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重组水疱性口炎病毒载体马尔堡疫苗在食蟹猴中的功效和免疫原性。

Efficacy and Immunogenicity of a Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine in Cynomolgus Macaques.

机构信息

Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Departments of Pathology, Microbiology and Immunology, Institute of Human Infection and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA.

出版信息

Viruses. 2024 Jul 24;16(8):1181. doi: 10.3390/v16081181.

Abstract

Filoviruses, like the Marburg (MARV) and Ebola (EBOV) viruses, have caused outbreaks associated with significant hemorrhagic morbidity and high fatality rates. Vaccines offer one of the best countermeasures for fatal infection, but to date only the EBOV vaccine has received FDA licensure. Given the limited cross protection between the EBOV vaccine and Marburg hemorrhagic fever (MHF), we analyzed the protective efficacy of a similar vaccine, rVSV-MARV, in the lethal cynomolgus macaque model. NHPs vaccinated with a single dose (as little as 1.6 × 10 pfu) of rVSV-MARV seroconverted to MARV G-protein prior to challenge on day 42. Vaccinemia was measured in all vaccinated primates, self-resolved by day 14 post vaccination. Importantly, all vaccinated NHPs survived lethal MARV challenge, and showed no significant alterations in key markers of morbid disease, including clinical signs, and certain hematological and clinical chemistry parameters. Further, apart from one primate (from which tissues were not collected and no causal link was established), no pathology associated with Marburg disease was observed in vaccinated animals. Taken together, rVSV-MARV is a safe and efficacious vaccine against MHF in cynomolgus macaques.

摘要

丝状病毒,如马尔堡病毒(MARV)和埃博拉病毒(EBOV),已引起与严重出血性发病率和高死亡率相关的暴发。疫苗是针对致命感染的最佳对策之一,但迄今为止,只有 EBOV 疫苗获得了 FDA 许可。鉴于 EBOV 疫苗和马尔堡出血热(MHF)之间的交叉保护作用有限,我们分析了类似疫苗 rVSV-MARV 在致命食蟹猴模型中的保护效力。在第 42 天接种 rVSV-MARV 疫苗的单剂量(低至 1.6×10 pfu)的 NHPs 会在挑战前针对 MARV G 蛋白产生血清转化。所有接种疫苗的灵长类动物都检测到了疫苗血症,并在接种后 14 天内自行消退。重要的是,所有接种疫苗的 NHPs 都能在致命 MARV 挑战中存活下来,并且没有出现与病态疾病相关的关键标志物的显著改变,包括临床症状和某些血液学和临床化学参数。此外,除了一只灵长类动物(未采集其组织,也未建立因果关系)外,未观察到接种动物中与马尔堡病相关的病理学。总之,rVSV-MARV 是一种安全有效的针对食蟹猴 MHF 的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e911/11359148/59e0a1df3a17/viruses-16-01181-g001.jpg

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