Preserving Immunogenicity of Lethally Irradiated Viral and Bacterial Vaccine Epitopes using a Radio- Protective Mn2+-Peptide Complex from Deinococcus

July 19, 2012

Elena K Gaidamakova, Ian A Myles, Dennis P McDaniel, Cedar J Fowler, Patricia A Valdez, Shruti Naik, Manoshi Gayen, Paridhi Gupt, Anuj Sharma, Pamela J Glass, Radha K Maheshwari , Sandip K Datta , Michael J Daly

Cell Host and Microbe

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.