Evaluation of two live, cold-passaged, temperature-sensitive respiratory syncytial virus vaccines in chimpanzees and in human adults, infants, and children.
Two live-attenuated, cold-passaged (cp), temperature-sensitive (ts) candidate vaccines, designated cpts530/1009 and cpts248/955, were attenuated, genetically stable, and immunogenic in chimpanzees and were highly attenuated for human adults. In respiratory syncytial virus (RSV)-seropositive children, cpts530/1009 was more restricted in replication than cpts248/955. In seronegative children, 10(4) pfu of cpts248/955 was insufficiently attenuated, and a high titer of vaccine virus was shed (mean peak titer, 10(4.4) pfu/mL), whereas 10(4) pfu of cpts530/1009 was relatively attenuated and restricted in replication (mean peak titer, 10(2.0) pfu/mL). At a dose of 10(5) pfu, cpts530/1009 was immunogenic in seronegative children (geometric mean titer of RSV neutralizing antibodies, 1:724). Transmission of either vaccine to seronegative placebo recipients occurred at a frequency of 20%-25%. Of importance, vaccine viruses recovered from chimpanzees and humans were ts. In contrast to previous studies, this study indicates that live attenuated RSV vaccines that are immunogenic and phenotypically stable can be developed. Additional studies are being conducted to identify a live RSV vaccine that is slightly more attenuated and less transmissible than cpts530/1009.
Karron
R A
RA
Center for Immunization Research, Department of International Health, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
Wright
P F
PF
Crowe
J E
JE
Clements-Mann
M L
ML
Thompson
J
J
Makhene
M
M
Casey
R
R
Murphy
B R
BR
D000293:Adolescent; D000328:Adult; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis* / Q000097:blood; D002460:Cell Line; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D016296:Mutagenesis; D009154:Mutation; D017817:Nasal Lavage Fluid / Q000276:immunology / Q000821:virology; D002679:Pan troglodytes; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000635:transmission; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D005472:Fluorouracil