1. Preserving immunogenicity of lethally irradiated viral and bacterial vaccine epitopes using a radio- protective Mn2+-Peptide complex from Deinococcus.
- Author
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Gaidamakova EK, Myles IA, McDaniel DP, Fowler CJ, Valdez PA, Naik S, Gayen M, Gupta P, Sharma A, Glass PJ, Maheshwari RK, Datta SK, and Daly MJ
- Subjects
- Animals, Bacteriophage lambda immunology, Encephalitis Virus, Venezuelan Equine immunology, Encephalitis Virus, Venezuelan Equine radiation effects, Epitopes immunology, Gamma Rays, Genome, Viral radiation effects, Manganese chemistry, Methicillin-Resistant Staphylococcus aureus immunology, Methicillin-Resistant Staphylococcus aureus pathogenicity, Mice, Peptides radiation effects, Solutions, Staphylococcal Infections immunology, Staphylococcal Infections prevention & control, Staphylococcal Vaccines immunology, Staphylococcal Vaccines radiation effects, Staphylococcus aureus immunology, Staphylococcus aureus radiation effects, Th17 Cells immunology, Viral Vaccines immunology, Viral Vaccines radiation effects, Bacterial Vaccines immunology, Bacterial Vaccines radiation effects, Deinococcus radiation effects, Epitopes radiation effects, Peptides chemistry
- 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
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