2024-03-29T10:16:18Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/96452022-06-29T14:53:23Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
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.
1757-4676
http://hdl.handle.net/20.500.12105/9645
29217660
10.15252/emmm.201708078
1757-4684
EMBO molecular medicine
Pneumoviridae
Neutralizing antibodies
Structure‐based design
Universal vaccines
Chimeric Pneumoviridae fusion proteins as immunogens to induce cross-neutralizing antibody responses