{"title":"带状疱疹 mRNA 疫苗在小鼠和猕猴体内诱导的疫苗免疫力优于许可疫苗。","authors":"Lulu Huang, Tongyi Zhao, Weijun Zhao, Andong Shao, Huajun Zhao, Wenxuan Ma, Yingfei Gong, Xianhuan Zeng, Changzhen Weng, Lingling Bu, Zhenhua Di, Shiyu Sun, Qinsheng Dai, Minhui Sun, Limei Wang, Zhenguang Liu, Leilei Shi, Jiesen Hu, Shentong Fang, Cheng Zhang, Jian Zhang, Guan Wang, Karin Loré, Yong Yang, Ang Lin","doi":"10.1080/22221751.2024.2309985","DOIUrl":null,"url":null,"abstract":"<p><p>Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2309985"},"PeriodicalIF":8.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860463/pdf/","citationCount":"0","resultStr":"{\"title\":\"Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques.\",\"authors\":\"Lulu Huang, Tongyi Zhao, Weijun Zhao, Andong Shao, Huajun Zhao, Wenxuan Ma, Yingfei Gong, Xianhuan Zeng, Changzhen Weng, Lingling Bu, Zhenhua Di, Shiyu Sun, Qinsheng Dai, Minhui Sun, Limei Wang, Zhenguang Liu, Leilei Shi, Jiesen Hu, Shentong Fang, Cheng Zhang, Jian Zhang, Guan Wang, Karin Loré, Yong Yang, Ang Lin\",\"doi\":\"10.1080/22221751.2024.2309985\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. 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引用次数: 0
摘要
带状疱疹仍然是一个重要的全球健康问题,主要发生在有水痘带状疱疹病毒(VZV)早期接触史的老年人和免疫力低下的人身上。尽管已获许可的 Shingrix 疫苗疗效显著,但其不良的致反应性和日益增长的全球需求导致疫苗短缺,这促使人们开发改良型或新型 VZV 疫苗。在这项研究中,我们开发了一种新型 VZV mRNA 候选疫苗(命名为 ZOSAL),其中包含编码全长糖蛋白 E 的序列优化的 mRNA,封装在可离子化的脂质纳米颗粒中。在小鼠和猕猴体内,ZOSAL 在多个方面都表现出优于 Shingrix 的免疫原性和安全性,尤其是在诱导强大的 T 细胞免疫方面。转录组分析表明,ZOSAL 和 Shingrix 都能强有力地激活先天性免疫分区,尤其是 I 型 IFN 信号转导和抗原处理/递呈。多变量相关分析进一步确定了先天区系中可预测 T 细胞反应程度的几个早期因素,这进一步加深了我们对两种不同 VZV 疫苗作用模式的理解。总之,我们的数据证明了 VZV mRNA 疫苗优于已获许可的亚单位疫苗。因此,mRNA 平台在下一代 VZV 疫苗开发中具有进一步研究的前景。
Herpes zoster mRNA vaccine induces superior vaccine immunity over licensed vaccine in mice and rhesus macaques.
Herpes zoster remains an important global health issue and mainly occurs in aged and immunocompromised individuals with an early exposure history to Varicella Zoster Virus (VZV). Although the licensed vaccine Shingrix has remarkably high efficacy, undesired reactogenicity and increasing global demand causing vaccine shortage urged the development of improved or novel VZV vaccines. In this study, we developed a novel VZV mRNA vaccine candidate (named as ZOSAL) containing sequence-optimized mRNAs encoding full-length glycoprotein E encapsulated in an ionizable lipid nanoparticle. In mice and rhesus macaques, ZOSAL demonstrated superior immunogenicity and safety in multiple aspects over Shingrix, especially in the induction of strong T-cell immunity. Transcriptomic analysis revealed that both ZOSAL and Shingrix could robustly activate innate immune compartments, especially Type-I IFN signalling and antigen processing/presentation. Multivariate correlation analysis further identified several early factors of innate compartments that can predict the magnitude of T-cell responses, which further increased our understanding of the mode of action of two different VZV vaccine modalities. Collectively, our data demonstrated the superiority of VZV mRNA vaccine over licensed subunit vaccine. The mRNA platform therefore holds prospects for further investigations in next-generation VZV vaccine development.
期刊介绍:
Emerging Microbes & Infections is a peer-reviewed, open-access journal dedicated to publishing research at the intersection of emerging immunology and microbiology viruses.
The journal's mission is to share information on microbes and infections, particularly those gaining significance in both biological and clinical realms due to increased pathogenic frequency. Emerging Microbes & Infections is committed to bridging the scientific gap between developed and developing countries.
This journal addresses topics of critical biological and clinical importance, including but not limited to:
- Epidemic surveillance
- Clinical manifestations
- Diagnosis and management
- Cellular and molecular pathogenesis
- Innate and acquired immune responses between emerging microbes and their hosts
- Drug discovery
- Vaccine development research
Emerging Microbes & Infections invites submissions of original research articles, review articles, letters, and commentaries, fostering a platform for the dissemination of impactful research in the field.