Furuyama Wakako, Shifflett Kyle, Pinski Amanda N, Griffin Amanda J, Feldmann Friederike, Okumura Atsushi, Gourdine Tylisha, Jankeel Allen, Lovaglio Jamie, Hanley Patrick W, Thomas Tina, Clancy Chad S, Messaoudi Ilhem, O'Donnell Kyle L, Marzi Andrea
Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Department of Molecular Biology and Biochemistry, University of California - Irvine, Irvine, CA 92697, USA.
bioRxiv. 2021 Jan 19:2021.01.19.426885. doi: 10.1101/2021.01.19.426885.
The ongoing pandemic of Coronavirus disease 2019 (COVID-19) continues to exert a significant burden on health care systems worldwide. With limited treatments available, vaccination remains an effective strategy to counter transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent discussions concerning vaccination strategies have focused on identifying vaccine platforms, number of doses, route of administration, and time to reach peak immunity against SARS-CoV-2. Here, we generated a single dose, fast-acting vesicular stomatitis virus-based vaccine derived from the licensed Ebola virus (EBOV) vaccine rVSV-ZEBOV, expressing the SARS-CoV-2 spike protein and the EBOV glycoprotein (VSV-SARS2-EBOV). Rhesus macaques vaccinated intramuscularly (IM) with a single dose of VSV-SARS2-EBOV were protected within 10 days and did not show signs of COVID-19 pneumonia. In contrast, intranasal (IN) vaccination resulted in limited immunogenicity and enhanced COVID-19 pneumonia compared to control animals. While IM and IN vaccination both induced neutralizing antibody titers, only IM vaccination resulted in a significant cellular immune response. RNA sequencing data bolstered these results by revealing robust activation of the innate and adaptive immune transcriptional signatures in the lungs of IM-vaccinated animals only. Overall, the data demonstrates that VSV-SARS2-EBOV is a potent single-dose COVID-19 vaccine candidate that offers rapid protection based on the protective efficacy observed in our study.
VSV vaccine protects NHPs from COVID-19 in 10 days.
2019年冠状病毒病(COVID-19)的持续大流行继续给全球医疗系统带来巨大负担。由于可用治疗方法有限,疫苗接种仍然是对抗严重急性呼吸综合征冠状病毒2(SARS-CoV-2)传播的有效策略。最近关于疫苗接种策略的讨论集中在确定疫苗平台、剂量数量、给药途径以及达到针对SARS-CoV-2的免疫峰值的时间。在此,我们开发了一种单剂量、基于水疱性口炎病毒的快速起效疫苗,该疫苗源自已获许可的埃博拉病毒(EBOV)疫苗rVSV-ZEBOV,表达SARS-CoV-2刺突蛋白和EBOV糖蛋白(VSV-SARS2-EBOV)。用单剂量VSV-SARS2-EBOV进行肌肉注射(IM)接种的恒河猴在10天内得到保护,未出现COVID-19肺炎的迹象。相比之下,与对照动物相比,鼻内(IN)接种导致免疫原性有限且COVID-19肺炎加重。虽然IM和IN接种均诱导了中和抗体滴度,但只有IM接种产生了显著的细胞免疫反应。RNA测序数据通过揭示仅在IM接种动物肺部先天和适应性免疫转录特征的强烈激活来支持这些结果。总体而言,数据表明VSV-SARS2-EBOV是一种有效的单剂量COVID-19疫苗候选物,基于我们研究中观察到的保护效果可提供快速保护。
VSV疫苗在10天内保护非人类灵长类动物免受COVID-19感染。