Expression of VP1 protein in the milk of transgenic mice: a potential oral vaccine protects against enterovirus 71 infection.
Enterovirus 71 (EV71) is the most common etiological agent detected in cases of hand-foot-and-mouth disease (HFMD) resulting in incidences of neurological complications and fatality in recent years. The clinical data have already shown the significant increase in recent EV71 epidemic activity throughout the Asia-Pacific region. Due to the lack of an effective antiviral agent, primary prevention of the disease, including the development of an effective vaccine, has been the top priority in terms of control strategies. In this study, we first generated a transgenic animal system to produce the EV71 VP1 capsid protein under the control of alpha-lactalbumin promoter and alpha-casein leader sequences. A high level of recombinant VP1 protein (2.51 mg/ml) was expressed and secreted into the milk of transgenic mice. Mouse pups that received VP1-transgenic milk orally demonstrated relatively better health conditions after challenge with the respective virus as compared with the non-transgenic milk fed group; moreover, the mice fed with the VP1-milk had body weights similar to those of the PBS placebo control groups. According to the serum-neutralization assay and serum antibody detection, the littermates suckling VP1-milk generated antibodies specific to EV71. Our data suggest that EV71 VP1-containing milk is suitable for development as a potential oral vaccine.
Chen
Hsiao-Ling
HL
Department of Molecular Biotechnology, Da-Yeh University, Changhwa 51501, Taiwan.
Huang
Jiun-Yan
JY
Chu
Te-Wei
TW
Tsai
Tung-Chou
TC
Hung
Che-Ming
CM
Lin
Chih-Cheng
CC
Liu
Fang-Chueh
FC
Wang
Li-Chung
LC
Chen
Yi-Ju
YJ
Lin
Ming-Fong
MF
Chen
Chuan-Mu
CM
D000284:Administration, Oral; D000375:Aging / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002675:Child, Preschool; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D015151:Immunoblotting; D007768:Lactalbumin / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D008892:Milk / Q000737:chemistry*; D009500:Neutralization Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D014760:Viral Fusion Proteins / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*
D000914:Antibodies, Viral; D036022:Capsid Proteins; D018076:DNA, Complementary; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; D007768:Lactalbumin