Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1984 Jan;81(1):193–197. doi: 10.1073/pnas.81.1.193

Construction of live vaccines using genetically engineered poxviruses: biological activity of vaccinia virus recombinants expressing the hepatitis B virus surface antigen and the herpes simplex virus glycoprotein D.

E Paoletti, B R Lipinskas, C Samsonoff, S Mercer, D Panicali
PMCID: PMC344637  PMID: 6320164

Abstract

Potential live vaccines using recombinant vaccinia viruses have been constructed for both hepatitis B and herpes simplex. These recombinant vaccinia viruses express cloned genes of the hepatitis B virus surface antigen (HBsAg) or the glycoprotein D from herpes simplex virus (HSV-gD). The HBsAg synthesized in vitro under the regulation of vaccinia virus is secreted from infected cells as a particle of approximately equal to 22 nm diameter with a density of 1.2 g/ml as determined on CsCl gradients. Inoculation of rabbits with the recombinant vaccinia virus that expresses the HBsAg elicits the production of high-titered antibodies. Synthesis of the HSV-gD was detected in tissue culture by radioimmunoassay on unfixed cells, suggesting that the HSV-gD synthesized by the recombinant vaccinia virus is membrane associated. Inoculation of rabbits with the recombinant vaccinia virus expressing HSV-gD resulted in the production of antibodies that reacted with authentic HSV-gD as detected by radioimmunoassay. Furthermore, the anti-serum was shown by plaque-reduction assay to neutralize the infectivity of herpes simplex virus. Immunization of mice with the vaccinia recombinant expressing HSV-gD gave complete protection on subsequent challenge with lethal doses of live herpes simplex virus.

