急性基孔肯雅病毒感染期间的病毒动力学:利用数学模型了解单克隆抗体在病毒清除和预防中的潜在作用

IF 4.6 3区 医学 Q1 VIROLOGY
Tey Putita Ou, Sopheak Sorn, Kunthy Nguon, Saraden In, Sreymom Ken, Sowath Ly, Claude Flamand, Nicolas Voirin, Marie Mandron, Hugh Watson, Veasna Duong
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引用次数: 0

摘要

基孔肯雅病毒(CHIKV)是一种致关节炎的甲病毒,对流行地区和新受影响地区构成重大公共卫生威胁。本研究探讨了病毒动力学、免疫反应和单克隆抗体(mAb)治疗在急性CHIKV感染期间减轻病毒血症和传播的潜力,为早期干预策略提供了新的见解。利用柬埔寨29例患者的数据,连续采样和病毒载量量化显示,人群平均病毒载量峰值出现在症状出现前约1.87天。与成人相比,儿童表现出更高的峰值病毒载量和更快的复制率,尽管各年龄组的症状严重程度和负担相似。IgM抗体在成人(中位数:4.1天)中比在儿童(中位数:5.1天;p = 0.036)。约50%的患者c反应蛋白(CRP)水平短暂升高,但与疾病严重程度无关。数学模型强调,在症状出现前3天给予预防性单抗治疗,可以显著降低病毒载量,并有可能预防可检测到的病毒血症。虽然这些发现强调了单克隆抗体作为一种早期治疗策略的潜力,但需要进一步的研究来评估这些结果的稳健性,并评估它们通过减少病毒血症和症状前传播来遏制CHIKV暴发的实际意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Viral Kinetics During Acute Chikungunya Virus Infection: Insights Into Potential Role of Monoclonal Antibodies in Viral Clearance and Prophylaxis Using Mathematical Modeling

Chikungunya virus (CHIKV), an arthritogenic alphavirus, is a significant public health threat in endemic and newly affected regions. This study investigates viral kinetics, immune responses, and the potential of monoclonal antibody (mAb) therapies to mitigate viraemia and transmission during acute CHIKV infection, providing novel insights into early intervention strategies. Using data from 29 patients in Cambodia, serial sampling and viral load quantification revealed that the population-average peak viral load occurred ~1.87 days prior to symptom onset. Children demonstrated higher peak viral loads and faster replication rates compared to adults, although symptom severity and burden were similar across age groups. IgM antibodies appeared earlier in adults (median: 4.1 days) than in children (median: 5.1 days; p = 0.036). C-reactive protein (CRP) levels were transiently elevated in about 50% of patients but showed no correlation with disease severity. Mathematical modeling highlighted that prophylactic mAb therapies, when administered 3 days before symptoms onset, could substantially reduce viral load and potentially prevent detectable viraemia. While these findings underscore the potential of mAbs as an early therapeutic strategy, further studies are necessary to evaluate the robustness of these results and assess their practical implications to curb CHIKV outbreaks by minimizing viraemia and presymptomatic transmission.

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来源期刊
Journal of Medical Virology
Journal of Medical Virology 医学-病毒学
CiteScore
23.20
自引率
2.40%
发文量
777
审稿时长
1 months
期刊介绍: The Journal of Medical Virology focuses on publishing original scientific papers on both basic and applied research related to viruses that affect humans. The journal publishes reports covering a wide range of topics, including the characterization, diagnosis, epidemiology, immunology, and pathogenesis of human virus infections. It also includes studies on virus morphology, genetics, replication, and interactions with host cells. The intended readership of the journal includes virologists, microbiologists, immunologists, infectious disease specialists, diagnostic laboratory technologists, epidemiologists, hematologists, and cell biologists. The Journal of Medical Virology is indexed and abstracted in various databases, including Abstracts in Anthropology (Sage), CABI, AgBiotech News & Information, National Agricultural Library, Biological Abstracts, Embase, Global Health, Web of Science, Veterinary Bulletin, and others.
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