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Journal of Virology, August 2006, p. 7799-7806, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00318-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Isolation and Characterization of Monoclonal Antibodies Which Neutralize Human Metapneumovirus In Vitro and In Vivo

Nancy D. Ulbrandt,1* Hong Ji,1 Nita K. Patel,1 Jeffrey M. Riggs,1 Yambasu A. Brewah,1 Shannon Ready,1 Nanci E. Donacki,1 Karyn Folliot,1 Arnita S. Barnes,1 Kannaki Senthil,1 Susan Wilson,1 Mingzhong Chen,1 Lori Clarke,1 Mia MacPhail,2 Jia Li,1 Robert M. Woods,1 Kathy Coelingh,2 Jennifer L. Reed,1 Michael P. McCarthy,1 David S. Pfarr,1 Albert D. M. E. Osterhaus,3 Ron A. M. Fouchier,3 Peter A. Kiener,1 and JoAnn A. Suzich1

MedImmune, Inc., 1 MedImmune Way, Gaithersburg, Maryland 20878,1 MedImmune Vaccines, 319 North Bernardo Ave., Mountain View, California 94043,2 Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands3

Received 14 February 2006/ Accepted 23 May 2006

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.

* Corresponding author. Mailing address: MedImmune, Inc., 1 MedImmune Way, Gaithersburg, MD 20878. Phone: (301) 398-4495. Fax: (301) 398-9495. E-mail: ulbrandtn{at}medimmune.com.

Journal of Virology, August 2006, p. 7799-7806, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00318-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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