Red Alga Porphyridium Supports High‐Yield Production of a Functional Chimeric Hepatitis B Surface Antigen With Strong Cellular and Humoral Immunogenicity

IF 10.5 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Ana‐Maria Pantazica, Alexander Hammel, Iuliana Caras, Irina Ionescu, Catalin Tucureanu, Adrian Onu, Maria Murace, Jihong Liu Clarke, Crina Stavaru, Norica Branza‐Nichita, Ralph Bock
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Abstract

Microalgae represent promising production factories for the light‐driven, cost‐effective production of recombinant proteins. The red microalga Porphyridium purpureum displays particularly favourable transgene expression properties due to the episomal maintenance of transformation vectors at high copy numbers in the nucleus. In this work, we explored the potential of Porphyridium purpureum to synthesise a candidate vaccine against Hepatitis B virus (HBV). We show high‐yield expression of an HBV chimeric surface antigen and efficient assembly of virus‐like particles (VLPs) in algal cells. We established a purification protocol for the VLPs and conducted vaccination studies in experimental animals. The results demonstrate that the alga‐produced HBV antigen elicits superior humoral and cellular immune responses compared to a commercial HBV vaccine produced in yeast. The antigen triggers virus‐neutralising antibodies against different HBV variants, including vaccine‐escape mutations that evade the immune response to current vaccines in humans. Our work establishes Porphyridium as a highly promising production platform for vaccines and other proteinaceous biopharmaceuticals.
红藻卟卟支持高效生产功能性嵌合乙型肝炎表面抗原,具有很强的细胞和体液免疫原性
微藻代表了光驱动、成本效益高的重组蛋白生产的有前途的生产工厂。红微藻紫卟啉(Porphyridium purpureum)表现出特别有利的转基因表达特性,这是由于其在细胞核内的高拷贝数转化载体的持续维持。在这项工作中,我们探索了紫卟啉合成乙型肝炎病毒(HBV)候选疫苗的潜力。我们在藻类细胞中展示了HBV嵌合表面抗原的高产表达和病毒样颗粒(vlp)的高效组装。我们建立了VLPs的纯化方案,并在实验动物中进行了疫苗接种研究。结果表明,与酵母生产的商业HBV疫苗相比,藻类生产的HBV抗原引起了更好的体液和细胞免疫反应。抗原触发针对不同HBV变体的病毒中和抗体,包括逃避人类对当前疫苗免疫反应的疫苗逃逸突变。我们的工作建立了卟啉作为一个非常有前途的生产平台疫苗和其他蛋白质生物制药。
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来源期刊
Plant Biotechnology Journal
Plant Biotechnology Journal 生物-生物工程与应用微生物
CiteScore
20.50
自引率
2.90%
发文量
201
审稿时长
1 months
期刊介绍: Plant Biotechnology Journal aspires to publish original research and insightful reviews of high impact, authored by prominent researchers in applied plant science. The journal places a special emphasis on molecular plant sciences and their practical applications through plant biotechnology. Our goal is to establish a platform for showcasing significant advances in the field, encompassing curiosity-driven studies with potential applications, strategic research in plant biotechnology, scientific analysis of crucial issues for the beneficial utilization of plant sciences, and assessments of the performance of plant biotechnology products in practical applications.
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