Immunogenicity and safety of Fluzone® intradermal and high-dose influenza vaccines in older adults ≥65 years of age: A randomized, controlled, phase II trial

Abstract

We conducted a randomized, controlled, multicenter, phase II study to evaluate the immunogenicity and safety of an investigational intradermal (ID) trivalent influenza vaccine (TIV) and a high-dose (HD) intramuscular (IM) TIV in older adults (≥65 years of age). Older adult subjects were immunized with ID vaccine containing either 15μg hemagglutinin (HA)/strain (n=636) or 21μg HA/strain (n=634), with HD IM vaccine containing 60μg HA/strain (n=320), or with standard-dose (SD) IM vaccine (Fluzone(®); 15μg HA/strain; n=319). For comparison, younger adults (18-49 years of age) were immunized with SD IM vaccine. In older adults, post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain. Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain. Results did not differ significantly for the two ID vaccine dosages. Post-vaccination geometric mean titers, seroconversion rates, and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and, for most measures, were comparable to those of younger adult SD IM vaccine recipients. Injection-site reactions, but not systemic reactions or unsolicited adverse events, were more common with the ID vaccines than with the IM vaccines. No treatment-related serious adverse events were reported. This study demonstrated that: (1) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults; (2) the HD vaccine was more immunogenic than the ID vaccines in older adults; and (3) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses (ClinicalTrials.gov identifier no.: NCT00551031).

Immunogenicity of intramuscular MF59-adjuvanted and intradermal administered influenza enhanced vaccines in subjects aged over 60: A literature review

“…The required 60% of seroprotected volunteers was reached in only some of the studies reporting the results for B strain with values ranging from 66.1 to 100%. Values below 60% were found in the first and second year of Arnou et al 28 (55.7 and 59.9%, respectively) and in Van Damme et al 30 The GMTR was in most instances >2 (range 2.5 and 3.7) except in the second year of Arnou et al, 28 Scheifele et al 31 (1.6) and Tsang et al 60 (1.7) studies. Seroconversion rates >30% were found in 6 trials (range 36.4-46.0%).…”

“…Table 2 reports HI antibody responses induced following administration of ID vaccine using BD's Soluvia to volunteers aged 60 y in the 9 different clinical studies considered in the present review. [28][29][30][31]41,[57][58][59][60] In the study by Arnou et al 28 the results over 3 consecutive years were reported and in one study 58 ) only the results for A/H3N2 strain were included. The total number of subjects examined was 5035 for A/H3N2 and 5100 for A/H1N1 and B antigens.…”

“…The values of the studies that did not satisfy EMA criteria 28,30,31,60 ranged from 15.8 to 17.2%. In all the years studied, 3 or at least 2 of the EMA immunogenicity criteria were satisfied, except the second year of the study by Arnou et al 28 when none of the immunogenicity criteria was satisfied and the studies conducted by Van Damme et al, 30 Scheifele et al 31 and Tsang et al 60 when only one value was reached. However, Van Damme et al, 30 and Scheifele et al, 31 measured antibody titers using both HI and SRH methods.…”

Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination

“…Integrating these transcriptional profiling data with genotyping information could provide further insights [27]. Additional experiments should also clarify whether alternate formulations of influenza vaccine developed for older adults, such as high-dose or intradermal preparations [28], are able to modify these alterations in gene expression.…”

Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview

“…Subjects immunized with ID vaccine were more likely to report more injection-site reactions. 85 An interesting study carried out by Gorse and co-workers assessed the safety and reactogenicity in case of revaccination with ID preparation, performing a phase II, active-controlled, multi-centre, open-label trial in 1,250 adults aged 18-64 years randomly assigned to ID or IM vaccine. Vaccines with ID vaccine reported erythema, induration, swelling, pruritus and ecchymosis more often than those receiving IM vaccine, especially if they had been immunized with ID vaccine in the previous year.…”