Influenza vaccination in children primed with MF59-adjuvanted or non-adjuvanted seasonal influenza vaccine

Abstract

Routine annual influenza immunization is increasingly recommended in young children. We compared the safety and immunogenicity of vaccination with trivalent inactivated influenza vaccine (TIV) versus MF59-adjuvanted TIV (aTIV) in children who received 2 half or full doses of aTIV or TIV, or non-influenza control vaccine, in an efficacy trial conducted 2 years earlier. 197 healthy children aged 30-96 months were randomized to receive vaccination with aTIV or TIV in 2010. To evaluate responses to the first follow-up seasonal vaccination after priming we excluded children who received influenza vaccine(s) in the 2009 pandemic year leaving 40 children vaccinated with aTIV, 26 children with TIV and 10 children with aTIV after a control vaccine in the parent study. Hemagglutination inhibiting antibodies were assayed on Days 1, 22 and 181. aTIV vaccination produced 6.9 to 8.0-fold higher antibody responses than the reference TIV-TIV regimen against A/H3N2 and B strains, which remained higher 6 months following vaccination. The response to the B/Victoria lineage antigen in the second year's vaccine (the first vaccine contained a B/Yamagata lineage antigen) demonstrated that aTIV primed for an adequate response after a single dose on Day 22 (GMTs 160, 95 to antigens in the 2 lineages, respectively), whereas TIV did not (GMTs 38, 20). Vaccination with aTIV produced slightly higher but acceptable local and systemic reactogenicity compared to TIV-TIV and TIV-aTIV mixed regimens. Within the limitations of a small study, the strong immune responses support the use of aTIV for vaccination in young children.

Keywords: AE, adverse event; CBER, Center for Biologics Evaluation & Research; CHMP, European Committee for Medicinal Products for Human Use; CI, confidence interval; FAS, full analyses set; GMR, geometric mean ratio; GMT, geometric mean titer; HI, hemagglutination inhibition; LAIV, live-attenuated influenza vaccine; MF59; SAE, serious adverse event; SD, standard deviation; TIV, trivalent inactivated influenza vaccine; aTIV, MF59-adjuvanted trivalent inactivated influenza vaccine; adjuvant; influenza; pediatric; revaccination; seasonal vaccine.

Figures

Figure 1.

Study flow.

Figure 2.

Homologous antibody responses in children 30-70%, the percentage of subjects achieving seroconversion should be ≥40% and geometric mean ratio should be >2.5. None of the subjects were vaccinated with seasonal or pandemic vaccine in 2009. Children vaccinated with non-influenza control during parent study only received aTIV in the extension study.

Figure 3.

Percentages of subjects with HI antibody titers ≥110 in children 30-