PURPOSE OF THE STUDY.
To evaluate the safety and immunogenicity of the quadrivalent recombinant influenza vaccine (RIV4) in comparison with the inactivated influenza vaccine in children and adolescents (ages 6–17 years).
The study included 219 healthy children and adolescents: 159 in an older cohort (9–17 years old) and 60 in a younger cohort (6–8 years old). Those with serious underlying conditions, febrile illnesses, or contraindications to either study vaccine and those receiving immunosuppressive therapy were excluded. Any use of systemic steroids during the protocol also resulted in removal from the immunogenicity studies.
This was an exploratory, observer-blind, parallel-group, phase 2 trial. The study subjects were enrolled sequentially by age; the older cohort was enrolled first in the late fall with the addition of the younger cohort during the winter. Subjects were randomly assigned 1:1 to receive the RIV4 or the inactivated quadrivalent influenza vaccine (IIV4). The recruitment of younger subjects was limited because of the start of influenza season. To evaluate the immunogenicity (efficacy) of the vaccination, serum samples were collected to evaluate hemagglutination inhibition antibody titers at 28 days before and after vaccination. Safety and tolerability data included material from diary cards and an evaluation of systemic and local site reactions. Telephone interviews were performed up to 6 months postvaccination to evaluate additional adverse events.
The study included results for 219 subjects total (159 older cohort and 60 younger cohort). There were 203 subjects who completed the 6-month follow-up evaluations. The mean subject was 12.7 years of age in the older cohort and 7.1 years of age in the younger cohort. The majority of subjects were white or black and/or African American. The study authors hypothesized that the immunogenicity of all 4 strains of RIV4 were noninferior to IIV4. Comparable antibody responses were noted after vaccination with both RIV4 and IIV4 for the entire study population measured as geometric mean titer ratios: H1N1 strain (0.6), H3N2 (0.6), influenza B Yamagata lineage (0.82), and influenza B Victoria lineage (1.05). The statistical analysis for noninferiority comparisons was limited in the younger cohort because of its smaller sample size. In regard to safety, there were no deaths or adverse events that resulted in a discontinuation of the vaccine series. The most common injection site reaction was mild-to-moderate pain. Systemic reactions reported included fatigue, myalgia, and headache, all of which were self-limited and of mild-to-moderate severity. Fevers were rare (<5%) in both groups, and no fevers >102°F were reported. Only 2% (4 of 217 subjects) developed viral infections within 28 days after vaccination.
The study authors concluded that RIV4 had comparable safety and immunogenicity to IIV4 in a pediatric population >6 years of age. Because this is a phase 2 exploratory trial, further studies will be necessary to evaluate its clinical efficacy in multiple influenza seasons.
This study revealed the safety and immunogenicity of RIV4, which was comparable with IIV4. As the study authors pointed out, a better characterization of this recombinant is necessary in multiple influenza seasons to determine its longitudinal efficacy. The rarity of reported adverse events dispels frequent caregiver misconceptions regarding influenza vaccination, such as the development of high fever and viral infection. Providers, when counseling families about the safety of influenza vaccination, can reference these data about vaccine safety.
- Copyright © 2018 by the American Academy of Pediatrics