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一种针对[具体疾病或病原体未明确]的多价疫苗的免疫信息学设计及其在小鼠模型中采用DNA初免-蛋白加强策略的评估。

Immunoinformatic design of a multivalent vaccine against and its evaluation in a murine model using a DNA prime-protein boost strategy.

作者信息

Molina Raúl E, Osorio Alberto, Flores-Concha Manuel, Gómez Leonardo A, Alvarado Ilse, Ferrari Italo, Oñate Angel

机构信息

Laboratory of Molecular Immunology, Department of Microbiology, Faculty of Biological Sciences, University of Concepción, Concepción, Chile.

Simes Educational Center, Santiago, Chile.

出版信息

Front Immunol. 2024 Nov 21;15:1456078. doi: 10.3389/fimmu.2024.1456078. eCollection 2024.

Abstract

INTRODUCTION

The development of effective vaccines against is critical due to its significant impact on human and animal health. The objective of this study was to design and evaluate and a multivalent vaccine based on the immunogenic potential of three selected open reading frames (ORFs) of .

METHODS

The designed construct, named S22, was analyzed to evaluate its physicochemical properties, antigenicity, allergenicity and toxicity. This construct was modeled and subjected to molecular dynamics analysis. Additionally, the antigenicity and protection induced by this construct was evaluated through assays immunizing BALB/c mice with protein (S22), DNA (pVS22) and combining both vaccine formats using a prime boost immunization strategy.

RESULTS

All bioinformatics analyses showed safe and high quality structural features, revealing favorable interactions between S22 and the TLR4/MD2 complex. Moreover, results from assays indicated that the S22 protein induced robust levels of IgG1 and IgG2a, suggesting a balanced Th1 and Th2 immune response. The DNA construct (pVS22) elicited primarily a Th1 response, whereas the use of a prime boost strategy, which combines both formats resulted in a balanced immune response with significant induction of lymphoproliferation and elevated.

DISCUSSION

Although our assays did not demonstrate the induction of a substantial protective response against , this construct was capable of inducing immunogenicity. This study highlights the utility of design for predicting and optimizing candidate vaccines and underscores the potential of using strategies such as prime boost, which incorporate antigens of different biological nature to modulate the immune response, while balancing parameters such as stability of the antigens and the cost of production.

摘要

引言

由于其对人类和动物健康有重大影响,开发针对[病原体名称未给出]的有效疫苗至关重要。本研究的目的是基于[病原体名称未给出]三个选定开放阅读框(ORF)的免疫原性潜力,设计并评估一种多价疫苗。

方法

对设计的名为S22的构建体进行分析,以评估其物理化学性质、抗原性、致敏性和毒性。对该构建体进行建模并进行分子动力学分析。此外,通过用蛋白质(S22)、DNA(pVS22)免疫BALB/c小鼠并使用初免-加强免疫策略结合两种疫苗形式,评估该构建体诱导的抗原性和保护作用。

结果

所有生物信息学分析均显示出安全且高质量的结构特征,揭示了S22与TLR4/MD2复合物之间的良好相互作用。此外,检测结果表明,S22蛋白诱导了高水平的IgG1和IgG2a,表明Th1和Th2免疫反应平衡。DNA构建体(pVS22)主要引发Th1反应,而使用结合两种形式的初免-加强策略导致免疫反应平衡,显著诱导淋巴细胞增殖并升高。

讨论

尽管我们的检测未证明对[病原体名称未给出]诱导出实质性的保护性反应,但该构建体能够诱导免疫原性。本研究强调了[疫苗名称未给出]设计在预测和优化候选疫苗方面的实用性,并强调了使用初免-加强等策略的潜力,这些策略结合了不同生物学性质的抗原以调节免疫反应,同时平衡抗原稳定性和生产成本等参数。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2471/11617539/44068a897ba9/fimmu-15-1456078-g001.jpg

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