Broadly neutralizing monoclonal antibodies against human adenovirus types 55, 14p, 7, and 11 generated with recombinant type 11 fiber knob.,Emerging Microbes & Infections

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Broadly neutralizing monoclonal antibodies against human adenovirus types 55, 14p, 7, and 11 generated with recombinant type 11 fiber knob.
Emerging Microbes & Infections ( IF 8.4 ) Pub Date : 2018-Dec-08 , DOI: 10.1038/s41426-018-0197-8
Xingui Tian ₁ , Ye Fan ₁ , Zhenwei Liu ₁ , Ling Zhang _{1,

2} , Jiayi Liao ₁ , Zhichao Zhou ₁ , Xiao Li ₁ , Tiantian Liu ₁ , Wenkuan Liu ₁ , Hongling Qiu ₃ , Rong Zhou ₁

Affiliation

The re-emerging human adenovirus types HAdV7, HAdV14, and HAdV55 of species B have caused severe lower respiratory tract diseases and even deaths during recent outbreaks. However, no adenovirus vaccine or therapeutic has been approved for general use. These adenoviruses attach to host cells via the knob domain of the fiber, using human desmoglein 2 as the primary cellular receptor. In this study, a recombinant HAdV11 fiber knob trimer (HAdV11FK) expressed in E. coli was shown to induce broadly neutralizing antibodies against HAdV11, -7, -14p1, and -55 in mice. Using HAdV11FK as an antigen, three monoclonal antibodies, 6A7, 3F11, and 3D8, with high neutralizing activity were generated. More importantly, the results of in vitro neutralization assays demonstrated that 3F11 and 3D8 cross-neutralized HAdV11, -7, and -55, but not HAdV14p1. The amino acids 251KE252 within the F-G loop may be the crucial amino acids in the conformational epitope recognized by 3F11, which is common to HAdV11, -7, -14p, and -55, but is not present in HAdV14p1 and HAdV3. A two-amino-acid deletion in the HAdV14p1 structure breaks the short alpha helix (248SREKE252) that is present in the HAdV7, -11, -55, and -14p fiber knob structures. Our findings add to the knowledge of adenovirus fiber structure and antibody responses and are important for the design of adenovirus vaccines and antiviral drugs with broad activity.

中文翻译：

使用重组11型纤维瘤产生的针对55、14p，7和11型人腺病毒的广泛中和单克隆抗体。

B物种的重新出现的人类腺病毒HAdV7，HAdV14和HAdV55类型已导致严重的下呼吸道疾病，甚至在最近的暴发中死亡。但是，尚未批准将腺病毒疫苗或治疗剂用于一般用途。这些腺病毒使用人桥粒芯蛋白2作为主要的细胞受体，通过纤维的结域附着在宿主细胞上。在这项研究中，表明在大肠杆菌中表达的重组HAdV11纤维三聚体（HAdV11FK）可以诱导小鼠中针对HAdV11，-7，-14p1和-55的广泛中和抗体。使用HAdV11FK作为抗原，产生了具有高中和活性的三种单克隆抗体6A7、3F11和3D8。更重要的是，体外中和试验的结果表明3F11和3D8交叉中和了HAdV11，-7和-55，但没有中和HAdV14p1。FG环内的氨基酸251KE252可能是3F11识别的构象表位中的关键氨基酸，这是HAdV11，-7，-14p和-55共有的，但在HAdV14p1和HAdV3中不存在。HAdV14p1结构中的两个氨基酸缺失会破坏HAdV7，-11，-55和-14p纤维结结构中存在的短α螺旋（248SREKE252）。我们的发现增加了腺病毒纤维结构和抗体反应的知识，对于设计具有广泛活性的腺病毒疫苗和抗病毒药物非常重要。HAdV14p1结构中的两个氨基酸缺失会破坏HAdV7，-11，-55和-14p纤维结结构中存在的短α螺旋（248SREKE252）。我们的发现增加了腺病毒纤维结构和抗体反应的知识，对于设计具有广泛活性的腺病毒疫苗和抗病毒药物非常重要。HAdV14p1结构中的两个氨基酸缺失会破坏HAdV7，-11，-55和-14p纤维结结构中存在的短α螺旋（248SREKE252）。我们的发现增加了腺病毒纤维结构和抗体反应的知识，对于设计具有广泛活性的腺病毒疫苗和抗病毒药物非常重要。

更新日期：2019-01-26

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