A novel quadrivalent seasonal influenza vaccine (FluCyd-vac) adjuvanted with hydroxypropropyl-b-cyclodextrin (HP-β-CyD) was found to be safe and immunogenic despite containing less hemagglutinin (HA) antigens than that of a standard influenza vaccine, according to results of a phase 1 clinical trial published in Vaccine.
Researchers conducted a randomized, single-blinded, phase 1 clinical trial to assess the safety and immunogenicity of FluCyd-vac. Healthy volunteers (N=36) were randomly assigned in a 2:1 fashion to receive either a standard influenza vaccine adjuvanted with a single dose of FluCyD-vac or standard influenza vaccine alone. The FluCyd-vac contained 9 mg of HA plus 20% weight per volume of HP-β-CyD, and the standard vaccine contained 15 mg of HA. The primary endpoint was the rate of solicited adverse events (AEs) within 7 days of FluCyD-vac receipt; secondary endpoints were the rate of severe AEs and immune responses induced by FluCyd-vac, assessed via measurement of HA inhibition titers. Flow cytometry was used to assess T-cell function in peripheral blood mononuclear cells after stimulation with a mixture of antigens from 4 influenza strains, including H1N1, H2N2, B/Yamagata, and B/Victoria.
Among participants in the FluCyd-vac (n=24) and standard vaccination (n=12) groups, the median age was 43.5 (range, 23-61) and 37.0 (range, 22-53) years, and 79.2% and 83.3% were women, respectively.
Overall, FluCyD-vac showed a similar safety profile to that of standard influenza vaccination. Within 7 days of vaccination receipt, the most common solicited AE among participants in both the FluCyd-vac vs standard vaccination groups was mild injection site pain (41.7% vs 50.0%), with no severe AEs reported by participants in either group. Of note, the rate of nasopharyngitis was increased among participants who received FlyCyd-vac vs those who received standard vaccination (16.7% vs 8.3%).
Although FlyCyd-vac contained 40% less HA antigens vs that of the standard influenza vaccine, HA inhibition titers measured 21 days after vaccination were similar between participants in both groups. No significant differences in the rate interferon-γ-releasing CD4+ T cells were noted among the 2 participants groups between baseline and after vaccination receipt. However, a significant increase in the rate of tumor necrosis factor-a-producing CD4+ T cells occurred among participants in the FluCyd-vac group between baseline (median, 0.075%) and day 21 (median, 0.092%) following vaccination (P =.00034).
This study was limited by its small sample size.
The activation of tumor necrosis factor-a and subsequent production of CD4+ T cells when HP-b-CyD is co-administered with HA antigens “could overcome the disadvantage of the relatively weak immunogenicity of the HA split vaccine,” the researchers concluded.
Disclosure: This research was supported by Daiichi Sankyo Co., Ltd. One author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Watanabe A, Nishida S, Burcu T, et al. Safety and immunogenicity of a quadrivalent seasonal influenza vaccine adjuvanted with hydroxypropyl-β-cyclodextrin: a phase 1 clinical trial. Vaccine. 2022;40(31):4150-4159. doi:10.1016/j.vaccine.2022.05.060