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.

Phase 2 evaluation of parainfluenza type 3 cold passage mutant 45 live attenuated vaccine in healthy children 6-18 months old.

A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)-cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6-18 months old; 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature > or =38 degrees C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum samples were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients; 84% of seronegative vaccine recipients developed a > or =4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1 : 25 in the vaccine group and <1 : 4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial.