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
Journal
Pediatric Infectious Disease Journal
Pages
E333-E339
Date Issued
2021
Author(s)
Kim J.H.
Drame M.
Puthanakit T.
Chiu N.-C.
Supparatpinyo K.
Chiu C.-H.
Chen P.-Y.
Hwang K.-P.
Danier J.
Friel D.
Salaun B.
Woo W.
Vaughn D.W.
Innis B.
Schuind A.
Abstract
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 ?g hemagglutinin (HA)/AS03B, 0.9 ?g HA/AS03C, 1.9 ?g HA/AS03C, 3.75 ?g HA/AS03Cor 3.75 ?g HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-a-tocopherol, with AS03Bthe highest amount. One year later, all subjects were to receive unadjuvanted 3.75 ?g 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 ?g HA/AS03Branked 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 ?g HA/AS03B, 0.9 ?g HA/AS03Cand 1.9 ?g HA/AS03Cformulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 ?g HA/AS03D) to 60.5% (1.9 ?g HA/AS03B). Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 ?g HA/AS03Bproviding the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age. ? 2021 Lippincott Williams and Wilkins. All rights reserved.
Subjects
AS03; children; dose finding; H5N1; influenza vaccine
SDGs
Other Subjects
immunological adjuvant; influenza vaccine; virus antibody; blood; clinical trial; controlled study; dose response; female; human; immunology; infant; influenza; Influenza A virus (H5N1); male; multicenter study; phase 2 clinical trial; preschool child; randomized controlled trial; vaccine immunogenicity; Adjuvants, Immunologic; Antibodies, Viral; Child, Preschool; Dose-Response Relationship, Immunologic; Female; Humans; Immunogenicity, Vaccine; Infant; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Influenza, Human; Male
Publisher
Lippincott Williams and Wilkins
Type
journal article