Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection

[tetano]

Front Immunol. 2019 Nov 13;10:2661. doi: 10.3389/fimmu.2019.02661. eCollection 2019. Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection.

Jawinski K¹, Hartmann M¹, Singh C², Kinnear E², Busse DC², Ciabattini A³, Fiorino F³, Medaglini D³, Trombetta CM⁴, Montomoli E^4,5, Contreras V⁶, Le Grand R⁶, Coiffier C⁷, Primard C⁸, Verrier B⁸, Tregoning JS².
Author information

1 Cilian AG, Munster, Germany. 2 Department of Infectious Disease, St Mary's Campus, Imperial College London, London, United Kingdom. 3 Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Siena, Italy. 4 Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. 5 VisMederi s.r.l., Siena, Italy. 6 CEA-Universit? Paris Sud 11-INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, IBFJ, Le Kremlin-Bic?tre, France. 7 Laboratoire de Biologie Tissulaire et d'Ing?nierie Th?rapeutique, UMR 5305, Universit? Lyon 1, CNRS, IBCP, Lyon, France. 8 Adjuvatis, Lyon, France.

Abstract

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.
Copyright ? 2019 Jawinski, Hartmann, Singh, Kinnear, Busse, Ciabattini, Fiorino, Medaglini, Trombetta, Montomoli, Contreras, Le Grand, Coiffier, Primard, Verrier and Tregoning.


KEYWORDS:

adjuvant; influena virus; nanoparticle; protozoa; vaccine manufacture

PMID: 31798589 PMCID: PMC6863932 DOI: 10.3389/fimmu.2019.02661
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