title: Preserving immunogenicity of lethally irradiated viral and bacterial vaccine epitopes using a radio- protective Mn2+-Peptide complex from Deinococcus.
abstract: Although pathogen inactivation by γ-radiation is an attractive approach for whole-organism vaccine development, radiation doses required to ensure sterility also destroy immunogenic protein epitopes needed to mount protective immune responses. We demonstrate the use of a reconstituted manganous peptide complex from the radiation-resistant bacterium Deinococcus radiodurans to protect protein epitopes from radiation-induced damage and uncouple it from genome damage and organism killing. The Mn(2+) complex preserved antigenic structures in aqueous preparations of bacteriophage lambda, Venezuelan equine encephalitis virus, and Staphylococcus aureus during supralethal irradiation (25-40 kGy). An irradiated vaccine elicited both antibody and Th17 responses, and induced B and T cell-dependent protection against methicillin-resistant S. aureus (MRSA) in mice. Structural integrity of viruses and bacteria are shown to be preserved at radiation doses far above those which abolish infectivity. This approach could expedite vaccine production for emerging and established pathogens for which no protective vaccines exist.
authors: Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Elena K
authors: EK
authors: Gaidamakova
authors: Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Ian A
authors: IA
authors: Myles
authors: Department of Microbiology and Immunology School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Dennis P
authors: DP
authors: McDaniel
authors: Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Cedar J
authors: CJ
authors: Fowler
authors: Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Patricia A
authors: PA
authors: Valdez
authors: Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.|Immunology Graduate group, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Shruti
authors: S
authors: Naik
authors: Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.|Biological Sciences Department, Birla Institute of Technology and Science, Pilani Campus, Rajasthan-333031, India.
authors: Manoshi
authors: M
authors: Gayen
authors: Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.|Biological Sciences Department, Birla Institute of Technology and Science, Pilani Campus, Rajasthan-333031, India.
authors: Paridhi
authors: P
authors: Gupta
authors: Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Anuj
authors: A
authors: Sharma
authors: Virology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
authors: Pamela J
authors: PJ
authors: Glass
authors: Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Radha K
authors: RK
authors: Maheshwari
authors: Bacterial Pathogenesis Unit, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Sandip K
authors: SK
authors: Datta
authors: Department of Pathology, School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors: Michael J
authors: MJ
authors: Daly
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology* / Q000528:radiation effects*; D010582:Bacteriophage lambda / Q000276:immunology; D034301:Deinococcus / Q000528:radiation effects*; D004666:Encephalitis Virus, Venezuelan Equine / Q000276:immunology / Q000528:radiation effects; D000939:Epitopes / Q000276:immunology / Q000528:radiation effects*; D005720:Gamma Rays; D016679:Genome, Viral / Q000528:radiation effects; D008345:Manganese / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D010455:Peptides / Q000737:chemistry* / Q000528:radiation effects; D012996:Solutions; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000276:immunology / Q000528:radiation effects; D013211:Staphylococcus aureus / Q000276:immunology / Q000528:radiation effects; D058504:Th17 Cells / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000528:radiation effects
chemical_list: D001428:Bacterial Vaccines; D000939:Epitopes; D010455:Peptides; D012996:Solutions; D013209:Staphylococcal Vaccines; D014765:Viral Vaccines; D008345:Manganese