A live human parainfluenza type 3 virus vaccine is attenuated and immunogenic in young infants.
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.
Karron
Ruth A
RA
Belshe
Robert B
RB
Wright
Peter F
PF
Thumar
Bhagvanji
B
Burns
Barbars
B
Newman
Frances
F
Cannon
Joan C
JC
Thompson
Juliette
J
Tsai
Theodore
T
Paschalis
Maribel
M
Wu
Shin-Lu
SL
Mitcho
Yvonne
Y
Hackell
Jill
J
Murphy
Brian R
BR
Tatem
Joanna M
JM
D000367:Age Factors; D000914:Antibodies, Viral / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007109:Immunity / Q000502:physiology; D007115:Immunization Schedule; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010224:Parainfluenza Virus 3, Human / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D011336:Probability; D012016:Reference Values; D010253:Respirovirus Infections / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology*
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines