An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation.
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.
National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Centre for Respiratory Infection, Imperial College London, London, United Kingdom.
Stephanie
S
Traub
Alexandra
A
Nikonova
Alan
A
Carruthers
Rebecca
R
Dunmore
Katherine A
KA
Vousden
Leila
L
Gogsadze
Weidong
W
Hao
Qing
Q
Zhu
Katie
K
Bernard
Jie
J
Zhu
Michael
M
Dymond
Gary R
GR
McLean
Ross P
RP
Walton
Nicholas
N
Glanville
Alison
A
Humbles
Musa
M
Khaitov
Ted
T
Wells
Roland
R
Kolbeck
Andrew J
AJ
Leishman
Matthew A
MA
Sleeman
Nathan W
NW
Bartlett
Sebastian L
SL
Johnston
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology*; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D019169:Jurkat Cells; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D010850:Picornaviridae Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011024:Pneumonia, Viral / Q000178:diet therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012229:Rhinovirus / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D053586:Virus Internalization / Q000187:drug effects*
D058846:Antibodies, Monoclonal, Murine-Derived; D018925:Chemokines; D007074:Immunoglobulin G; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1