In this study, we demonstrate that an anti-ICAM-1 domain-specific antibody can effectively block entry and replication in an in vivo model of human rhinovirus infection and reduce rhinovirus-induced exacerbation of allergic airway inflammation, without preventing ICAM-1 interaction with its cellular ligand LFA-1, which is required for cell recruitment during respiratory infections. This evidence concerns the gene ICAM1 and respiratory tract infectious disorder.