Research Articles A recombinant platform for flavivirus vaccines and diagnostics using chimeras of a new insect-specific virus

Flaviviruses such as dengue, yellow fever, Zika, West Nile, and Japanese encephalitis virus present substantial global health burdens. New vaccines are being sought to address safety and manufacturing issues associated with current live attenuated vaccines. Here, we describe a new insect-specific flavivirus, Binjari virus, which was found to be remarkably tolerant for exchange of its structural protein genes (prME) with those of the aforementioned pathogenic vertebrate-infecting flaviviruses (VIFs). Chimeric BinJ/VIF-prME viruses remained replication defective in vertebrate cells but replicated with high efficiency in mosquito cells. Cryo–electron microscopy and monoclonal antibody binding studies illustrated that the chimeric BinJ/VIF-prME virus particles were structurally and immunologically similar to their parental VIFs. Pilot manufacturing in C6/36 cells suggests that high yields can be reached up to 109.5 cell culture infectious dose/ml or 7 mg/liter. BinJ/VIF-prME viruses showed utility in diagnostic (microsphere immunoassays and ELISAs using panels of human and equine sera) and vaccine applications (illustrating protection against Zika virus challenge in murine IFNAR–/– mouse models). BinJ/VIF-prME viruses thus represent a versatile, noninfectious (for vertebrate cells), high-yield technology for generating chimeric flavivirus particles with low biocontainment requirements.
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research

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Discussion Dengue is an important arboviral infection that affects about 40% of the world population. It is found mainly in topical and subtropical areas of the world mainly in developing countries but it range is spreading including the United States. A review of common arboviruses can be found here. It is a flaviavirus with 4 distinct serotypes named DENV-1 through DENV-4 and is spread by A. aegypti a day biting mosquito. Infection with one serotype confers immunity to that serotype but not the others. It does offer some protection for cross-infection but this only lasts a few months. Incubation period is 3-14 days with ...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Many flaviviruses including dengue (DENV), and Zika (ZIKV) have attracted significant attention in the past few years. As many flaviviruses are spread by arthropods, most of the world’s population is at risk of encountering a flavivirus, and infection with these viruses has created a significant disease burden worldwide. Vaccination against flaviviruses is thought to be one of the most promising avenues for reducing the disease burden associated with these viruses. The optimism surrounding a vaccine approach is supported by the highly successful vaccines for yellow fever and Japanese Encephalitis. Central to the deve...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Dengue virus (DENV) is a member of the Flavivirus family that includes Zika virus (ZIKV), West Nile virus, Japanese encephalitis virus, and yellow fever virus. As the most prevalent of the flaviviruses, DENV is responsible for tens of millions of infections each year. The clinical manifestations of infection with one of the four DENV serotypes (DENV1–4) range from no symptoms to hemorrhagic fever and shock (“severe dengue”), which is fatal in ~25,000 patients annually. Many factors contribute to the development of severe dengue, including the DENV serotype and host expression of certain HLA alleles; howev...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We describe the unexpected binding of S-layer to cells devoid of DC-SIGN but also confirm that the presence of DC-SIGN was essential for S-layer’s antiviral activity. S-layer protein exerted its antiviral effect with different kinetics than mannan, a known viral inhibitor that also acts on DC-SIGN (Yu et al., 2017). Together our results suggest that inhibition of viral entry by S-layer occurs via a novel S-layer/DC-SIGN interaction. Materials and Methods Isolation of S-Layer Proteins S-layer proteins were extracted from overnight cultures of L. acidophilus ATCC 4356 cells grown in MRS medium at 37°C by using 6...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, we evaluated ATA as a potential antiviral drug against ZIKV replication. The antiviral activity of ATA against ZIKV replication in vitro showed median inhibitory concentrations (IC50) of 13.87 ± 1.09 μM and 33.33 ± 1.13 μM in Vero and A549 cells, respectively; without showing any cytotoxic effect in both cell lines (median cytotoxic concentration (CC50)> 1,000 μM). Moreover, ATA protected both cell types from ZIKV-induced cytopathic effect (CPE) and apoptosis in a time- and concentration-dependent manner. In addition, pre-treatment of Vero cells with ATA for up to 72 h also resulted...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
Conclusions Apart West Nile virus (78), thousands of congenital microcephaly cases, fetal brain tissue damage and neurological syndromes have been associated with ZIKV infection. Unfortunately, the epidemics of this mosquito born, and a relative stable virus is on a rise. Although congenital microcephaly is a rare disorder however, due to lack of standardized diagnostic test facilities, the incidence in the geographically widespread ZIKV epidemic regions is higher. Animals studies showed that ZIKV is a neurotropic virus. It directly targets the developing embryonic brain cells by inducing apoptosis, cell-cycle arrest, and...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Publication date: 5 February 2019Source: Cell Reports, Volume 26, Issue 6Author(s): Henry Puerta-Guardo, Dustin R. Glasner, Diego A. Espinosa, Scott B. Biering, Mark Patana, Kalani Ratnasiri, Chunling Wang, P. Robert Beatty, Eva HarrisSummaryFlaviviruses cause systemic or neurotropic-encephalitic pathology in humans. The flavivirus nonstructural protein 1 (NS1) is a secreted glycoprotein involved in viral replication, immune evasion, and vascular leakage during dengue virus infection. However, the contribution of secreted NS1 from related flaviviruses to viral pathogenesis remains unknown. Here, we demonstrate that NS1 fro...
Source: Cell Reports - Category: Cytology Source Type: research
LITFL • Life in the Fast Lane Medical Blog LITFL • Life in the Fast Lane Medical Blog - Emergency medicine and critical care medical education blog aka Tropical Travel Trouble 010 Peer Reviewer: Dr Jennifer Ho, ID physician QLD, Australia You are an ED doc working in Perth over schoolies week. An 18 yo man comes into ED complaining of fever, rash a “cracking headache” and body aches. He has just hopped off the plane from Bali where he spent the last 2 weeks partying, boozing and running amok. He got bitten by “loads” of mosquitoes because he forgot to take insect repellent. On e...
Source: Life in the Fast Lane - Category: Emergency Medicine Authors: Tags: Clinical Cases Tropical Medicine arthralgia dengue fever rash Source Type: blogs
Abstract Dengue virus infection elicits immune responses to multiple viral antigens including antibodies to dengue non-structural protein 1 (NS1) which are rapidly induced and detected within days of infection. The recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV; Sanofi Pasteur) uses the yellow fever vaccine virus as a back-bone but expresses dengue virus pre-membrane and envelop proteins. Since CYD-TDV does not express dengue NS1, we evaluated the utility of dengue NS1-specific IgG antibodies as biomarkers of dengue exposure in CYD-TDV recipients and controls. We optimized and evaluated a quant...
Source: Journal of Virological Methods - Category: Virology Authors: Tags: J Virol Methods Source Type: research
AbstractMosquitos are responsible for a number of protozoal and viral diseases. Malaria, dengue, Japanese encephalitis (JE) and chikungunya epidemics occur commonly all over the world, leading to marked mortality and morbidity in children. Zika, Yellow fever and West Nile fever are others requiring prevention. Environmental control and mosquito bite prevention are useful in decreasing the burden of disease but vaccination has been found to be most cost-effective and is the need of the hour. RTS,S/AS01 vaccine is the first malaria vaccine being licensed for use againstP. falciparum malaria. Dengvaxia (CYD-TDV) against dengu...
Source: Indian Journal of Pediatrics - Category: Pediatrics Source Type: research
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