Clinical phase II and III studies of an AS03-adjuvanted H5N1 influenza vaccine produced in an EB66
Adult
Antibodies, Viral
/ blood
Cell Culture Techniques
/ methods
Double-Blind Method
Drug Combinations
Female
Humans
Immunogenicity, Vaccine
Influenza A Virus, H5N1 Subtype
Influenza Vaccines
/ administration & dosage
Influenza, Human
/ prevention & control
Injections, Intramuscular
Male
Middle Aged
Polysorbates
/ administration & dosage
Random Allocation
Squalene
/ administration & dosage
Vaccination
Young Adult
alpha-Tocopherol
/ administration & dosage
AS03
EB66® cells
H5N1 influenza
Journal
Influenza and other respiratory viruses
ISSN: 1750-2659
Titre abrégé: Influenza Other Respir Viruses
Pays: England
ID NLM: 101304007
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
09
11
2018
revised:
09
11
2019
accepted:
21
04
2020
pubmed:
25
6
2020
medline:
24
8
2021
entrez:
25
6
2020
Statut:
ppublish
Résumé
We have developed an AS03-adjuvanted H5N1 influenza vaccine produced in an EB66 In accordance with Japanese guidelines for development of pandemic prototype vaccines, the phase II study was conducted in a double-blind, randomized, parallel-group comparison study and the phase III study was conducted in an open-label, non-randomized, uncontrolled study. Healthy adult volunteers aged 20 - 64 years enrolled in the phase II and III studies (N = 248 and N = 369) received KD-295 intramuscularly twice with a 21-day interval. After administration, immune response and adverse events were evaluated. In the phase II study, four different vaccine formulations were compared: MA (3.75 μg hemagglutinin [HA] antigen + AS03 adjuvant system), MB (3.75 μg HA + 1/2AS03), HA (7.5 μg HA + AS03), and HB (7.5 μg HA + 1/2AS03). In the phase III study, the MA formulation was further evaluated. In the phase II study, all four vaccine formulations were well-tolerated and no SAE related to vaccination were observed. The MA formulation was slightly more immunogenic and less reactogenic among the vaccine formulations. Therefore, the MA formulation was selected for the phase III study, and it was well-tolerated and no serious adverse drug reactions were observed. The vaccine fulfilled the three immunogenicity criteria described in the Japanese guidelines. These data indicate that the MA formulation of KD-295 was well-tolerated and highly immunogenic and it can be considered a useful pandemic and pre-pandemic influenza vaccine.
Sections du résumé
BACKGROUND
We have developed an AS03-adjuvanted H5N1 influenza vaccine produced in an EB66
OBJECTIVES
In accordance with Japanese guidelines for development of pandemic prototype vaccines, the phase II study was conducted in a double-blind, randomized, parallel-group comparison study and the phase III study was conducted in an open-label, non-randomized, uncontrolled study.
METHODS
Healthy adult volunteers aged 20 - 64 years enrolled in the phase II and III studies (N = 248 and N = 369) received KD-295 intramuscularly twice with a 21-day interval. After administration, immune response and adverse events were evaluated. In the phase II study, four different vaccine formulations were compared: MA (3.75 μg hemagglutinin [HA] antigen + AS03 adjuvant system), MB (3.75 μg HA + 1/2AS03), HA (7.5 μg HA + AS03), and HB (7.5 μg HA + 1/2AS03). In the phase III study, the MA formulation was further evaluated.
RESULTS
In the phase II study, all four vaccine formulations were well-tolerated and no SAE related to vaccination were observed. The MA formulation was slightly more immunogenic and less reactogenic among the vaccine formulations. Therefore, the MA formulation was selected for the phase III study, and it was well-tolerated and no serious adverse drug reactions were observed. The vaccine fulfilled the three immunogenicity criteria described in the Japanese guidelines.
CONCLUSIONS
These data indicate that the MA formulation of KD-295 was well-tolerated and highly immunogenic and it can be considered a useful pandemic and pre-pandemic influenza vaccine.
Identifiants
pubmed: 32579785
doi: 10.1111/irv.12755
pmc: PMC7431644
doi:
Substances chimiques
Antibodies, Viral
0
Drug Combinations
0
Influenza Vaccines
0
Polysorbates
0
Squalene
7QWM220FJH
AS03 adjuvant
A7YT618XBV
alpha-Tocopherol
H4N855PNZ1
Types de publication
Clinical Trial, Phase II
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
551-563Informations de copyright
© 2020 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.
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