Pharming vaccines for hepatitis and cytomegalovirus: Towards the development of multivalent and subunit vaccines for oral delivery of antigens

被引：7

作者：

Alli Z. ^{[1
]}

Sardana R.K. ^{[1
]}

Pierre B. ^{[1
,5
]}

Andonov A. ^{[3
]}

Robert L.S. ^{[4
]}

Schernthaner J.P. ^{[4
]}

Porter S.L. ^{[5
]}

Dudani A.K. ^{[2
,5
]}

Ganz P.R. ^{[1
,5
]}

Tackaberry E.S. ^{[1
,5
]}

Altosaar I. ^{[1
]}

机构：

[1] Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ont. KlN 6N5

[2] Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ont.

[3] Health Canada, National Microbiology Laboratory, Winnipeg, Man. R3E 3R2

[4] Agriculture and Agri-food Canada, Eastern Cereal Oilseed Research Centre (ECORC), Ottawa

[5] Centre for Biologies Research, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa

来源：

Phytochemistry Reviews | 2002年 / 1卷 / 1期

基金：

加拿大自然科学与工程研究理事会;

关键词：

Double 35S promoter; Glutelin1; promoter; Human cytomegalovirus glycoprotein B; Multivalent vaccines; Oral antigens; Oral immunization; Recombinant protein expression; Subunit vaccines; Transgenic seeds; Truncated hepatitis B core particle;

D O I：

10.1023/A:1015832302721

中图分类号：

学科分类号：

摘要：

A plant based high fidelity vaccine production system is being developed with emphasis on producing antigens capable of being orally delivered in multivalent or subunit plant packets. Plant-based edible vaccines may provide an attractive, safe and inexpensive alternative to conventional vaccine production. Edible plant tissues are not normally antigenic in nature. However, foreign antigens from common infectious organisms like hepatitis-B virus (HBV) can be produced along with naturally occurring storage proteins in DNA-transformed plants. Upon administration via the oral route, these transgenic plant tissues may mobilize the protective humoral and mucosal immune responses to challenge the natural infectious agent. When tobacco, carrot and rice plants were transformed with the truncated version of the HBV nucleocapsid gene expression construct, non-infective hepatitis B viral core particles were observed via electron microscopy. A second plant codon-optimised HBV expression construct was designed that included the extensin signal sequence for augmented HBV particle accumulation. Upon transformation of tobacco plants with the codon-optimised construct, over 4 times more transgenic plants with high levels of expression of the HBV nucleocapsid protein were generated in comparison with a similar vector containing the unmodified wild-type HBV gene codon sequence. Further analysis via Western blotting confirmed the presence of the viral antigen in the total protein extracts from transgenic tobacco leaves and seeds. Electron microscopy showed that the expressed protein self-assembled into viral-like particles of 25-30 nm in diameter. To develop an edible subunit vaccine in plant seeds, a third plant transformation construct was used for the synthesis of the human cytomegalovirus glycoprotein B (HCMV gB) subunit. The gB protein derived from tobacco seeds retained critical structural features including epitopes for neutralizing antibodies and was targeted to the protein storage vesicles of tobacco seed endosperm. Two different strains of mice were orally immunized with tobacco seeds containing low concentrations of HCMV gB, with varying dosages, but without adjuvant. No anti-gB response was detected in intestinal or serum samples. However, a systemic immune response to normal tobacco seed proteins was observed in both strains of mice. While higher expression levels of antigens in seeds must be achieved, seeds may provide an effective and immunostimulatory vehicle for delivering edible vaccines to the intestinal mucosa. One of the outstanding challenges includes defining optimum conditions of antigen presentation, dosage and immunization schedules that will induce strong mucosal and/or systemic immune responses in heterogeneous populations. Here we review the different strategies being employed to produce specific oral antigens in plant tissues. © 2002 Kluwer Academic Publishers.

引用

页码：55 / 66

页数：11

共 58 条

[1]

Adeli K., Altosaar I., Compartmentalization of seed reserve proteins. Proposed discriminatory factors, FEBS Lett., 178, pp. 193-198, (1984)

[2]

Alli Z., Expression of Biologically Active Human Granulocyte Macrophage Colony Stimulating Factor in the Seeds of Transgenic Tobacco, (2001)

[3]

Alli Z., Sardana R.K., Andonov A., Robert L.S., Schemthaner J.P., Altosaar I., Biological assembly of truncated hepatitis core antigen in transgenic plants: Towards oral delivery of lowcost vaccines, Seventh Annual National Conference and Exhibition, (2000)

[4]

Alli Z., Sardana R.K., Dudani A., Tackaberry E., Ganz P.R., Panahi M., Narayanan M., Altosaar I., Harvesting of human serum cytokines from endosperm expression systems: Evaluation of stability of antecedent and E. coli derived cytokines in biological assays, Seventh Annual National Conference and Exhibition, (2000)

[5]

Alli Z., Sardana R.K., Andonov A., Robert L.S., Schernthaner J.P., Altosaar I., Plant codon-optimised hepatitisB core particle gene increases assembly of viral particles in transgenic plants: A technological advancement towards increased antibody titre from oral vaccines, Eighth Annual National Conference and Exhibition, (2001)

[6]

Alli Z., Sardana R.K., Andonov A., Robert L.S., Schernthaner J.P., Altosaar I., B-Glucuronidase protein expressed in three different bioreactor lines of transgenic carrot: Towards augmented, therapeutic peptide yields from edible plant tissues, Eighth Annual National Conference and Exhibition, (2001)

[7]

Arakawa T., Chong D.K., Langridge W.H.R., Efficacy of a food plant-based oral cholera toxin B subunit vaccine, Nature Biotechnol., 16, pp. 292-297, (1998)

[8]

Arakawa T., Yu J., Daniel K.X.C., Hough J., Engen P.C., Langridge W.H.R., A plant-based cholera toxin B subunit-insulin fusion protein protects against the development of autoimmune diabetes, Nature Biotechnol., 16, pp. 934-938, (1998)

[9]

Brennan F.R., Bellaby T., Helliwell S.M., Jones T.D., Kamstrup S., Dalsgaard K., Flock J.I., Hamilton W.D., Chimeric plant virus particles administered nasally or orally induce systemic and mucosal immune responses in mice, J. Virol., 73, pp. 930-938, (1999)

[10]

Chargelegue D., Obregon P., Drake P.M., Transgenic plants for vaccine production: Expectations and limitations, Trends Plant Sci., 6, pp. 495-496, (2001)

← 1 2 3 4 5 6 →