Development and characterization of cold-adapted viruses for use as live virus vaccines

Vaccine. 1985 Dec;3(5):355-69. doi: 10.1016/0264-410x(85)90124-0.


Representative viruses from twelve RNA and two DNA virus genera have been successfully adapted to growth at sub-optimal temperature (cold-adapted). In almost every case, there was a correlation between acquisition of the cold-adaptation phenotype and loss of virulence in the normal host whether animal or man. Overall, the best method of cold adaptation to develop a live virus vaccine line appeared to be a stepwise lowering of the growth temperature allowing time for multiple lesions to occur and/or be selected. In addition, the starting virus should be a recent isolate not as yet adapted to a tissue culture host and the cold-adaptation process should then occur in a host heterologous to the virus' normal host. These viruses have been reviewed in the light of their cold-adaptation method and successful production of an attenuated line as virus vaccine candidate. Finally, detailed information is presented for the cold-adaptation process in influenza virus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acclimatization
  • Animals
  • Cell Line
  • Cold Temperature
  • DNA Viruses / genetics
  • Genetic Variation
  • Humans
  • Orthomyxoviridae / genetics
  • RNA Viruses / genetics
  • Vaccines*
  • Viruses / genetics*
  • Viruses / growth & development
  • Viruses / immunology


  • Vaccines