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Journal of Virology, January 2002, p. 251-258, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.251-258.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Neutralizing Human Fab Fragments against Measles Virus Recovered by Phage Display

Cristina de Carvalho Nicacio,1 R. Anthony Williamson,2 Paul W. H. I. Parren,2 Åke Lundkvist,1,3 Dennis R. Burton,2 and Ewa Björling1,4*

Microbiology and Tumor Biology Center, Karolinska Institutet, S-171 77 Stockholm,1 Swedish Institute for Infectious Disease Control, S-171 82 Stockholm,3 The South Hospital, Research Center, Karolinska Institutet, S-118 83 Stockholm, Sweden,4 Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, California 920372

Received 13 July 2001/ Accepted 27 September 2001

Five human recombinant Fab fragments (Fabs) specific for measles virus (MV) proteins were isolated from three antibody phage display libraries generated from RNAs derived from bone marrow or splenic lymphocytes from three MV-immune individuals. All Fabs reacted in an enzyme-linked immunosorbent assay with MV antigens. In radioimmunoprecipitation assays two of the Fabs, MV12 and MT14, precipitated an {oslash}80-kDa protein band corresponding to the hemagglutinin (H) protein from MV-infected Vero cell cultures, while two other Fabs, MT64 and GL29, precipitated an {oslash}60-kDa protein corresponding the nucleocapsid (N) protein. In competition studies with MV fusion, H- and N protein-specific monoclonal antibodies (MAbs), the H-specific Fabs predominantly blocked the binding of H-specific MAbs, while the N-specific Fabs blocked MAbs to N. In addition, N-specific Fabs bound to denatured MV N protein in Western blotting. The specificity of the fifth Fab, MV4, could not be determined. By plaque reduction assays, three of the five Fabs, MV4, MV12, and MT14, exhibited neutralizing activity (80% cutoff) against MV (LEC-KI strain) at concentrations ranging between {approx}2 and 7 µg ml-1. Neutralization capacity against MV strains Edmonston and Schwarz was also detected, albeit at somewhat higher Fab concentrations. In conclusion, three neutralizing Fabs were isolated, two of them reactive against the H glycoprotein of MV and another reactive against an undefined epitope. This is the first study in which MV-neutralizing human recombinant Fab antibodies have been isolated from phage display libraries.

* Corresponding author. Mailing address: Microbiology and Tumor Biology Center, Box 280, Karolinska Institutet, S-171 77 Stockholm, Sweden. Phone: 46 8 728 63 22. Fax: 46 8 33 07 44. E-mail: ewa.bjorling{at}mtc.ki.se.

Journal of Virology, January 2002, p. 251-258, Vol. 76, No. 1
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.1.251-258.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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