Abstract
Hepatitis B virus (HBV) is the cause of a debilitating and potentially fatal disease, and possibly also of primary hepato-cellular carcinoma1. A vaccine against hepatitis B would therefore be of considerable biomedical significance. One such vaccine, produced from the 22-nm particle form of hepatitis B surface antigen (HBsAg), has recently been found effective in clinical tests2, but being derived from the sera of chronic carriers, it is expensive and its supply limited. The application of recombinant DNA methods can, in principle, provide a limitless source of vaccine. HBV DNA has been cloned in bacteria and the genes coding for HBsAg and hepatitis B core antigen (HBcAg) identified3–5. Small amounts of both antigens have been synthesized in Escherichia coli3,6,7 and to enhance this synthesis we have constructed plasmids capable of expressing the genes for the antigens under the control of the efficient tryptophan (trp) operon regulatory region8. We describe here the construction of such recombinant plasmids which direct the synthesis of high levels of HBcAg and a β-lactamase: HBsAg fusion polypeptide.
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References
Zuckerman, A. J. J. Tox. envir. Hlth 5, 275–280 (1979).
Szmuness, W. et al. New Engl. J. Med. 303, 833–841 (1980).
Pasek, M. et al. Nature 282, 575–579 (1979).
Galibert, F. et al. Nature 281, 646–650 (1979).
Valenzuela, P. et al. in Animal Virus Genetics (ed. Fields, B. N., Jaenisch, R. & Fox, C. F.) 57–71 (Academic, New York, 1980).
Burrel, C. J. et al. Nature 279, 43–47 (1979).
Charnay, P. et al. Nature 286, 893–895 (1980).
Hallewell, R. A. & Emtage, S. Gene 9, 27–47 (1980).
Morse, D. E., Mosteller, R. D. & Yanofsky, C. Cold Spring Harb. Symp. quant. Biol. 34, 725–740 (1969).
Lee, F., Bertrand, K., Bennett, G. & Yanofsky, C. J. molec. Biol. 121, 193–227 (1978).
Shine, J. & Dalgarno, L. Nature 254, 34–38 (1975).
Goeddel, D. et al. Nature 281, 544–548 (1979).
Roberts, T. M. et al. Proc. natn. Acad. Sci. U.S.A. 76, 5596–5600 (1979).
Christie, G. & Platt, T. J. molec. Biol. 143, 335–341 (1980).
Miozzari, G. F. & Yanofsky, C. J. Bact. 133, 1457–1466 (1978).
Tacon, W. et al. Molec. gen. Genet. 177, 427–438 (1980).
Martial, J. A., Hallewell, R. A., Baxter, J. D. & Goodman, H. M. Science 205, 602–607 (1979).
Grantham, R., Gautier, C., Gouy, M., Mercier, R. & Pavez, A. Nucleic Acids Res. 8, 49–61 (1980).
Fraser, T. H. & Bruce, B. J. Proc. natn. Acad. Sci. U.S.A. 75, 5936–5940 (1978).
Murakami, K., Voellmy, K. & Goldberg, A. L. J. biol. Chem. 254, 8194–8200 (1979).
Cabral, G. A. et al. J. gen. Virol. 38, 339–350 (1978).
Takahashi, K. et al. J. Immun. 122, 275–279 (1979).
Ohori, H. et al. Intervirology 13, 74–82 (1980).
Bennett, G. N., Schweingruber, M. E., Brown, K. D., Squires, C. & Yanofsky, C. Proc. natn. Acad. Sci. U.S.A. 73, 2351–2355 (1976).
Maniatis, T., Jeffrey, A. & van de Sande, H. Biochemistry 14, 3787–3794 (1975).
Smith, H. O. Meth. Enzym. 65, 371–380 (1980).
Boyer, H. W. & Roulland-Dussoix, D. J. molec. Biol. 41, 459–472 (1969).
Birnboim, H. C. & Doly, J. Nucleic Acids Res. 7, 1513–1523 (1979).
Maxam, A. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Yoo, J. O. & Agarwal, K. L. J. biol. Chem. 255, 6445–6449 (1980).
Ullrich, A. et al. Science 196, 1313–1319 (1977).
Cohen, S. N., Chang, A. C. Y. & Hsu, L. Proc. natn. Acad. Sci. U.S.A. 69, 2110–2114 (1972).
Miller, J. H. in Experiments in Molecular Genetics, Appendix I (Cold Spring Harbor Laboratory, New York, 1972).
Barnes, W. M. Science 195, 393–395 (1977).
Ling, C. M. & Overby, L. R. J. Immun. 109, 834–841 (1972).
Laemmli, U. K. Nature 227, 680–685 (1977).
Roychoudhury, R., Jay, E. & Wu, R. Nucleic Acids Res. 3, 863–877 (1976).
Chang, A. C. Y. et al. Nature 275, 617–624 (1978).
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Edman, J., Hallewell, R., Valenzuela, P. et al. Synthesis of hepatitis B surface and core antigens in E. coli. Nature 291, 503–506 (1981). https://doi.org/10.1038/291503a0
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DOI: https://doi.org/10.1038/291503a0
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