title: Identification of antibody neutralization epitopes on the fusion protein of human metapneumovirus.
abstract: Human metapneumovirus (hMPV) is genetically related to respiratory syncytial virus (RSV); both cause respiratory tract illnesses ranging from a mild cough to bronchiolitis and pneumonia. The F protein-directed monoclonal antibody (mAb) palivizumab has been shown to prevent severe lower respiratory tract RSV infection in animals and humans. We have previously reported on a panel of mAbs against the hMPV F protein that neutralize hMPV in vitro and, in two cases, in vivo. Here we describe the generation of hMPV mAb-resistant mutants (MARMs) to these neutralizing antibodies. Sequencing the F proteins of the hMPV MARMs identified several neutralizing epitopes. Interestingly, some of the epitopes mapped on the hMPV F protein coincide with homologous regions mapped previously on the RSV F protein, including the site against which the broadly protective mAb palivizumab is directed. This suggests that these homologous regions play important, conserved functions in both viruses.
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Ulbrandt
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Nita K
authors.initials: NK
authors.lastname: Patel
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Arnita S
authors.initials: AS
authors.lastname: Barnes
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Wilson
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kiener
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: JoAnn
authors.initials: J
authors.lastname: Suzich
authors.affiliation: MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: McCarthy
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D029121:Metapneumovirus / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D009500:Neutralization Tests; D013329:Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D014760:Viral Fusion Proteins