosarcoma cells, indicating that tomato fruit expressing VP1 was successful in orally immunizing mice. Moreover, the proliferation of spleen cells from orally immunized mice was stimulated by VP1 protein, and provided further evidence of both humoral and cellular immunity. Results of this study not only demonstrate the feasibility of using transgenic tomato as an oral vaccine to generate protective immunity in mice against EV71, but also suggest the probability of enterovirus vaccine development.
Chen
Hsuan-Fu
HF
Institute of Plant Biology and Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC.
Chang
Meng-Huei
MH
Chiang
Bor-Luen
BL
Jeng
Shih-Tong
ST
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004770:Enterovirus / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018551:Solanum lycopersicum / Q000235:genetics*; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D030821:Plants, Genetically Modified; D021382:Protein Sorting Signals / Q000235:genetics; D013154:Spleen / Q000276:immunology; D022462:Vaccines, Edible / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics* / Q000276:immunology
D000914:Antibodies, Viral; D036022:Capsid Proteins; D016207:Cytokines; D021382:Protein Sorting Signals; D022462:Vaccines, Edible; D014614:Vaccines, Synthetic; D014765:Viral Vaccines