Remdesivir postexposure prophylaxis limits measles-induced "immune amnesia" and measles antibody responses in macaques.

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
JCI insight Pub Date : 2025-04-22 eCollection Date: 2025-06-09 DOI:10.1172/jci.insight.190740
Andy Kwan Pui Chan, Liting Liu, William R Morgenlander, Manjusha Thakar, Nadine A Peart Akindele, Jacqueline Brockhurst, Shristi Ghimire, Maggie L Bartlett, Kelly A Metcalf Pate, Victor C Chu, Meghan S Vermillion, Danielle P Porter, Tomas Cihlar, Michael J Mina, H Benjamin Larman, Diane E Griffin
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Abstract

Measles remains one of the most important causes of worldwide morbidity and mortality in children. Measles virus (MeV) replicates extensively in lymphoid tissue, and most deaths are due to other infectious diseases associated with MeV-induced loss of circulating antibodies to other pathogens. To determine whether remdesivir, a broad-spectrum direct-acting antiviral, affects MeV-induced loss of antibody to other pathogens, we expanded the VirScan technology to detect antibodies to both human and macaque pathogens. We measured the antibody reactivity to MeV and non-MeV viral peptides using plasma from MeV-infected macaques that received remdesivir either as postexposure prophylaxis (PEP) (d3-d14) or as late treatment (LT) (d11-d22) in comparison with macaques that were not treated. Remdesivir PEP, but not LT, limited the loss of antibody to non-MeV pathogens. Remdesivir PEP also limited the antibody response to MeV with a decrease in both the magnitude and breadth of the epitopes recognized. LT had little effect on the magnitude of the MeV-specific antibody response but affected the breadth of the response. Therefore, early, but not late, treatment of measles with the direct-acting antiviral remdesivir prevents the loss of antibody to other pathogens but decreases the response to MeV.

雷姆德西韦暴露后预防限制了猕猴麻疹诱导的“免疫健忘症”和麻疹抗体反应。
麻疹仍然是全世界儿童发病和死亡的最重要原因之一。麻疹病毒(MeV)在淋巴组织中广泛复制,大多数死亡是由于与MeV引起的其他病原体循环抗体丧失相关的其他传染病。为了确定remdesivir(一种广谱直接作用抗病毒药物)是否影响mev诱导的针对其他病原体的抗体丢失,我们扩展了VirScan技术来检测针对人类和猕猴病原体的抗体。与未接受瑞德西韦治疗的猕猴相比,我们使用感染MeV的猕猴血浆测量了抗体对MeV和非MeV病毒肽的反应性,这些猕猴接受了瑞德西韦作为暴露后预防(d3-14, PEP)或晚期治疗(d11-22, LT)。Remdesivir PEP,而不是LT,限制了抗体对非mev病原体的损失。Remdesivir PEP也限制了抗体对MeV的反应,其识别的表位的大小和宽度都有所降低。LT对mev特异性抗体反应的大小影响不大,但影响反应的广度。因此,用直接作用的抗病毒药物瑞德西韦早而不晚地治疗麻疹,可防止针对其他病原体的抗体丢失,但会降低对MeV的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
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