新型多价肺炎球菌疫苗在成人中的安全性和免疫原性：一项 1 期随机临床试验。
Safety and immunogenicity of a novel multiple antigen pneumococcal vaccine in adults: A Phase 1 randomised clinical trial.
机构信息
ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
ImmunoBiology Ltd, Babraham Research Campus, Cambridge, UK.
出版信息
Vaccine. 2017 Dec 18;35(51):7181-7186. doi: 10.1016/j.vaccine.2017.10.076. Epub 2017 Nov 10.
BACKGROUND
Pneumococcal vaccines, combining multiple protein antigens, provide an alternative approach to currently marketed vaccines and may provide broader protection against pneumococcal disease. This trial evaluated the safety and immunogenicity of a novel vaccine candidate PnuBioVax in healthy young adults.
METHODS
In a Phase 1 double-blind study, 36 subjects (18-40 years) were randomised to receive 3 doses of PnuBioVax, 28 days apart, at one of three dose levels (50, 200, 500 µg) or placebo. Safety assessments included rates of emergent adverse events (AEs), injection site and systemic reactions. Immunogenicity endpoints included antibody titre against PnuBioVax and selected pneumococcal antigens.
RESULTS
In the placebo (n=9) and PnuBioVax (n=27) vaccinated subjects, there were 15 and 72, reported TEAEs, respectively. The majority of TEAEs were classified as common vaccine related AEs. There were no serious AEs. Common vaccine-related AEs occurred in 13 PnuBioVax (48%) and 2 placebo (22%) subjects and were all headaches (mild and moderate). Injection site reactions, mostly pain and tenderness (graded mild or moderate) were reported, in particular in the 200 µg and 500 µg PnuBioVax groups. There were no clinically significant changes in vital signs, ECG or blood chemistries. Subjects receiving the higher dose (200 and 500 μg) demonstrated a greater fold increase in IgG titre compared with the starting dose (50 μg) or the placebo group. The fold-increase was statistically significantly higher for 200 and 500µg PnuBioVax vs 50µg PnuBioVax and placebo at each timepoint post-immunisation. Most subjects receiving 200 and 500 µg PnuBioVax demonstrated a ≥2-fold increase in antibody against pneumolysin (Ply), Pneumococcal surface antigen (PsaA), PiaA (Pneumococcal iron acquisition), PspA (Pneumococcal surface protein A) and pilus proteins (RrgB and RrgA).
CONCLUSIONS
All dose levels were considered safe and well tolerated. There was a statistically significant increase in anti-PnuBioVax IgG titres at the 200 and 500 µg dose levels compared to 50 µg and placebo.
TRIAL REGISTRATION NUMBER
NCT02572635https://www.clinicaltrials.gov.
背景
结合多种蛋白抗原的肺炎球菌疫苗为目前市场上的疫苗提供了一种替代方法，可能对肺炎球菌疾病提供更广泛的保护。本试验评估了新型疫苗候选物 PnuBioVax 在健康年轻成年人中的安全性和免疫原性。
方法
在一项 1 期双盲研究中，36 名（18-40 岁）受试者随机接受 3 剂 PnuBioVax，间隔 28 天，剂量水平为 3 种（50、200、500μg）或安慰剂。安全性评估包括急性不良事件（AE）的发生率、注射部位和全身反应。免疫原性终点包括针对 PnuBioVax 和选定肺炎球菌抗原的抗体滴度。
结果
在安慰剂（n=9）和 PnuBioVax（n=27）接种组中，分别报告了 15 例和 72 例 TEAEs。大多数 TEAEs 被归类为常见疫苗相关 AE。没有严重的 AE。13 名 PnuBioVax（48%）和 2 名安慰剂（22%）受试者出现常见疫苗相关 AE，均为头痛（轻度和中度）。报告了注射部位反应，主要为疼痛和压痛（分级为轻度或中度），特别是在 200μg 和 500μg PnuBioVax 组。生命体征、心电图或血液化学无临床显著变化。接受高剂量（200 和 500μg）的受试者与起始剂量（50μg）或安慰剂组相比，IgG 滴度的增加幅度更大。在每次免疫接种后，与 50μg PnuBioVax 和安慰剂相比，200μg 和 500μg PnuBioVax 的 IgG 滴度增加幅度均统计学显著更高。大多数接受 200μg 和 500μg PnuBioVax 的受试者针对肺炎球菌溶解素（Ply）、肺炎球菌表面抗原（PsaA）、PiaA（肺炎球菌铁摄取）、PspA（肺炎球菌表面蛋白 A）和菌毛蛋白（RrgB 和 RrgA）的抗体增加了≥2 倍。
结论
所有剂量水平均被认为是安全且耐受良好的。与 50μg 和安慰剂相比，200μg 和 500μg 剂量水平的抗 PnuBioVax IgG 滴度有统计学显著增加。
试验注册号
NCT02572635https://www.clinicaltrials.gov。
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