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单克隆抗体疗法可保护非人灵长类动物免受拉沙病毒的黏膜暴露。

Monoclonal antibody therapy protects nonhuman primates against mucosal exposure to Lassa virus.

机构信息

Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.

Zalgen Labs, LLC, Frederick, MD, USA.

出版信息

Cell Rep Med. 2024 Feb 20;5(2):101392. doi: 10.1016/j.xcrm.2024.101392. Epub 2024 Jan 26.

DOI:10.1016/j.xcrm.2024.101392
PMID:38280377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10897540/
Abstract

Lassa fever (LF) is an acute viral illness that causes thousands of deaths annually in West Africa. There are currently no Lassa virus (LASV) vaccines or antivirals approved for human use. Recently, we showed that combinations of broadly neutralizing human monoclonal antibodies (BNhuMAbs) known as Arevirumab-2 or Arevirumab-3 protected up to 100% of cynomolgus macaques against challenge with diverse lineages of LASV when treatment was initiated at advanced stages of disease. This previous work assessed efficacy against parenteral exposure. However, transmission of LASV to humans occurs primarily by mucosal exposure to virus shed from Mastomys rodents. Here, we describe the development of a lethal intranasal exposure macaque model of LF. This model is employed to show that Arevirumab cocktails rescue 100% of macaques from lethal LASV infection when treatment is initiated 8 days after LASV exposure. Our work demonstrates BNhuMAbs have utility in treating LASV infection acquired through mucosal exposure.

摘要

拉沙热（LF）是一种急性病毒性疾病，每年在西非导致数千人死亡。目前尚无获准用于人类的拉沙病毒（LASV）疫苗或抗病毒药物。最近，我们发现，被称为 Arevirumab-2 或 Arevirumab-3 的广泛中和人类单克隆抗体（BNhuMAbs）组合，在疾病晚期开始治疗时，可保护高达 100%的食蟹猴免受不同 LASV 谱系的挑战。这项先前的工作评估了针对肠外暴露的疗效。然而，LASV 向人类的传播主要是通过粘膜暴露于从 Mastomys 啮齿动物中排出的病毒。在这里，我们描述了致命性鼻腔暴露食蟹猴 LF 模型的开发。该模型用于证明，当 LASV 暴露后 8 天开始治疗时，Arevirumab 鸡尾酒可挽救 100%的猕猴免受致命性 LASV 感染。我们的工作表明，BNhuMAbs 在治疗通过粘膜暴露获得的 LASV 感染方面具有实用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/b89aa7996728/gr7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/d846090e1210/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/3c00cac03004/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/1afd2fdda2a1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/9826accb851e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/54c2bd5ce153/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/b89aa7996728/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/afcdaf7eab86/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/3cba286ac6f8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/d846090e1210/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/3c00cac03004/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/1afd2fdda2a1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/9826accb851e/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/54c2bd5ce153/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bb6/10897540/b89aa7996728/gr7.jpg

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