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推进疫苗开发的优雅且创新的重编码策略

Elegant and Innovative Recoding Strategies for Advancing Vaccine Development.

作者信息

Meurens François, Renois Fanny, Karniychuk Uladzimir

机构信息

Centre de Recherche en Infectiologie Porcine et Avicole, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC J2S 2M2, Canada.

Department of Veterinary Microbiology and Immunology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E2, Canada.

出版信息

Vaccines (Basel). 2025 Jan 16;13(1):78. doi: 10.3390/vaccines13010078.

Abstract

Recoding strategies have emerged as a promising approach for developing safer and more effective vaccines by altering the genetic structure of microorganisms, such as viruses, without changing their proteins. This method enhances vaccine safety and efficacy while minimizing the risk of reversion to virulence. Recoding enhances the frequency of CpG dinucleotides, which in turn activates immune responses and ensures a strong attenuation of the pathogens. Recent advancements highlight synonymous recoding's potential, offering improved genetic stability and immunogenicity compared to traditional methods. Live vaccines attenuated using classical methods pose a risk of reversion to virulence and can be time-consuming to produce. Synonymous recoding, involving numerous codon alterations, boosts safety and vaccine stability. One challenge is balancing attenuation with yield; however, innovations like Zinc-finger antiviral protein (ZAP) knockout cell lines can enhance vaccine production. Beyond viral vaccines, recoding can apply to bacterial vaccines, as exemplified by modified and strains, which show reduced virulence. Despite promising results, challenges like ensuring genetic stability, high yield, and regulatory approval remain. Briefly, ongoing research aims to harness these innovations for comprehensive improvements in vaccine design and deployment. In this commentary, we sought to further engage the community's interest in this elegant approach by briefly highlighting its main advantages, disadvantages, and future prospects.

摘要

重新编码策略已成为一种有前景的方法,可通过改变病毒等微生物的基因结构而不改变其蛋白质来开发更安全、更有效的疫苗。这种方法提高了疫苗的安全性和有效性,同时将恢复毒力的风险降至最低。重新编码提高了CpG二核苷酸的频率,进而激活免疫反应并确保病原体的强烈减毒。最近的进展突出了同义重新编码的潜力,与传统方法相比,它具有更高的遗传稳定性和免疫原性。使用传统方法减毒的活疫苗存在恢复毒力的风险,并且生产可能耗时。涉及众多密码子改变的同义重新编码提高了安全性和疫苗稳定性。一个挑战是在减毒和产量之间取得平衡;然而,像锌指抗病毒蛋白(ZAP)敲除细胞系这样的创新可以提高疫苗产量。除了病毒疫苗,重新编码还可应用于细菌疫苗,如修饰的 和 菌株所示,它们的毒力降低。尽管取得了有希望的结果,但仍存在确保遗传稳定性、高产量和监管批准等挑战。简而言之,正在进行的研究旨在利用这些创新全面改进疫苗设计和部署。在这篇评论中,我们试图通过简要强调其主要优点、缺点和未来前景,进一步激发科学界对这种精妙方法的兴趣。

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