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1. Fear of mating out (FOMO): voyeurism does not increase mating propensity in fruit flies

Author

Regina Vega-Trejo, Krish Sanghvi, Biliana Todorova, Irem Sepil, and Eleanor Bath

Subjects
Mate choice, Fruit flies, Behavioural plasticity, Social cues, Medicine, Science
Abstract

Abstract Mate availability and social information can influence mating behaviour in both males and females. Social information obtained from conspecifics can influence mate choice, particularly shown by studies on mate choice copying. However, the role of directly observing conspecific mating on mating behaviour has been less explored. As such, whether conspecifics are copulating or not could inform ‘observers’ about the availability of mates, or even stimulate observers to mate themselves. Using Drosophila melanogaster, we tested whether exposure to the visual cue of a mating pair would increase the mating propensity of an observer pair (i.e., voyeur). We followed a factorial design where a male-female pair (voyeur flies) were placed together with or without visual access to another pair of flies (who were either mating or not mating). We found no evidence that mating latency or duration of mating were affected by whether voyeurs had visual access to a mating or non-mating pair. These results could be due to biological factors (e.g., use of other non-visual cues by flies to acquire information related to sex), or methodological limitations of our study (e.g., flies unable to watch other pairs). Generally, our results suggest that fruit flies do not use visual cues from conspecifics mating to adjust their own mating latency or mating duration.

Published
2024
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2. Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques

Author

Biliana Todorova, Lucille Adam, Slobodan Culina, Raphaël Boisgard, Frédéric Martinon, Antonio Cosma, Mart Ustav, Thierry Kortulewski, Roger Le Grand, and Catherine Chapon

Subjects
Medicine, Science
Abstract

Abstract In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates. In vivo fibered confocal microscopy and dynamic ex vivo imaging revealed that EP promotes the mobility of Langerhans cells (LC) and their interactions with transfected cells prior to their migration from the epidermis. At the peak of vaccine expression, we detected antigen in damaged keratinocyte areas in the epidermis and we characterized recruited immune cells in the skin, the hypodermis and the subcutaneous muscle. EP alone was sufficient to induce the production of pro-inflammatory cytokines in the skin and significantly increased local concentrations of Transforming Growth Factor (TGF)-alpha and IL-12. Our results show the kinetics of inflammatory processes in response to EP of the skin, and reveal its potential as a vaccine adjuvant.

Published
2017
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4. IgG Subclass-Dependent Pulmonary Antigen Retention during Acute IgG-Dependent Systemic Anaphylaxis in Mice

Author

Biliana Todorova, Ophélie Godon, Eva Conde, Caitlin M. Gillis, Bruno Iannascoli, Odile Richard-Le Goff, Daniel Fiole, Lubka T. Roumenina, Jeanette H. W. Leusen, Andrew J. Murphy, Lynn E. Macdonald, Laurent L. Reber, Friederike Jönsson, and Pierre Bruhns

Subjects
Complement C1q, Immunology, Receptors, IgG, Antigen-Antibody Complex, Allergens, Receptors, Complement, Mice, Inbred C57BL, Disease Models, Animal, Mice, 1107 Immunology, Immunoglobulin G, Immunology and Allergy, Animals, Anaphylaxis, Lung
Abstract

Mouse models of active systemic anaphylaxis rely predominantly on IgG Abs forming IgG–allergen immune complexes that induce IgG receptor–expressing neutrophils and monocytes/macrophages to release potent mediators, leading to systemic effects. Whether anaphylaxis initiates locally or systemically remains unknown. In this study, we aimed at identifying the anatomical location of IgG–allergen immune complexes during anaphylaxis. Active systemic anaphylaxis was induced following immunization with BSA and i.v. challenge with fluorescently labeled BSA. Ag retention across different organs was examined using whole-body fluorescence imaging, comparing immunized and naive animals. Various mouse models and in vivo deletion strategies were employed to determine the contribution of IgG receptors, complement component C1q, myeloid cell types, and anaphylaxis mediators. We found that following challenge, Ag diffused systemically, but specifically accumulated in the lungs of mice sensitized to that Ag, where it formed large Ab-dependent aggregates in the vasculature. Ag retention in the lungs did not rely on IgG receptors, C1q, neutrophils, or macrophages. IgG2a-mediated, but neither IgG1- nor IgG2b-mediated, passive systemic anaphylaxis led to Ag retention in the lung. Neutrophils and monocytes significantly accumulated in the lungs after challenge and captured high amounts of Ag, which led to downmodulation of surface IgG receptors and triggered their activation. Thus, within minutes of systemic injection in sensitized mice, Ag formed aggregates in the lung and liver vasculature, but accumulated specifically and dose-dependently in the lung. Neutrophils and monocytes recruited to the lung captured Ag and became activated. However, Ag aggregation in the lung vasculature was not necessary for anaphylaxis induction.

