PMID- 27886076 OWN - NLM STAT- MEDLINE DCOM- 20170913 LR - 20201209 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 8 IP - 11 DP - 2016 Nov 23 TI - Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses. LID - 319 AB - Inactivated vaccines are commonly produced by incubating pathogens with chemicals such as formaldehyde or beta-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. FAU - Fertey, Jasmin AU - Fertey J AD - Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. jasmin.fertey@izi.fraunhofer.de. FAU - Bayer, Lea AU - Bayer L AD - Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. lea.bayer@izi.fraunhofer.de. FAU - Grunwald, Thomas AU - Grunwald T AD - Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. thomas.grunwald@izi.fraunhofer.de. FAU - Pohl, Alexandra AU - Pohl A AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. pohl-alexandra@web.de. FAU - Beckmann, Jana AU - Beckmann J AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. jana.beckmann@fep.fraunhofer.de. FAU - Gotzmann, Gaby AU - Gotzmann G AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. gaby.gotzmann@fep.fraunhofer.de. FAU - Casado, Javier Portillo AU - Casado JP AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. javier.portillo@fep.fraunhofer.de. FAU - Schonfelder, Jessy AU - Schonfelder J AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. jessy.schoenfelder@fep.fraunhofer.de. FAU - Rogner, Frank-Holm AU - Rogner FH AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. frank-holm.roegner@fep.fraunhofer.de. FAU - Wetzel, Christiane AU - Wetzel C AD - Fraunhofer-Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, Winterbergstrasse 28, 01277 Dresden, Germany. christiane.wetzel@fep.fraunhofer.de. FAU - Thoma, Martin AU - Thoma M AD - Fraunhofer Institute for Manufacturing Engineering and Automation IPA, Nobelstrasse 12, 70569 Stuttgart, Germany. martin.thoma@ipa.fraunhofer.de. FAU - Bailer, Susanne M AU - Bailer SM AD - Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstrasse 12, 70569 Stuttgart, Germany. susanne.bailer@igb.fraunhofer.de. AD - Institute for Interfacial Engineering and Plasma Technology IGVP, University of Stuttgart, 70569 Stuttgart, Germany. susanne.bailer@igb.fraunhofer.de. FAU - Hiller, Ekkehard AU - Hiller E AD - Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstrasse 12, 70569 Stuttgart, Germany. ekkehard.hiller@cvuas.bwl.de. FAU - Rupp, Steffen AU - Rupp S AD - Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB, Nobelstrasse 12, 70569 Stuttgart, Germany. steffen.rupp@igb.fraunhofer.de. FAU - Ulbert, Sebastian AU - Ulbert S AD - Fraunhofer-Institute for Cell Therapy and Immunology IZI, Perlickstrasse 1, 04103 Leipzig, Germany. sebastian.ulbert@izi.fraunhofer.de. LA - eng PT - Journal Article DEP - 20161123 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Antigens, Bacterial) RN - 0 (Antigens, Viral) RN - 0 (Vaccines, Inactivated) SB - IM MH - Antigens, Bacterial/immunology/*radiation effects MH - Antigens, Viral/immunology/*radiation effects MH - Disinfection/*methods MH - Electrons MH - Escherichia coli/immunology/*radiation effects MH - *Radiation, Ionizing MH - Vaccines, Inactivated/immunology MH - Viruses/immunology/*radiation effects PMC - PMC5127033 OTO - NOTNLM OT - influenza A OT - low-energy electron irradiation OT - pathogen inactivation OT - vaccines COIS- The technology described in this manuscript is part of an IP application (WO 2015011265). EDAT- 2016/11/26 06:00 MHDA- 2017/09/14 06:00 PMCR- 2016/11/01 CRDT- 2016/11/26 06:00 PHST- 2016/10/06 00:00 [received] PHST- 2016/11/15 00:00 [revised] PHST- 2016/11/16 00:00 [accepted] PHST- 2016/11/26 06:00 [entrez] PHST- 2016/11/26 06:00 [pubmed] PHST- 2017/09/14 06:00 [medline] PHST- 2016/11/01 00:00 [pmc-release] AID - v8110319 [pii] AID - viruses-08-00319 [pii] AID - 10.3390/v8110319 [doi] PST - epublish SO - Viruses. 2016 Nov 23;8(11):319. doi: 10.3390/v8110319.