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抗 A(H1N1)流感病毒 HA 鼠源单克隆抗体的制备、鉴定及其保护效果的研究

Generation, characterization, and protective ability of mouse monoclonal antibodies against the HA of A (H1N1) influenza virus.

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Geriatrics, Shaoxing People's Hospital, Shaoxing, China.

出版信息

J Med Virol. 2022 Jun;94(6):2558-2567. doi: 10.1002/jmv.27584. Epub 2022 Jan 18.

Abstract

Influenza virus infections pose a continuous threat to human health. Although vaccines function as a preventive and protective tool, they may not be effective due to antigen drift or an inaccurate prediction of epidemic strains. Monoclonal antibodies (mAbs) have attracted wide attention as a promising therapeutic method for influenza virus infections. In this study, three hemagglutinin (HA)-specific mAbs, named 2A1, 2H4, and 2G2, respectively, were derived from mice immunized with the HA protein from A/Michigan/45/2015(H1N1). The isolated mAbs all displayed hemagglutination inhibition activity and the 2G2 mAb exhibited the strongest neutralization effect. Two amino acid mutations (A198E and G173E), recognized in the process of selection of mAb-resistant mutants, were located in antigenic site Sb and Ca1, respectively. In prophylactic experiments, all three mAbs could achieve 100% protection in mice infected with a lethal dose of A/Michigan/45/2015(H1N1). A dose of 1 mg/kg for 2H4 and 2G2 was sufficient to achieve a full protective effect. Therapeutic experiments showed that all three mAbs could protect mice from death if they received the mAb administration at 6 h postinfection, and 2G2 was still protective after 24 h. Our findings indicate that these three mAbs may have potential prevention and treatment value in an H1N1 epidemic, as well as in the study of antigen epitope recognition.

摘要

流感病毒感染对人类健康构成持续威胁。尽管疫苗是一种预防和保护工具,但由于抗原漂移或对流行株的预测不准确,它们可能并不有效。单克隆抗体 (mAb) 作为流感病毒感染的一种有前途的治疗方法引起了广泛关注。在这项研究中,分别从用 A/Michigan/45/2015(H1N1) 的 HA 蛋白免疫的小鼠中衍生出三种血凝素 (HA)-特异性 mAb,分别命名为 2A1、2H4 和 2G2。分离出的 mAb 均显示出血凝抑制活性,并且 2G2 mAb 显示出最强的中和效果。在选择 mAb 抗性突变体的过程中识别出的两个氨基酸突变 (A198E 和 G173E) 分别位于抗原表位 Sb 和 Ca1 中。在预防性实验中,三种 mAb 都能在感染致死剂量 A/Michigan/45/2015(H1N1) 的小鼠中达到 100%的保护。2H4 和 2G2 的 1mg/kg 剂量足以实现完全保护效果。治疗实验表明,如果在感染后 6 小时给予 mAb,三种 mAb 都能保护小鼠免于死亡,并且在 24 小时后 2G2 仍然具有保护作用。我们的研究结果表明,这三种 mAb 可能具有在 H1N1 流行期间以及在抗原表位识别研究中预防和治疗的潜在价值。

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