Immunogenicity and pathogenicity of a triple temperature-sensitive modified respiratory syncytial virus in adult volunteers.
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.
Pringle
C R
CR
Biological Sciences Department, University of Warwick, Coventry, UK.
Filipiuk
A H
AH
Robinson
B S
BS
Watt
P J
PJ
Higgins
P
P
Tyrrell
D A
DA
D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009500:Neutralization Tests; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D010253:Respirovirus Infections / Q000517:prevention & control*; D013696:Temperature; D014765:Viral Vaccines / Q000302:isolation & purification / Q000494:pharmacology; D014774:Virulence / Q000235:genetics
D000914:Antibodies, Viral; D014765:Viral Vaccines