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马多克隆抗体可预防小鼠感染急性基孔肯雅病毒。

Equine Polyclonal Antibodies Prevent Acute Chikungunya Virus Infection in Mice.

机构信息

Emergent BioSolutions Canada Inc., Winnipeg, MB R3T 5Y3, Canada.

Institute for Human Infections and Immunity, Department of Microbiology and Immunology, University of Texas Medical Branch Galveston, Galveston, TX 77555, USA.

出版信息

Viruses. 2023 Jun 29;15(7):1479. doi: 10.3390/v15071479.

Abstract

Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen that causes chikungunya disease (CHIK); the disease is characterized by fever, muscle ache, rash, and arthralgia. This arthralgia can be debilitating and long-lasting, seriously impacting quality of life for years. Currently, there is no specific therapy available for CHIKV infection. We have developed a despeciated equine polyclonal antibody (CHIKV-EIG) treatment against CHIKV and evaluated its protective efficacy in mouse models of CHIKV infection. In immunocompromised (IFNAR) mice infected with CHIKV, daily treatment for five consecutive days with CHIKV-EIG administered at 100 mg/kg starting on the day of infection prevented mortality, reduced viremia, and improved clinical condition as measured by body weight loss. These beneficial effects were seen even when treatment was delayed to 1 day after infection. In immunocompetent mice, CHIKV-EIG treatment reduced virus induced arthritis (including footpad swelling), arthralgia-associated cytokines, viremia, and tissue virus loads in a dose-dependent fashion. Collectively, these results suggest that CHIKV-EIG is effective at preventing CHIK and could be a viable candidate for further development as a treatment for human disease.

摘要

基孔肯雅病毒(CHIKV)是一种经蚊子传播的病原体,可引起基孔肯雅热(CHIK);该疾病的特征是发热、肌肉疼痛、皮疹和关节痛。这种关节痛可能使人虚弱且持久,严重影响生活质量多年。目前,尚无针对 CHIKV 感染的特定疗法。我们已经开发出一种针对 CHIKV 的去特异性马多克隆抗体(CHIKV-EIG)治疗方法,并在 CHIKV 感染的小鼠模型中评估了其保护效果。在感染 CHIKV 的免疫功能低下(IFNAR)小鼠中,从感染当天开始,每天连续 5 天用 100mg/kg 的 CHIKV-EIG 进行治疗,可以预防死亡、降低病毒血症并改善体重减轻等临床症状。即使在感染后 1 天开始治疗,也能看到这些有益的效果。在免疫功能正常的小鼠中,CHIKV-EIG 治疗以剂量依赖的方式减轻了病毒引起的关节炎(包括足垫肿胀)、关节痛相关细胞因子、病毒血症和组织病毒载量。总的来说,这些结果表明 CHIKV-EIG 能有效预防 CHIK,可能是进一步开发用于治疗人类疾病的可行候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/18ba/10384969/d03c81923f0e/viruses-15-01479-g001.jpg

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