Plant-derived measles virus hemagglutinin protein induces neutralizing antibodies in mice.
Measles remains a significant problem in both the developed and developing world, and new measles vaccination strategies need to be developed. This paper examines the strategy of utilizing transgenic plants expressing a measles antigen for the development of an oral sub-unit measles vaccine. A 1.8 kb fragment encompassing the coding region of the measles virus hemagglutinin (H) protein was cloned into a plant expression cassette. Three different expression constructs were tested: pBinH (H gene alone), pBinH/KDEL (addition of a C-terminal endoplasmic reticulum-retention sequence SEKDEL) and pBinSP/H/KDEL (further addition of an authentic N-terminal plant signal peptide). The highest levels of recombinant H protein production were observed in plants transformed with pBinH/KDEL. Mice inoculated intraperitoneally with transgenic plant derived recombinant H protein produced serum anti-H protein antibodies that neutralized the measles virus (MV) in vitro. Mice gavaged with transgenic tobacco leaf extracts also developed serum H protein-specific antibodies with neutralizing activity against MV in vitro. These results indicate that the plant-derived measles H protein is immunogenic when administered orally and that, with further development, oral vaccination utilizing transgenic plants may become a viable approach to measles vaccine development.
Infectious Diseases Unit, Alfred Hospital, Monash University, Commercial Road, Vic. 3181, Prahran, Australia
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Huang
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Dry
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Webster
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Strugnell
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Wesselingh
D000284:Administration, Oral; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001483:Base Sequence; D005260:Female; D005822:Genetic Vectors; D006389:Hemagglutinins, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D008458:Measles Vaccine / Q000008:administration & dosage / Q000235:genetics / Q000302:isolation & purification; D008459:Measles virus / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D030821:Plants, Genetically Modified; D010947:Plants, Toxic; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014026:Nicotiana / Q000235:genetics
D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D008458:Measles Vaccine; D011994:Recombinant Proteins