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The design of new vaccines

Published online by Cambridge University Press:  19 September 2011

Sydney Cohen
Affiliation:
Department of Chemical Pathology, United Medical and Dental Schools, Guy's Hospital Medical School, London SE1 9RT, England
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Abstract

The prospects for vaccine development have been transformed by the advent of hybridoma technology for the production of specific monoclonal antibodies and recombinant DNA technology which permits the in vitro expression of genes coding for protective antigens of pathogenic organisms. These techniques are leading to the refinement of existing vaccines and the production of new vaccines against organisms which either cannot be cultured in vitro at all, e.g. hepatitis-B, or can be cultured only on a limited scale, e.g. plasmodial species. The techniques allow for the novel production of both live and dead vaccines. New live vaccines are produced using either site-directed mutagenesis or insertion of genes into hosts such as vaccinia virus, which is a potential carrier of polyvalent vaccines. New subunit vaccines are produced by expression of appropriate genes in E. coli, yeast cells or mammalian cell lines and some, e.g. hepatitis-B surface antigen (HBsAg) are at an advanced stage of development. Recombinant subunit vaccines are also being produced against the sporozoite and blood stages of malaria. Problems, in regard to the development of malaria vaccines, concern the antigenic plasticity of plasmodia and the need to induce both antibody and cell-mediated immunity; nevertheless, the work shows considerable promise of success.

Résumé

Les études pour le développement de vaccins ont été transformées par l'apparition de la technologie des hybridomes pour la production d'anticorps monoclonaux spécifiques et par la technologie de recombinaison de l'ADN qui permet l'expression in vitro des gènes codant pour les antigènes protecteurs des organismes pathogènes. Ces techniques conduisent au raffinement des vaccins existants et à la production de nouveaux vaccins contre des organismes qui soit ne peuvent pas du tout être cultivés in vitro, par exemple l'hépatite B, soit peuvent seulement être cultivés à petite échelle, par exemple les espèces Plasmodium. Ces techniques permettent la production nouvelle à la fois de vaccins vivants et de vaccins morts. De nouveaux vaccins vivants sont produits en utilisant soit la mutagenèse dirigé de sites, soit l'insertion de gènes dans des hôtes tels que le virus de la vaccine qui est un vecteur potentiel pour des vaccins polyvalents. De nouveaux vaccins à partir de sous-unités antigèniques sont produits par expression des gènes appropriés chez E. coli, chez la levure ou chez des lignées cellulaires de mammifères et certains (comme par exemple l'antigène S de l'hépatite B) sont à des stades avancés de développement. Des vaccins à partir de sous-unités recombinées sont également produits contre les stades sporozoite et sanguins du paludisme. Les problèmes liés au développement de vaccins antipaludiques concernent la plasticité antigènique des Plasmodium et le besoin d'induire à la fois l'immunité par anticorps et l'immunité cellulaire; néanmoins, les travaux donnent de considérables promesses de succès.

