Recombinant-Derived Modified-Live Herpesvirus Vaccines

  • Saul Kit


Swine pseudorabies (PR; Aujezky’s disease [AD]) and infectious bovine rhinotracheitis (IBR) are important veterinary diseases, each of which cost American farmers over 30 million dollars annually. Killed and modified-live virus (MLV) vaccines have been used in the United States and in other countries for over 25 years to control AD and IBR, but these conventional vaccines have had numerous shortcomings with regard to safety and efficacy. First, despite the intensive use of the conventional vaccines, AD- and IBR morbidity and mortality have increased. For example, about 10% of the sixty million swine in the United States are now infected with PRV compared with about 1% in 1972. Second, animals vaccinated with conventional killed or MLV vaccines remained susceptible to infection at a later time with virulent field strains, and often shed virulent virus, thereby spreading infection in the herd. Third, the intramuscular (IM) administration of MLV IBR vaccines has been hampered by the hazards of vaccine-induced abortions. As an alternative, temperature-sensitive IBR vaccines have been used, but these specialized vaccines could only be administered by the inconvenient and laborious intranasal (IN) route. Virus replication in the deep tissues of the body to amplify the immune response was, by definition, restricted. Fourth, some of the conventional AD vaccines, though safe for swine, were unsafe for oother animal species.


