Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age: Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study

Background: This phase 2 observer-blind, randomized, multicenter, dose-ranging study evaluated immunogenicity and safety of different formulations of an AS03-adjuvanted H5N1 influenza vaccine in children 6-35 months of age. Methods: One hundred eighty-five children randomized into 5 groups [1.9 mg hemagglutinin (HA)/AS03_B, 0.9 g HA/AS03_C, 1.9 g HA/AS03_C, 3.75 mg HA/AS03_Cor 3.75 mg HA/AS03_D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03_Bthe highest amount. One year later, all subjects were to receive unadjuvanted 3.75 mg HA as antigen challenge. Immunogenicity was assessed 21 days after primary vaccination (day 42) and 7 days after antigen challenge (day 392). Immunogenicity-fever index, based on hemagglutination inhibition and microneutralization antibody titers at day 42 and fever 7 days after each vaccination, was used to guide the selection of an acceptable formulation. Results: After primary vaccination, formulations elicited strong homologous immune responses with all subjects' hemagglutination inhibition titers ≥1:40 post-vaccination. Immunogenicity-fever index based on hemagglutination inhibition and microneutralization assays showed that 1.9 mg HA/AS03_Branked the highest. Antibody levels persisted >4 times above baseline 12 months after primary vaccination with all formulations (day 385). Antibodies increased >4-fold after antigen challenge (day 392/day 385) with 1.9 mg HA/AS03_B, 0.9 mg HA/AS03_Cand 1.9 mg HA/AS03_Cformulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 mg HA/AS03_D) to 60.5% (1.9 mg HA/AS03_B). Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 mg HA/AS03^Bproviding the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.