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 huma...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Pathogens |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935498/pdf/?tool=EBI |
| _version_ | 1819231319670915072 |
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| author | Stephanie Traub Alexandra Nikonova Alan Carruthers Rebecca Dunmore Katherine A Vousden Leila Gogsadze Weidong Hao Qing Zhu Katie Bernard Jie Zhu Michael Dymond Gary R McLean Ross P Walton Nicholas Glanville Alison Humbles Musa Khaitov Ted Wells Roland Kolbeck Andrew J Leishman Matthew A Sleeman Nathan W Bartlett Sebastian L Johnston |
| author_facet | Stephanie Traub Alexandra Nikonova Alan Carruthers Rebecca Dunmore Katherine A Vousden Leila Gogsadze Weidong Hao Qing Zhu Katie Bernard Jie Zhu Michael Dymond Gary R McLean Ross P Walton Nicholas Glanville Alison Humbles Musa Khaitov Ted Wells Roland Kolbeck Andrew J Leishman Matthew A Sleeman Nathan W Bartlett Sebastian L Johnston |
| author_sort | Stephanie Traub |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T11:43:05Z |
| format | Article |
| id | doaj.art-4f4766f10a70461e92a26bb6d95085f3 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-23T11:43:05Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-4f4766f10a70461e92a26bb6d95085f32022-12-21T17:48:25ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-01-0198e100352010.1371/journal.ppat.1003520An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation.Stephanie TraubAlexandra NikonovaAlan CarruthersRebecca DunmoreKatherine A VousdenLeila GogsadzeWeidong HaoQing ZhuKatie BernardJie ZhuMichael DymondGary R McLeanRoss P WaltonNicholas GlanvilleAlison HumblesMusa KhaitovTed WellsRoland KolbeckAndrew J LeishmanMatthew A SleemanNathan W BartlettSebastian L JohnstonHuman 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935498/pdf/?tool=EBI |
| spellingShingle | Stephanie Traub Alexandra Nikonova Alan Carruthers Rebecca Dunmore Katherine A Vousden Leila Gogsadze Weidong Hao Qing Zhu Katie Bernard Jie Zhu Michael Dymond Gary R McLean Ross P Walton Nicholas Glanville Alison Humbles Musa Khaitov Ted Wells Roland Kolbeck Andrew J Leishman Matthew A Sleeman Nathan W Bartlett Sebastian L Johnston An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. PLoS Pathogens |
| title | An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. |
| title_full | An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. |
| title_fullStr | An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. |
| title_full_unstemmed | An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. |
| title_short | An anti-human ICAM-1 antibody inhibits rhinovirus-induced exacerbations of lung inflammation. |
| title_sort | anti human icam 1 antibody inhibits rhinovirus induced exacerbations of lung inflammation |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23935498/pdf/?tool=EBI |
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