Centre for Human Drug Research, Leiden, the Netherlands; Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands.
Mucosis B.V., Groningen, the Netherlands; 3D-PharmXchange, Tilburg, the Netherlands.
Vaccine. 2024 Sep 17;42(22):125836. doi: 10.1016/j.vaccine.2024.03.063. Epub 2024 May 20.
Intranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry. Immunogenicity of intranasal vaccination can be improved through the use of adjuvants. Bacteria-like particles derived fromLactococcus lactishave the potential to serve as a vaccine adjuvant.This clinical study investigated the safety, reactogenicity and immunogenicity of intranasal seasonal influenza vaccine adjuvanted with gram-positive matrix particles (FluGEM®).
This was a first-in-human, randomized, double-blind, controlled, dose-escalation study performed at the Centre for Human Drug Research (CHDR), the Netherlands. Participants aged 18-49 were randomized in a 3:1 ratio to receive FluGem® in ascending doses (two-dose regimens) together with a standard trivalent inactivated influenza vaccine or unadjuvanted TIV only. Primary outcomes were safety and tolerability. Secondary outcomes were serum hemagglutination inhibition (HI) antibody titers and mucosal IgA. The most immunogenic dose was used in an additionalelderly cohort (>65 years).
Ninty participants were included. Intranasal FluGem®was safe and well tolerated. The majority of adverse events were mild (97.4 %) with (un)solicited adverse events comparable across all dose levels and control groups. All groups showed geometric mean increases ≥ 2.5-fold. Seroconversion (≥40 % participants) was achieved at both day 21 (single-dose) and 42 (two-dose) for the 1.25 mg dose and on day 42 (two-dose only) for the 2.5 mg dose. Highest geometric mean IgA increases were observed in the 1.25 mg group on day 21. Immunogenicity was less pronounced in elderly.
Intranasal vaccination of FluGEM®was safe and tolerable in healthy adult volunteers aged 18-49 years and 65 and older. Highest immunogenicity was observed for 1.25 mg and 2.5 mg doses (compared to 5 mg) suggesting a potential non-linear dose-response relationship.More research is needed to further investigate the capabilities of bacteria-like peptides as adjuvants.
鼻腔内给药为呼吸道疫苗提供了许多优势，例如在病毒进入部位引发全身和黏膜免疫。通过使用佐剂可以提高鼻内接种的免疫原性。源自乳球菌的细菌样颗粒具有作为疫苗佐剂的潜力。这项临床研究调查了革兰氏阳性基质颗粒（FluGEM®）佐剂的季节性流感鼻内疫苗的安全性、反应原性和免疫原性。
这是在荷兰人类药物研究中心（CHDR）进行的首次人体、随机、双盲、对照、剂量递增研究。18-49 岁的参与者按照 3:1 的比例随机分为两组，分别接受递增剂量的 FluGEM®（两剂量方案）与标准三价灭活流感疫苗或仅无佐剂 TIV 联合接种。主要结局为安全性和耐受性。次要结局为血清血凝抑制（HI）抗体滴度和黏膜 IgA。在另外一个老年队列（>65 岁）中使用最具免疫原性的剂量。
共纳入 90 名参与者。鼻腔内 FluGEM®安全且耐受良好。大多数不良事件为轻度（97.4%），且各剂量水平和对照组的不良事件发生率相似。所有组的几何平均增加均≥2.5 倍。在第 21 天（单剂量）和第 42 天（双剂量），1.25mg 剂量组和第 42 天（仅双剂量），2.5mg 剂量组的血清转化率（≥40%的参与者）均达到 40%。在第 21 天，1.25mg 组观察到最高的几何平均 IgA 增加。在老年人中，免疫原性较低。
在 18-49 岁和 65 岁及以上的健康成年志愿者中，鼻腔内接种 FluGEM®是安全且耐受的。观察到 1.25mg 和 2.5mg 剂量（与 5mg 相比）的最高免疫原性，表明可能存在非线性剂量反应关系。需要进一步研究来进一步探索细菌样肽作为佐剂的能力。
