Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection
Current influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the conte...
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doaj-09463d6bdf634220b38f8e9744e2fabe2020-11-25T01:32:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02661496102Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza InfectionKarina Jawinski0Marcus Hartmann1Charanjit Singh2Ekaterina Kinnear3David C. Busse4Annalisa Ciabattini5Fabio Fiorino6Donata Medaglini7Claudia Maria Trombetta8Emanuele Montomoli9Emanuele Montomoli10Vanessa Contreras11Roger Le Grand12Celine Coiffier13Charlotte Primard14Bernard Verrier15John S. Tregoning16Cilian AG, Munster, GermanyCilian AG, Munster, GermanyDepartment of Infectious Disease, St Mary's Campus, Imperial College London, London, United KingdomDepartment of Infectious Disease, St Mary's Campus, Imperial College London, London, United KingdomDepartment of Infectious Disease, St Mary's Campus, Imperial College London, London, United KingdomLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, ItalyLaboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Siena, ItalyDepartment of Molecular and Developmental Medicine, University of Siena, Siena, ItalyVisMederi s.r.l., Siena, ItalyCEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Le Kremlin-Bicêtre, FranceCEA-Université Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Le Kremlin-Bicêtre, FranceLaboratoire de Biologie Tissulaire et d'Ingénierie Thérapeutique, UMR 5305, Université Lyon 1, CNRS, IBCP, Lyon, FranceAdjuvatis, Lyon, FranceAdjuvatis, Lyon, FranceDepartment of Infectious Disease, St Mary's Campus, Imperial College London, London, United KingdomCurrent influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the context of an emerging pandemic strain. Here we explore the production of recombinant influenza haemagglutinin using the ciliated protozoan Tetrahymena thermophila. For the first time we were able to produce haemagglutinin from both seasonal influenza A and B strains. This ciliate derived material was immunogenic, inducing an antibody response in both mice and non-human primates. Mice immunized with ciliate derived haemagglutinin were protected against challenge with homologous influenza A or B viruses. The antigen could also be combined with submicron particles containing a Nod2 ligand, significantly boosting the immune response and reducing the dose of antigen required. Thus, we show that Tetrahymena can be used as a manufacturing platform for viral vaccine antigens.https://www.frontiersin.org/article/10.3389/fimmu.2019.02661/fullinfluena virusprotozoaadjuvantnanoparticlevaccine manufacture |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karina Jawinski Marcus Hartmann Charanjit Singh Ekaterina Kinnear David C. Busse Annalisa Ciabattini Fabio Fiorino Donata Medaglini Claudia Maria Trombetta Emanuele Montomoli Emanuele Montomoli Vanessa Contreras Roger Le Grand Celine Coiffier Charlotte Primard Bernard Verrier John S. Tregoning |
spellingShingle |
Karina Jawinski Marcus Hartmann Charanjit Singh Ekaterina Kinnear David C. Busse Annalisa Ciabattini Fabio Fiorino Donata Medaglini Claudia Maria Trombetta Emanuele Montomoli Emanuele Montomoli Vanessa Contreras Roger Le Grand Celine Coiffier Charlotte Primard Bernard Verrier John S. Tregoning Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection Frontiers in Immunology influena virus protozoa adjuvant nanoparticle vaccine manufacture |
author_facet |
Karina Jawinski Marcus Hartmann Charanjit Singh Ekaterina Kinnear David C. Busse Annalisa Ciabattini Fabio Fiorino Donata Medaglini Claudia Maria Trombetta Emanuele Montomoli Emanuele Montomoli Vanessa Contreras Roger Le Grand Celine Coiffier Charlotte Primard Bernard Verrier John S. Tregoning |
author_sort |
Karina Jawinski |
title |
Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection |
title_short |
Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection |
title_full |
Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection |
title_fullStr |
Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection |
title_full_unstemmed |
Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection |
title_sort |
recombinant haemagglutinin derived from the ciliated protozoan tetrahymena thermophila is protective against influenza infection |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-11-01 |
description |
Current influenza vaccines manufactured using eggs have considerable limitations, both in terms of scale up production and the potential impact passaging through eggs can have on the antigenicity of the vaccine virus strains. Alternative methods of manufacture are required, particularly in the context of an emerging pandemic strain. Here we explore the production of recombinant influenza haemagglutinin using the ciliated protozoan Tetrahymena thermophila. For the first time we were able to produce haemagglutinin from both seasonal influenza A and B strains. This ciliate derived material was immunogenic, inducing an antibody response in both mice and non-human primates. Mice immunized with ciliate derived haemagglutinin were protected against challenge with homologous influenza A or B viruses. The antigen could also be combined with submicron particles containing a Nod2 ligand, significantly boosting the immune response and reducing the dose of antigen required. Thus, we show that Tetrahymena can be used as a manufacturing platform for viral vaccine antigens. |
topic |
influena virus protozoa adjuvant nanoparticle vaccine manufacture |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02661/full |
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