Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults
Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults
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DOI：
10.1016/j.vaccine.2012.10.080
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发表时间：
2012-12-14
期刊：
影响因子：
5.5
通讯作者：
Gurunathan, Sanjay
中科院分区：
文献类型：
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作者：
Seiberling, Michael;Bologa, Monica;Gurunathan, Sanjay
背景资料：基于保守蛋白抗原的肺炎球菌疫苗具有潜在的抗肺炎链球菌保护作用。目的：研究肺炎链球菌重组蛋白疫苗的安全性和免疫原性。方法：该I期、探索性、开放标签、单中心临床研究招募成人（18-50岁）。试验性安全性队列的参与者接受了6 μ g的单次肌内注射。安全性审查后，入组了3个剂量队列（6、25和100 μ g）;受试者接受了2次注射，间隔约30天。在每个剂量水平下每次注射后进行设盲安全性审查后，分配第二次注射和后续剂量队列。安全性终点包括征集性注射部位和全身反应、非征集性不良事件、严重不良事件和安全性实验室检查的发生率。免疫原性终点包括抗PhtD抗体的水平，通过ELISA.Results测量：63名参与者被招募，并收到试点安全剂量（n = 3）或至少1个剂量的PhtD候选疫苗在6 μ g（n =20），25 μ g（n = 20），或100 μ g（n =20）。未发现安全性问题。未报告疫苗相关严重不良事件。最常见的征集性注射部位反应为疼痛，最常见的征集性全身反应为肌痛和头痛;大多数反应为轻度和一过性。观察到的几何平均浓度（95% CI）为200.99 ELISA单位（148.46、272.10）、352.07（193.49，640.63）和699.15 6、25和100 μ g剂量队列中注射后1分别为（405.49，1205.48），（275.56，519.21）、837.32（539.29，1300.04）和1568.62（1082.92，2272.16）。征集性反应的频率在100 μ g剂量下最高。第二次注射显著增加了抗PhtD抗体的水平（ClinicalTrials.gov注册号NCT 01444001）。(C)2012爱思唯尔有限公司保留所有权利。
Background: Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.Objective: To explore safety and immunogenicity of a recombinant protein vaccine candidate against S. pneumoniae composed of adjuvanted pneumococcal histidine triad protein D (PhtD).Methods: This phase I, exploratory, open-label, single-center clinical study enrolled adults (18-50 years). Participants in a pilot safety cohort received a single intramuscular injection of 6 mu g. Following safety review, 3 dose cohorts were enrolled (6, 25, and 100 mu g); participants received 2 injections administered approximately 30 days apart. Assignment of the second injection and successive dose cohorts were made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events, serious adverse events, and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD antibodies as measured by ELISA.Results: Sixty-three participants were enrolled and received the pilot safety dose (n = 3) or at least 1 dose of PhtD vaccine candidate at 6 mu g (n =20), 25 mu g (n = 20), or 100 mu g (n =20). No safety concerns were identified. No vaccine-related serious adverse event was reported. The most common solicited injection site reaction was pain and most common solicited systemic reactions were myalgia and headache; most reactions were mild and transient. Observed geometric mean concentrations (95% CI) were 200.99 ELISA units (148.46, 272.10), 352.07 (193.49, 640.63), and 699.15 (405.49, 1205.48) post-injection 1 in the 6, 25, and 100 mu g dose cohorts, respectively, and 378.25 (275.56, 519.21), 837.32 (539.29, 1300.04), and 1568.62 (1082.92, 2272.16) post-injection 2.Conclusions: All dose levels were safe and immunogenic. The frequency of solicited reactions was highest at the 100 mu g dose. Administration of a second injection significantly increased the levels of anti-PhtD antibodies (ClinicalTrials.gov registry no. NCT01444001). (C) 2012 Elsevier Ltd. All rights reserved.