Evaluation of cold-adapted and temperature-sensitive mutants of parainfluenza virus type 3 in weanling hamsters.

Cold-adapted (ca) and temperature-sensitive (ts) mutants of parainfluenza virus 3 were produced by serially passaging wild type (wt) parainfluenza virus 3 at 20 degrees C 45 times. Previously, plaque-purified viruses (clones) were selected from the wt parent and from cold passage levels 7, 12, 18, and 45 and characterized in vitro. In the present study, we evaluated at least one mutant from each cold passage level for attenuation in hamsters. Four of the five mutants tested were ts and ca (one each from cold passage levels 7, 12, 18, and 45) and one was ca but not ts (from cold passage 18). Groups of hamsters were inoculated intranasally with either parent wt or mutant virus. Four or five hamsters from each group were sacrificed prior to inoculation and daily on the first, second, third, fourth, and sixth or seventh day postinoculation and the amount of virus in nasal turbinates and lungs was quantitated. The quantity of virus recovered from the hamsters and the parainfluenza virus 3 antibody titers were inversely related to the cold passage level. Two of the mutants did not replicate in hamsters. Cold adaptation of parainfluenza virus 3 resulted in progressive attenuation of the virus in weanling hamsters. These highly attenuated mutants are suitable for evaluation in children as live virus vaccines.