Abstract
Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo.
Highlights
Human rhinoviruses (HRVs) infect the upper respiratory tracts of healthy subjects and cause around three quarters of common colds [1,2]
We were interested in identifying antibodies suitable to inhibit HRV-intercellular adhesion molecule-1 (ICAM-1) interactions for the potential treatment of HRV-induced exacerbations in airway disease without compromising the host leukocyte trafficking by interference of ICAM-1 interactions with the integrin LFA-1
Biotinylated Hu ICAM-1, a chimeric protein consisting of domain 1 of human ICAM-1 and domains 2– 5 of mouse ICAM-1 (Hu1 Mu2-5), murine ICAM-1 (Mu ICAM-1) and insulin as a control protein were incubated with 14C11 or 84H10 to test their binding specificity
Summary
Human rhinoviruses (HRVs) infect the upper respiratory tracts of healthy subjects and cause around three quarters of common colds [1,2]. HRV infections are associated with the majority of acute exacerbations of chronic obstructive pulmonary disease (COPD) [10,11] and cystic fibrosis [12] and cause life-threatening illnesses in susceptible populations such as infants [13], the elderly [14] and immuno-compromised individuals [15]. Against this background, there is an urgent need to develop effective medications to combat HRV induced illnesses.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
