Identification of antibody neutralization epitopes on the fusion protein of human metapneumovirus.
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.
Ulbrandt
Nancy D
ND
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Ji
Hong
H
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Patel
Nita K
NK
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Barnes
Arnita S
AS
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Wilson
Susan
S
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Kiener
Peter A
PA
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
Suzich
JoAnn
J
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
McCarthy
Michael P
MP
MedImmune, Inc. 1 MedImmune Way, Gaithersburg, MD 20878, USA.
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*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D014760:Viral Fusion Proteins