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.
Highlights
The establishment of HIV infection in the mucosa during sexual transmission is dependent on the virus ability of the virus to overcome layers of innate barriers/responses and find HIV target cells where the infection can be initiated
We evaluated whether anti-HIV IgM monoclonal antibodies were capable of inhibiting HIV-1 transcytosis through a polarized epithelial cell barrier in vitro
In an intestinal epithelial cell line expressing pIgR, that the antibodies were transported from the basolateral side to the apical surface
Summary
The establishment of HIV infection in the mucosa during sexual transmission is dependent on the virus ability of the virus to overcome layers of innate barriers/responses and find HIV target cells where the infection can be initiated. Several anti-V3 IgM clones were detected, with the epitope recognition of the amino acid sequence 294–323, which contain the most conserved amino acids G-P-G V3-tip sequence in the HIV V3 region They differed in avidity index, and in the size of the epitopes mapped[20]. A typical and highly relevant property with IgM antibodies is their relatively weak epitope-binding affinity, but their multi-valency still develop a fair avidity or “stickiness” against a target protein such as gp[120]. This property make IgM molecules interesting to study, but hard to investigate in their detailed fine-epitope-specificity. Antibodies against HIV gp[120] amino acid residues 421–433 that are present before viral exposure have been shown to neutralize different HIV subtypes[27]
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