Safety and Immunogenicity of a Recombinant Influenza Vaccine: A Randomized Trial.

OBJECTIVES: The recombinant influenza vaccine is well established in adults ≥18 years of age for preventing seasonal influenza disease. In this randomized controlled trial, we compared the safety and immunogenicity of the quadrivalent, recombinant influenza vaccine (RIV4) versus the inactivated influenza vaccine in children and adolescents 6 to 17 years of age. METHODS: Two age cohorts were enrolled sequentially: 159 subjects aged 9 to 17 years and, after reviewing for safety, 60 children aged 6 to 8 years. Enrollment of the younger children was halted prematurely at the onset of the influenza season. Subjects in each cohort were randomly assigned 1:1 to the RIV4 or inactivated vaccine. Hemagglutination inhibition antibody titers were obtained before and 28 days after vaccination. Tolerability and safety were monitored for 7 days and 6 months after vaccination, respectively. RESULTS: Both vaccines were well tolerated in both age groups, and long-term follow-up revealed no vaccine-related adverse events. Overall, immunogenicity (geometric mean titers and seroconversion rate differences) provided comparable antibody responses to most antigens in both vaccines in the older subjects. Low responses to the influenza B Victoria lineage in both vaccines made interpretation difficult. Immunogenicity in younger children was similar, but the truncated sample size was insufficient to support noninferiority comparisons. CONCLUSIONS: Despite low responses to influenza B lineages in both vaccines, the RIV4 provided safety and immunogenicity that were comparable to those of the licensed inactivated vaccine in pediatric subjects, which was most convincing in those aged 9 to 17 years. Future confirmatory clinical efficacy trials may be used to support the recombinant influenza vaccine as an alternative for the pediatric age group of ≥6 years.