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首页> 外文期刊>Vaccine >Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis
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Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis

机译：基于登革2型嵌合蛋白P64k结构域III和脑膜炎奈瑟氏球菌的两个成分的非人类灵长类动物制剂的免疫学评估

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摘要

The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope protein from dengue 2 virus fused to the carrier protein P64k. This construct completely protected monkeys against viral challenge when the Freund's adjuvant was employed. Therefore, to define suitable formulations for human use, the present work relies on the evaluation of PD5, produced with a high purity and under GMP conditions, when formulated either with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The antibody response to the formulation containing the CPS-A was clearly superior to that of the formulation with OMV. The experiment of in vivo protection supported this evidence, since only the group immunized with PD5 and CPS-A was partially protected upon viral challenge. This is the first study in which the polysaccharide A of N. meningitidis is successfully employed as adjuvant for viral antigen
机译：开发基于重组蛋白的成功的登革热疫苗的主要问题是必须使用有效的佐剂来达到适当的功能性免疫反应。我们的小组报告了重组蛋白PD5的表达，表征和免疫学评估，该蛋白包含与融合到载体蛋白P64k的登革热2病毒包膜蛋白的结构域III。当使用弗氏佐剂时，该构建体完全保护了猴子免受病毒攻击。因此，要确定适合人类使用的制剂，当与外膜囊泡（OMV）或血清群A荚膜多糖（CPS-A）一起配制时，本工作依赖于对高纯度，在GMP条件下生产的PD5的评估来源于脑膜炎奈瑟氏球菌，两者均吸附在氢氧化铝上。对含有CPS-A的制剂的抗体应答明显优于具有OMV的制剂的抗体应答。体内保护实验支持了这一证据，因为只有PD5和CPS-A免疫的组在受到病毒攻击后才得到部分保护。这是首次成功将脑膜炎奈瑟氏球菌多糖A用作病毒抗原佐剂的研究

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