Immunogenicity and safety of the new intradermal influenza vaccine in adults and elderly: A randomized phase 1/2 clinical trial

Abstract

BackgroundRecent clinical evidence indicates that an intradermal (ID) delivery of vaccines confers superior immunogenicity as compared to a standard intramusclular or subcutaneous (SC) delivery. MethodsIn this exploratory study, 600 healthy adults were randomized to 6 study groups with subgroups of young adults (20–64 years old) and older adults (65 years and older). The subjects were either injected by a novel ID injection system with a single dose of 6, 9, or 15μg HA or two doses (21 days apart) of 15μg HA per strain or injected by an SC injection method with a single or two doses (21 days apart) of 15μg HA per strain. Immunogenicity was assessed using hemagglutination inhibition (HAI) titer and microneutralization titer on Days 0, 10, 21, and 42. Solicited and unsolicited adverse events were recorded for 7 and 21 days post-vaccination, respectively. ResultsIn both young adults and older adults groups, the geometric titer (GMT) ratios of HAI in the ID 15μg HA group were higher than those in the SC 15μg HA group on both Day 10 and Day 21, while those in the ID 6 and ID 9μg HA groups were comparable with those in the SC 15μg HA group. The kinetics of GMTs of HAI suggested that the ID vaccine has the potential to induce the prompt immune response, which is rather hampered in older adults as seen in the SC vaccine groups. The injection-site AEs were generally mild and transient, and did not occur in a dose or dosage-dependent manner. ConclusionsThe results of this study clearly suggest that the immunologic profile of the ID vaccine is better than that of the SC vaccine, while the safety profile of the ID vaccine is similar to that of the SC vaccine. In this exploratory study with almost 100 subjects per each group, single or two-dose administration of the ID vaccine containing 15μg HA was suggested to be an appropriate regimen in order to prevent influenza and to reduce the associated disease burden. Trial registrationJAPIC Clinical Trials Information (JapicCTI-132096).