Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus—A New Method for the Generation of Bacterial Vaccines with Increased Efficacy

Abstract

Bacterial pathogens cause severe infections worldwide in livestock and in humans, and antibiotic resistance further increases the importance of prophylactic vaccines. Inactivated bacterial vaccines (bacterins) are usually produced via incubation of the pathogen with chemicals such as formaldehyde, which is time consuming and may cause loss of immunogenicity due to the modification of structural components. We evaluated low-energy electron irradiation (LEEI) as an alternative method to generate a bacterin. Rodentibacter pneumotropicus, an invasive Gram-negative murine pathogen, was inactivated with LEEI and formaldehyde. LEEI resulted in high antigen conservation, and LPS activity was significantly better maintained when compared with formaldehyde treatment. Immunization of mice with LEEI-inactivated R. pneumotropicus elicited a strong immune response with no detectable bacterial burden upon sublethal challenge. The results of this study suggest the inactivation of bacteria with LEEI as an alternative, fast and efficient method to generate bacterial vaccines with increased efficacy.

Automated application of low energy electron irradiation enables inactivation of pathogen- and cell-containing liquids in biomedical research and production facilities

“…Consequently, irradiated viruses or bacteria are highly efficient as vaccines against a variety of human or animal infections, and the technology can be used to inactivate pathogens in various biological samples [9][10][11] . There are several advantages over chemical inactivation (currently the only way to produce inactivated vaccines), including the lack of toxic chemicals like formaldehyde, high reproducibility, high conservation of antigenic content and short reaction time 3,9,[12][13][14] .…”

Gamma-Irradiated Fowl Cholera Mucosal Vaccine: Potential Vaccine Candidate for Safe and Effective Immunization of Chicken Against Fowl Cholera

“…The curve takes a step down when the chickens were dead. volumes within a short time via damage of nucleic acid (11). Several previous reports have suggested that nucleic acids rather than proteins are the primary targets of gamma irradiation to inactivate microorganisms.…”

“…Gamma irradiation has been used extensively as an alternative inactivation method of pathogens because of its high penetrability, which allows bacterial inactivation in large volumes within a short time via damage of nucleic acid ( 11 ). Several previous reports have suggested that nucleic acids rather than proteins are the primary targets of gamma irradiation to inactivate microorganisms.…”

“…Exposure to optimum doses of gamma radiation disrupts the genetic material of the pathogens, making the microorganism unable to replicate, so it cannot establish an infection yet leaving some residual metabolic activity. Therefore, the irradiated microorganisms may still find its natural target in the host and could effectively be immunogenic ( 11 ). The major advantage of ionizing radiation in vaccine development compared to ultraviolet or chemical agents is its ability to effectively penetrate through most biological materials and specifically target nucleic acids whilst causing less damage to surface antigenic protein, making it preferable to develop safe and simple vaccines ( 12 ).…”

Electron-Beam Inactivation of Human Rotavirus (HRV) for the Production of Neutralizing Egg Yolk Antibodies

“…Studies in our laboratories have shown that bacterial cells when inactivated retain their metabolism for specific periods of time in a state termed, Metabolically Active yet Non-culturable (MAyNC) ( 4 ). This technology is used commercially for different applications ( 2 , 3 ), but its use for pathogen inactivation in pharmaceutical development is relatively new. High energy eBeam (HEEB) equipment are bulky and require large concrete structures and, therefore, often difficult to incorporate into existing production lines.…”