Published
2022

5. Evidence that neutrophils do not promote Echis carinatus venom-induced tissue destruction

Author

Friederike Jönsson, Bruno Iannascoli, Bianca Balbino, Laurent L. Reber, Julien Stackowicz, Ophélie Godon, Pierre Bruhns, Biliana Todorova, Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), This work was supported by the Institut Pasteur, the French 'Institut National de la Santé et de la Recherche Médicale' (INSERM) and the European Research Council Seventh Framework Programme (ERC-2013-CoG 616050). J.S. acknowledges support from École Normale Supérieure Paris-Saclay, B.B. is supported by a stipend from the Pasteur—Paris University (PPU) International Ph.D. Program, F.J. is an employee of the Centre National de La Recherche Scientifique (CNRS), L.L.R. acknowledges support from the European Commission Marie Skłodowska-Curie Individual Fellowship (H2020-MSCA-IF-2014 656086)., European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), European Project: 656086,H2020,H2020-MSCA-IF-2014,AllergyBLOCK(2015), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], HAL-SU, Gestionnaire, Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID, and Blocking peanut allergy through protective IgG antibodies - AllergyBLOCK - - H20202015-10-01 - 2017-09-30 - 656086 - VALID

Subjects
0301 basic medicine, Science, 030231 tropical medicine, Immunology, General Physics and Astronomy, Inflammation, Venom, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Viperidae, biology.animal, medicine, lcsh:Science, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, ComputingMilieux_MISCELLANEOUS, Innate immunity, Multidisciplinary, Innate immune system, biology, General Chemistry, biology.organism_classification, 030104 developmental biology, Echis carinatus, lcsh:Q, medicine.symptom, Leukocyte Reduction Procedures
Abstract

International audience

Published
2018
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6. IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Author

Bianca Balbino, George Delidakis, Tae Hyun Kang, Makiko Watanabe, Kendra Triplett, Anja Lux, Navin Varadarajan, Odile Richard-Le Goff, Oana I. Lungu, Pierre Bruhns, George Georgiou, Corrine Alford, Gabrielle Romain, Margaret A. Lindorfer, Wissam Charab, Falk Nimmerjahn, Yan Jessie Zhang, Hidetaka Tanno, Wupeng Yan, Nicholas M. Marshall, Moses Donkor, Chang-Han Lee, Jiwon Lee, Ronald P. Taylor, Biliana Todorova, University of Texas at Austin [Austin], University of Houston, Anticorps en Thérapie et Pathologie, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Erlangen-Nürnberg [Germany], University of Virginia School of Medicine [US], Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), University of Virginia, Department of Biochemistry and Molecular Genetics (xxx), University of Virginia [Charlottesville], We thank Y. Tanno for assistance with protein expression, A. Bui for assistance with liquid chromatography–tandem mass spectrometry, P. Tucker (University of Texas at Austin) for cancer cell lines, D. Lee (MD Anderson Cancer Center) for patient-derived primary acute lymphocytic leukemia cells, the Macromolecular Crystallography Facility of the University of Texas at Austin, the Berkeley Center for Structural Biology, the Advanced Light Source (supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under contract DE-AC02-05CH11231), the Proteomics Facility at the University of Texas at Austin (supported by grant RP110782 from the Cancer Prevention Research Training Program), and A. Nicola and the Plate-Forme d'Imagerie Dynamique (Institut Pasteur, Paris) for help with the bioluminescence experiments. Supported by the Clayton Foundation, the Institut Pasteur (P.B. laboratory), the Institut National de la Santé et de la Recherche Médicale (P.B. laboratory), the European Research Council Seventh Frame-work Program (ERC-2013-CoG 616050 for the P.B. laboratory), the Pasteur–Paris University International PhD program (B.B.), the Cancer Prevention Research Training Program (RP140108 to M.D., RP160015 to H.T., and RP130570 to N.V.), the American Cancer Society (123506-PF-13-354-01-CDD to N.M.), Uehara Memorial Foundation (H.T.), Japan Society for the Promotion of Science (H.T.), Deutsche Forschungsgemeinschaft (CRC1181-A07 to F.N.), the US National Institutes of Health (R01CA174385 to N.V., and R01 GM104896 to Y.J.Z.) and the Welch Foundation (F-1778 to Y.J.Z.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Cancer Prevention and Research Institute of Texas., European Project: 616050,EC:FP7:ERC,ERC-2013-CoG,MYELOSHOCK(2014), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Virginia, Martin, Marie, and Role of myeloid cells, their mediators and their antibody receptors in allergic shock (anaphylaxis) using humanized mouse models and clinical samples - MYELOSHOCK - - EC:FP7:ERC2014-09-01 - 2019-08-31 - 616050 - VALID

