An mRNA vaccine to prevent genital herpes.
An mRNA vaccine to prevent genital herpes.
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DOI：
10.1016/j.trsl.2021.12.006
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Friedman HM
中科院分区：
文献类型：
--
作者：
Awasthi S;Friedman HM
2019年，两种针对冠状病毒病安全高效的核苷修饰mRNA疫苗的快速开发改变了疫苗领域。mRNA技术具有加速免疫原发现、诱导稳健的免疫应答和快速规模化生产的优点。生殖器疱疹疫苗的研制工作已经进行了80年，但没有成功。mRNA技术的出现有可能改变这种说法。生殖器疱疹疫苗的研制是一项高度优先的公共卫生工作。预防性生殖器疱疹疫苗应预防HSV-1和HSV-2生殖器病变和潜伏部位背根神经节感染。疫苗的免疫力应该可以持续几十年，也许在加强剂量的帮助下。虽然这些目标一直难以实现，但核苷修饰的mRNA-脂质纳米颗粒疫苗的新努力显示出巨大的前景。我们回顾了过去在大型3期试验中不成功或部分成功的疫苗开发方法，并描述了从这些试验中吸取的教训。我们讨论了我们的三价mRNA-脂质纳米颗粒的预防性生殖器疱疹疫苗的方法和疫苗诱导更高滴度的中和抗体和更持久的CD 4 + T滤泡辅助细胞和记忆B细胞反应比蛋白佐剂疫苗的能力。
The rapid development of two nucleoside-modified mRNA vaccines that are safe and highly effective against coronavirus disease 2019 has transformed the vaccine field. The mRNA technology has the advantage of accelerated immunogen discovery, induction of robust immune responses, and rapid scale up of manufacturing. Efforts to develop genital herpes vaccines have been ongoing for 8 decades without success. The advent of mRNA technology has the potential to change that narrative. Developing a genital herpes vaccine is a high public health priority. A prophylactic genital herpes vaccine should prevent HSV-1 and HSV-2 genital lesions and infection of dorsal root ganglia, the site of latency. Vaccine immunity should be durable for decades, perhaps with the assistance of booster doses. While these goals have been elusive, new efforts with nucleoside-modified mRNA-lipid nanoparticle vaccines show great promise. We review past approaches to vaccine development that were unsuccessful or partially successful in large phase 3 trials, and describe lessons learned from these trials. We discuss our trivalent mRNA-lipid nanoparticle approach for a prophylactic genital herpes vaccine and the ability of the vaccine to induce higher titers of neutralizing antibodies and more durable CD4+ T follicular helper cell and memory B cell responses than protein-adjuvanted vaccines.
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