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Développement d'anticorps monoclonaux humains de type IgA dirigés contre la partie C-terminale de la protéine d'enveloppe gp41 du VIH-1

Abstract : Sexual transmission of the Human Immunodeficiency Virus is the major mode of contamination (80%) for this pathogen (UNAIDS). This mode of transmission involves a passage of the virus though the mucosa and an interaction with epithelial cells and immune cells present in the mucosa (dendritic cells, macrophages and lymphocytes). Mucosa represents the major site of exposure for the organism to environmental antigens. The IgA expressed in the lumen of mucosa are the first line of immune defence against infection and colonization of mucosa. IgA are able to interact with glycoproteins (gp) expressed on the surface of HIV and prevent infection and/or block epithelial transcytosis. In this study we have investigated the prevalence of SIgA anti-MPER present in the parotid saliva of Exposed to HIV but Seronegative individuals (ESN). This study has allowed us to validate gp41 as an immunogen of interest for the generation of neutralizing IgA. IgA1 were generated in a chimeric mice model α1Kl that produced humanized IgA1 type antibodies. Immunizations of these mice has led to the elicitation of six monoclonal antibodies specific to the MPER region able to recognize extended conformational neutralizing epitopes of 2F5 and 4E10, two broadly neutralizing monoclonal antibodies specific to MPER. Elicited IgA1 have potent neutralizing properties for both laboratory and primary HIV strains. Characterization studies of the antiviral functions of these antibodies will further define the mode of action of these antibodies. To our knowledge, these anti-MPER humanized monoclonal neutralizing IgA1 antibodies are the first of this type described to date in the literature. By their low immunogenicity and autoreactivity, these antibodies can be easily integrated into local therapeutic approaches or passive serotherapy for protection in animal models such as the macaque challenged with SHIV. All the results of my PhD work confirm the great interest of gp41-specific SIgA as therapeutic agents against HIV
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https://theses.hal.science/tel-00999342
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Submitted on : Tuesday, June 3, 2014 - 2:33:11 PM
Last modification on : Monday, June 21, 2021 - 4:05:17 PM
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  • HAL Id : tel-00999342, version 1

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Fahd Benjelloun. Développement d'anticorps monoclonaux humains de type IgA dirigés contre la partie C-terminale de la protéine d'enveloppe gp41 du VIH-1. Médecine humaine et pathologie. Ecole Nationale Supérieure des Mines de Saint-Etienne, 2013. Français. ⟨NNT : 2013STET008T⟩. ⟨tel-00999342⟩

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