ИСТИНА

Tick-borne encephalitis virus (TBEV) is a major cause of acute neurological infections in Northern Eurasia with manifestations ranging from mild flu-like disease to severe meningitis and encephalitis. Cases of persistent TBEV infection have also been documented. Four inactivated vaccines against TBEV have been in use for several decades and have proven their efficacy, but rare cases of breakthrough infections have been described. Earlier it has been shown by detection of antibodies to non-structural proteins that vaccination against TBEV prevents the disease, but may not prevent the replication of the virus. Since the viral replication is a prerequisite for neuroinvasion and consequent viral persistence in CNS, the aim of this study was to attempt to detect the TBEV in the brain of immunized mice after infection with virulent TBEV strains. A series of experiments was conducted to assess the influence of different factors on the efficacy of vaccination. During the experiments inbred and outbred mice of different sex and age were immunized twice using commercialy available vaccines against TBE. After two weeks all animals were infected with different strains and doses of the virus and monitored for disease progression and death. Samples of the brain tissue were collected and studied for the presence of TBEV RNA using RT-qPCR. Passages in cell culture and brains of suckling mice were used in an attempt to isolate the infectious virus. Vaccination successfully protected inbred BALB/c mice from the disease after inoculation with a high dose (1600 LD50) of the TBEV strain Vasilchenko. More heterogenous outbred ICR mice showed lower susceptibility to 85 LD50 of this strain than inbred mice, but were less protected by the vaccine. Then, three different vaccines were tested against three subtypes of the virus and demonstrated variable levels of protection. Viral RNA was detected in the brains of all survived non-immunized mice and in 38% and 26% of samples from immunized mice with and without clinical symptoms, respectively. Thus, the vaccination provided a significant level of protection against neuroinvasion (p<0.01), but the virus was detected in the CNS of some healthy immunized animals. We were not able to isolate the infectious virus from any sample. The obtained results support the overall efficacy of inactivated vaccines against an array of strains of TBEV and show that vaccination confers significant protection against neuroinvasion, but may not always prevent the virus from entering the CNS even in the absence of clinical symptoms.