Pringle C R, Filipiuk A H, Robinson B S, Watt P J, Higgins P, Tyrrell D A
Biological Sciences Department, University of Warwick, Coventry, UK.
Vaccine. 1993;11(4):473-8. doi: 10.1016/0264-410x(93)90290-e.
The immunogenicity and pathogenicity of a strain of respiratory syncytial (RS) virus modified by sequential induction of three temperature-sensitive (ts) mutations have been evaluated by intranasal administration to 22 adult volunteers. This modified virus, a triple ts mutant designated ts1C, was derived from a double mutant ts1B evaluated in a previous trial. The original isolate (strain RSS-2) and all its derivatives were propagated throughout in human diploid cells in a specially assigned laboratory. The triple mutant ts1C is unable to multiply in MRC-5 cells at 37 degrees C and above. Following nasal administration of ts1C, immune responses were observed in volunteers with low pre-existing neutralizing antibody titres. The ability of mutant ts1C to induce upper respiratory tract disease in adults was greatly diminished in comparison with the non-ts wild-type virus, but not markedly more so than a previously tested double ts mutant (ts1B) which replicates at 37 degrees C. Mutant ts1C, however, may have greater potential as a live vaccine in view of its inherently greater genetic stability.
