Zootecnica International - World Poultry Journal

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MDV vaccines: looking to the future

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N. Osterrieder

Department of Microbiology and Immunology,
College of Veterinary Medicine,
Cornell University, Ithaca,
NY, USA

Marek's disease (MD) has been successfully controlled by modified live vaccines, which have been in use since the early 1970's (7). Shortly after the discovery that MD virus (MDV) was a member of the Herpesviridae, the herpesvirus of turkeys (HVT), a close relative of MDV, was employed for vaccinations, and virulent (v) MDV field strains were effectively controlled. After a decade of HVT vaccination, vaccine breaks by so-called very virulent (vv) MDV's were observed, which led to the introduction in the US of the avirulent Gallid herpesvirus 3 strain SB-1 as an MD vaccine (1, 4).
In the early 1990's, vv+ strains emerged in the presence of HVT-SB-1 vaccination, and MD is currently controlled by vaccination with attenuated MDV strain CVI988-Rispens, which has been used in Europe since the early 1970's (2, 3).

The re-emergence of MD in the face of comprehensive vaccination has taught us that MDV can evolve to overcome vaccine protection, although the direct correlation between virulence and vaccination lately has been under debate and cannot be viewed as an absolute fact. It is undisputed, however, that breaks of the CVI988 vaccine have occurred, and several isolates have been obtained; among them is the EU1 strain that causes MD in CVI988-vaccinated animals (5, 6).

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In the years to come, a more virulent generation of MDV strains is likely to emerge, which makes the development of novel vaccines critical. In the quest for more effective and biologically safe MD vaccines, the potential of vectored subunit vaccines has been explored, and improved modified live vaccines and DNA vaccines based on entire genomes cloned as bacterial artificial chromosomes (BAC) have been developed and tested.
While the use of vectored subunit vaccines is biologically safe and can be beneficial in prime-boost vaccine regimens, the replication-competence and in vivo amplification of vaccine viruses appears to be critical pre-requisite for complete protection. In this respect, the use of permanent cell lines to produce vaccine viruses may be of advantage. BAC DNA vaccines would - if successful - combine the best of all worlds: a safe, stable and easy to produce vaccine from which replicating virus is reconstituted in vivo. The general feasibility of successful BAC DNA vaccination has been demonstrated, however, the efficiency of vaccine virus reconstitution is poor. Further work is necessary to optimize the efficiency of virus reconstitution upon DNA administration.

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References

  1. 1. Calnek, B. W., K. A. Schat, M. C. Peckham, and J. Fabricant. 1983. Field trials with a bivalent vaccine (HVT and SB-1) against Marek's disease. Avian Dis. 27:844-849.
  2. Rispens, B. H., H. van Vloten, N. Mastenbroek, H. J. Maas, and K. A. Schat. 1972. Control of Marek's disease in the Netherlands. I. Isolation of an avirulent Marek's disease virus (strain CVI 988) and its use in laboratory vaccination trials. Avian Dis. 16:108-125.
  3. Rispens, B. H., H. van Vloten, N. Mastenbroek, J. L. Maas, and K. A. Schat. 1972. Control of Marek's disease in the Netherlands. II. Field trials on vaccination with an avirulent strain (CVI 988) of Marek's disease virus. Avian Dis. 16:126-138.
  4. Schat, K. A. and B. W. Calnek. 1978. Protection against Marek's disease-derived tumor transplants by the nononcogenic SB-1 strain of Marek's disease virus. Infect. Immun. 22:225-232.
  5. Schumacher, D., B. K. Tischer, J. P. Teifke, K. Wink, and N. Osterrieder. 2002. Generation of a permanent cell line that supports efficient growth of Marek's disease virus (MDV) by constitutive expression of MDV glycoprotein E. Journal of General Virology 83:1987-1992.
  6. Tischer, B. K., D. Schumacher, M. Beer, J. Beyer, J. P. Teifke, K. Osterrieder, K. Wink, V. Zelnik, F. Fehler, and N. Osterrieder. 2002. A DNA vaccine containing an infectious Marek's disease virus genome can confer protection against tumorigenic Marek's disease in chickens. J. Gen. Virol. 83:2367-2376.
  7. Witter, R. L. 2001. Protective efficacy of Marek's disease Vaccines. Marek's Disease 255:57-90.

From Proceedings of the "7th International Symposium on Marek's disease", St. Catherine's College, Oxford, United Kingdom.