Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise

Kubinski, Mareike; Beicht, Jana; Gerlach, Thomas; Volz, Asisa; Sutter, Gerd; Rimmelzwaan, Guus F.

doi:10.3390/vaccines8030451

Cited by 58 publications

(64 citation statements)

References 248 publications

(453 reference statements)

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“…Several VLP vaccine candidates have been developed employing the E protein as antigen [11,12]. Flavivirus E protein comprises the majority of the virion structure and surface [13].…”

Section: Introductionmentioning

confidence: 99%

A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model

et al. 2021

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Powassan virus (POWV) is a tick-borne flavivirus circulating in North America and the Russian Far East that can cause severe neuroinvasive diseases, including encephalitis, meningitis, and meningoencephalitis. The reported neuroinvasive case fatality is about 10%, and approximately 50% of the survivors from the neuroinfection exhibit long-lasting or permanent neurological sequelae. Currently, treatment of POWV infection is supportive, and no FDA-approved vaccines or specific therapeutics are available. A novel Powassan vaccine candidate was created using virus-like particle technology (POW-VLP) and assembled with the viral structural proteins pre-Membrane (prM) and Envelope (E). Western blot immunoassay demonstrated high antigenicity of POW-VLP structural proteins. Transmission electron microscopy indicated that the POW-VLP exhibited icosahedral morphology typical of flaviviruses. A dose-escalation study in a murine model was performed to test immunogenicity and safety. Serum antibody was tested by ELISA, demonstrating that POW-VLP afforded 100% seroconversion to the E protein. Reporter viral-particle neutralization assay demonstrated high levels of neutralizing antibodies in the serum of immunized mice. Hybridomas expressing monoclonal antibodies were produced following POW-VLP immunization. The POW-VLP vaccine candidate created in this study provides a strategy for inducing protective antibodies against Powassan neuroinvasive infection.

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“…Several VLP vaccine candidates have been developed employing the E protein as antigen [11,12]. Flavivirus E protein comprises the majority of the virion structure and surface [13].…”

Section: Introductionmentioning

confidence: 99%

A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model

et al. 2021

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“…Despite SARS-CoV-2 being a primarily respiratory pathogen, viral antigens were also found in the brain parenchyma and in single cases in the cerebrospinal fluid (CSF) of severely affected COVID-19 patients [ 268 , 269 , 270 ]. Song et al [ 271 ] demonstrated neuroinvasion of SARS-CoV-2 in human brain organoids, ACE2-expressing mice, and in human post-mortem tissues. Despite neurological symptoms that are associated with COVID-19, as well as long COVID-19, SARS-CoV-2 mostly is a respiratory pathogen and only rarely causes neurotropic infections.…”

Section: Innovative Tlr Agonist Mediated Intervention Strategies and Enhancement Of Vaccine Responses Against Neurotropic Virus Infectionmentioning

confidence: 99%

Toll-like Receptors in Viral Encephalitis

Gern

Mulenge

Pavlou

et al. 2021

Viruses

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Viral encephalitis is a rare but serious syndrome. In addition to DNA-encoded herpes viruses, such as herpes simplex virus and varicella zoster virus, RNA-encoded viruses from the families of Flaviviridae, Rhabdoviridae and Paramyxoviridae are important neurotropic viruses. Whereas in the periphery, the role of Toll-like receptors (TLR) during immune stimulation is well understood, TLR functions within the CNS are less clear. On one hand, TLRs can affect the physiology of neurons during neuronal progenitor cell differentiation and neurite outgrowth, whereas under conditions of infection, the complex interplay between TLR stimulated neurons, astrocytes and microglia is just on the verge of being understood. In this review, we summarize the current knowledge about which TLRs are expressed by cell subsets of the CNS. Furthermore, we specifically highlight functional implications of TLR stimulation in neurons, astrocytes and microglia. After briefly illuminating some examples of viral evasion strategies from TLR signaling, we report on the current knowledge of primary immunodeficiencies in TLR signaling and their consequences for viral encephalitis. Finally, we provide an outlook with examples of TLR agonist mediated intervention strategies and potentiation of vaccine responses against neurotropic virus infections.

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“…Flavivirus infections are of global importance for human health and pose increasing threats, as illustrated by the spread of dengue (DEN), Zika, West Nile, and tick-borne encephalitis virus (TBE) viruses (reviewed in [ 1 , 2 ]). These pathogens are transmitted to humans by specific arthropod vectors, either mosquitoes (dengue, Zika, West Nile, yellow fever, and Japanese encephalitis viruses) or ticks (TBE virus).…”

Section: Introductionmentioning

confidence: 99%

Different Cross-Reactivities of IgM Responses in Dengue, Zika and Tick-Borne Encephalitis Virus Infections

Stiasny

Malafa

Aberle

et al. 2021

Viruses

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Flaviviruses circulate worldwide and cause a number of medically relevant human diseases, such as dengue, Zika, yellow fever, and tick-borne encephalitis (TBE). Serology plays an important role in the diagnosis of flavivirus infections, but can be impeded by antigenic cross-reactivities among flaviviruses. Therefore, serological diagnosis of a recent infection can be insufficiently specific, especially in areas where flaviviruses co-circulate and/or vaccination coverage against certain flaviviruses is high. In this study, we developed a new IgM assay format, which is well suited for the specific diagnosis of TBE, Zika and dengue virus infections. In the case of TBE and Zika, the IgM response proved to be highly specific for the infecting virus. In contrast, primary dengue virus infections induced substantial amounts of cross-reactive IgM antibodies, which is most likely explained by structural peculiarities of dengue virus particles. Despite the presence of cross-reactive IgM, the standardized nature and the quantitative read-out of the assay even allowed the serotype-specific diagnosis of recent dengue virus infections in most instances.

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Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise

Cited by 58 publications

References 248 publications

A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model

A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model

Toll-like Receptors in Viral Encephalitis

Different Cross-Reactivities of IgM Responses in Dengue, Zika and Tick-Borne Encephalitis Virus Infections

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