Subjects
Cytotoxicity, Immunologic, 0301 basic medicine, Cellular immunity, MESH: Complement C1q, MESH: Immunotherapy, Crystallography, X-Ray, Mass Spectrometry, MESH: Antibodies, Monoclonal, Mice, Tandem Mass Spectrometry, Neoplasms, Immunology and Allergy, MESH: Animals, MESH: Neoplasms, Cytotoxicity, Receptor, MESH: Phagocytosis, MESH: Crystallization, MESH: Immunoglobulin G, biology, Effector, Antibodies, Monoclonal, MESH: Enzyme-Linked Immunosorbent Assay, MESH: Chromatography, Gel, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, 3. Good health, Cell biology, MESH: Surface Plasmon Resonance, Chromatography, Gel, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, Lymphoma, Large B-Cell, Diffuse, Antibody, Crystallization, Lymphoma, B-Cell, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Enzyme-Linked Immunosorbent Assay, In Vitro Techniques, MESH: Receptors, IgG, MESH: Immunoglobulin Fc Fragments, 03 medical and health sciences, Classical complement pathway, Immune system, Phagocytosis, Cell Line, Tumor, Animals, Humans, MESH: Cytotoxicity, Immunologic, MESH: Mice, MESH: Lymphoma, B-Cell, MESH: In Vitro Techniques, MESH: Mass Spectrometry, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH: Humans, Complement C1q, Receptors, IgG, MESH: Tandem Mass Spectrometry, Surface Plasmon Resonance, MESH: Crystallography, X-Ray, Immunoglobulin Fc Fragments, Complement system, MESH: Burkitt Lymphoma, 030104 developmental biology, Immunoglobulin G, biology.protein, MESH: Lymphoma, Large B-Cell, Diffuse, MESH: Chromatography, Liquid, Chromatography, Liquid
Abstract

International audience; Engineered crystallizable fragment (Fc) regions of antibody domains, which assume a unique and unprecedented asymmetric structure within the homodimeric Fc polypeptide, enable completely selective binding to the complement component C1q and activation of complement via the classical pathway without any concomitant engagement of the Fcγ receptor (FcγR). We used the engineered Fc domains to demonstrate in vitro and in mouse models that for therapeutic antibodies, complement-dependent cell-mediated cytotoxicity (CDCC) and complement-dependent cell-mediated phagocytosis (CDCP) by immunological effector molecules mediated the clearance of target cells with kinetics and efficacy comparable to those of the FcγR-dependent effector functions that are much better studied, while they circumvented certain adverse reactions associated with FcγR engagement. Collectively, our data highlight the importance of CDCC and CDCP in monoclonal-antibody function and provide an experimental approach for delineating the effect of complement-dependent effector-cell engagement in various therapeutic settings.

Published
2017
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7. Electroporation as a vaccine delivery system and a natural adjuvant to intradermal administration of plasmid DNA in macaques

