Recombinant flagellins with deletions in domains D1, D2, and D3: Characterization as novel immunoadjuvants

Autor: Roman Jerala, Paula Mercedes Berguer, Karolina Ivičak-Kocjan, Martín Rumbo, Julien Tabareau, Jean-Claude Sirard, Marina Elizabeth Biedma, Agustina Juliana Errea, Gustavo Parisi, Daphnée Soulard, Delphine Cayet, Griselda Moreno, Andrés Hugo Rossi
Přispěvatelé: Instituto de Estudios Inmunológicos y Fisiopatológicos, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Fundación Instituto Leloir [Buenos Aires], University of Ljubljana, Universidad Nacional de Quilmes (UNQ), The work was funded by the institutional support from France(Inserm, CNRS, Institut Pasteur de Lille, and Université de Lille),and Argentina (CONICET), as well as grants from InsermTransfert (grant CoPoC MucoFlag), ECOS - French Ministry forResearch and Higher Education – Argentinean Ministry of Science,Technology and Productive Innovation (grant number A12B03),Agencia Nacional de Promoción Científica y Tecnológica (grantnumber PICTO GSK 0048), and MINCYT-MHEST - Slovenian Ministry of Science - Argentinean Ministry of Science, Technologyand Productive Innovation (grant number SLO1406). AE receiveda Bernardo Houssay fellowship from CONICET. MEB and AR are fellows from CONICET., Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Sirard, Jean-Claude
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Models
Molecular
Antigenicity
[SDV.IMM] Life Sciences [q-bio]/Immunology
medicine.medical_treatment
FLAGELLIN
[SDV]Life Sciences [q-bio]
030231 tropical medicine
ANTIGEN
Microbiology
law.invention
Ciencias Biológicas
Mice
03 medical and health sciences
0302 clinical medicine
Adjuvants
Immunologic
Antigen
law
medicine
Animals
IMMUNOSTIMULATION
030212 general & internal medicine
Immunity
Mucosal
Sequence Deletion
Innate immune system
General Veterinary
General Immunology and Microbiology
biology
Public Health
Environmental and Occupational Health
Salmonella enterica
Bioquímica y Biología Molecular
Acquired immune system
Immunity
Innate
Recombinant Proteins
Mice
Inbred C57BL
[SDV] Life Sciences [q-bio]
Toll-Like Receptor 5
Infectious Diseases
TLR5
BACTERIA
biology.protein
Recombinant DNA
Molecular Medicine
bacteria
[SDV.IMM]Life Sciences [q-bio]/Immunology
Adjuvant
Flagellin
CIENCIAS NATURALES Y EXACTAS
Signal Transduction
Zdroj: Vaccine
Vaccine, 2019, 37 (4), pp.652-663. ⟨10.1016/j.vaccine.2018.12.009⟩
Vaccine, Elsevier, 2019, 37 (4), pp.652-663. ⟨10.1016/j.vaccine.2018.12.009⟩
ISSN: 0264-410X
Popis: Bacterial flagellin activates the innate immune system and ultimately the adaptive immune system through a Toll-like receptor 5 (TLR5)-dependent signaling mechanism. Given that TLR5 is widely distributed in epithelia, flagellin is currently being developed as a mucosal adjuvant. Flagellin FliC from Salmonella enterica has four domains: the conserved D0 and D1 domains and the hypervariable D2 and D3 domains. The deletion of D3 and partial deletion of D2 in the recombinant FliCD174-400 strongly impairs flagellin’s intrinsic antigenicity but does not affect the TLR5-dependent immunostimulation activity, i.e., the capacity to promote innate responses and adaptive responses to co-administered antigens. Here, we describe the development of novel recombinant flagellins with various deletions encompassing all of D2 and D3, and part of D1. Most of the recombinant molecules conserved an a-helical secondary structure that was as resistant to heat denaturation as the native protein. Whereas the recombinant flagellins’ ability to trigger TLR5 varied markedly in vitro, most gave equivalent in vivo TLR5- dependent innate immune responses following intranasal administration of 2 lg of flagellin to mice. Concordantly, the recombinant flagellins were also valuable respiratory adjuvants for eliciting antibody responses to the foreign antigen ovalbumin, although their intrinsic antigenicity was decreased compared to the native flagellin and not increased compared to FliCD174-400. Our results show that the additional deletions of D2 and the distal part of D1 of FliCD174-400 does not impact on antigenicity and does not significantly modify the immunostimulatory adjuvant activity. Altogether, this study generated a novel set of recombinant flagellin that constitutes a portfolio of TLR5-dependent candidate adjuvants for vaccination. Fil: Biedma, Marina Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Cayet, Delphine. Centre d’Infection et d’Immunité de Lille; Francia. Inserm; Francia Fil: Tabareau, Julien. Centre d’Infection et d’Immunité de Lille; Francia. Inserm; Francia Fil: Rossi, Andrés Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Ivičak Kocjan, Karolina. University of Ljubljana; Eslovenia Fil: Moreno, Griselda Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Errea, Agustina Juliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Soulard, Daphnée. Centre d’Infection et d’Immunité de Lille; Francia. Inserm; Francia Fil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Jerala, Roman. University of Ljubljana; Eslovenia Fil: Berguer, Paula Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Rumbo, Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Sirard, Jean Claude. Centre d’Infection et d’Immunité de Lille; Francia. Inserm; Francia
Databáze: OpenAIRE
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