Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan; Laboratory of Thermo-therapeutics for vascular dysfunction, Osaka University, Suita, Osaka, Japan.
Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Japan.
Vaccine. 2022 Jul 29;40(31):4150-4159. doi: 10.1016/j.vaccine.2022.05.060. Epub 2022 Jun 4.
Hydroxypropyl-β-cyclodextrin (HP-β-CyD), an oligosaccharide used as an excipient in pharmaceutical preparation, was recently reported to function as a vaccine adjuvant to co-administered antigens. In this study, we investigated the safety and immunogenicity of a seasonal influenza vaccine adjuvanted with HP-β-CyD (FluCyD-vac) in healthy adults compared with those of a standard seasonal influenza vaccine (Flu-vac).
We conducted a single-blinded randomized phase 1 clinical trial study, and used two quadrivalent split seasonal influenza vaccines: FluCyD-vac containing 9 μg of HA/strain and 20% w/v of HP-β-CyD, and Flu-vac containing 15 μg of hemagglutinin (HA)/strain only. All participants were randomly assigned to receive a single dose of Flu/CyD-vac or Flu-vac at a ratio of 2:1. We assessed solicited and unsolicited adverse events (AEs) and immune responses using hemagglutination inhibition (HI) titers. In addition, we assessed T-cell function in peripheral blood mononuclear cells (PBMCs), after stimulation with HA vaccine strains, using flow cytometry.
Among 36 healthy volunteers enrolled in the study (FluCyD-vac, n = 24; Flu-vac, n = 12), FluCyD-vac was well tolerated. Most of the solicited AEs were mild local skin reactions at the injection site. No serious AEs were reported in either group. HI titers 21 days after vaccination with FluCyD-vac were comparable with those of Flu-vac and sufficient to meet international criteria, despite reduced HA antigen doses. When PBMCs were stimulated with the four HA antigens in the vaccine, tumor necrosis factor (TNF)-α-producing CD4 T cells were enhanced in the FluCyD-vac group.
FluCyD-vac was well-tolerated and immunogenic, despite containing 40% less HA antigens than Flu-vac. This study showed that HP-β-CyD is a potentially safe, novel adjuvant for human influenza vaccine.
UMIN000028530.
羟丙基-β-环糊精（HP-β-CyD）是一种用作药物制剂赋形剂的寡糖，最近有报道称其可作为佐剂与共给药的抗原协同作用。在这项研究中，我们研究了与标准季节性流感疫苗（Flu-vac）相比，用 HP-β-CyD（FluCyD-vac）佐剂的季节性流感疫苗在健康成年人中的安全性和免疫原性。
我们进行了一项单盲随机 1 期临床试验研究，使用了两种四价季节性流感疫苗：含 9μg 血凝素（HA）/株和 20%w/v HP-β-CyD 的 FluCyD-vac，以及仅含 15μg 血凝素（HA）/株的 Flu-vac。所有参与者均随机接受一剂 Flu/CyD-vac 或 Flu-vac，比例为 2:1。我们使用血凝抑制（HI）滴度评估了有或无的不良事件（AE）和免疫反应。此外，我们使用流式细胞术评估了刺激后外周血单核细胞（PBMC）中的 T 细胞功能。
在纳入研究的 36 名健康志愿者中（FluCyD-vac，n=24；Flu-vac，n=12），FluCyD-vac 具有良好的耐受性。大多数有或无的不良事件是轻度的局部皮肤反应。两组均未报告严重不良事件。FluCyD-vac 接种后 21 天的 HI 滴度与 Flu-vac 相当，且尽管 HA 抗原剂量减少，但足以达到国际标准。当用疫苗中的四种 HA 抗原刺激 PBMC 时，FluCyD-vac 组的肿瘤坏死因子（TNF）-α产生 CD4 T 细胞增强。
尽管 FluCyD-vac 中的 HA 抗原含量比 Flu-vac 少 40%，但仍具有良好的耐受性和免疫原性。这项研究表明，HP-β-CyD 是一种安全、新型的人用流感疫苗佐剂。
UMIN000028530。
