Isolation and characterization of monoclonal antibodies which neutralize human metapneumovirus in vitro and in vivo.
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.
Ulbrandt
Nancy D
ND
MedImmune, Inc., 1 MedImmune Way, Gaithersburg, MD 20878, USA. ulbrandtn@medimmune.com
Ji
Hong
H
Patel
Nita K
NK
Riggs
Jeffrey M
JM
Brewah
Yambasu A
YA
Ready
Shannon
S
Donacki
Nanci E
NE
Folliot
Karyn
K
Barnes
Arnita S
AS
Senthil
Kannaki
K
Wilson
Susan
S
Chen
Mingzhong
M
Clarke
Lori
L
MacPhail
Mia
M
Li
Jia
J
Woods
Robert M
RM
Coelingh
Kathy
K
Reed
Jennifer L
JL
McCarthy
Michael P
MP
Pfarr
David S
DS
Osterhaus
Albert D M E
AD
Fouchier
Ron A M
RA
Kiener
Peter A
PA
Suzich
JoAnn A
JA
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*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014760:Viral Fusion Proteins