Full text

PDF
194

Images in this article

194Image
on p.194
195Image
on p.195

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander J. J., Bey E. M., Geddes E. W., Lecatsas G. Establishment of a continuously growing cell line from primary carcinoma of the liver. S Afr Med J. 1976 Dec 18;50(54):2124–2128. [PubMed] [Google Scholar]
  2. Christman J. K., Gerber M., Price P. M., Flordellis C., Edelman J., Acs G. Amplification of expression of hepatitis B surface antigen in 3T3 cells cotransfected with a dominant-acting gene and cloned viral DNA. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1815–1819. doi: 10.1073/pnas.79.6.1815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Galibert F., Mandart E., Fitoussi F., Tiollais P., Charnay P. Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature. 1979 Oct 25;281(5733):646–650. doi: 10.1038/281646a0. [DOI] [PubMed] [Google Scholar]
  4. Gerin J. L., Holland P. V., Purcell R. H. Australia antigen: large-scale purification from human serum and biochemical studies of its proteins. J Virol. 1971 May;7(5):569–576. doi: 10.1128/jvi.7.5.569-576.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hirschman S. Z., Price P., Garfinkel E., Christman J., Acs G. Expression of cloned hepatitis B virus DNA in human cell cultures. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5507–5511. doi: 10.1073/pnas.77.9.5507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kirschner H., Kochen M., Hirt H. M., Munk K. Immunological studies of hsv-infection of resistant and susceptible inbred strains of mice. Z Immunitatsforsch Immunobiol. 1978 Mar;154(2):147–154. [PubMed] [Google Scholar]
  7. Lee G. T., Para M. F., Spear P. G. Location of the structural genes for glycoproteins gD and gE and for other polypeptides in the S component of herpes simplex virus type 1 DNA. J Virol. 1982 Jul;43(1):41–49. doi: 10.1128/jvi.43.1.41-49.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lopez C. Genetics of natural resistance to herpesvirus infections in mice. Nature. 1975 Nov 13;258(5531):152–153. doi: 10.1038/258152a0. [DOI] [PubMed] [Google Scholar]
  9. MacNab G. M., Alexander J. J., Lecatsas G., Bey E. M., Urbanowicz J. M. Hepatitis B surface antigen produced by a human hepatoma cell line. Br J Cancer. 1976 Nov;34(5):509–515. doi: 10.1038/bjc.1976.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mackett M., Smith G. L., Moss B. Vaccinia virus: a selectable eukaryotic cloning and expression vector. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7415–7419. doi: 10.1073/pnas.79.23.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Marion P. L., Salazar F. H., Alexander J. J., Robinson W. S. Polypeptides of hepatitis B virus surface antigen produced by a hepatoma cell line. J Virol. 1979 Dec;32(3):796–802. doi: 10.1128/jvi.32.3.796-802.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McAuliffe V. J., Purcell R. H., Gerin J. L. Type B hepatitis: a review of current prospects for a safe and effective vaccine. Rev Infect Dis. 1980 May-Jun;2(3):470–492. doi: 10.1093/clinids/2.3.470. [DOI] [PubMed] [Google Scholar]
  13. Nakano E., Panicali D., Paoletti E. Molecular genetics of vaccinia virus: demonstration of marker rescue. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1593–1596. doi: 10.1073/pnas.79.5.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Norrild B. Immunochemistry of herpes simplex virus glycoproteins. Curr Top Microbiol Immunol. 1980;90:67–106. doi: 10.1007/978-3-642-67717-5_4. [DOI] [PubMed] [Google Scholar]
  15. Panicali D., Davis S. W., Mercer S. R., Paoletti E. Two major DNA variants present in serially propagated stocks of the WR strain of vaccinia virus. J Virol. 1981 Mar;37(3):1000–1010. doi: 10.1128/jvi.37.3.1000-1010.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Panicali D., Davis S. W., Weinberg R. L., Paoletti E. Construction of live vaccines by using genetically engineered poxviruses: biological activity of recombinant vaccinia virus expressing influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5364–5368. doi: 10.1073/pnas.80.17.5364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Panicali D., Paoletti E. Construction of poxviruses as cloning vectors: insertion of the thymidine kinase gene from herpes simplex virus into the DNA of infectious vaccinia virus. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4927–4931. doi: 10.1073/pnas.79.16.4927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pourcel C., Louise A., Gervais M., Chenciner N., Dubois M. F., Tiollais P. Transcription of the hepatitis B surface antigen gene in mouse cells transformed with cloned viral DNA. J Virol. 1982 Apr;42(1):100–105. doi: 10.1128/jvi.42.1.100-105.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Robinson W. S. The genome of hepatitis B virus. Annu Rev Microbiol. 1977;31:357–377. doi: 10.1146/annurev.mi.31.100177.002041. [DOI] [PubMed] [Google Scholar]
  20. Ruyechan W. T., Morse L. S., Knipe D. M., Roizman B. Molecular genetics of herpes simplex virus. II. Mapping of the major viral glycoproteins and of the genetic loci specifying the social behavior of infected cells. J Virol. 1979 Feb;29(2):677–697. doi: 10.1128/jvi.29.2.677-697.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Smith G. L., Mackett M., Moss B. Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen. Nature. 1983 Apr 7;302(5908):490–495. doi: 10.1038/302490a0. [DOI] [PubMed] [Google Scholar]
  22. Tiollais P., Charnay P., Vyas G. N. Biology of hepatitis B virus. Science. 1981 Jul 24;213(4506):406–411. doi: 10.1126/science.6264599. [DOI] [PubMed] [Google Scholar]
  23. Watson R. J., Weis J. H., Salstrom J. S., Enquist L. W. Herpes simplex virus type-1 glycoprotein D gene: nucleotide sequence and expression in Escherichia coli. Science. 1982 Oct 22;218(4570):381–384. doi: 10.1126/science.6289440. [DOI] [PubMed] [Google Scholar]
  24. Weir J. P., Bajszár G., Moss B. Mapping of the vaccinia virus thymidine kinase gene by marker rescue and by cell-free translation of selected mRNA. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1210–1214. doi: 10.1073/pnas.79.4.1210. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES