中和单克隆抗体在小鼠模型中作为致命H10N7禽流感感染的有效治疗和预防药物

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Ping Wang, Jiamin Fu, Linfang Cheng, Sijing Yan, Han Wu, Fumin Liu, Hangping Yao, Nanping Wu, Lihua Xu, Haibo Wu
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引用次数: 0

摘要

H10亚型禽流感病毒(AIV)在全世界家禽中广泛存在,对动物健康构成重大威胁。随着近年来人类感染H10亚型aiv的散发和死亡病例的出现,开发中和性单克隆抗体(mab)来治疗流感已势在必行。本研究采用A/chicken/Zhejiang/2CP8/2014 (H10N7)血凝素(HA)蛋白免疫BALB/c小鼠,筛选出8种HA特异性单克隆抗体。利用体外血凝抑制和微量中和试验对单克隆抗体的特性进行了测试和评价。我们选择了两个单抗(1E10和2A9),通过酶联免疫吸附试验和免疫荧光试验进一步研究了它们的特性和功能,包括它们与抗原的亲和力和结合特异性。我们鉴定了在两种单抗的免疫压力下产生的H10N7菌株的突变表位(K165E和N170D)。此外,我们用H10N7病毒感染小鼠,并使用这两种单抗进行了预防和治疗试验。结果表明,这两种单克隆抗体在体内均具有明显的中和能力。与同型IgG对照组相比,在预防和治疗实验中,实验组小鼠的体重均大于对照组。综上所述,本研究制备的单克隆抗体有望成为临床抗病毒治疗H10 aiv致死性感染的有效药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neutralizing monoclonal antibodies as effective therapeutics and prophylactics against lethal H10N7 avian influenza infection in a mouse model.

The H10 subtype of avian influenza virus (AIV) is widespread in poultry worldwide and poses a significant threat to animal health. With the emergence of sporadic and fatal cases in humans infected with H10 subtype AIVs in recent years, it is imperative to develop neutralizing monoclonal antibodies (mAbs) to treat influenza clinically. In this study, BALB/c mice were immunized with A/chicken/Zhejiang/2CP8/2014 (H10N7) haemagglutinin (HA) protein, and eight HA-specific mAbs were subsequently screened. The characteristics of the mAbs were tested and evaluated using haemagglutination inhibition and microneutralization assays in vitro. We selected two mAbs (1E10 and 2A9) to further study their characteristics and functions, including their affinity and specificity of binding to antigens via enzyme-linked immunosorbent assays and immunofluorescence assays. We identified the mutant epitopes (K165E and N170D) of the H10N7 strain produced under the immune pressure of the two mAbs. Furthermore, we infected mice with the H10N7 virus and conducted prophylactic and therapeutic trials using the two mAbs. The results indicated that both mAbs have obvious neutralization ability in vivo. Compared with those in the isotype IgG control group, the weights of the mice in the experimental groups were greater in the prophylactic and therapeutic experiments. In conclusion, the mAbs produced in this study are expected to be effective drugs for clinical antiviral therapy against lethal infection by H10 AIVs.

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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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