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oai:repisalud.isciii.es:20.500.12105/68252025-05-27T11:28:53Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Mas-Lloret, Vicente author Rodriguez, Laura author Olmedillas Cela, Eduardo author Cano, Olga author Palomo-Sanz, Concepcion author Terrón-Orellana, Maria Carmen author Luque, Daniel author Melero, Jose Antonio author McLellan, Jason S author 2016-09-09 Human metapneumovirus (hMPV) is a paramyxovirus that is a common cause of bronchiolitis and pneumonia in children less than five years of age. The hMPV fusion (F) glycoprotein is the primary target of neutralizing antibodies and is thus a critical vaccine antigen. To facilitate structure-based vaccine design, we stabilized the ectodomain of the hMPV F protein in the postfusion conformation and determined its structure to a resolution of 3.3 Å by X-ray crystallography. The structure resembles an elongated cone and is very similar to the postfusion F protein from the related human respiratory syncytial virus (hRSV). In contrast, significant differences were apparent with the postfusion F proteins from other paramyxoviruses, such as human parainfluenza type 3 (hPIV3) and Newcastle disease virus (NDV). The high similarity of hMPV and hRSV postfusion F in two antigenic sites targeted by neutralizing antibodies prompted us to test for antibody cross-reactivity. The widely used monoclonal antibody 101F, which binds to antigenic site IV of hRSV F, was found to cross-react with hMPV postfusion F and neutralize both hRSV and hMPV. Despite the cross-reactivity of 101F and the reported cross-reactivity of two other antibodies, 54G10 and MPE8, we found no detectable cross-reactivity in the polyclonal antibody responses raised in mice against the postfusion forms of either hMPV or hRSV F. The postfusion-stabilized hMPV F protein did, however, elicit high titers of hMPV-neutralizing activity, suggesting that it could serve as an effective subunit vaccine. Structural insights from these studies should be useful for designing novel immunogens able to induce wider cross-reactive antibody responses. PLoS Pathog. 2016 Sep 9;12(9):e1005859. 10.1371/journal.ppat.1005859 1553-7374 1553-7374 PLoS pathogens 27611367 http://hdl.handle.net/20.500.12105/6825 Engineering, Structure and Immunogenicity of the Human Metapneumovirus F Protein in the Postfusion Conformation