The
intercellular adhesion molecule 1 (ICAM-1) is used as cellular receptor by 90% of human rhinoviruses (HRV). Recently, a recombinant, soluble
ICAM-1 (sICAM-1) has been shown to be effective in prevention of the cytopathic effect of rhinovirus
infection in vitro. Aim of this study was the production of molecules with multivalent binding sites. Different chimeric
proteins were constructed by fusion of two or five extracellular domains of
ICAM-1 with the constant regions of
IgA1,
IgM and
IgG1 by polymerase chain reactions (PCR).
IgA- and
IgG-immunoadhesion molecules were expressed in eucaryotic cells as dimers,
IgM-immunoadhesion molecules as decamers. Immunoadhesion molecules were compared to sICAM-1 for their ability to neutralize HRV: The chimeric
protein of five N-terminal domains of
ICAM-1 and the constant regions of
IgA1 was 150 times more potent than sICAM-1 in neutralizing HRV. The first and the second N-terminal of
ICAM-1 fused to
IgA1 or
IgM were five times more active, however, fused to
IgG1 four times less active than sICAM-1. Sedimentation analyses of [H3]-leucin labled HRV after preincubation with the different immunoadhesion molecules showed a dose-dependent induction of a conformational change of the viral
capsid proteins. The order of efficiency of the chimeric
proteins was consistent to the neutralizing experiments. Our results showed that HRV neutralizing can be dramatically increased by multimerization of
ICAM-1. The chimeric molecule between
IgA1 and
ICAM-1 seems to be a potential candidate for clinical testing to prevent and treat HRV-
infections.