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Antimicrobial Agents and Chemotherapy, May 2003, p. 1503-1508, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1503-1508.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Prevention of Human Rhinovirus Infection by Multivalent Fab Molecules Directed against ICAM-1

Catherine H. Charles, Guang X. Luo, Lori A. Kohlstaedt, Ianessa G. Morantte, Elliott Gorfain, Linguang Cao, Jimmy H. Williams, and Fang Fang^*

Perlan Therapeutics, San Diego, California

Received 7 October 2002/ Returned for modification 20 December 2002/ Accepted 11 February 2003

We have developed a technology for improving avidity by making bivalent, trivalent, or tetravalent recombinant polypeptides. We designed tripartite proteins consisting of the Fab fragment of an antibody fused with a hinge derived from human immunoglobulin D that was further linked to polymerization domains derived from human coiled-coil proteins. We report here on the application of this method with a Fab domain directed against the major human rhinovirus receptor, intercellular adhesion molecule 1 (ICAM-1). Multivalent anti-ICAM-1 molecules were produced in bacteria and purified as soluble preassembled homogeneous proteins at high yield. These proteins successfully blocked rhinovirus infection in vitro, with the efficiency increasing from monomer to dimer, trimer, and tetramer. The diminished dissociation rate of these multivalent antibodies and their improved efficacy in preventing rhinovirus infection provide a foundation for producing prophylactic and therapeutic molecules against human rhinovirus, the causative agent of the majority of common colds.

Present address: The Salk Institute, San Diego, Calif.

Present address: RNAture, Irvine, Calif.

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