Herpes Simplex Virus Type Thymidine Kinase Rift Valley Fever Rift Valley Fever Virus Pseudorabies Virus 
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  1. Allen, G. P., and Coogle, L. D., 1988, Characterization of an equine herpesvirus type 1 gene encoding a glycoprotein (gp13) with homology to herpes simplex virus glycoprotein C, J. Virol., 62:2850.PubMedGoogle Scholar
  2. Buller, R. M. L., Smith, G. L., Cremer, K., Notkins, A. L., and Moss, B., 1985, Decreased virulence of recombinant vaccinia virus expression vectors is associated with a thymidine kinase-negative phenotype, Nature, 317:813.PubMedCrossRefGoogle Scholar
  3. Davison, A. J., and Scott, J. E., 1986, The complete DNA sequence of varicella-zoster virus, J. Gen. Virol., 67:1759.PubMedCrossRefGoogle Scholar
  4. Dowbenko, D. J., and Lasky, L. A., 1984, Extensive homology between the herpes simplex virus type 2 glycoprotein F gene and the herpes simplex virus type 1 glycoprotein gene, J. Virol., 52:154.PubMedGoogle Scholar
  5. Dubbs, D. R., and Kit, S., 1964a, Isolation and properties of vaccinia mutants deficient in thymidine kinase-inducing activity, Virology, 22:214.PubMedCrossRefGoogle Scholar
  6. Dubbs, D. R., and Kit, S., 1964b, Mutant strains of herpes simplex deficient in thymidine kinase-inducing activity, Virology 22:493.PubMedCrossRefGoogle Scholar
  7. Field, H. J., and Wildy, P., 1978, The pathogenicity of thymidine kinase deficient mutants of herpes simplex in mice, J. Hyg. (Cambridge), 81:267.CrossRefGoogle Scholar
  8. Frink, R. J., Eisenberg R., Cohen, G., and Wagner, E. K., 1983, Detailed analysis of the portion of the herpes simplex virus type 1 genome encoding glycoprotein C., J. Virol., 45:634.PubMedGoogle Scholar
  9. Glorioso, J., Kees, U., Kumel, G., Kirchner, H., and Krammer, P., 1985, Identification of herpes simplex virus type 1 (HSV-1) glycoprotein gC as the immunodominant antigen for HSV-1-specific memory cytotoxic T lymphocytes, J. Immunol., 135:575.PubMedGoogle Scholar
  10. Hopp, T. P., and Woods, K. R., 1981, Prediction of protein antigenic determinants from amino acid sequences, Proc. Nat. Acad. Sci. USA, 78:3824.PubMedCrossRefGoogle Scholar
  11. Horohov, D. W., Moore, R. N., and Rouse, B. T., 1985, Production of soluble suppresor factors by herpes simplex virus-stimulated splenocytes from herpes simplex virus-immune mice, J. Virol., 54:798.PubMedGoogle Scholar
  12. Iglesias, G., Pijoan, C., and Molitor, T., 1988a, Replication of pseudorabies virus in swine alveolar macrophages, Chapt. IV, in: “Proc. 10th Int. Cong. Pig. Vet. Soc.,” Rio de Janiero, Brazil.Google Scholar
  13. Iglesias, G., Pijoan, C., and Molitor, T., 1988b, Effects of pseudorabies virus infection on alveolar macrophages functions, Chapt. IV, in: “Proc. 10th Int. Cong. Pig Vet. Soc.,” Rio de Janiero, Brazil.Google Scholar
  14. Jennings, S. T., Rice, P. L., Kloszewski, E. D., Anderson, R. W., Thompson, D. L., and Tevethia, S. S., 1985, Effect of herpes simplex virus types 1 and 2 on surface expression of class I major histocompatability complex antigens on infected cells, J. Virol., 56:757.PubMedGoogle Scholar
  15. Kit, S., 1985, Thymidine kinase, Microbiol. Sci., 2:369.PubMedGoogle Scholar
  16. Kit, S., 1989, Safety and efficacy of genetically engineered Aujeszky’s disease vaccines, in: “Papers presented at the Commis. Europ. Commun. (CEC) Symposium on Vaccination and Control of Aujeszky’s Disease,” Brussels, Belgium (in press).Google Scholar
  17. Kit, S., Dubbs, D. R., Piekarski, L. J., and Hsu, T. C., 1963, Deletion of thymidine kinase activity from L cells resistant to bromodeoxyuridine, Exp. Cell Res., 31:297.PubMedCrossRefGoogle Scholar
  18. Kit, S., Kit, M., Bartkoski, M. J., and Dees, C., 1987a, Genetically engineered pseudorabies virus vaccine with deletions in thymidine kinase and glycoprotein genes, in: “Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases,” R. M. Chanock, R. A. Lerner, F. Brown, and H. Ginsberg, eds., Cold Spring Harbor Laboratory.Google Scholar
  19. Kit, S., Kit, M., and McConnell, S., 1986, Intramuscular and intravaginal vaccination of pregnant cows with thymidine kinase-negative, temperature-resistant infectious bovine rhinotracheitis virus (bovine herpesvirus 1), Vaccine, 4:55.PubMedCrossRefGoogle Scholar
  20. Kit, S., Kit, M., and Pirtle, E. C., 1985, Attenuated properties of thymidine kinase-negative deletion mutant of pseudorabies virus, Am. J. Vet. Res., 46:1359.PubMedGoogle Scholar
  21. Kit, S., and Qavi, H., 1983, Thymidine kinase (TK) induction after infection of TK-deficient rabbit cell mutants with bovine herpesvirus type 1 (BHV-1). Isolation of TK- BHV-1 mutants, Virology, 130:381.Google Scholar
  22. Kit, S., Qavi, H., Dubbs, D. R., and Otsuka, H., 1983, Attenuated marmoset herpesvirus isolated from recombinants of virulent marmoset herpesvirus and hybrid plasmids, J. Med. Virol., 12:25.PubMedCrossRefGoogle Scholar
  23. Kit, S., Sheppard, M., Ichimura, H., and Kit, M., 1987b, Second-generation pseudorabies virus vaccine with deletions in thymidine kinase and glycoprotein genes. Am. J. Vet. Rs., 48.7800.Google Scholar
  24. Klein, R. J., 1982, The pathogenesis of acute, latent, and recurrent herpes simplex virus infections, Arch. Virol., 72:143.PubMedCrossRefGoogle Scholar
  25. Lomniczi, B., Kaplan, A. S., and Ben-Porat, T., 1987a, Multiple defects in the genome of pseudorabies virus can affect virulence without detectably affecting replication in cell culture, Virology, 161:181.PubMedCrossRefGoogle Scholar
  26. Lomniczi, B., Watanabe, S., Ben-Porat, T., and Kaplan, A. S., 1984, Genetic basis of the neurovirulence of pseudorabies virus. J. Virol., 52:198.PubMedGoogle Scholar
