Abstract
Tick-borne encephalitis virus (TBEV) is one of the most prevalent and medically important tick-borne arboviruses in Eurasia. There are overlapping foci of two flaviviruses: TBEV and Omsk hemorrhagic fever virus (OHFV) in Russia. Inactivated vaccines exist only against TBE. There are no antiviral drugs for treatment of both diseases. Optimal animal models are necessary to study efficacy of novel vaccines and treatment preparations against TBE and relative flaviviruses. The models for TBE and OHF using subcutaneous inoculation were tested in Cercopithecus aethiops and Macaca fascicularis monkeys with or without prior immunization with inactivated TBE vaccine. No visible clinical signs or severe pathomorphological lesions were observed in any monkey infected with TBEV or OHFV. C. aethiops challenged with OHFV showed massive hemolytic syndrome and thrombocytopenia. Infectious virus or viral RNA was revealed in visceral organs and CNS of C. aethiops infected with both viruses; however, viremia was low. Inactivated TBE vaccines induced high antibody titers against both viruses and expressed booster after challenge. The protective efficacy against TBE was shown by the absence of virus in spleen, lymph nodes and CNS of immunized animals after challenge. Despite the absence of expressed hemolytic syndrome in immunized C. aethiops TBE vaccine did not prevent the reproduction of OHFV in CNS and visceral organs. Subcutaneous inoculation of M. fascicularis with two TBEV strains led to a febrile disease with well expressed viremia, fever, and virus reproduction in spleen, lymph nodes and CNS. The optimal terms for estimation of the viral titers in CNS were defined as 8–16 days post infection. We characterized two animal models similar to humans in their susceptibility to tick-borne flaviviruses and found the most optimal scheme for evaluation of efficacy of preventive and therapeutic preparations. We also identified M. fascicularis to be more susceptible to TBEV than C. aethiops.
Highlights
A group of tick-borne mammalian flaviviruses includes agents of serious human diseases, such as tick-borne encephalitis (TBE), Powassan encephalitis, Omsk hemorrhagic fever (OHF), Kyasanur forest disease (KFD) and viruses that do not lead to disease in humans in nature, such as Langat virus (LGT) and Louping ill virus
We modeled immunization with commercial inactivated vaccine against TBE and s/c challenge of two different monkey species with two highly virulent Tick-borne encephalitis virus (TBEV) strains and one OHF virus (OHFV) strain
Development of the preventive and therapeutic antiviral preparations critically depends on the employment of an adequate model for the evaluation of their efficacy. The efficacy of such preparations is estimated based on the ability to prevent acute infection, to reduce the level of animal death in experiments or to at least mitigate their clinical signs. For these purposes a mouse model is routinely used, because mice are highly susceptible to peripheral inoculation with TBEV
Summary
A group of tick-borne mammalian flaviviruses includes agents of serious human diseases, such as tick-borne encephalitis (TBE), Powassan encephalitis, Omsk hemorrhagic fever (OHF), Kyasanur forest disease (KFD) and viruses that do not lead to disease in humans in nature, such as Langat virus (LGT) and Louping ill virus. TBE morbidity has increased by nearly 40% in Europe between 1974 and 2004 [1], and by 10-fold in Russia between 1974 and 1996, and currently remains high [2]. TBE in humans can progress as inapparent or acute forms with varying degrees of severity. In Russia 3–10% of acute TBE cases become chronic. Morbidity of Powassan, OHF and KFD is sporadic [3,4,5] and there are no vaccines against them
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