TY - JOUR
T1 - Immunogenicity and Safety of AS03-adjuvanted H5N1 Influenza Vaccine in Children 6-35 Months of Age
T2 - Results From a Phase 2, Randomized, Observer-blind, Multicenter, Dose-ranging Study
AU - Kim, Joon Hyung
AU - Drame, Mamadou
AU - Puthanakit, Thanyawee
AU - Chiu, Nan Chang
AU - Supparatpinyo, Khuanchai
AU - Huang, Li Min
AU - Chiu, Cheng Hsun
AU - Chen, Po Yen
AU - Hwang, Kao Pin
AU - Danier, Jasur
AU - Friel, Damien
AU - Salaun, Bruno
AU - Woo, Wayne
AU - Vaughn, David W.
AU - Innis, Bruce
AU - Schuind, Anne
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - 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)/AS03B, 0.9 g HA/AS03C, 1.9 g HA/AS03C, 3.75 mg HA/AS03Cor 3.75 mg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03Bthe 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/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 mg HA/AS03B, 0.9 mg HA/AS03Cand 1.9 mg HA/AS03Cformulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 mg HA/AS03D) to 60.5% (1.9 mg HA/AS03B). Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 mg HA/AS03Bproviding the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.
AB - 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)/AS03B, 0.9 g HA/AS03C, 1.9 g HA/AS03C, 3.75 mg HA/AS03Cor 3.75 mg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03Bthe 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/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 mg HA/AS03B, 0.9 mg HA/AS03Cand 1.9 mg HA/AS03Cformulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 mg HA/AS03D) to 60.5% (1.9 mg HA/AS03B). Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 mg HA/AS03Bproviding the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.
KW - AS03
KW - H5N1
KW - children
KW - dose finding
KW - influenza vaccine
UR - https://www.scopus.com/pages/publications/85112751314
U2 - 10.1097/INF.0000000000003247
DO - 10.1097/INF.0000000000003247
M3 - 文章
C2 - 34285165
AN - SCOPUS:85112751314
SN - 0891-3668
VL - 40
SP - E333-E339
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
IS - 9
ER -
