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Updated: Nov 3, 2025
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Experimental Assessment of Possible Factors Associated with Tick-Borne Encephalitis Vaccine Failure
Ksenia Tuchynskaya1, Viktor Volok1,2, Victoria Illarionova1,2
1FSBSI "Chumakov FSC R&D IBP RAS", 108819 Moscow, Russia.
Abstract:
Currently the only effective measure against tick-borne encephalitis (TBE) is vaccination. Despite the high efficacy of approved vaccines against TBE, rare cases of vaccine failures are well documented. Both host- and virus-related factors can account for such failures. In this work, we studied the influence of mouse strain and sex and the effects of cyclophosphamide-induced immunosuppression on the efficacy of an inactivated TBE vaccine. We also investigated how an increased proportion of non-infectious particles in the challenge TBE virus would affect the protectivity of the vaccine. The vaccine efficacy was assessed by mortality, morbidity, levels of viral RNA in the brain of surviving mice, and neutralizing antibody (NAb) titers against the vaccine strain and the challenge virus. Two-dose vaccination protected most animals against TBE symptoms and death, and protectivity depended on strain and sex of mice. Immunosuppression decreased the vaccine efficacy in a dose-dependent manner and changed the vaccine-induced NAb spectrum. The vaccination protected mice against TBE virus neuroinvasion and persistence. However, viral RNA was detected in the brain of some asymptomatic animals at 21 and 42 dpi. Challenge with TBE virus enriched with non-infectious particles led to lower NAb titers in vaccinated mice after the challenge but did not affect the protective efficacy.
Insights
Vaccination effectively prevents tick-borne encephalitis (TBE), but failures can occur. This study reveals host factors like mouse strain, sex, and immunosuppression impact vaccine efficacy against TBE virus.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Tick-borne encephalitis (TBE) is a significant neurological disease preventable by vaccination.
- Despite high efficacy, rare TBE vaccine failures necessitate understanding influencing factors.
- Host and viral elements can contribute to TBE vaccine ineffectiveness.
Purpose of the Study:
- To investigate host factors (mouse strain, sex, immunosuppression) affecting inactivated TBE vaccine efficacy.
- To assess the impact of non-infectious viral particles on TBE vaccine protectivity.
- To evaluate TBE vaccine performance using mortality, morbidity, viral RNA levels, and neutralizing antibody titers.
Main Methods:
- Assessed vaccine efficacy via mortality, morbidity, brain viral RNA, and neutralizing antibody (NAb) titers in mice.
- Administered two doses of an inactivated TBE vaccine.
- Induced immunosuppression using cyclophosphamide.
- Challenged vaccinated mice with TBE virus, including preparations with increased non-infectious particles.
Main Results:
- Two-dose vaccination generally protected against TBE, with efficacy varying by mouse strain and sex.
- Cyclophosphamide-induced immunosuppression reduced vaccine efficacy in a dose-dependent manner, altering NAb profiles.
- Vaccination prevented TBE virus neuroinvasion and persistence, though viral RNA was found in some asymptomatic mice.
- Enriching challenge virus with non-infectious particles lowered NAb titers but did not compromise protective efficacy.
Conclusions:
- Mouse strain, sex, and immunosuppression significantly influence TBE vaccine efficacy.
- The inactivated TBE vaccine provides robust protection against neuroinvasion and mortality.
- Further research into host-pathogen interactions is crucial for optimizing TBE prevention strategies.