Author

Raphaël Boisgard, Roger Le Grand, Frédéric Martinon, Biliana Todorova, Thierry Kortulewski, Antonio Cosma, Mart Ustav, Catherine Chapon, Slobodan Culina, Lucille Adam, 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), Institut des Maladies Emergentes et des Thérapies Innovantes (IMETI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-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), Institute of Technology [Tartu, Estonia], University of Tartu, Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by French government 'Programme d’Investissements d’Avenir' (PIA) under Grant ANR-11-INBS-0008 funding the Infectious Disease Models and Innovative Therapies (IDMIT, Fontenay-aux-Roses, France) infrastructure and PIA grants ANR-10-LABX-77 and ANR-10-EQPX-02-01 funding the Vaccine Research Institute (VRI, Créteil, France), the FlowCyTech facility, respectively. It was also funded by the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS), FIT Biotech and the EPIVAC European project (European Commission, grant LSHP-CT-2006-037651)., 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), European Project: 38932,EPIVAC, Martinon, Frédéric, 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, Development of multi-step improved epidermis-specific vaccine candidate against HIV1/AIDS - EPIVAC - 38932 - OLD, Vaccine Research Institute (VRI), CEA - Université Paris Sud 11 - INSERM U1184, DRF/Jacob/Immunology of Viral infections and Autoimmune Diseases (IMVA), IDMIT infrastructure, 92265, Fontenay-aux-Roses, France, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay

Subjects
Keratinocytes, 0301 basic medicine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Gene Expression, 0302 clinical medicine, prevention, Vaccines, DNA, Multidisciplinary, Electroporation, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Cytokines, Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Inflammation Mediators, Keratinocyte, Adjuvant, Plasmids, electroporation, Injections, Intradermal, [SDV.IMM] Life Sciences [q-bio]/Immunology, Science, Antigen-Presenting Cells, Biology, Article, DNA vaccination, 03 medical and health sciences, Immune system, Adjuvants, Immunologic, Antigen, medicine, Animals, Antigens, Inflammation, Epidermis (botany), HIV, vaccination, 030104 developmental biology, Langerhans Cells, Immunology, Cancer research, Macaca, Immunization, Epidermis, Ex vivo, 030215 immunology
Abstract

International audience; In vivo electroporation (EP) is used to enhance the uptake of nucleic acids and its association with DNA vaccination greatly stimulates immune responses to vaccine antigens delivered through the skin. However, the effect of EP on cutaneous cell behavior, the dynamics of immune cell recruitment and local inflammatory factors, have not been fully described. Here, we show that intradermal DNA vaccination combined with EP extends antigen expression to the epidermis and the subcutaneous skin muscle in non-human primates. In vivo fibered confocal microscopy and dynamic ex vivo imaging revealed that EP promotes the mobility of Langerhans cells (LC) and their interactions with transfected cells prior to their migration from the epidermis. At the peak of vaccine expression, we detected antigen in damaged keratinocyte areas in the epidermis and we characterized recruited immune cells in the skin, the hypodermis and the subcutaneous muscle. EP alone was sufficient to induce the production of pro-inflammatory cytokines in the skin and significantly increased local concentrations of Transforming Growth Factor (TGF)-alpha and IL-12. Our results show the kinetics of inflammatory processes in response to EP of the skin, and reveal its potential as a vaccine adjuvant. Among the various vaccination approaches against infectious diseases such as human immunodeficiency virus (HIV), deoxyribonucleic acid (DNA) vaccines have several advantages: they are easily produced, provide opportunities for molecular engineering, lack anti-vector immunity, and have the potential to promote both cellular and humoral immune responses 1. However, despite their high immunogenicity in murine models, DNA vaccines have shown poor efficacy in large animal models and humans 2. New strategies to improve DNA vaccines include the optimization of transcriptional control elements and codons 3-5 , the use of adjuvants, such as Toll-like receptor (TLR) ligands 6 , cytokine expressing plasmids 7-9 or apoptosis-based adjuvants 10-12 and the choice of an appropriate delivery system such as local electroporation (EP) 13-15. In particular, EP has been largely used to enhance plasmid DNA uptake and increase the number of antigen-producing cells 16, 17. In addition, EP modifies blood vessel permeability and facilitates leukocyte extrava-sation in the exposed area 18. However, the effects of EP on cutaneous antigen presenting cells (APCs) and on the dynamics of cell recruitment at the vaccine site have not been fully described. In a previous study, we demonstrated that intradermal (id) administration of the auxo-GTU ®-multiHIV plasmid (GTU for Gene Transport Unit) combined with noninvasive EP induces a strong and persistent poly-functional T-cell response in macaques 19. Here, we investigated the early events that occur in the skin and the 1 CEA-Université Paris Sud 11-INSERM U1184, DRF/Jacob/Immunology of Viral infections and Autoimmune Diseases (IMVA), IDMIT infrastructure, 92265, Fontenay-aux-Roses