  27. Lomniczi, B., Watanabe, S., Ben-Porat, T., and Kaplan, A. S., 1987b, Genome location and identification of functions defective in the Bartha vaccine strain of pseudorabies virus, J. Virol., 61:796.PubMedGoogle Scholar
  28. Longnecker, R., and Roizman, B., 1987, Clustering of genes dispensable for growth in culture in the S component of the HSV-1 genome, Science, 236: 573.PubMedCrossRefGoogle Scholar
  29. McGeoch, D. J., 1985, On the predictive recognition of signal peptide sequences, Vir. Res., 3:271.CrossRefGoogle Scholar
  30. McGinley, M. J., and Platt, K. B., 1988, Studies on the ability of 98-kilodalton pseudorabies virus diagnostic antigen to detect latent infections induced by low-dose exposure to the virus. Am. J. Vet. Res. 49:1489.PubMedGoogle Scholar
  31. Mettenleiter, T. C., Lomniczi, B., Sugg, N., Schrueurs, C., and Ben-Porat, T., 1988, Host cell-specific growth advantage of pseudorabies virus with a deletion in the genome sequences encoding a structural glycoprotein, J. Virol., 62:12.PubMedGoogle Scholar
  32. Mettenleiter, T. C., Lukacs, N., and Rziha, H.-J., 1985, Pseudorabies virus avirulent strains fail to express a major glycoprotein. J. Virol., 56: 307.PubMedGoogle Scholar
  33. Mettenleiter, T. C., Schreurs, C., Thiel, H.-J., and Rziha, H.-J., 1987a, Variability of pseudorabies virus glycoprotein I expression, Virology, 158:141.PubMedCrossRefGoogle Scholar
  34. Mettenleiter, T. C., Zsak, L., Kaplan, A. S., Ben-Porat, T., and Lomniczi, B., 1987b, Role of a structural glycoprotein of pseudorabies in virus virulence, J. Virol., 61:4030.PubMedGoogle Scholar
  35. Oliver, R. E., Motha, M. X. J., Worthington, R. W., Penrose, M. E., Poole, W. S., 1988, Protection of piglets against a virulent New Zealand isolate of Aujeszky’s disease virus by vaccination with a novel genetically-engineered vaccine, New Zeald. Vet. J., 36:100.CrossRefGoogle Scholar
  36. Otsuka, H., and Kit, S., 1984, Nucleotide sequence of the marmoset herpesvirus thymidine kinase gene and predicted amino acid sequence of thymidine kinase polypeptide, Virology, 135:316.PubMedCrossRefGoogle Scholar
  37. Petrovskis, E. A., Wardley, R. C., Berlinski, P. J., Thomsen, D. R., Meyer, A. L., and Post, L. E., 1988, Important role of pseudorabies virus glycoprotein I (GI) in efficacy of live vaccines, in: “Abstracts of 5th Int. Symp. Immunobiol. Proteins and Peptides,” Chateau Lake Louise, Alberta, Canada.Google Scholar
  38. Reeves, D. E., 1988, Results of a field study using a genetically altered modified live pseudorabies vaccine in an eradication program, in: “Proc. Annu. Mtg. Am. Assoc. Swine Practitioners,” St. Louis, MO.Google Scholar
  39. Robbins, A. K., Watson, R. J., Whealy, M. E., Hays, W. W., and Enquist, L. W., 1986, Characterization of a pseudorabies virus glycoprotein gene with homology to herpes simplex virus type 1 and type 2 glycoprotein C, J. Virol., 58:339.PubMedGoogle Scholar
  40. Robbins, A. K., Weis, J. H., Enquist, L. W., and Watson, R. J., 1984, Construction of E. coli expression plasmid libraries: localization of a pseudorabies virus glycoprotein gene, J. Molec. Appl. Genet., 2:485.Google Scholar
  41. Sheppard, M., Otsuka, H., Kit, M., and Kit, S., 1986, Transcription and in vitro translation of pseudorabies virus (PRV) thymidine kinase (TK) gene, in: “Abstracts of 86th Annu. Mtg. Amer. Soc. Microbiol.,” Washington, D. C.Google Scholar
  42. Srinivasappa, J., Saegusa, J., Prabhakar, B. S., Gentry, M. K., Buchmeier, J., Wiktor, T. J., Koprowski, H., Oldstone, M. B. A., and Notkins, A. L., 1986, Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues, J. Virol., 57:397.PubMedGoogle Scholar
  43. Stanberry, L. R., Bernstein, D. I., Kit, S., and Myers, M. G., 1985, Genital reinfection after recovery from initial genital infection with herpes simplex virus type 2 in guinea pigs, J. Infect. Dis., 153:1055.CrossRefGoogle Scholar
  44. Swain, M. A., Peet, R. W., Galloway, D. A., 1985, Characterization of the gene encoding herpes simplex virus type 2 glycoprotein C and comparison with the type 1 counterpart, J. Virol., 53:561.PubMedGoogle Scholar
  45. Tenser, R. B., Ressel, S. J., Fralish, F. A., and Jones, J. C., 1983, The role of pseudorabies virus thymidine kinase expression in trigeminal ganglion infection, J. Gen. Virol., 64:1369.PubMedCrossRefGoogle Scholar
  46. Thacker, B., Maes, R., Bartkoski, M., and Kolar, J., 1988a, Immunogenicity, efficacy, and safety of a modified-live, thymidine kinase negative, gIII deleted pseudorabies virus vaccine, Chapt. IV, in: “Proc. 10th Int. Cong. Pig Vet. Soc.,” Rio de Janiero, Brazil.Google Scholar
  47. Thacker, B., Maes, R., Gonzalez, P., and Han C., 1988b. Development of latency in vaccinated or passibly immune pigs experimentally infected with “Proc. virus, Chapt. IV, in: Proc. 10 Int. Cong. Pig Vet. Soc.,” Rio de Janiero, Brazil.Google Scholar
  48. Van Oirschot, J. T., and Gielkens, A. L. J., 1987, Vaccines against Aujeszky’s disease: comparison of efficacy, DNA fingerprints and antibody response to glycoprotein I, Vet. Quart., 9 (Suppl. 1):37S.CrossRefGoogle Scholar
  49. Van Oirschot, J. T., Rziha, H. J., Moonen, L. A. M., Pol, J. M. A., and Van Zaane, D., 1986, Differentiation of serum antibodies from pigs vaccinated or infected with Aujeszky’s disease virus by a competitive enzyme immunoassay, J. Gen. Virol., 67:1179.PubMedCrossRefGoogle Scholar
  50. Von Heijne, G., 1986, A new method for predicting signal sequence cleavage sites, Nucl. Acids Res., 14:4683.CrossRefGoogle Scholar
  51. Wilbur, W. J., and Lipman, D. J., 1983, Rapid similarity searches of nucleic acid and protein data banks, Proc. Nat. Acad. Sci. USA, 80:726.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1989

Authors and Affiliations

  • Saul Kit
    • 1
  1. 1.Division of Biochemical VirologyBaylor College of MedicineHoustonUSA

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