Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy.
A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.
Wright
P F
PF
Division of Infectious Disease, Dept. of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. peter.wright@mcmail.vanderbilt.edu
Karron
R A
RA
Belshe
R B
RB
Thompson
J
J
Crowe
J E
JE
Boyce
T G
TG
Halburnt
L L
LL
Reed
G W
GW
Whitehead
S S
SS
Anderson
E L
EL
Wittek
A E
AE
Casey
R
R
Eichelberger
M
M
Thumar
B
B
Randolph
V B
VB
Udem
S A
SA
Chanock
R M
RM
Murphy
B R
BR
D000914:Antibodies, Viral / Q000097:blood; D001942:Breast Feeding; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007223:Infant; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013696:Temperature; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D017201:Virus Shedding
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D014613:Vaccines, Attenuated; D014765:Viral Vaccines