Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines

Zhang, Naru; Li, Chaoqun; Jiang, Shibo; Du, Lanying

doi:10.3390/vaccines8030481

Cited by 13 publications

(8 citation statements)

References 119 publications

(151 reference statements)

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“…Due to the success of the VLP platform, multiple flavivirus vaccine candidates have been developed. The ability of flavivirus prM-E or C-prM-E polyprotein to self-assemble into an enveloped VLP with similar morphology to the wild-type virus has been harnessed to create highly immunogenic recombinant vaccines [27,28].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The epitopes in E proteins of ZIKV may display differently depending on how the E protein is presented. The E protein presented as a part of virus-like particles (VLPs) [37] may be different from E protein presented as a part of rVSV pseudovirion. Regardless, our results showed clearly that the rVSV-ZIKV-msp-E-Gtc vaccine induced a highly protective immune response against ZIKV infection in the absence of PrM or in the absence of VLPs.…”

Section: Discussionmentioning

confidence: 99%

Induction of protective immune responses against a lethal Zika virus challenge post-vaccination with a dual serotype of recombinant vesicular stomatitis virus carrying the genetically modified Zika virus E protein gene

Choi

Kim

et al. 2021

Journal of General Virology

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The development of a vaccine to prevent Zika virus (ZIKV) infection has been one of the priorities in infectious disease research in recent years. There have been numerous attempts to develop an effective vaccine against ZIKV. It is imperative to choose the safest and the most effective ZIKV vaccine from all candidate vaccines to control this infection globally. We have employed a dual serotype of prime-boost recombinant vesicular stomatitis virus (VSV) vaccine strategy, to develop a ZIKV vaccine candidate, using a type 1 IFN-receptor knock-out (Ifnar −/−) mouse model for challenge studies. Prime vaccination with an attenuated recombinant VSV Indiana serotype (rVSVInd) carrying a genetically modified ZIKV envelope (E) protein gene followed by boost vaccination with attenuated recombinant VSV New Jersey serotype (rVSVNJ) carrying the same E gene induced robust adaptive immune responses. In particular, rVSV carrying the ZIKV E gene with the honeybee melittin signal peptide (msp) at the N terminus and VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the C terminus of the E gene induced strong protective immune responses. This vaccine regimen induced highly potent neutralizing antibodies and T cell responses in the absence of an adjuvant and protected Ifnar -/- mice from a lethal dose of the ZIKV challenge.

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“…This makes VLPs a promising approach for developing safe and effective DENV vaccines. VLP-based DENV vaccines were described by Zhang et al in 2020, but neither of them was developed with NS1 proteins [ 54 ]. One example is given with C-terminal truncated DENV-2 NS1 loaded in N , N , N -trimethyl chitosan nanoparticles (NS1 1–279 TMC NPs) investigated in a murine model and in humans ex vivo [ 41 ].…”

Section: Soluble Ns1 As a Significant Focus For Dengue Vaccine Strategiesmentioning

confidence: 99%

Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

et al. 2021

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The mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often fatal. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of four genetically related but antigenically distinct serotypes DENV-1–DENV-4. The growing burden of the four DENV serotypes has intensified both basic and applied research to better understand dengue physiopathology. Research has shown that the secreted soluble hexameric form of DENV nonstructural protein-1 (sNS1) plays a significant role in the pathogenesis of severe dengue. Here, we provide an overview of the current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. We discuss the potential use of sNS1 in future vaccine development and its potential to improve dengue vaccine efficiency, particularly against severe dengue illness.

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Recent Advances in the Development of Virus-Like Particle-Based Flavivirus Vaccines

Cited by 13 publications

References 119 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

Induction of protective immune responses against a lethal Zika virus challenge post-vaccination with a dual serotype of recombinant vesicular stomatitis virus carrying the genetically modified Zika virus E protein gene

Viral Toxin NS1 Implication in Dengue Pathogenesis Making It a Pivotal Target in Development of Efficient Vaccine

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