Mas-Lloret, VicenteRodriguez, LauraOlmedillas Cela, EduardoCano, OlgaPalomo-Sanz, ConcepcionTerrón-Orellana, Maria CarmenLuque, DanielMelero, Jose AntonioMcLellan, Jason S2018-12-122018-12-122016-09-09PLoS Pathog. 2016 Sep 9;12(9):e1005859.1553-7374http://hdl.handle.net/20.500.12105/6825Human 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.engVoRhttp://creativecommons.org/licenses/by/4.0/Amino Acid SequenceAnimalsAntibodies, MonoclonalAntibodies, NeutralizingAntibodies, ViralAntigens, ViralCross ReactionsCrystallography, X-RayFemaleGenetic EngineeringHumansMetapneumovirusMiceMice, Inbred BALB CModels, MolecularMolecular ConformationRespiratory Syncytial Virus, HumanSequence AlignmentViral Fusion ProteinsAtribución 4.0 Internacional27611367129e100585910.1371/journal.ppat.10058591553-7374PLoS pathogensopen access