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1. Synthetic self-assembling ADDomer platform for highly efficient vaccination by genetically encoded multiepitope display

Author

Véronique Josserand, Céline Terrat, Matthew Williams, Pascal Fender, Frederic Garzoni, Laurence Chaperot, Fruzsina Rabi, Emilie Stermann, Christopher J. Woods, Bernard Verrier, Joshua C. Bufton, Phil Bates, Gerardo Viedma, Mélanie Guidetti, Imre Berger, Charles Vragniau, Christiane Schaffitzel, 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), University of Bristol [Bristol], Imophoron Ltd, Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Oracle Cloud Development Centre, 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, Max Planck-Bristol Centre for Minimal Biology, COIFFIER, Celine, 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), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de biologie structurale (IBS - UMR 5075), 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 Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), ANIMAGE, Rhône-Alpes Genopole, University of Cambridge [UK] (CAM), Laboratoire recherche et développement, EFS, Laboratoire européen de biologie moléculaire - European Molecular Biology Laboratory (EMBL Grenoble), and European Molecular Biology Laboratory [Grenoble] (EMBL)

Subjects
Models, Molecular, Scaffold, minimal biology, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Protein Conformation, Computer science, viruses, advanced computing, Epitope, Epitopes, Synthetic biology, 0302 clinical medicine, Virus-like particle, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Structural Biology, Nanotechnology, ComputingMilieux_MISCELLANEOUS, Research Articles, Vaccines, Synthetic, 0303 health sciences, Multidisciplinary, Protein therapeutics, Vaccination, SciAdv r-articles, 3. Good health, Vaccinology, Nanomedicine, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Synthetic Biology, Genetic Engineering, Research Article, BrisSynBio, Computational biology, Communicable Diseases, Biodesign, Adenoviridae, Structure-Activity Relationship, Viral Proteins, 03 medical and health sciences, [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology, Self assembling, Humans, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, 030304 developmental biology, Bristol BioDesign Institute, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, SYNTHETIC BIOLOGY, [CHIM.POLY]Chemical Sciences/Polymers, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Infectious disease (medical specialty), Communicable Disease Control, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Vaccine, Epitope Mapping
Abstract

ADDomer is a synthetic, self-assembling, virus-like particle platform that enables highly efficient vaccination., Self-assembling virus-like particles represent highly attractive tools for developing next-generation vaccines and protein therapeutics. We created ADDomer, an adenovirus-derived multimeric protein-based self-assembling nanoparticle scaffold engineered to facilitate plug-and-play display of multiple immunogenic epitopes from pathogens. We used cryo–electron microscopy at near-atomic resolution and implemented novel, cost-effective, high-performance cloud computing to reveal architectural features in unprecedented detail. We analyzed ADDomer interaction with components of the immune system and developed a promising first-in-kind ADDomer-based vaccine candidate to combat emerging Chikungunya infectious disease, exemplifying the potential of our approach.

Published
2019
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2. ENETS Newsletter Winter 2014

Author

Ylenia Perone, Elizabeth K. Nousen, Gabriella Deli, Sámuel Komoly, Pasquale Vitale, Werner Druck Medien Ag, Alain Caraty, Clive W. Coen, Claudia Pivonello, Renata S. Auriemma, Volker Fendrich, Carla Giordano, Luciana Granieri, Zsolt Liposits, Zsuzsanna Bardóczi, Edit Bosnyák, Erik Hrabovszky, Anett Szilvásy-Szabó, Maurizio Gasperi, Peter H. Kann, Fruzsina Rabi, Asli Silahtaroglu, Imre Kalló, Mariano Galdiero, Juliana G. Franco, Gergely Feher, Jens D. Mikkelsen, Barbara Vida, Chiara Simeoli, Annamaria Colao, Max B. Albers, Mariarosaria Negri, Jens Waldmann, Silke Herzer, Richard Knoop, Imre Farkas, Gabriella Pusch, Björn Meister, Satz Mengensatzproduktion, Detlef K. Bartsch, Rosario Pivonello, Elinor L. Sullivan, Tamas F. Molnar, and Teresa Mannarino

