A live human parainfluenza type 3 virus vaccine is attenuated
and immunogenic in young infants.
Karron RA, Belshe RB, Wright PF, Thumar B, Burns B, Newman F, Cannon JC,
Thompson J, Tsai T, Paschalis M, Wu SL, Mitcho Y, Hackell J, Murphy BR, Tatem
JM.
BACKGROUND: Parainfluenza type 3 virus (PIV-3) infections cause lower
respiratory tract illness in children throughout the world. A licensed PIV-3
vaccine is not yet available. METHODS: A live attenuated cold-adapted (ca) and
temperature-sensitive (ts) PIV-3 vaccine, designated cp-45, was evaluated
sequentially in open label studies in 20 adults and in placebo-controlled,
double blind studies in 24 PIV-3-seropositive children, 52 PIV-3-seronegative
infants and children and 49 infants 1 to 2 months old. A single dose of this
intranasal vaccine was evaluated in adults [106 plaque-forming units (pfu)] and
seropositive children, and 104 and 105 pfu were evaluated in seronegative
children. In the infant study, two 104 pfu doses of vaccine were administered at
1- or 3-month intervals. Safety, infectivity, immunogenicity and phenotypic
stability of the vaccine were evaluated in all cohorts. RESULTS: The cp-45
vaccine was well-tolerated in all age groups and infected 94% of vaccinated
seronegative children and 94% of vaccinated infants. Although immunization with
the first dose of cp-45 diminished the replication of a second dose in all
infants, those immunized after 3 months shed vaccine virus more frequently than
those immunized after 1 month (62% vs. 24%, respectively). Antibody responses to
PIV-3 were readily detected in seronegative children with a variety of assays;
however, the IgA response to the viral hemagglutinin-neuraminidase was the best
measure of immunogenicity in young infants. Of 109 vaccine virus specimens
recovered from nasal washes, 98 were ts and 11 were temperature-sensitive
intermediate (tsi) viruses, with pinpoint plaques visible at 40 degrees C. tsi
viruses appeared transiently at the time of peak viral replication, represented
a very small proportion of the total virus shed and were not associated with
changes in clinical status. ca revertants were not detected. CONCLUSIONS: The
cp-45 vaccine is appropriately attenuated and immunogenic in infants as young as
1 month of age. Further development of this vaccine is warranted.
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as providing medical or legal advice. The decision whether or not to vaccinate
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