Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study

Abstract

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3–8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3–8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Immunogenicity and safety of a multi-dose quadrivalent inactivated influenza vaccine in individuals aged 6 months to 17 years: a randomized phase III trial

“…8,23 Our study was limited in that only around half of the planned number of children aged 3 − 8 years were enrolled. Nevertheless, the overall safety of the PFS format in this age group has been previously demonstrated in a large phase III study 19 and there was no evidence that the safety profiles of the MDV and PFS formats differed in the other age groups in our study. Additionally, our study did not evaluate the MDV Figure 2.…”

Immunogenicity and Safety of the New Inactivated Quadrivalent Influenza Vaccine Vaxigrip Tetra: Preliminary Results in Children ≥6 Months and Older Adults

“…The immunogenicity and safety of Vaxigrip Tetra have been investigated in six phase III clinical trials in subjects aged ≥3 years and in one recent phase III clinical study conducted on children aged 6–35 months ( Table 2 ). Three of these studies were considered pivotal investigations, since their aim was to characterize Vaxigrip Tetra immunogenicity for approval in the EU [ 81 , 82 , 83 ]. The licensed Vaxigrip Tetra formulated through a revised process was evaluated by these three main trials [ 81 , 82 , 83 ] and by another involving adults aged 18–60 years [ 84 ].…”

“…Three of these studies were considered pivotal investigations, since their aim was to characterize Vaxigrip Tetra immunogenicity for approval in the EU [ 81 , 82 , 83 ]. The licensed Vaxigrip Tetra formulated through a revised process was evaluated by these three main trials [ 81 , 82 , 83 ] and by another involving adults aged 18–60 years [ 84 ]. Two phase III clinical trial were considered supportive; these were conducted on adults, the elderly and children from 9 years of age, and investigated Vaxigrip Tetra batches produced with the same method as Vaxigrip [ 85 , 86 ].…”

“…A subsequent phase III randomized, double-blind, active-controlled, multi-center study conducted in Finland, Poland, Mexico, and Taiwan on 1242 children aged 3 to 8 years during the 2013/2014 Northern Hemisphere influenza season (GQM02; EudraCT No. 2011-005374-33) investigated the immunogenicity and the safety profile of Vaxigrip Tetra (which contained the 4 Northern Hemisphere 2013/2014 influenza strains recommended by the WHO and the EU) in comparison with its trivalent counterpart 2013–2014 formulation (TIV-1, Vaxigrip ® ), which contained both A strains and the B Victoria lineage strain, and an investigational TIV (TIV-2) containing both A strains and the B Yamagata lineage strain [ 82 ]. HI titers at the baseline (indicated as day 0) and 28 days after the last vaccination were measured in order to evaluate antibody responses induced by QIV and by TIVs.…”

“…In addition, it was observed that QIV displayed higher immunogenicity towards influenza B strains than a TIV formulated with the alternative B strain lineage. In detail, although the HI antibody titers were relatively high at the baseline, probably as a consequence of natural exposure to the same strains or to one similar to those contained in the QIV formulation, GMTs were enhanced at least 6-fold for all vaccine strains upon QIV immunization [ 82 ]. Seroprotection against all the strains was achieved in almost all vaccines [ 82 ], whereas seroconversion rates were similar to those found by Cadorna [ 86 ] in children and adolescents aged from 9 to 17 years, ranging from 64.8% to 88.5% for all four strains [ 82 ].…”