title: Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses.
abstract: Inactivated vaccines are commonly produced by incubating pathogens with chemicals such as formaldehyde or β-propiolactone. This is a time-consuming process, the inactivation efficiency displays high variability and extensive downstream procedures are often required. Moreover, application of chemicals alters the antigenic components of the viruses or bacteria, resulting in reduced antibody specificity and therefore stimulation of a less effective immune response. An alternative method for inactivation of pathogens is ionizing radiation. It acts very fast and predominantly damages nucleic acids, conserving most of the antigenic structures. However, currently used irradiation technologies (mostly gamma-rays and high energy electrons) require large and complex shielding constructions to protect the environment from radioactivity or X-rays generated during the process. This excludes them from direct integration into biological production facilities. Here, low-energy electron irradiation (LEEI) is presented as an alternative inactivation method for pathogens in liquid solutions. LEEI can be used in normal laboratories, including good manufacturing practice (GMP)- or high biosafety level (BSL)-environments, as only minor shielding is necessary. We show that LEEI efficiently inactivates different viruses (influenza A (H3N8), porcine reproductive and respiratory syndrome virus (PRRSV), equine herpesvirus 1 (EHV-1)) and bacteria (Escherichia coli) and maintains their antigenicity. Moreover, LEEI-inactivated influenza A viruses elicit protective immune responses in animals, as analyzed by virus neutralization assays and viral load determination upon challenge. These results have implications for novel ways of developing and manufacturing inactivated vaccines with improved efficacy.
authors.affiliation: Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. jasmin.fertey@izi.fraunhofer.de.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fertey
authors.affiliation: Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. lea.bayer@izi.fraunhofer.de.
authors.forename: Lea
authors.initials: L
authors.lastname: Bayer
authors.affiliation: Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. thomas.grunwald@izi.fraunhofer.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Grunwald
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. pohl-alexandra@web.de.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pohl
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. jana.beckmann@fep.fraunhofer.de.
authors.forename: Jana
authors.initials: J
authors.lastname: Beckmann
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. gaby.gotzmann@fep.fraunhofer.de.
authors.forename: Gaby
authors.initials: G
authors.lastname: Gotzmann
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. javier.portillo@fep.fraunhofer.de.
authors.forename: Javier Portillo
authors.initials: JP
authors.lastname: Casado
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. jessy.schoenfelder@fep.fraunhofer.de.
authors.forename: Jessy
authors.initials: J
authors.lastname: Schönfelder
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. frank-holm.roegner@fep.fraunhofer.de.
authors.forename: Frank-Holm
authors.initials: FH
authors.lastname: Rögner
authors.affiliation: Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. christiane.wetzel@fep.fraunhofer.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Wetzel
authors.affiliation: Fraunhofer Institute for Manufacturing Engineering and Automation IPA, Nobelstrasse 12, 70569 Stuttgart, Germany. martin.thoma@ipa.fraunhofer.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Thoma
authors.affiliation: Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstrasse 12, 70569 Stuttgart, Germany. susanne.bailer@igb.fraunhofer.de.|Institute for Interfacial Engineering and Plasma Technology IGVP, University of Stuttgart, 70569 Stuttgart, Germany. susanne.bailer@igb.fraunhofer.de.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Bailer
authors.affiliation: Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstrasse 12, 70569 Stuttgart, Germany. ekkehard.hiller@cvuas.bwl.de.
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Hiller
authors.affiliation: Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstrasse 12, 70569 Stuttgart, Germany. steffen.rupp@igb.fraunhofer.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rupp
authors.affiliation: Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. sebastian.ulbert@izi.fraunhofer.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ulbert
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000528:radiation effects*; D000956:Antigens, Viral / Q000276:immunology / Q000528:radiation effects*; D004203:Disinfection / Q000379:methods*; D004583:Electrons; D004926:Escherichia coli / Q000276:immunology / Q000528:radiation effects*; D011839:Radiation, Ionizing; D015164:Vaccines, Inactivated / Q000276:immunology; D014780:Viruses / Q000276:immunology / Q000528:radiation effects*
chemical_list: D000942:Antigens, Bacterial; D000956:Antigens, Viral; D015164:Vaccines, Inactivated
keywords: influenza A; low-energy electron irradiation; pathogen inactivation; vaccines