Finkensieper et al.
Low-energy electron irradiation of tick-borne encephalitis virus provides a protective inactivated vaccine
Front Immunol. 2022;13:825702. doi: 10.3389/fimmu.2022.825702.
TBE vaccines are produced by inactivation of whole virus concentrations by formaldehyde (FA) treatment and the antigens are then adsorbed to aluminum hydroxide (alum). Alternative approaches to prepare TBE vaccines have been discussed earlier (see e.g., Snapshot week 22/2019, week 43/2018, week 41/2018). Quite another approach is to inactivate the virus by low energy electron irradiation (LEEI).
TBE virus strain Hypr 9BMP purified from BHK-21 cell culture was completely inactivated by 20 kGy. Inactivated virus equivalent to 106 TCID50 (either by LEEI or for control by FA) was mixed with alum and was used to immunize BALB/c mice. The antibody titers in mice receiving LEEI-inactivated TBE virus antigens were significantly higher one week after the second injection (ELISA). A third immunization increased the antibody titers and the difference in immunogenicity remained statistically significant.
Using urea as a chaotropic agent, the avidity of the antibodies was analyzed by ELISA and the LEEI-inactivated experimental vaccine produced higher antibody avidity compared to FA-treated virus. The higher immunogenicity of LEEI-treated virus could be verified by a focus-reduction neutralization test.
When mice were challenged with active TBE virus, sham-immunized mice became ill and 4/8 (50%) died. In contrast, none of the LEEI- or FA-inactivated mice showed clinical symptoms or died. Viral RNA could not be detected in the brain of euthanized vaccinated mice.
In summary, it was shown that LEEI inactivated TBE virus concentrations induced high antibody titers and could protect mice against challenge with active virus. Inactivation by LEEI is worth to be further evaluated as an alternative to chemical inactivation.