A plant-based multicomponent vaccine protects mice from enteric diseases.
Cholera toxin (CT) B and A2 subunit complementary DNAs (cDNAs) were fused to a rotavirus enterotoxin and enterotoxigenic Escherichia coli fimbrial antigen genes and transferred into potato. Immunoblot and enzyme-linked immunosorbent assay (ELISA) results indicated that the fusion antigens were synthesized in transformed tuber tissues and assembled into cholera holotoxin-like structures that retained enterocyte-binding affinity. Orally immunized mice generated detectable levels of serum and intestinal antibodies against the pathogen antigens. Elevated levels of interleukin 2 (IL2) and interferon gamma (INFgamma) detected in immunogen-challenged spleen cells from the immunized mice indicated the presence of a strong Th1 immune response to the three plant-synthesized antigens. This result was supported by flow cytometry analysis of immunized mouse spleen cells that showed a significant increase in CD4+ lymphocyte numbers. Diarrhea symptoms were reduced in severity and duration in passively immunized mouse neonates following rotavirus challenge. The results suggest that food plants can function as vaccines for simultaneous protection against infectious virus and bacterial diseases.
Yu
J
J
Department of Biochemistry and Center for Molecular Biology and Gene Therapy, Loma Linda University, Loma Linda, CA 92350, USA.
Langridge
W H
WH
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology; D002772:Cholera Toxin / Q000096:biosynthesis / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases; D003967:Diarrhea / Q000517:prevention & control; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D036781:Fimbriae Proteins; D010861:Fimbriae, Bacterial / Q000276:immunology; D005434:Flow Cytometry; D017343:Genes, Plant; D005822:Genetic Vectors; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008957:Models, Genetic; D030821:Plants, Genetically Modified; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012401:Rotavirus / Q000235:genetics; D011198:Solanum tuberosum / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013272:Stomach Diseases / Q000517:prevention & control*; D018417:Th1 Cells / Q000378:metabolism; D013997:Time Factors; D014612:Vaccines / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000276:immunology
D000941:Antigens; D001426:Bacterial Proteins; D018076:DNA, Complementary; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D017361:Viral Nonstructural Proteins; C022924:colonization factor antigens; D036781:Fimbriae Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D002772:Cholera Toxin; D012321:DNA-Directed RNA Polymerases