Human noroviruses cause an estimated 685 million infections and 200,000 deaths annually worldwide. Although vaccines against GII.4 and GI.1 genotypes are under development, no information is available regarding vaccines or monoclonal antibodies to other noroviral genotypes. Here, we developed two variable-domain llama heavy-chain antibody fragment (VHHs) clones, 7C6 and 1E4, against GII.4 and GII.17 human noroviruses, respectively. Although 7C6 cross-reacted with virus-like particles (VLPs) of GII.17, GII.6, GII.3, and GII.4, it neutralized only GII.4 norovirus. In contrast, 1E4 reacted with and neutralized only GII.17 VLPs. Both VHHs blocked VLP binding to human iPSC-derived intestinal epithelial cells and carbohydrate attachment factors. Using these two VHHs, we produced a heterodimeric VHH fragment that neutralized both GII.4 and GII.17 noroviruses. Because VHH fragments are heat- and acid-stable recombinant monoclonal antibodies, the heterodimer likely will be useful for oral immunotherapy and prophylaxis against GII.4 and GII.17 noroviruses in young, elderly, or immunocompromised persons.

中文翻译：

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一种针对诺如病毒感染的被动免疫疗法的异二聚体抗体片段。

人类诺如病毒估计每年在全球范围内引起6.85亿次感染和20万例死亡。尽管针对GII.4和GI.1基因型的疫苗正在开发中，但尚无有关针对其他诺如病毒基因型的疫苗或单克隆抗体的信息。在这里，我们开发了分别针对GII.4和GII.17人诺如病毒的两个可变域美洲驼重链抗体片段（VHHs）克隆7C6和1E4。尽管7C6与GII.17，GII.6，GII.3和GII.4的病毒样颗粒（VLP）发生交叉反应，但仅中和了GII.4诺如病毒。相反，1E4仅与GII.17 VLP反应并中和。两种VHH均阻断VLP与人iPSC来源的肠上皮细胞和碳水化合物附着因子的结合。使用这两个VHH，我们产生了一个中和GII.4和GII的异二聚VHH片段。17种诺如病毒。由于VHH片段是热稳定和酸稳定的重组单克隆抗体，因此异二聚体可能会在年轻人，老年人或免疫功能低下的人群中用于口服免疫治疗和预防GII.4和GII.17诺如病毒。