Lett Martin Joseph, Otte Fabian, Hauser David, Schön Jacob, Kipfer Enja Tatjana, Hoffmann Donata, Halwe Nico J, Breithaupt Angele, Ulrich Lorenz, Britzke Tobias, Kochmann Jana, Corleis Björn, Zhang Yuepeng, Urda Lorena, Cmiljanovic Vladimir, Lang Christopher, Beer Martin, Mittelholzer Christian, Klimkait Thomas
Molecular Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Institute of Diagnostic Virology, Friedrich-Loeffler-Institute, Greifswald - Isle of Riems, Greifswald, Germany.
NPJ Vaccines. 2024 Oct 30;9(1):206. doi: 10.1038/s41541-024-00992-z.
Vaccines have played a central role in combating the COVID-19 pandemic, but newly emerging SARS-CoV-2 variants are increasingly evading first-generation vaccine protection. To address this challenge, we designed "single-cycle infection SARS-CoV-2 viruses" (SCVs) that lack essential viral genes, possess distinctive immune-modulatory features, and exhibit an excellent safety profile in the Syrian hamster model. Animals intranasally vaccinated with an Envelope-gene-deleted vaccine candidate were fully protected against an autologous challenge with the SARS-CoV-2 virus through systemic and mucosal humoral immune responses. Additionally, the deletion of immune-downregulating viral genes in the vaccine construct prevented challenge virus transmission to contact animals. Moreover, vaccinated animals displayed neither tissue inflammation nor lung damage. Consequently, SCVs hold promising potential to induce potent protection against COVID-19, surpassing the immunity conferred by natural infection, as demonstrated in human immune cells.
疫苗在抗击新冠疫情中发挥了核心作用，但新出现的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变种越来越多地逃避第一代疫苗的保护。为应对这一挑战，我们设计了“单周期感染SARS-CoV-2病毒”（SCV），其缺乏必需的病毒基因，具有独特的免疫调节特性，并且在叙利亚仓鼠模型中表现出优异的安全性。用一种缺失包膜基因的候选疫苗经鼻内接种的动物，通过全身和黏膜体液免疫反应，对SARS-CoV-2病毒的自体攻击具有完全的保护作用。此外，疫苗构建体中免疫下调病毒基因的缺失可防止攻击病毒传播给接触动物。而且，接种疫苗的动物既没有出现组织炎症，也没有出现肺部损伤。因此，如在人类免疫细胞中所证明的那样，SCV具有诱导针对新冠病毒产生有效保护的巨大潜力，超过自然感染所赋予的免疫力。
