Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study
Safety and immunogenicity of a candidate bioconjugate vaccine against Shigella dysenteriae type 1 administered to healthy adults: A single blind, partially randomized Phase I study
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DOI：
10.1016/j.vaccine.2015.06.102
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发表时间：
2015-08-26
期刊：
影响因子：
5.5
通讯作者：
Fonck, Veronica Gambillara
中科院分区：
文献类型：
--
作者：
Hatz, Christoph F. R.;Bally, Bettina;Fonck, Veronica Gambillara
背景：志贺氏菌在流行国家引起严重疾病，尤其是儿童。针对志贺氏菌的候选疫苗已经进行了几项有效性试验，但缺乏保护，安全性问题或制造挑战阻碍了成功的市场批准。结合疫苗已显示对不同病原体（即，脑膜炎奈瑟菌、肺炎志贺氏菌、流感嗜血杆菌）。生物结合技术，利用这里的志贺氏菌候选疫苗，提供了一种新的和潜在的更简单的方式来开发和生产疫苗的主要原因之一的发病率和死亡率在发展中国家。在一项单盲、部分随机I期研究中，评价了由志贺氏菌01脂多糖的多糖组分与铜绿假单胞菌外毒素蛋白A（EPA）缀合制成的志贺氏菌生物缀合物疫苗（GVXN SD 133）在健康成人中的免疫原性和安全性。40名受试者（10个在每个剂量组; 2微克或10微克，有或没有铝佐剂）接受两次注射，间隔60天，并随访150 days.Results：两种剂量和制剂耐受性良好，安全性和reactogenicity的配置文件是一致的，与其他结合疫苗，adjuvanted或没有，独立的剂量和注射次数。GVXN SD 133疫苗在所有接种组的所有时间点均引起统计学显著的O 1特异性体液应答。组间比较未显示免疫球蛋白G和A的几何平均滴度在任何接种后时间点的统计学显著差异。结论：本研究表明，GVXN SD 133疫苗具有令人满意的安全性。它引起了显着的体液反应志贺氏菌O 1多糖在所有剂量的测试。蛋白质载体还引发了功能性抗体，显示了该技术在保留糖和结合蛋白表位方面的优势。(C)2015由Elsevier Ltd.出版
Background: Shigellae cause severe disease in endemic countries, especially in children. Several efficacy trials have been conducted with candidate vaccines against Shigellae, but the lack of protection, the safety concerns, or manufacturing challenges hindered successful market approval. Conjugated vaccines have been shown to be safe and effective for different pathogens (i.e., Neisseria meningitidis, Shigella pneumonia, Haemophilus influenzae). The bio-conjugation technology, exploited here for the Shigella dysenteriae candidate vaccine, offers a novel and potentially simpler way to develop and produce vaccines against one of the major causes of morbidity and mortality in developing countries.Methods: A novel S. dysenteriae bioconjugate vaccine (GVXN SD133) made of the polysaccharide component of the Shigella 01 lipopolysaccharide, conjugated to the exotoxin protein A of Pseudomonas aeruginosa (EPA), was evaluated for immunogenicity and safety in healthy adults in a single blind, partially randomized Phase I study. Forty subjects (10 in each dose group; 2 mu g or 10 mu g with or without aluminium adjuvant) received two injections 60 days apart and were followed-up for 150 days.Results: Both doses and formulations were well tolerated; the safety and reactogenicity profiles were consistent with that of other conjugated vaccines, adjuvanted or not, independent of the dose and the number of injections. The GVXN SD133 vaccine elicited statistically significant O1 specific humoral responses at all time points in all vaccination groups. Between-group comparisons did not show statistically significant differences in geometric mean titers of immunoglobulin G and A at any post-vaccination time point.Conclusions: This study demonstrated that the GVXN SD133 vaccine has a satisfactory safety profile. It elicited a significant humoral response to Shigella O1 polysaccharides at all doses tested. The protein carrier also elicited functional antibodies, showing the technology's advantages in preserving both sugar and conjugated protein epitopes. (C) 2015 Published by Elsevier Ltd.