Published
2017
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8. Fibered Confocal Fluorescence Microscopy for the Noninvasive Imaging of Langerhans Cells in Macaques

Author

Roger Le Grand, Biliana Todorova, Raphaël Boisgard, Mélanie Rathaux, Sabine Tricot, Catherine Chapon, and Nina Salabert

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, lcsh:Medical technology, Article Subject, Confocal, law.invention, 03 medical and health sciences, 0302 clinical medicine, Single-cell analysis, In vivo, Confocal microscopy, law, Microscopy, Fluorescence microscope, medicine, Animals, Radiology, Nuclear Medicine and imaging, Microscopy, Confocal, Chemistry, Antibodies, Monoclonal, HLA-DR Antigens, 3. Good health, 030104 developmental biology, lcsh:R855-855.5, Epidermal Cells, Microscopy, Fluorescence, Langerhans Cells, Macaca, Epidermis, Single-Cell Analysis, Preclinical imaging, Ex vivo, 030215 immunology, Research Article
Abstract

Purpose. We developed a new approach to visualize skin Langerhans cells by in vivo fluorescence imaging in nonhuman primates. Procedures. Macaques were intradermally injected with a monoclonal, fluorescently labeled antibody against HLA-DR molecule and were imaged for up to 5 days by fibered confocal microscopy (FCFM). Results. The network of skin Langerhans cells was visualized by in vivo fibered confocal fluorescence microscopy. Quantification of Langerhans cells revealed no changes to cell density with time. Ex vivo experiments confirmed that injected fluorescent HLA-DR antibody specifically targeted Langerhans cells in the epidermis. Conclusions. This study demonstrates the feasibility of single-cell, in vivo imaging as a noninvasive technique to track Langerhans cells in nontransgenic animals.

Published
2017

9. CD34-derived dendritic cells transfected ex vivo with HIV-Gag mRNA induce polyfunctional T-cell responses in nonhuman primates

Author

Antonio Cosma, Guido Vanham, Catherine Chapon, Roger Le Grand, Jacques Banchereau, Lucille Adam, Dapeng Li, Nathalie Dereuddre-Bosquet, Olivier Epaulard, Biliana Todorova, Sandra Zurawski, Sangkon Oh, Frédéric Martinon, Gerard Zurawski, Gabrielle Romain, and Ellen Van Gulck

Subjects
Interleukin 2, integumentary system, Langerin, biology, Monocyte, T cell, Immunology, Antigen presentation, chemical and pharmacologic phenomena, hemic and immune systems, medicine.anatomical_structure, Immune system, Antigen, medicine, biology.protein, Immunology and Allergy, Antigen-presenting cell, medicine.drug
Abstract

The pivotal role of DCs in initiating immune responses led to their use as vaccine vectors. However, the relationship between DC subsets involved in antigen presentation and the type of elicited immune responses underlined the need for the characterization of the DCs generated in vitro. The phenotypes of tissue-derived APCs from a cynomolgus macaque model for human vaccine development were compared with ex vivo-derived DCs. Monocyte/macrophages predominated in bone marrow (BM) and blood. Myeloid DCs (mDCs) were present in all tested tissues and were more highly represented than plasmacytoid DCs (pDCs). As in human skin, Langerhans cells (LCs) resided exclusively in the macaque epidermis, expressing CD11c, high levels of CD1a and langerin (CD207). Most DC subsets were endowed with tissue-specific combinations of PRRs. DCs generated from CD34+ BM cells (CD34-DCs) were heterogeneous in phenotype. CD34-DCs shared properties (differentiation and PRR) of dermal and epidermal DCs. After injection into macaques, CD34-DCs expressing HIV-Gag induced Gag-specific CD4+ and CD8+ T cells producing IFN-γ, TNF-α, MIP-1β, or IL-2. In high responding animals, the numbers of polyfunctional CD8+ T cells increased with the number of booster injections. This DC-based vaccine strategy elicited immune responses relevant to the DC subsets generated in vitro.

