Wang Ping, Fu Jiamin, Cheng Linfang, Yan Sijing, Wu Han, Liu Fumin, Yao Hangping, Wu Nanping, Xu Lihua, Wu Haibo
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, and National Clinical Research Center for Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, 310003, China.
Animal Husbandry and Veterinary Institute, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, China.
Vet Res. 2025 Apr 2;56(1):75. doi: 10.1186/s13567-025-01504-0.
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.
禽流感病毒(AIV)的H10亚型在全球家禽中广泛传播,对动物健康构成重大威胁。近年来,随着感染H10亚型AIV的人类散发病例和致死病例的出现,开发用于临床治疗流感的中和单克隆抗体(mAb)势在必行。在本研究中,用A/鸡/浙江/2CP8/2014(H10N7)血凝素(HA)蛋白免疫BALB/c小鼠,随后筛选出8种HA特异性mAb。使用体外血凝抑制和微量中和试验对mAb的特性进行测试和评估。我们选择了两种mAb(1E10和2A9)进一步研究其特性和功能,包括通过酶联免疫吸附试验和免疫荧光试验检测它们与抗原结合的亲和力和特异性。我们鉴定了在两种mAb的免疫压力下产生的H10N7毒株的突变表位(K165E和N170D)。此外,我们用H10N7病毒感染小鼠,并使用这两种mAb进行预防性和治疗性试验。结果表明,两种mAb在体内均具有明显的中和能力。在预防性和治疗性实验中,与同型IgG对照组相比,实验组小鼠的体重更大。总之,本研究中产生 的mAb有望成为临床抗H10 AIV致死性感染的有效抗病毒治疗药物。