Laboratory of DNA Viruses, Division of Viral Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Influenza Other Respir Viruses. 2023 May;17(5):e13152. doi: 10.1111/irv.13152.
Highly pathogenic avian H5 influenza viruses have spread and diversified genetically and antigenically into multiple clades and subclades. Most isolates of currently circulating H5 viruses are in clade 2.3.2.1 or 2.3.4.4.
Panels of murine monoclonal antibodies (mAbs) were generated to the influenza hemagglutinin (HA) of H5 viruses from the clade 2.3.2.1 H5N1 vaccine virus A/duck/Bangladesh/19097/2013 and the clade 2.3.4.4 H5N8 vaccine virus A/gyrfalcon/Washington/41088-6/2014. Antibodies were selected and characterized for binding, neutralization, epitope recognition, cross-reactivity with other H5 viruses, and the ability to provide protection in passive transfer experiments.
All mAbs bound homologous HA in an ELISA format; mAbs 5C2 and 6H6 were broadly binding for other H5 HAs. Potently neutralizing mAbs were identified in each panel, and all neutralizing mAbs provided protection in passive transfer experiments in mice challenged with a homologous clade influenza virus. Cross-reacting mAb 5C2 neutralized a wide variety of clade 2.3.2.1 viruses, as well as H5 viruses from other clades, and also provided protection against heterologous H5 clade influenza virus challenge. Epitope analysis indicated that the majority of mAbs recognized epitopes in the globular head of the HA. The mAb 5C2 appeared to recognize an epitope below the globular head but above the stalk region of HA.
The results suggested that these H5 mAbs would be useful for virus and vaccine characterization. The results confirmed the functional cross-reactivity of mAb 5C2, which appears to bind a novel epitope, and suggest the therapeutic potential for H5 infections in humans with further development.
高致病性禽流感 H5 病毒在遗传和抗原上已经扩散和多样化，形成了多个分支和亚分支。目前流行的 H5 病毒大多数属于 2.3.2.1 或 2.3.4.4 分支。
针对来自 2.3.2.1 分支的 H5N1 疫苗病毒 A/鸭/孟加拉国/19097/2013 和 2.3.4.4 分支的 H5N8 疫苗病毒 A/白尾海雕/华盛顿/41088-6/2014 的流感血凝素（HA），生成了 panels 的鼠源单克隆抗体（mAbs）。对抗体进行了结合、中和、表位识别、与其他 H5 病毒的交叉反应性以及在被动转移实验中提供保护的能力的选择和表征。
所有 mAbs 在 ELISA 格式中均与同源 HA 结合；mAbs 5C2 和 6H6 对其他 H5 HAs 的结合具有广谱性。在每个 panel 中都鉴定出了具有强大中和能力的 mAbs，所有中和 mAbs 在被动转移实验中均能为同源流感病毒攻击的小鼠提供保护。具有交叉反应性的 mAb 5C2 中和了广泛的 2.3.2.1 分支病毒以及来自其他分支的 H5 病毒，也为针对异源 H5 分支流感病毒的攻击提供了保护。表位分析表明，大多数 mAbs 识别 HA 球形头部的表位。mAb 5C2 似乎识别 HA 球形头部下方但茎部上方的表位。
结果表明，这些 H5 mAbs 将有助于病毒和疫苗的特征分析。结果证实了 mAb 5C2 的功能交叉反应性，它似乎结合了一个新的表位，并提示在进一步开发后，mAb 5C2 可能具有治疗人类 H5 感染的潜力。
