This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Williams, J. V.
Right arrow Articles by Williamson, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Williams, J. V.
Right arrow Articles by Williamson, R. A.

 Previous Article  |  Next Article 

Journal of Virology, August 2007, p. 8315-8324, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00106-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A Recombinant Human Monoclonal Antibody to Human Metapneumovirus Fusion Protein That Neutralizes Virus In Vitro and Is Effective Therapeutically In Vivo{triangledown} ,{dagger}

John V. Williams,1,4,§* Zhifeng Chen,2,§ Gabriella Cseke,3 David W. Wright,3 Christopher J. Keefer,1 Sharon J. Tollefson,1 Ann Hessell,2 Amy Podsiad,1 Bryan E. Shepherd,5 Pietro Paolo Sanna,6 Dennis R. Burton,2 James E. Crowe Jr.,1,4 and R. Anthony Williamson2

Departments of Pediatrics,1 Chemistry,3 Microbiology and Immunology,4 Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee,5 Departments of Immunology,2 Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California6

Received 16 January 2007/ Accepted 14 May 2007

Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is a major cause of lower-respiratory-tract disease. hMPV is associated with more severe disease in infants and persons with underlying medical conditions. Animal studies have shown that the hMPV fusion (F) protein alone is capable of inducing protective immunity. Here, we report the use of phage display technology to generate a fully human monoclonal antibody fragment (Fab) with biological activity against hMPV. Phage antibody libraries prepared from human donor tissues were selected against recombinant hMPV F protein with multiple rounds of panning. Recombinant Fabs then were expressed in bacteria, and supernatants were screened by enzyme-linked immunosorbent assay and immunofluorescent assays. A number of Fabs that bound to hMPV F were isolated, and several of these exhibited neutralizing activity in vitro. Fab DS7 neutralized the parent strain of hMPV with a 60% plaque reduction activity of 1.1 µg/ml and bound to hMPV F with an affinity of 9.8 x10–10 M, as measured by surface plasmon resonance. To test the in vivo activity of Fab DS7, groups of cotton rats were infected with hMPV and given Fab intranasally 3 days after infection. Nasal turbinates and lungs were harvested on day 4 postinfection and virus titers determined. Animals treated with Fab DS7 exhibited a >1,500-fold reduction in viral titer in the lungs, with a modest 4-fold reduction in the nasal tissues. There was a dose-response relationship between the dose of DS7 and virus titer. Human Fab DS7 may have prophylactic or therapeutic potential against severe hMPV infection.

* Corresponding author. Mailing address: Pediatric Infectious Diseases, Vanderbilt University Medical Center, D-7235 Medical Center North, 1161 21st Avenue South, Nashville, TN 37232. Phone: (615) 936-2186. Fax: (615) 343-9723. E-mail: john.williams{at}vanderbilt.edu

{triangledown} Published ahead of print on 23 May 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

§ These authors contributed equally to this work.

Journal of Virology, August 2007, p. 8315-8324, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00106-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Darniot, M., Pitoiset, C., Petrella, T., Aho, S., Pothier, P., Manoha, C. (2009). Age-Associated Aggravation of Clinical Disease after Primary Metapneumovirus Infection of BALB/c Mice. J. Virol. 83: 3323-3332 [Abstract] [Full Text]  
  • Deffrasnes, C., Hamelin, M.-E., Prince, G. A., Boivin, G. (2008). Identification and Evaluation of a Highly Effective Fusion Inhibitor for Human Metapneumovirus. Antimicrob. Agents Chemother. 52: 279-287 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»