Current development of Zika virus vaccines with special emphasis on virus-like particle technology

Cimica, Velasco; Galarza, Jose M.; Rashid, Sujatha; Stedman, Timothy T.

doi:10.1080/14760584.2021.1945447

Cited by 9 publications

(40 citation statements)

References 172 publications

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“…While Zika VLPs expressed in baculovirus in one other study contained very high concentrations of the uncleaved prM and prM‐E gps, 28 we were unable to identify either of these proteins in any of our insect or mammalian cell expressed Zika VLPs using our well‐tested WHO human anti‐Asian ZIKV strain IgG PAb Diagnostic Standard. As such, this is consistent with other reports of very low or no uncleaved prM gps being observed in Zika VLPs expressed in mammalian cells 10,17,19,27 …”

Section: Discussionsupporting

confidence: 93%

“…As such, this is consistent with other reports of very low or no uncleaved prM gps being observed in Zika VLPs expressed in mammalian cells. 10,17,19,27 We therefore believe that our findings make these permanent baculovirus Zika VLP expression products suitable for further testing as potentially superior reagents for diagnostic (ELISA, neutralization/ ADE) assays and immunogenicity assessments, possibly leading to candidate vaccine trials.…”

Section: Discussionmentioning

confidence: 85%

“…15 Several important problems, however, need to be resolved using these mammalian cell systems which include: (a) the variability of furin cleavage, (b) differences in N-linked glycosylation in different cell lines and (c) their relatively low yields and high product in costs, 16 as well as their development mainly in transient recombinant expression systems, such as the HEK293T cell systems for them and Zika VLPs. 10,[17][18][19] Despite the glycosylation system in insect cells being less complex than that of mammalian cells, many natural vectors of flaviviruses are insects such as Aedes spp. (e.g., DENV and ZIKV) and Culex spp.…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Zika virus‐like particle development using Baculovirus spp. constructs

Malogolovkin

Davies

Abouelhadid

et al. 2022

Journal of Medical Virology

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Zika virus (ZIKV) is one of several examples of an unprecedented pandemic spread and against which there is currently no suitable vaccine or treatment. Here, we constructed and characterized recombinant baculovirus‐derived ZIKV‐like particles (Zika VLPs) to study ZIKV‐antibody interactions. These VLPs, uniquely consisted of the full‐length ZIKV capsid (C), pre‐membrane (prM), and envelope (E) proteins with either: a) the viral nonstructural NS2B and NS3 protease unit under one or two different promoters or b) an alternative host‐cell furin protease encoding cleavage sequence inserted between the C and prM genes, together with lobster tropomyosin leader and honeybee signal sequences with one promoter for increased extracellular secretion. All these Zika VLPs displayed typical virion morphology in transmission electron microscopic analysis when expressed in both insect (Sf9) and mammalian (HEK293T) cells and no uncleaved prM glycoprotein was detected, as are present on immature virions. The importance of glycosylation of the E glycoprotein was shown by the effects on both polyclonal and monoclonal antibody reactions after these N‐linked carbohydrate residues were disrupted by oxidation or enzymatic cleavage. Importantly, the construct which contained the host‐cell furin protease cleavage sequence together with a lobster tropomyosin leader and honeybee signal sequences under one promoter produced higher Zika VLP titers and protein concentrations and which can now be tested as a superior construct in multifunctional diagnostic (ELISA and neutralization/antibody‐dependent enhancement) assays and immunogenic assessments possibly leading to vaccine trials.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Enhanced Zika virus‐like particle development using Baculovirus spp. constructs

Malogolovkin

Davies

Abouelhadid

et al. 2022

Journal of Medical Virology

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“…After washing with PBST, ZIKV-infected cell lysates were added and incubated for 1 h at RT. Wells were washed with PBST, incubated with anti-ZIKV E rabbit polyclonal R34 IgG (9) at 6 μg/ml in PBST for 1 h at RT, then washed again. Antibodies bound to ZIKV envelope protein were detected using HRP-conjugated anti-rabbit IgG 7090 (Abcam) and TMB substrate (Life Technologies).…”

Section: Methodsmentioning

confidence: 99%

“…During the past few years, several candidate vaccines have been developed and tested in preclinical stages (7)(8)(9) and the most promising ones have now moved to clinical trials (10,11). Preclinical tests for ZIKV vaccine candidates are performed on murine or nonhuman primate (NHP) models.…”

Section: Introductionmentioning

confidence: 99%

Validation of an engineered Zika virus-like particle vaccine candidate in a mosquito-mouse transmission model

Mancini

Tandavanitj

Ant

et al. 2022

Preprint

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The primary route of Zika virus (ZIKV) transmission is through the bite of an infected Aedes mosquito, when it probes the skin of a vertebrate host during a blood meal. Viral particles are injected into the bite site together with mosquito saliva and a complex mixture of other components. Some of them are shown to play a key role in the augmentation of the arbovirus infection in the host, with increased viremia and/or morbidity. This vector-derived contribution to the infection is not usually considered when vaccine candidates are tested in preclinical animal models. In this study, we performed a preclinical validation of a promising ZIKV vaccine candidate in a mosquito-mouse transmission model using both Asian and African ZIKV lineages. Mice were immunized with engineered ZIKV virus-like particles and subsequently infected through the bite of ZIKV-infected Ae. aegypti mosquitoes. Despite a mild increase in viremia in mosquito-infected mice compared to those infected through traditional needle injection, the vaccine protected the animals from developing the disease and strongly reduced viremia. In addition, during peak viremia, naïve mosquitoes were allowed to feed on infected vaccinated and non-vaccinated mice. Our analysis of viral titers in mosquitos showed that the vaccine was able to inhibit virus transmission from the host to the vector.

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