A randomized, double-blind study of the safety, transmissibility and phenotypic and genotypic stability of cold-adapted influenza virus vaccine.
BACKGROUND
Live attenuated influenza vaccine (LAIV; FluMist) is a trivalent vaccine containing cold-adapted influenza vaccine viruses that infect and replicate in cells lining the nasopharynx to induce immunity. Recovery of viruses (shedding) is measured by culture of nasal specimens. Shedding of vaccine viruses is not equated with transmission because transmission requires more virus than is detected in many nasal swabs. Previous studies with LAIV did not detect transmission to close contacts. The primary objective of this study was to estimate the probability of transmission to placebo contacts in a day care setting.


METHODS
One hundred ninety-seven healthy children aged 9 to 36 months attending day care were randomized to receive vaccine or placebo. Postvaccination viral shedding, safety, genotype and phenotype of shed viruses and probability of transmission were assessed.


RESULTS
Eighty percent of 98 vaccine recipients shed at least one vaccine strain. No clinically significant differences in solicited adverse events attributable to vaccine occurred; safety profiles were similar in both groups. Vaccine virus isolates retained their phenotypic characteristics (cold adaptation and temperature sensitivity) and did not revert at nucleotides known to confer an attenuating phenotype. There was one confirmed transmission of a vaccine strain to a single placebo recipient. According to the Reed-Frost model, the calculated probability of transmission to a child after contact with a single vaccinated child was 0.58% (95% confidence interval, 0-1.7%). There was no increased reactogenicity or other safety concerns in the recipient child.


CONCLUSIONS
Young children in a day care setting had a high rate of shedding and a low rate of transmission. No clinically significant illness occurred among children who received vaccine or placebo or in the child to whom the vaccine virus was transmitted.
Vesikari
Timo
T
University of Tampere, Tampere, Finland.
Karvonen
Aino
A
Korhonen
Tiina
T
Edelman
Kati
K
Vainionpää
R
R
Salmi
Aimo
A
Saville
Melanie K
MK
Cho
Iksung
I
Razmpour
Ahmad
A
Rappaport
Ruth
R
O'Neill
Robert
R
Georgiu
Alice
A
Gruber
William
W
Mendelman
Paul M
PM
Forrest
Bruce
B
D002656:Child Day Care Centers; D002675:Child, Preschool; D018562:Disease Transmission, Infectious; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission* / Q000821:virology; D008297:Male; D010641:Phenotype; D010919:Placebos; D011446:Prospective Studies; D017201:Virus Shedding
D007252:Influenza Vaccines; D010919:Placebos