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Clinical Trial
. 2021 Sep 1;40(9):e333-e339.
doi: 10.1097/INF.0000000000003247.

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

Joon Hyung Kim  1 , Mamadou Drame  2 , Thanyawee Puthanakit  3 , Nan-Chang Chiu  4 , Khuanchai Supparatpinyo  5 , Li-Min Huang  6 , Cheng-Hsun Chiu  7 , Po-Yen Chen  8 , Kao-Pin Hwang  9 , Jasur Danier  10 , Damien Friel  11 , Bruno Salaun  12 , Wayne Woo  13 , David W Vaughn  14 , Bruce Innis  15 , Anne Schuind  16
Affiliations
Clinical Trial

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

Joon Hyung Kim et al. Pediatr Infect Dis J. .

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 µg hemagglutinin (HA)/AS03B, 0.9 µg HA/AS03C, 1.9 µg HA/AS03C, 3.75 µg HA/AS03C or 3.75 µg HA/AS03D] were to receive 2 doses administered 21 days apart (primary vaccination). AS03 was classified by amount of DL-α-tocopherol, with AS03B the highest amount. One year later, all subjects were to receive unadjuvanted 3.75 µg 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 µg HA/AS03B ranked 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 µg HA/AS03B, 0.9 µg HA/AS03C and 1.9 µg HA/AS03C formulations. Overall per subject, the incidence of fever ranged from 28.6% (3.75 µg HA/AS03D) to 60.5% (1.9 µg HA/AS03B).

Conclusions: All formulations were highly immunogenic and demonstrated acceptable safety profiles, with the 1.9 µg HA/AS03B providing the most favorable balance of immunogenicity versus reactogenicity for use in children 6-35 months of age.

Trial registration: ClinicalTrials.gov NCT02719743.

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Conflict of interest statement

J.H.K., M.D., J.D., D.F. and B.S. are employees of the GSK group of companies. W.W., D.W.V., B.I. and A.S. were employees of the GSK group of companies during the conduct of the study. J.H.K., B.S., M.D., J.D., W.W. and A.S. hold shares from the GSK group of companies. T.P., N.-C.C., K.S. and L.-M.H. received funds from the GSK group of companies through their institution for the conduct of the study. L.-M.H. received personal fees from the GSK group of companies for educational lectures. J.H.K., M.D., T.P., N.-C.C., K.S., L.-M.H., J.D., D.F., B.S., W.W., D.W.V., B.I. and A.S. declare no other financial and nonfinancial relationships and activities. K.-P.H., P.-Y.C. and C.-H.C. declare no financial and nonfinancial relationships and activities and no conflicts of interest.

Figures

FIGURE 1.
FIGURE 1.
Immunogenicity index, fever index and immunogenicity-fever index for H5N1 HI and MN antibodies at day 42 (ATP cohort for immunogenicity). AS03 is an adjuvant system containing DL-α-tocopherol and squalene in oil-in-water emulsion (AS03B containing 5.93 mg DL-α-tocopherol, AS03C containing 2.97 mg DL-α-tocopherol, and AS03D containing 1.48 mg DL-α-tocopherol).
FIGURE 2.
FIGURE 2.
Mean geometric increase for vaccine homologous hemagglutinin and microneutralizing antibodies at day 392 versus day 385 (adapted ATP cohort for immunogenicity). AS03 is an adjuvant system containing DL-α-tocopherol and squalene in oil-in-water emulsion (AS03B containing 5.93 mg DL-α-tocopherol, AS03C containing 2.97 mg DL-α-tocopherol, and AS03D containing 1.48 mg DL-α-tocopherol).
FIGURE 3.
FIGURE 3.
Overall per-subject incidence of general adverse events (AEs; %) during the 7-day (days 0–6) postvaccination period across the primary dose series (TVC).* *Detailed results are provided in Supplemental Digital Content 6; http://links.lww.com/INF/E463. AS03 is an adjuvant system containing DL-α-tocopherol and squalene in oil-in-water emulsion (AS03B containing 5.93 mg DL-α-tocopherol, AS03C containing 2.97 mg DL-α-tocopherol, and AS03D containing 1.48 mg DL-α-tocopherol).
See this image and copyright information in PMC

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