title: Isolation and characterization of monoclonal antibodies which neutralize human metapneumovirus in vitro and in vivo.
abstract: Human metapneumovirus (hMPV) is a recently described member of the Paramyxoviridae family/Pneumovirinae subfamily and shares many common features with respiratory syncytial virus (RSV), another member of the same subfamily. hMPV causes respiratory tract illnesses that, similar to human RSV, occur predominantly during the winter months and have symptoms that range from mild to severe cough, bronchiolitis, and pneumonia. Like RSV, the hMPV virus can be subdivided into two genetic subgroups, A and B. With RSV, a single monoclonal antibody directed at the fusion (F) protein can prevent severe lower respiratory tract RSV infection. Because of the high level of sequence conservation of the F protein across all the hMPV subgroups, this protein is likely to be the preferred antigenic target for the generation of cross-subgroup neutralizing antibodies. Here we describe the generation of a panel of neutralizing monoclonal antibodies that bind to the hMPV F protein. A subset of these antibodies has the ability to neutralize prototypic strains of both the A and B hMPV subgroups in vitro. Two of these antibodies exhibited high-affinity binding to the F protein and were shown to protect hamsters against infection with hMPV. The data suggest that a monoclonal antibody could be used prophylactically to prevent lower respiratory tract disease caused by hMPV.
authors.affiliation: MedImmune, Inc., 1 MedImmune Way, Gaithersburg, MD 20878, USA. ulbrandtn@medimmune.com
authors.forename: Nancy D
authors.initials: ND
authors.lastname: Ulbrandt
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Nita K
authors.initials: NK
authors.lastname: Patel
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Riggs
authors.forename: Yambasu A
authors.initials: YA
authors.lastname: Brewah
authors.forename: Shannon
authors.initials: S
authors.lastname: Ready
authors.forename: Nanci E
authors.initials: NE
authors.lastname: Donacki
authors.forename: Karyn
authors.initials: K
authors.lastname: Folliot
authors.forename: Arnita S
authors.initials: AS
authors.lastname: Barnes
authors.forename: Kannaki
authors.initials: K
authors.lastname: Senthil
authors.forename: Susan
authors.initials: S
authors.lastname: Wilson
authors.forename: Mingzhong
authors.initials: M
authors.lastname: Chen
authors.forename: Lori
authors.initials: L
authors.lastname: Clarke
authors.forename: Mia
authors.initials: M
authors.lastname: MacPhail
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Robert M
authors.initials: RM
authors.lastname: Woods
authors.forename: Kathy
authors.initials: K
authors.lastname: Coelingh
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Reed
authors.forename: Michael P
authors.initials: MP
authors.lastname: McCarthy
authors.forename: David S
authors.initials: DS
authors.lastname: Pfarr
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.forename: Ron A M
authors.initials: RA
authors.lastname: Fouchier
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kiener
authors.forename: JoAnn A
authors.initials: JA
authors.lastname: Suzich
mesh_terms: D000911:Antibodies, Monoclonal / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000302:isolation & purification* / Q000494:pharmacology / Q000627:therapeutic use; D002478:Cells, Cultured; D006801:Humans; D029121:Metapneumovirus / Q000276:immunology*; D018184:Paramyxoviridae Infections / Q000517:prevention & control*; D012141:Respiratory Tract Infections / Q000517:prevention & control* / Q000821:virology; D014760:Viral Fusion Proteins / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014760:Viral Fusion Proteins