An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

PLoS Pathogens

Michael Dymond¹  Andrew J. Leishman¹  Ted Wells¹  Qing Zhu²  Alison Humbles²  Weidong Hao²  Katie Bernard²  Roland Kolbeck²  Alan Carruthers³  Katherine A. Vousden³  Matthew A. Sleeman³  Rebecca Dunmore³  Musa Khaitov⁴  Nathan W. Bartlett⁵  Ross P. Walton⁵  Sebastian L. Johnston⁵  Stephanie Traub⁵  Gary R. McLean⁵  Leila Gogsadze⁵  Jie Zhu⁵  Alexandra Nikonova⁵  Nicholas Glanville⁵ 

[1] AstraZeneca, Charnwood, United Kingdom;MedImmune LLC, Gaithersburg, Maryland, United States of America;MedImmune Ltd, Cambridge, United Kingdom;NRC Institute of Immunology FMBA, Moscow, Russia;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

关键词: Antibodies;    Inflammation;    Rhinovirus infection;    Cytokines;    Enzyme-linked immunoassays;    Genetically modified animals;    Respiratory infections;    Chemokines;   

DOI  :  10.1371/journal.ppat.1003520

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY