The association of the temperature-sensitive phenotype with viral attenuation in animals and humans: implications for the development and use of live virus vaccines.

Viruses that possess temperature-sensitive mutations are consistently attenuated in vivo compared with the wild-type parental strains. Such temperature-sensitive (ts) mutants are currently used in several live attenuated virus vaccines and have been proposed for use against several additional viral diseases, including influenza. This paper reviews the following: (1) the evidence that the ts mutation itself is responsible for attenuation; (2) experimental infection of animals and humans with ts mutant viruses; (3) the experience of humans with naturally occurring ts mutants; and (4) the rationale for the use of ts mutants in live virus vaccines. In addition, the potential of ts mutants to produce altered patterns of disease is considered. After the known and potential benefits and possible risks involved in the use of ts mutant viruses are weighed, the continuing use and development of vaccines using live attenuated ts virus seems warranted.