Safety and tolerability of cold-adapted influenza vaccine, trivalent, in infants younger than 6 months of age

Pediatrics. 2008 Mar;121(3):e568-73. doi: 10.1542/peds.2007-1405. Epub 2008 Feb 25.


Objective: Young children are at high risk for influenza-related complications. Vaccination of close household contacts is recommended to provide indirect protection to children <6 months of age. Studies have shown that live, cold-adapted influenza vaccine, trivalent, is efficacious in children. To assess the risks associated with inadvertent exposure of infants to vaccine viruses from vaccinated contacts, this study was designed to evaluate the safety and tolerability of cold-adapted influenza vaccine, trivalent, administered intranasally to healthy children 6 to <24 weeks of age.

Methods: Healthy infants aged 6 to <16 weeks and 16 to <24 weeks, respectively, were randomly assigned to receive 2 doses of influenza vaccine, or placebo intranasally 35 +/- 7 days apart. Reactogenicity events were monitored for 11 days after each dose. Other adverse events were monitored through 28 to 35 days after dose 2.

Results: Of the infants aged 6 to <16 weeks, 31 received influenza vaccine and 28 received placebo, and of those aged 16 to <24 weeks, 30 received influenza vaccine and 31 received placebo. In the 6- to <16-week cohort, more influenza vaccine, recipients experienced irritability (66.7% vs 35.7%) and runny nose or nasal congestion (63.3% vs 33.3%) after dose 1 but not dose 2. There were no significant increases in any other reactogenicity events or adverse events in the vaccine recipients compared with the placebo group.

Conclusions: Although there was an increase in mild reactogenicity events in children 6 to <16 weeks of age, cold-adapted influenza vaccine, trivalent, was generally well tolerated in infants 6 to <24 weeks of age. These findings support further evaluation of cold-adapted influenza vaccine, trivalent, in infants <6 months of age.

Trial registration: NCT00192348.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Age Factors
  • Cold Temperature
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions*
  • Female
  • Finland
  • Follow-Up Studies
  • Humans
  • Immunization Schedule
  • Infant
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / adverse effects
  • Influenza, Human / prevention & control*
  • Male
  • Probability
  • Reference Values
  • Risk Assessment
  • Vaccination / methods
  • Vaccines, Attenuated / administration & dosage*


  • Influenza Vaccines
  • Vaccines, Attenuated

Associated data