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oai:repisalud.isciii.es:20.500.12105/96452025-05-14T13:32:14Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc Olmedillas Cela, Eduardo author Cano, Olga author Martinez, Isidoro author Luque, Daniel author Terrón-Orellana, Maria Carmen author McLellan, Jason S author Melero, Jose Antonio author Mas-Lloret, Vicente author 2018 Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV However, no cross-neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins. Based on crystal structures of hRSV F and hMPV F, we designed chimeric F proteins in which certain residues of well-characterized antigenic sites were swapped between the two antigens. The antigenic changes were monitored by ELISA with virus-specific monoclonal antibodies. Inoculation of mice with these chimeras induced polyclonal cross-neutralizing antibody responses, and mice were protected against challenge with the virus used for grafting of the heterologous antigenic site. These results provide a proof of principle for chimeric fusion proteins as single immunogens that can induce cross-neutralizing antibody and protective responses against more than one human pneumovirus. EMBO Mol Med. 2018 Feb;10(2):175-187. 10.15252/emmm.201708078 1757-4684 1757-4676 EMBO molecular medicine 29217660 http://hdl.handle.net/20.500.12105/9645 Pneumoviridae Neutralizing antibodies Structure‐based design Universal vaccines Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses