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5 results on '"Fahd Benjelloun"'

1. Seminal Plasma Exposures Strengthen Vaccine Responses in the Female Reproductive Tract Mucosae

Author

Romain Marlin, Marie-Thérèse Nugeyre, Nicolas Tchitchek, Matteo Parenti, Cécile Lefebvre, Hakim Hocini, Fahd Benjelloun, Claude Cannou, Silvia Nozza, Nathalie Dereuddre-Bosquet, Yves Levy, Françoise Barré-Sinoussi, Gabriella Scarlatti, Roger Le Grand, and Elisabeth Menu

Subjects
female reproductive tract (FRT), seminal plasma, vaccine, mucosa, HIV-1, Immunologic diseases. Allergy, RC581-607
Abstract

HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity, however, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of non-human primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Furthermore, the frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells, and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.

Published
2019
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2. Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry

Author

Elisabeth Menu, Nathalie Dereuddre-Bosquet, Claude Cannou, Roger Le Grand, Matteo Parenti, Hakim Hocini, Marie-Thérèse Nugeyre, Françoise Barré-Sinoussi, Romain Marlin, Nicolas Tchitchek, Fahd Benjelloun, Yves Levy, Gabriella Scarlatti, Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Direction Internationale de l'Institut Pasteur, San Raffaele Scientific Institute, Vita-Salute San Raffaele University and Center for Translational Genomics and Bioinformatics, This work was supported by the French Government Programme d’Investissements d’Avenir (Grant ANR-11-INBS-0008 funding the Infectious Disease Models and Innovative Therapies infrastructure and Grants ANR-10-LABX-77 and ANR-10-EQPX-02-01 funding the Vaccine Research Institute and the FlowCyTech facility, respectively)., We thank Dr. Anne-Sophie Beignon, Dr. Antonio Cosma, Dr. Mireille Centlivre, and the B Cell and Mucosae division members for scientific discussions, D. Young for critical editing of the manuscript, Transgene for providing the wt MVA strain, l'Agence nationale de recherche sur le sida et les hépatites virales /INSERM and the Vaccine Research Institute for providing the MVA–HIV-B vaccine, the Infectious Disease Models and Innovative Therapies Core Facilities for animal intervention and sampling, Rahima Yousfi for technical assistance, and Dr. Bernard Verrier for providing the p24 HIV-1 Ag., ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-EQPX-0002,FlowCyTech,Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales(2010), Vaccine Research Institute (VRI), Bidault, Floran, Infrastructures - Infrastructure nationale pour la modélisation des maladies infectieuses humaines - - IDMIT2011 - ANR-11-INBS-0008 - INBS - VALID, Laboratoires d'excellence - Initiative for the creation of a Vaccine Research Institute - - VRI2010 - ANR-10-LABX-0077 - LABX - VALID, and Equipements d'excellence - Plateforme de phénotypage en Mass cytométrie pour l'analyse multiparamétrique de biomarqueurs complexes de l'efficacité de nouvelles stratégies thérapeutiques ou vaccinales - - FlowCyTech2010 - ANR-10-EQPX-0002 - EQPX - VALID

Subjects
0301 basic medicine, T-Lymphocytes, viruses, [SDV]Life Sciences [q-bio], Uterus, Antibodies, Viral, Reproductive Tract Infections, chemistry.chemical_compound, Vaccinia, Immunology and Allergy, Antigens, Viral, Cells, Cultured, AIDS Vaccines, Immunity, Cellular, Vaccination, Innate lymphoid cell, Genitalia, Female, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Female, Primates, endocrine system, Genetic Vectors, Immunology, Antigen-Presenting Cells, Vaccinia virus, Biology, Virus, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Immune system, Disease Transmission, Infectious, medicine, Animals, Humans, Cervix, Viral Vaccines, Virology, Immunity, Humoral, Immunoglobulin A, 030104 developmental biology, chemistry, Immunoglobulin G, HIV-1, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Immunologic Memory, CD8
Abstract

The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalization of immune cells in the FRT was supported by transcriptomic analyses and a correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab responses in the FRT.

Published
2017
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3. First Membrane Proximal External Region-Specific Anti-HIV1 Broadly Neutralizing Monoclonal IgA1 Presenting Short CDRH3 and Low Somatic Mutations

Author

Alexandre Girard, Fabienne Jospin, Christian Genin, Gaël Champier, Bernard Verrier, Stéphane Paul, Michel Cogné, Nicole M. Thielens, Blandine Chanut, Nicolas Rochereau, Zeliha Oruc, Nadine Vincent, Fahd Benjelloun, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet [Saint-Étienne] (UJM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, B-Cell Design (B-Cell Design), Groupe d'Immunité des Muqueuses et Agents Pathogènes, Université de Lyon, Université Jean Monnet - Saint-Étienne (UJM), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Immunoglobulin A, Saliva, Somatic cell, viruses, Immunology, Fluorescent Antibody Technique, Mice, Transgenic, HIV Antibodies, Gp41, Epitope, Epitopes, Mice, 03 medical and health sciences, Animals, Immunology and Allergy, Mucous Membrane, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Antibodies, Monoclonal, virus diseases, Antibodies, Neutralizing, Virology, HIV Envelope Protein gp41, Recombinant Proteins, 3. Good health, 030104 developmental biology, Transcytosis, Mutation, Monoclonal, HIV-1, biology.protein, Viral load
Abstract

Mucosal HIV-1–specific IgA have been described as being able to neutralize HIV-1 and to block viral transcytosis. In serum and saliva, the anti-HIV IgA response is predominantly raised against the envelope of HIV-1. In this work, we describe the in vivo generation of gp41-specific IgA1 in humanized α1KI mice to produce chimeric IgA1. Mice were immunized with a conformational immunogenic gp41-transfected cell line. Among 2300 clones screened by immunofluorescence microscopy, six different gp41-specific IgA with strong recognition of gp41 were identified. Two of them have strong neutralizing activity against primary HIV-1 tier 1, 2, and 3 strains and present a low rate of somatic mutations and autoreactivity, unlike what was described for classical gp41-specific IgG. Epitopes were identified and located in the hepted repeat 2/membrane proximal external region. These Abs could be of interest in prophylactic treatment to block HIV-1 penetration in mucosa or in chronically infected patients in combination with antiretroviral therapy to reduce viral load and reservoir.

Published
2016
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4. The local environment orchestrates mucosal decidual macrophage differentiation and substantially inhibits HIV-1 replication

Author

Héloïse Quillay, H. El Costa, Marion Duriez, J Ighil, Romain Marlin, Françoise Barré-Sinoussi, Fahd Benjelloun, C. de Truchis, Elisabeth Menu, Claude Cannou, M. Rahmati, Marie-Thérèse Nugeyre, Régulation des Infections Rétrovirales, Institut Pasteur [Paris], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Antoine Béclère, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by ANRS (HEC and HQfinancial support and grant #12165/13129), Sidaction (HEC and MD financial support and grant# AI20-3-01671), the TOTAL Foundation, INSERM, and Institut Pasteur, Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and MENU, Elisabeth

Subjects
Cyclin-Dependent Kinase Inhibitor p21, 0301 basic medicine, Cellular differentiation, Immunology, HIV Infections, Biology, Virus Replication, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Interferon, Decidua, medicine, Humans, Immunology and Allergy, Macrophage, Interferon gamma, Receptor, Immunity, Mucosal, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cells, Cultured, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Macrophages, Cell Differentiation, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Cellular Microenvironment, Toll-Like Receptor 7, Viral replication, Toll-Like Receptor 8, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, HIV-1, Female, Ex vivo, 030215 immunology, medicine.drug
Abstract

International audience; Macrophages from the decidua basalis (dM), the main uterine mucosa during pregnancy, are weakly permissive to HIV-1 infection. Here, we investigated the mechanisms underlying this natural control. We show, by using freshly purified decidual macrophages and ex vivo human decidual explants, that the local decidual environment influences dM differentiation and naturally protects these cells from HIV-1 infection. Interferon (IFN)-γ, present in the decidual tissue, contributes to maintenance of the dM phenotype and restricts HIV-1 infection by mechanisms involving the cyclin-dependent kinase inhibitor p21Cip1/Waf1. We also found that activation of Toll-like receptors 7 and 8 expressed by dM reinforces the low permissivity of dM to HIV-1 by restricting viral replication and inducing secretion of cytokines in the decidual environment, including IFN-γ, that shape dM plasticity. A major challenge for HIV-1 eradication is to control infection of tissue-resident macrophages in the female reproductive tract. Our findings provide clues to the development of novel strategies to prevent HIV-1 macrophage infection.

Published
2016
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5. Role of human immunodeficiency virus type 1 envelope structure in the induction of broadly neutralizing antibodies

Author

Christian Genin, Bernard Verrier, P. Lawrence, Stéphane Paul, and Fahd Benjelloun

Subjects
biology, Immunology, Human immunodeficiency virus (HIV), Viremia, HIV Antibodies, medicine.disease, medicine.disease_cause, Microbiology, Virology, Antibodies, Neutralizing, Neutralization, Viral Envelope Proteins, Insect Science, biology.protein, medicine, HIV-1, Minireview, Antibody, Elite controllers
Abstract

Very soon after the discovery of neutralizing antibodies (NAbs) toward human immunodeficiency virus type 1 (HIV-1) infection, it became apparent that characterization of these NAbs would be an important step in finding a cure for or a vaccine to eradicate HIV-1. Since the initial description of broadly cross-clade NAbs naturally produced in HIV-1 patients, numerous studies have described new viral targets for these antibodies. More recently, studies concerning new groups of patients able to control their viremia, such as long-term nonprogressors (LTNPs) or elite controllers, have described the generation of numerous envelope-targeted NAbs. Recent studies have marked a new stage in research on NAbs with the description of antibodies obtained from a worldwide screening of HIV-positive patients. These studies have permitted the discovery of NAb families with great potential for both neutralization and neutralization breadth, such as PG, PGT, CH, and highly active agonistic anti-CD4 binding site antibodies (HAADs), of which VRC01 and its variants are members. These antibodies are able to neutralize more than 80% of circulating strains without any autoreactivity and can be rapidly integrated into clinical trials in order to test their protective potential. In this review, we will focus on new insights into HIV-1 envelope structure and their implications for the generation of potent NAbs.

Published
2012

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