Low-Energy Electron Irradiation of Tick-Borne Encephalitis Virus Provides a Protective Inactivated Vaccine

Abstract

Tick-borne encephalitis virus (TBEV) is a zoonotic flavivirus which is endemic in many European and Asian countries. Humans can get infected with TBEV usually via ticks, and possible symptoms of the infection range from fever to severe neurological complications such as encephalitis. Vaccines to protect against TBEV-induced disease are widely used and most of them consist of whole viruses, which are inactivated by formaldehyde. Although this production process is well established, it has several drawbacks, including the usage of hazardous chemicals, the long inactivation times required and the potential modification of antigens by formaldehyde. As an alternative to chemical treatment, low-energy electron irradiation (LEEI) is known to efficiently inactivate pathogens by predominantly damaging nucleic acids. In contrast to other methods of ionizing radiation, LEEI does not require substantial shielding constructions and can be used in standard laboratories. Here, we have analyzed the potential of LEEI to generate a TBEV vaccine and immunized mice with three doses of irradiated or chemically inactivated TBEV. LEEI-inactivated TBEV induced binding antibodies of higher titer compared to the formaldehyde-inactivated virus. This was also observed for the avidity of the antibodies measured after the second dose. After viral challenge, the mice immunized with LEEI- or formaldehyde-inactivated TBEV were completely protected from disease and had no detectable virus in the central nervous system. Taken together, the results indicate that LEEI could be an alternative to chemical inactivation for the production of a TBEV vaccine.

Apicomplexan parasites are attenuated by low-energy electron irradiation in an automated microfluidic system and protect against infection with Toxoplasma gondii

“…LEEI conditions for C. parvum and T. gondii were established that reproducibly caused delay or incapability to grow in vitro. In accordance to data of previous studies with LEEI-treated pathogens (Bayer et al 2018 ; Fertey et al 2020 ; Finkensieper et al 2022 ), the antigenicity of C. parvum and T. gondii was not considerably changed during the irradiation process compared to non-irradiated controls. Our in vitro data also indicate that LEEI-treated T. gondii was not able to differentiate from its tachyzoite stage to bradyzoite cysts.…”

“…Due to the low penetration depth of the low-energy electrons (Gotzmann et al 2018 ; Wetzel et al 2010 ), the liquids need to be processed as thin films. Whereas for the treatment of viruses and bacteria processes for automated continuous application of LEEI have been developed, such automated processes do not yet exist for eukaryotic cells, which are more vulnerable to ionizing irradiation and hence tolerate only lower doses (Alsharifi and Müllbacher 2010 ; Fertey et al 2020 ; Finkensieper et al 2022 ; Thabet et al 2019 ; Walcher et al 2021 ). We present here the development of an LEEI process for the treatment of eukaryotic cells and irradiated tachyzoites of T. gondii and oocysts of C. parvum for the first time with different doses of low-energy electrons.…”

Immunization with different recombinant West Nile virus envelope proteins induces varying levels of serological cross-reactivity and protection from infection

“…Focus Reduction Neutralization Test (FRNT) was performed as previously described ( Finkensieper et al., 2022 ). In short, mouse sera taken three weeks after the second immunization were heat inactivated (56°C for 30 min), serially diluted in microplates and incubated with 75 FFU of purified WNV Ita09 for 1h at 37°C.…”

Immune Responses Following Administration of Whole Gamma Irradiated SARS-CoV-2 Vaccine Stabilized With Disaccharide Trehalose on Syrian Hamster Model

“…Although inactivation with formalin is well established, the process has serious drawbacks, e.g., formalin is toxic and there are problems with residual traces in the nal product. In addition, formalin leads to cross-linking and changes in structural components and damages antigenic structures, which affects the antigenicity of vaccines [9]. Other chemicals such as beta-propiolactone are also very dangerous.…”

“…Other chemicals such as beta-propiolactone are also very dangerous. Therefore, an alternative to the chemical inactivation method must be found to produce an inactivated vaccine [9]. Recently, ionizing irradiation (gamma radiation by Co-60, X-rays, and electron beams) has been considered as an alternative for vaccine development.…”