Immunity to TBEV Related Flaviviruses with Reduced Pathogenicity Protects Mice from Disease but Not from TBEV Entry into the CNS

Abstract

Tick-borne encephalitis virus (TBEV) is a leading cause of vector-borne viral encephalitis with expanding endemic regions across Europe. In this study we tested in mice the efficacy of preinfection with a closely related low-virulent flavivirus, Langat virus (LGTV strain TP21), or a naturally avirulent TBEV strain (TBEV-280) in providing protection against lethal infection with the highly virulent TBEV strain (referred to as TBEV-Hypr). We show that prior infection with TP21 or TBEV-280 is efficient in protecting mice from lethal TBEV-Hypr challenge. Histopathological analysis of brains from nonimmunized mice revealed neuronal TBEV infection and necrosis. Neuroinflammation, gliosis, and neuronal necrosis was however also observed in some of the TP21 and TBEV-280 preinfected mice although at reduced frequency as compared to the nonimmunized TBEV-Hypr infected mice. qPCR detected the presence of viral RNA in the CNS of both TP21 and TBEV-280 immunized mice after TBEV-Hypr challenge, but significantly reduced compared to mock-immunized mice. Our results indicate that although TBEV-Hypr infection is effectively controlled in the periphery upon immunization with low-virulent LGTV or naturally avirulent TBEV 280, it may still enter the CNS of these animals. These findings contribute to our understanding of causes for vaccine failure in individuals vaccinated with TBE vaccines.

Cross-reactive antibodies against Langat virus protect mice from lethal tick-borne encephalitis virus infection

“…However, qPCR detected small amount of viral RNA in one of the four survivors from the LGTV serum recipient groups. This is in accordance with our previous work where we also found TBEV in the brain despite of protective immunity induced by prior LGTV infection (24). It is likely that virus that escapes immune detection in the periphery, enters and replicates within the CNS before the resident glial cells combined with infiltrating immune cells clear the infection.…”

“…TBEV antigen was mostly found in the cytoplasm of cells that appeared to be neurons according to distribution and morphology. This is consistent with previous findings (24). In four mice from the LGTV infected serum r e c i p i e n t g r o u p , n o T B E V E p r o t e i n w a s d e t e c t e d immunohistochemically.…”

“…Based on the information obtained from this and a previous study (24), we conclude that LGTV-specific antibodies that recognize TBEV antigens are main contributors of protection. On the other hand, T cells in the absence of antibody-mediated virus control may contribute to pathological changes.…”

“…Previously we have shown that s.c. administration of LGTV protects mice against subsequent lethal challenge infection with TBEV (24). In the present study, we aimed at defining the correlates of protection induced by LGTV acting against TBEV.…”

Genetically engineered bacterial‐like particles induced specific cellular and humoral immunity as effective tick‐borne encephalitis virus vaccine

“…However, the pathogenicity is not sure to disappear completely, carrying the risk of virulence reversion, [5][6][7] and a certain level of neurotoxicity persists. [8][9][10] There is an urgent need to develop a TBE vaccine with favorable safety and immunogenicity profiles.…”