The common cold is the most prevalent disease affecting humans, and 70 percent of cases are caused by rhinoviruses (HRV). The majority of HRV serotypes bind ICAM-1 on nasal epithelial cells as the initial step in the infectious cycle; therefore preventing HRV from binding to ICAM-l should prevent HRV attachment and thereby either prevent or shorten the duration and decrease symptoms of existing colds. A human clinical trial using intranasal administration of an anti-ICAM-1 whole antibody delayed the onset of colds by up to 2 days and decreased symptoms 50 percent but failed to prevent initial infection. It is now known that the antibody-ICAM-l dissociation rate is similar to that of the HRV virion itself indicating that the antibody has no innate advantage in functional affinity over the virus in occupying available receptors. The goal of these studies is to generate reagents and preclinical data using a high functional affinity antibody construct directed against ICAM-1 for the prevention and treatment of human rhinovirus (HRV) infections. Several multivalent, humanized antibody constructs will be expressed in E. coli, and evaluated for efficacy in protecting susceptible cells in vitro. The data generated in these studies will be used in support of human clinical trials.
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| Charles, Catherine H; Luo, Guang X; Kohlstaedt, Lori A et al. (2003) Prevention of human rhinovirus infection by multivalent fab molecules directed against ICAM-1. Antimicrob Agents Chemother 47:1503-8 |
