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A Heterologous Viral Protein Scaffold for Chimeric Antigen Design: An Example PCV2 Virus Vaccine Candidate.
Viruses ( IF 3.8 ) Pub Date : 2020-03-31 , DOI: 10.3390/v12040385
Emilio Lamazares 1 , Fernando Gutiérrez 1 , Angela Hidalgo 1 , Nicolas A Gutiérrez 1 , Felipe I Espinoza 1 , Oliberto Sánchez 1 , Marcelo Cortez-San Martín 2 , Carolina Mascayano 3 , Javier González 4 , José Saavedra 2 , Claudia Altamirano 5 , Manuel Mansur 6 , Álvaro Ruiz 7 , Jorge R Toledo 1
Affiliation  

Recombinant vaccines have low-cost manufacturing, regulatory requirements, and reduced side effects compared to attenuated or inactivated vaccines. In the porcine industry, post-weaning multisystemic disease syndrome generates economic losses, characterized by progressive weight loss and weakness in piglets, and it is caused by porcine circovirus type 2 (PCV2). We designed a chimeric antigen (Qm1) to assemble the main exposed epitopes of the Cap-PCV2 protein on the capsid protein of the tobacco necrosis virus (TNV). This design was based on the Cap-N-terminal of an isolated PCV2 virus obtained in Chile. The virus was characterized, and the sequence was clustered within the PCV2 genotype b clade. This chimeric protein was expressed as inclusion bodies in both monomeric and multimeric forms, suggesting a high-molecular-weight aggregate formation. Pigs immunized with Qm1 elicited a strong and specific antibody response, which reduced the viral loads after the PCV2 challenge. In conclusion, the implemented design allowed for the generation of an effective vaccine candidate. Our proposal could be used to express the domains or fragments of antigenic proteins, whose structural complexity does not allow for low-cost production in Escherichia coli. Hence, other antigen domains could be integrated into the TNV backbone for suitable antigenicity and immunogenicity. This work represents new biotechnological strategies, with a reduction in the costs associated with vaccine development.

中文翻译:

用于嵌合抗原设计的异源病毒蛋白支架:示例PCV2病毒疫苗候选对象。

与减毒或灭活疫苗相比,重组疫苗具有低成本的生产,法规要求并减少了副作用。在猪产业中,断奶后多系统疾病综合症会造成经济损失,其特征是体重逐渐减轻和仔猪无力,这是由猪圆环病毒2型(PCV2)引起的。我们设计了一种嵌合抗原(Qm1),将Cap-PCV2蛋白的主要暴露表位组装在烟草坏死病毒(TNV)的衣壳蛋白上。该设计基于在智利获得的分离的PCV2病毒的Cap-N末端。对该病毒进行了表征,并将该序列聚集在PCV2基因型b进化枝内。该嵌合蛋白以单体和多聚体形式表达为包涵体,表明形成高分子量聚集体。用Qm1免疫的猪引发了强烈而特异性的抗体反应,从而降低了PCV2攻击后的病毒载量。总之,实施的设计可以产生有效的候选疫苗。我们的建议可用于表达抗原蛋白的结构域或片段,其结构复杂性不允许在大肠杆菌中低成本生产。因此,可以将其他抗原结构域整合到TNV骨架中以获得合适的抗原性和免疫原性。这项工作代表了新的生物技术策略,并降低了与疫苗开发相关的成本。实施的设计可以产生有效的候选疫苗。我们的建议可用于表达抗原蛋白的结构域或片段,其结构复杂性不允许在大肠杆菌中低成本生产。因此,可以将其他抗原结构域整合到TNV骨架中以获得合适的抗原性和免疫原性。这项工作代表了新的生物技术策略,并降低了与疫苗开发相关的成本。实施的设计可以产生有效的候选疫苗。我们的建议可用于表达抗原蛋白的结构域或片段,其结构复杂性不允许在大肠杆菌中低成本生产。因此,可以将其他抗原结构域整合到TNV骨架中以获得合适的抗原性和免疫原性。这项工作代表了新的生物技术策略,并降低了与疫苗开发相关的成本。
更新日期:2020-04-20
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