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首页> 外文期刊>Vaccine >Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein
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Hepatitis B virus-like particles expressing Plasmodium falciparum epitopes induce complement-fixing antibodies against the circumsporozoite protein

机译：表达疟原虫的乙型肝炎病毒样颗粒表达疟原虫表位诱导抗环孢子蛋白蛋白质的补体固定抗体

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The repetitive structure of compact virus-like particles (VLPs) provides high density displays of antigenic sequences, which trigger key parts of the immune system. The hepatitis B virus (HBV) and human papilloma virus (HPV) vaccines exploit the assembly competence of structural proteins, which are the effective immunogenic components of the prophylactic HBV and HPV vaccines, respectively. To optimize vaccine designs and to promote immune responses against protective epitopes, the "Asp-Ala-Asp-Pro" (NANP)-repeat from the Plasmodium falciparum circumsporozoite protein (CSP) was expressed within the exposed, main antigenic site of the small HBV envelope protein (HBsAgS); this differs from the RTS,S vaccine, in which CSP epitopes are fused to the N-terminus of HBsAgS. The chimeric HBsAgS proteins are assembly competent, produce VLPs, and provide a high antigenic density of the NANP repeat sequence. Chimeric VLPs with four or nine NANP-repeats (NANP4 and NANP9, respectively) were expressed in mammalian cells, the HBsAgS- and CSP-specific antigenicity of the VLPs was determined, and the immunogenicity of the VLPs assessed in relation to the induction of anti-HBsAgS and anti-CSP antibody responses. The chimeric VLPs induced high anti-CSP titres in BALB/c mice independent of the number of the NANP repeats. However, the number of NANP repeats influenced the activity of vaccine-induced antibodies measured by complement fixation to CSP, one of the proposed effector mechanisms for Plasmodium neutralization in vivo. Sera from mice immunized with VLPs containing nine NANP repeats performed better in the complement fixation assay than the group with four NANP repeats. The effect of the epitope-specific density on the antibody quality may instruct VLP platform designs to optimize immunological outcomes and vaccine efficacy. (C) 2019 Elsevier Ltd. All rights reserved.
机译：紧凑型病毒样颗粒（VLP）的重复结构提供了高密度显示的抗原序列，其触发免疫系统的关键部分。乙型肝炎病毒（HBV）和人乳头瘤病毒（HPV）疫苗利用结构蛋白的组装能力，其分别是预防性HBV和HPV疫苗的有效免疫原性组分。为了优化疫苗设计并促进免疫反应对抗保护性表位，“ASP-ALA-ASP-PRO”（NANP） - 来自疟原虫环孢菌素蛋白（CSP）的释放，在暴露的小HBV的主要抗原位点内表达包络蛋白（HBsAgs）;这与RTS，S疫苗不同，其中CSP表位融合到HBsAgs的N-末端。嵌合HBsAgs蛋白质是组装能力，产生VLP，并提供NANP重复序列的高抗原密度。在哺乳动物细胞中表达具有四个或九个NANP重复（NANP4和NANP9）的嵌合VLP，测定VLP的HBsAgs和CSP特异性抗原性，并且VLP的免疫原性与诱导抗体进行评估-hbsags和抗CSP抗体反应。嵌合VLP在BALB / C小鼠中诱导高抗CSP滴度，与NANP重复的数量无关。然而，NANP重复的数量影响通过补体固定对CSP测量的疫苗诱导的抗体的活性，该疟原虫中和体内疟原虫中和的效应机制之一。用含有含有九个NANP重复的VLP免疫的小鼠的血清比具有四个NANP重复的组的补体固定测定更好。表位特异性密度对抗体质量的影响可能指示VLP平台设计优化免疫学结果和疫苗疗效。 （c）2019 Elsevier Ltd.保留所有权利。

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