Published
2012
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10. Intradermal injection of an anti-Langerin-HIVGag fusion vaccine targets epidermal Langerhans cells in nonhuman primates and can be tracked in vivo

Author

Nathalie Dereuddre-Bosquet, Antonio Cosma, Jacques Banchereau, Thierry Kortulewski, Biliana Todorova, Sandra Zurawski, Catherine Chapon, Frédéric Martinon, Raphaël Boisgard, Yves Levy, Gerard Zurawski, Roger Le Grand, Nina Salabert, 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), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-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)-Université Paris-Saclay-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Baylor Institute for Immunology Research (BIIR), Laboratoire de Recherche sur l'Instabilité Génétique (LRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Baylor College of Medecine, 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), This work was supported by research grants from the NIH (2U19AI057234-06), the ANRS HIV vaccine program, the University of Paris Sud (Attractivité PSUD), the ADITEC program (280873), the ANR (Program PECSDDeli) and the Vaccine Research Institute (VRI). N. Salabert and B. Todorova received fellowships from the Commissariat a l’Energie Atomique (CEA) and (Agence Nationale pour la Recherche contre le SIDA et les maladies hépatiques), respectively., Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Martinon, Frédéric, and Vaccine Research Institute [Créteil, France] (VRI)

Subjects
0301 basic medicine, Intravital Microscopy, medicine.medical_treatment, [SDV]Life Sciences [q-bio], HIV Core Protein p24, Antibodies, Viral, Langerhans cell, Fluorescence imaging, chemistry.chemical_compound, Nonhuman primate, Immunology and Allergy, Skin, Vaccines, biology, integumentary system, Optical Imaging, Vaccination, Imidazoles, Antibodies, Monoclonal, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Resiquimod, Adjuvant, Injections, Intradermal, Langerin, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.drug_class, Immunology, Monoclonal antibody, 03 medical and health sciences, Immune system, Antigens, CD, medicine, Animals, Humans, Lectins, C-Type, Macaca fascicularis, Mannose-Binding Lectins, 030104 developmental biology, Epidermal Cells, chemistry, Immunization, Langerhans Cells, biology.protein, Epidermis
Abstract

International audience; The development of new immunization strategies requires a better understanding of early molecular and cellular events occurring at the site of injection. The skin is particularly rich in immune cells and represents an attractive site for vaccine administration. Here, we specifically targeted vaccine antigens to epidermal Langerhans cells (LCs) using a fusion protein composed of HIV antigens and a monoclonal antibody targeting Langerin. We developed a fluorescence imaging approach to visualize, in vivo, the vaccine-targeted cells. Studies were performed in nonhuman primates (NHPs) because of their relevance as a model to assess human vaccines. We directly demonstrated that in NHPs, intra-dermally injected anti-Langerin-HIVGag specifically targets epidermal LCs and induces rapid changes in the LC network, including LC activation and migration out of the epider-mis. Vaccine targeting of LCs significantly improved anti-HIV immune response without requirement of an adjuvant. Although the co-injection of the TLR-7/8 synthetic ligand, R-848 (resiquimod), with the vaccine, did not enhance significantly the antibody response, it stimulated recruitment of HLA-DR+ inflammatory cells to the site of immunization. This study allowed us to characterize the dynamics of early local events following the injection of a vaccine-targeted epidermal LCs and R-848. Keywords: Fluorescence imaging r Langerhans cell r Nonhuman primate r Skin r Vaccination Additional supporting information may be found in the online version of this article at the publisher's web-site

Published
2016
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11. Erratum: Corrigendum: IgG Fc domains that bind C1q but not effector Fcγ receptors delineate the importance of complement-mediated effector functions

Author

Corrine Alford, Gabrielle Romain, Margaret A. Lindorfer, Falk Nimmerjahn, Wissam Charab, Moses Donkor, Navin Varadarajan, George Delidakis, Bianca Balbino, Anja Lux, Hidetaka Tanno, Wupeng Yan, Ronald P. Taylor, Kendra Triplett, Pierre Bruhns, Odile Richard-Le Goff, Chang-Han Lee, Tae Hyun Kang, George Georgiou, Oana I. Lungu, Biliana Todorova, Jiwon Lee, Nicholas M. Marshall, Makiko Watanabe, and Yan Jessie Zhang

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Nat, Effector, Immunology, Immunology and Allergy, Effector functions, Biology, Receptor, Complement (complexity), Cell biology
Abstract

Nat. Immunol.; doi:10.1038/ni.3770; corrected online 27 June 2017 In the version of this article initially published online, the labels identifying each plot in Figure 1b were missing. The labels are as follows (left to right): CHO, FcγRI, FcγRIIaR131, FcγRIIaH131, FcγRIIb, FcγRIIIaF158 and FcγRIIIaV158.

Published
2017
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