Type
Research Article
Copyright
Copyright © ICIPE 1986

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References

EFERENCES

Allison, A. C. and Eugui, E. M. (1983) The role of cellmediated immune responses in resistance to malaria, with special reference to oxidant stress. A. Rev. Immun. 1, 361392.CrossRefGoogle ScholarPubMed
Almond, J. W. and Cann, A. J. (1984) Attenuation. In New Trends in Vaccines (Edited by Roitt, I. M.), pp. 1356. Academic Press, London.Google Scholar
Buller, R. M., Smith, G. L., Cremer, K. and Notkins, A. L. (1985) Infectious vaccinia virus TK-recombinants that express foreign genes are less virulent than wild-type virus in mice. Vaccines '85, Cold Harbor Symposium, pp. 163167.Google Scholar
Chen, D. H., Tigelaar, R. E. and Weinbaum, F. I. (1977) Immunity to sporozoite-induced malaria infection in mice I. The effect of immunisation of T and B cell deficient mice. J. Immun. 118, 13221327.CrossRefGoogle ScholarPubMed
Cherry, J. D., Feigen, R. D., Lobes, L. A. and Shakelford, P. G. (1972) Atypical measles in children previously immunised with attenuated measles virus vaccines. Pediatrics 50, 712717.CrossRefGoogle ScholarPubMed
Coppel, R. L., Cowman, A. F., Anders, R. F., Bianco, A. E., Saint, R. B., Lingelbach, K. L., Kemp, D. J. and Brown, G. V. (1984) Immune sera recognise on erythrocytes a Plasmodium fakiparum antigen composed of repeated amino sequences. Nature 310, 789792.CrossRefGoogle ScholarPubMed
Dame, J. B., Williams, J. L., McCutchan, T. F., Weber, J. L., Writz, R. A., Hockmeyer, W. T., Maloy, W. L., Haynes, J. D., Schneider, I., Roberts, D., Sanders, G. S., Reddy, E. P., Diggs, C. L. and Miller, L. H. (1984) Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium fakiparum. Science 225, 593599.CrossRefGoogle Scholar
David, P. H., Hudson, D. E., Hadley, T. J., Klotz, F. W. and Miller, L. H. (1985) Immunisation of monkeys with a 140 kD merozoite surface protein of Plasmodium knowlesi malaria; appearance of alternate forms of this protein. J. Immun. 134, 41464152.CrossRefGoogle Scholar
Deans, J. A. and Cohen, S. (1983) Immunology of malaria. A. Rev. Microbiol. 37, 2549.CrossRefGoogle ScholarPubMed
Godson, G. N., Ellis, J., Lupski, J. R., Ozaki, L. S. and Svec, P. (1984) Structure and organisation of genes for sporozoite surface antigens. Phil. Trans. R. Soc. Lond. B 307, 129139.Google ScholarPubMed
Hall, R., Hyde, J. E., Goman, M., Simmons, D. L., Hope, I. A., Mackay, M., Scaife, J., Merhli, B., Richie, R. and Stocker, J. (1984) Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. Nature 311, 379382.CrossRefGoogle ScholarPubMed
Harris, T. J. R. (1984) Gene cloning in vaccine research. In New Trends in Vaccines (Edited by Roitt, I. M.), pp. 5792. Academic Press, London.Google Scholar
Holder, A. A. and Freeman, R. R. (1984) Protective antigens of rodent and human bloodstage malaria. Phil. Trans. R. Soc. Lond. B 307, 171177.Google ScholarPubMed
Kaper, J. B., Levine, M. M., Lockman, H. A., Baldini, M. M., Black, R. E., Clements, M. L. and Morris, J. G. (1985) Development and testing of a recombinant live oral cholera vaccine. Vaccines '85, Cold Spring Harbor Symposium, pp. 107111.Google Scholar
Nussenzweig, R. S. and Nussenzweig, B. (1984) Development of sporozoite vaccines. Phil. Trans. R. Soc. Lond. B 307, 117128.Google ScholarPubMed
Paoletti, E., Perkus, M. E., Piccini, A., Wos, S. M., Linpinskas, B. R. and Mercer, S. R. (1985) Genetically engineered poxviruses expressing multiple foreign genes. Vaccines '85, Cold Spring Harbor Symposium, pp. 147150.Google Scholar
Patzer, A. D., Hershberg, R. D. and Eichberg, J. W. (1985) Recombinant hepatitis-B surface antigen vaccine from a continuous cell line. Vaccines '85, Cold Spring Harbor Symposium, pp. 261264.Google Scholar
Perlman, H., Berzins, K., Wahldren, M., Carlsson, J., Bjorkman, A., Pattaroyo, M. E. and Perlmann, P. (1984) Antibodies in malaria sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium fakiparum. J. exp. Med. 159, 16861704.CrossRefGoogle Scholar
Valenzuela, P., Coit, D., Medina-Selby, M. A., Kuo, C. H., van Nest, G., Burke, R. L., Urdea, M. S. and Graves, P. V. (1985) Antigen engineering in yeast: synthesis and assembly of hybrid HBsAg-HSV-1 gD partices. Vaccines '85, Cold Spring Harbor Symposium, pp. 285290.Google Scholar