O'Donnell Kyle L, Gourdine Tylisha, Fletcher Paige, Shifflett Kyle, Furuyama Wakako, Clancy Chad S, Marzi Andrea
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Vaccines (Basel). 2022 Mar 12;10(3):435. doi: 10.3390/vaccines10030435.
The continued progression of the COVID-19 pandemic can partly be attributed to the ability of SARS-CoV-2 to mutate and introduce new viral variants. Some of these variants with the potential to spread quickly and conquer the globe are termed variants of concern (VOC). The existing vaccines implemented on a global scale are based on the ancestral strain, which has resulted in increased numbers of breakthrough infections as these VOC have emerged. It is imperative to show protection against VOC infection with newly developed vaccines. Previously, we evaluated two vesicular stomatitis virus (VSV)-based vaccines expressing the SARS-CoV-2 spike protein alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV) and demonstrated their fast-acting potential. Here, we prolonged the time to challenge; we vaccinated hamsters intranasally (IN) or intramuscularly 28 days prior to infection with three SARS-CoV-2 VOC-the Alpha, Beta, and Delta variants. IN vaccination with either the VSV-SARS2 or VSV-SARS2-EBOV resulted in the highest protective efficacy as demonstrated by decreased virus shedding and lung viral load of vaccinated hamsters. Histopathologic analysis of the lungs revealed the least amount of lung damage in the IN-vaccinated animals regardless of the challenge virus. This data demonstrates the ability of a VSV-based vaccine to not only protect from disease caused by SARS-CoV-2 VOC but also reduce viral shedding.
新冠疫情的持续蔓延，部分原因可归咎于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的变异能力，以及由此产生的新病毒变种。其中一些有可能迅速传播并席卷全球的变种被称为“关注变种”（VOC）。全球范围内现有的疫苗是基于原始毒株研发的，随着这些关注变种的出现，突破性感染的数量有所增加。因此，研发出能预防关注变种感染的新型疫苗势在必行。此前，我们评估了两种基于水疱性口炎病毒（VSV）的疫苗，一种单独表达SARS-CoV-2刺突蛋白（VSV-SARS2），另一种与埃博拉病毒糖蛋白联合表达（VSV-SARS2-EBOV），并证明了它们具有快速起效的潜力。在此，我们延长了攻毒时间；在感染三种SARS-CoV-2关注变种——阿尔法、贝塔和德尔塔变种之前28天，我们通过鼻腔内（IN）或肌肉内途径给仓鼠接种疫苗。鼻腔内接种VSV-SARS2或VSV-SARS2-EBOV均产生了最高的保护效力，接种疫苗的仓鼠病毒脱落量和肺部病毒载量降低证明了这一点。对肺部的组织病理学分析显示，无论攻毒病毒是什么，鼻腔内接种疫苗的动物肺部损伤最少。这些数据表明，基于VSV的疫苗不仅能够预防SARS-CoV-2关注变种引起的疾病，还能减少病毒脱落。
