title: A Chimeric Pneumovirus Fusion Protein Carrying Neutralizing Epitopes of Both MPV and RSV.
abstract: Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are paramyxoviruses that are responsible for substantial human health burden, particularly in children and the elderly. The fusion (F) glycoproteins are major targets of the neutralizing antibody response and studies have mapped dominant antigenic sites in F. Here we grafted a major neutralizing site of RSV F, recognized by the prophylactic monoclonal antibody palivizumab, onto HMPV F, generating a chimeric protein displaying epitopes of both viruses. We demonstrate that the resulting chimeric protein (RPM-1) is recognized by both anti-RSV and anti-HMPV F neutralizing antibodies indicating that it can be used to map the epitope specificity of antibodies raised against both viruses. Mice immunized with the RPM-1 chimeric antigen generate robust neutralizing antibody responses to MPV but weak or no cross-reactive recognition of RSV F, suggesting that grafting of the single palivizumab epitope stimulates a comparatively limited antibody response. The RPM-1 protein provides a new tool for characterizing the immune responses resulting from RSV and HMPV infections and provides insights into the requirements for developing a chimeric subunit vaccine that could induce robust and balanced immunity to both virus infections.
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, United States of America.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States of America.|Monroe Carell Jr. Children's Hospital at Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Pickens
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States of America.|Monroe Carell Jr. Children's Hospital at Vanderbilt University, Nashville, TN, United States of America.
authors.forename: Jarrod J
authors.initials: JJ
authors.lastname: Mousa
authors.affiliation: Howard Hughes Medical Institute, Northwestern University, Evanston, IL, United States of America.|Department of Molecular Biosciences, Northwestern University, Evanston, IL, United States of America.
authors.forename: George P
authors.initials: GP
authors.lastname: Leser
authors.affiliation: Howard Hughes Medical Institute, Northwestern University, Evanston, IL, United States of America.|Department of Molecular Biosciences, Northwestern University, Evanston, IL, United States of America.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lamb
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, United States of America.|Monroe Carell Jr. Children's Hospital at Vanderbilt University, Nashville, TN, United States of America.|Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Crowe
authors.affiliation: Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, United States of America.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Jardetzky
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000918:Antibody Specificity; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins