Borys Dorota, Smulders Ronald, Haranaka Miwa, Nakano Takashi, Chichili Gurunadh R, Ebara Masaki, Hashimoto Atsuki, Iwahana Mioko, Oizumi Yuki, Nanra Jasdeep, Malley Richard, Sebastian Shite
GSK, Avenue Fleming 20, 1300 Wavre, Belgium.
Astellas Pharma Global Development, Inc., 2375 Waterview Drive, Northbrook, IL 60062, United States.
Vaccine. 2025 Jan 12;44:126545. doi: 10.1016/j.vaccine.2024.126545. Epub 2024 Nov 29.
The burden of pneumococcal diseases remains high in Japan. Pn-MAPS24v is a novel MAPS-based vaccine containing complexes of 24 serotype-specific polysaccharides (PS), non-covalently coupled with fusion protein 1 (CP1). This study evaluated the safety and immunogenicity of different dose levels of Pn-MAPS24v, administered in Japanese adults either subcutaneously (SC) or intramuscularly (IM).
In this phase 1, dose-escalation, observer-blind trial conducted in Japan, 54 pneumococcal vaccine-naïve adults aged 20-49 years (stage 1), and 72 adults aged 65-85 years (stage 2) were sequentially enrolled. In stage 1, participants were randomized 1:1 (SC:IM) to receive a single Pn-MAPS24v dose at one of the dose levels (1 μg, 2 μg, or 5 μg per PS). In stage 2, participants were randomized 3:1 (Pn-MAPS24v:23-valent pneumococcal polysaccharide vaccine [PPSV23]) and 1:1 (SC:IM) to receive a single dose of either Pn-MAPS24v (one of three dose levels), or PPSV23. Solicited adverse events (AEs) were collected through 7 days post-vaccination, and treatment-emergent AEs (TEAEs) up to 1 month post-vaccination. Serotype-specific opsonophagocytic activity titers and immunoglobulin G (IgG) concentrations, as well as anti-CP1 IgG concentrations were measured before and 1 month post-vaccination.
No safety or reactogenicity concerns were identified in any age category across groups. No grade 3-4 TEAEs, serious AEs, or deaths were reported. Regardless of the age category, dose level, administration route, or study vaccine, the frequency of reported TEAEs was low and all vaccine-related TEAEs were mild. Pain, tenderness, and fatigue were the most frequently reported solicited AEs. One month post-vaccination, Pn-MAPS24v induced serotype-specific immune responses that were comparable or higher than those elicited by PPSV23. The immune responses were similar after SC and IM administration.
Pn-MAPS24v showed an acceptable safety profile and was immunogenic after SC and IM administration, therefore supporting the further development of Pn-MAPS24v in Japan.
gov: NCT04265911.
在日本，肺炎球菌疾病的负担仍然很高。Pn-MAPS24v是一种基于新型多抗原肽系统（MAPS）的疫苗，包含24种血清型特异性多糖（PS）与融合蛋白1（CP1）非共价偶联的复合物。本研究评估了不同剂量水平的Pn-MAPS24v在日本成年人中皮下注射（SC）或肌肉注射（IM）后的安全性和免疫原性。
在日本进行的这项1期剂量递增、观察者盲法试验中，依次纳入了54名20-49岁未接种过肺炎球菌疫苗的成年人（1期）和72名65-85岁的成年人（2期）。在1期，参与者按1:1随机分组（SC:IM），接受三种剂量水平之一（每PS 1μg、2μg或5μg）的单次Pn-MAPS24v剂量。在2期，参与者按3:1随机分组（Pn-MAPS24v:23价肺炎球菌多糖疫苗[PPSV23]）并按1:1随机分组（SC:IM），接受单次剂量的Pn-MAPS24v（三种剂量水平之一）或PPSV23。在接种疫苗后7天内收集主动报告的不良事件（AE），在接种疫苗后1个月内收集治疗中出现的不良事件（TEAE）。在接种疫苗前和接种后1个月测量血清型特异性调理吞噬活性滴度、免疫球蛋白G（IgG）浓度以及抗CP1 IgG浓度。
在各年龄组的任何组中均未发现安全性或反应原性问题。未报告3-4级TEAE、严重AE或死亡病例。无论年龄组、剂量水平、给药途径或研究疫苗如何，报告的TEAE频率都很低，且所有与疫苗相关的TEAE均为轻度。疼痛、压痛和疲劳是最常报告的主动AE。接种疫苗1个月后，Pn-MAPS24v诱导的血清型特异性免疫反应与PPSV23诱导的免疫反应相当或更高。皮下注射和肌肉注射后的免疫反应相似。
Pn-MAPS24v显示出可接受的安全性概况，皮下注射和肌肉注射后具有免疫原性，因此支持Pn-MAPS24v在日本的进一步开发。
美国国立医学图书馆临床试验注册中心：NCT04265911。
