Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro
Abstract The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins....
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Nature Portfolio
2018
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oai:doaj.org-article:db3d020458384367b482041f7b42c9a32021-12-02T11:40:45ZHuman IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro10.1038/s41598-018-28242-y2045-2322https://doaj.org/article/db3d020458384367b482041f7b42c9a32018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28242-yhttps://doaj.org/toc/2045-2322Abstract The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission.Claudia DevitoRada EllegårdTina FalkebornLennart SvenssonMats OhlinMarie LarssonKristina BrolidenJorma HinkulaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
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Medicine R Science Q Claudia Devito Rada Ellegård Tina Falkeborn Lennart Svensson Mats Ohlin Marie Larsson Kristina Broliden Jorma Hinkula Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
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Abstract The importance of natural IgM antibodies in protection against infections is still emerging and these antibodies have a potential role in the maintenance of homeostasis through clearance of apoptotic bodies, complement-dependent mechanisms, inflammation and exclusion of misfolded proteins. Natural IgM act as a first line of defence against unknown hazardous factors and are present in most vertebrates. We investigated the functional capacity of anti-HIV-1 IgM monoclonal antibodies, from a combinatorial Fab library derived from healthy individuals, and evaluated their protective role in inhibiting HIV-1 in vitro when passing across the human mucosal epithelial barrier. Primary HIV-1 isolates were efficiently transmitted over the tight polarized epithelial cells when added to their apical surface. Efficient inhibition of HIV-1 transmission was achieved when anti-HIV-1 IgM monoclonal antibodies were added to the basolateral side of the cells. Two of these human IgM MoAbs had the ability to neutralize HIV and reduced infection of dendritic cells in primary cervico-vaginal tissue biopsies in vitro. This indicates a potential role of natural IgM antibodies in the reduction of HIV-1 transmission in mucosal tissues and improve our understanding of how natural IgM antibodies against a neutralizing epitope could interfere with viral transmission. |
format |
article |
author |
Claudia Devito Rada Ellegård Tina Falkeborn Lennart Svensson Mats Ohlin Marie Larsson Kristina Broliden Jorma Hinkula |
author_facet |
Claudia Devito Rada Ellegård Tina Falkeborn Lennart Svensson Mats Ohlin Marie Larsson Kristina Broliden Jorma Hinkula |
author_sort |
Claudia Devito |
title |
Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
title_short |
Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
title_full |
Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
title_fullStr |
Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
title_full_unstemmed |
Human IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
title_sort |
human igm monoclonal antibodies block hiv-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/db3d020458384367b482041f7b42c9a3 |
work_keys_str_mv |
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