Subjects
Gerontology, Cellular and Molecular Neuroscience, medicine.medical_specialty, Endocrinology, Endocrine and Autonomic Systems, Endocrinology, Diabetes and Metabolism, Internal medicine, medicine, Psychology
Published
2013
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3. Contents Vol. 98, 2013

Author

Sámuel Komoly, Ylenia Perone, Jens Waldmann, Satz Mengensatzproduktion, Elizabeth K. Nousen, Pasquale Vitale, Barbara Vida, Alain Caraty, Mariarosaria Negri, Chiara Simeoli, Maurizio Gasperi, Tamas F. Molnar, Carla Giordano, Asli Silahtaroglu, Mariano Galdiero, Max B. Albers, Detlef K. Bartsch, Rosario Pivonello, Claudia Pivonello, Renata S. Auriemma, Imre Kalló, Juliana G. Franco, Teresa Mannarino, Zsuzsanna Bardóczi, Erik Hrabovszky, Clive W. Coen, Gabriella Deli, Fruzsina Rabi, Imre Farkas, Björn Meister, Anett Szilvásy-Szabó, Werner Druck Medien Ag, Annamaria Colao, Volker Fendrich, Zsolt Liposits, Gergely Feher, Peter H. Kann, Jens D. Mikkelsen, Edit Bosnyák, Silke Herzer, Richard Knoop, Elinor L. Sullivan, Gabriella Pusch, and Luciana Granieri

Subjects
Cellular and Molecular Neuroscience, medicine.medical_specialty, Endocrinology, Traditional medicine, Endocrine and Autonomic Systems, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, medicine, business
Published
2014
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4. Gonadotropin-releasing hormone neurones innervate kisspeptin neurones in the female mouse brain

Author

Jens D. Mikkelsen, Clive W. Coen, Zsolt Liposits, Barbara Vida, Fruzsina Rabi, Anett Szilvásy-Szabó, Alain Caraty, Imre Farkas, Imre Kalló, Zsuzsanna Bardóczi, Erik Hrabovszky, Tamas F. Molnar, Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine [Budapest] (KOKI), Hungarian Academy of Sciences (MTA)-Hungarian Academy of Sciences (MTA), Department of Neuroscience, Faculty of Information Technology, Pázmány Péter Catholic University, Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Department of Translational Neurobiology, Neurobiology Research Unit, Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Division of Women's Health, School of Medicine, King‘s College London, National Science Foundation of Hungary (OTKA K101326, OTKA K83710, OTKA K100722), European Community’s Seventh Framework Pro- gramme (FP7/2007–2013) under Grant Agreement 245009, Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA)

Subjects
Endocrinology, Diabetes and Metabolism, Fluorescent Antibody Technique, Gonadotropin-releasing hormone, souris, reciprocal innervation, immunohistochimie, anteroventral periventricular nucleus, Gonadotropin-Releasing Hormone, Mice, 0302 clinical medicine, Endocrinology, Kisspeptin, rostral periventricular area of the third ventricle, Asymmetric synapse, neurone, Neural Pathways, arcuate nucleus, Neurons, 0303 health sciences, Kisspeptins, Microscopy, Confocal, Brain, asymmetric synapse, Immunohistochemistry, Hypothalamus, cerveau, Female, Anteroventral periventricular nucleus, hormones, hormone substitutes, and hormone antagonists, Autre (Sciences du Vivant), hormone grh, medicine.medical_specialty, endocrine system, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Ovariectomy, microscopie confocale, Neuropeptide, Mice, Inbred Strains, Neurotransmission, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Imaging, Three-Dimensional, femelle, Arcuate nucleus, Internal medicine, medicine, Animals, immunofluorescence, 030304 developmental biology, Third Ventricle, Endocrine and Autonomic Systems, kisspeptine, Arcuate Nucleus of Hypothalamus, Estrogens, Dendrites, Microscopy, Electron, nervous system, Synapses, oestrogen, Neuroscience, 030217 neurology & neurosurgery
Abstract

Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation.

Published
2013
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