Genetic stability of live-attenuated Zika vaccine candidates

Publication date: Available online 4 September 2019Source: Antiviral ResearchAuthor(s): Antonio E. Muruato, Chao Shan, Camila R. Fontes-Garfias, Yang Liu, Qiang Gao, Scott C. Weaver, Pei-Yong ShiAbstractZika virus (ZIKV) has drawn global attention as the etiologic agent of Zika Congenital Syndrome in babies born to infected pregnant women. To prevent future ZIKV outbreaks and protect persons at risk for severe disease, we developed two live-attenuated vaccine (LAV) candidates containing 10- or 20-nucleotide deletions in the 3′UTR of the viral genome (Δ10 and Δ20). After a single-dose immunization, both Δ10 and Δ20 LAVs protected mice and non-human primates against ZIKV infection. Here, we characterized the stability, safety, and efficacy of the LAVs after continuously culturing them on manufacture Vero cells for ten rounds. Whole genome sequencing showed that passage 10 (P10) LAVs retained the engineered Δ10 and Δ20 deletions; one to four additional mutations emerged at different regions of the genome. In A129 mice, the P10 LAVs exhibited viremia higher than the un-passaged LAVs, but lower than wild-type ZIKV; unlike wild-type ZIKV-infected mice, none of the P10 LAV-infected mice developed disease or death, demonstrating that the P10 LAVs remained attenuated. Mice immunized with a single dose of the P10 LAVs developed robust neutralizing antibody titers (1/1,000 to 1/10,000) and were protected against epidemic ZIKV challenge. The P10 ...
Source: Antiviral Therapy - Category: Virology Source Type: research

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Abstract Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the s...
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research
her For the first 60 years following its isolation, Zika virus (ZIKV) remained a relatively poorly described member of the Flaviviridae family. However, since 2007, it has caused a series of increasingly severe outbreaks and is now associated with neurological symptoms such as Guillain-Barré syndrome and congenital Zika syndrome (CZS). A number of reports have improved our understanding of rare complications that may be associated with ZIKV infection in adults, the areas of the body to which it spreads, and viral persistence in various tissues. Likewise, studies on the effect of ZIKV infection during pregnan...
Source: Viruses - Category: Virology Authors: Tags: Review Source Type: research
Abstract Zika virus (ZIKV) has drawn global attention as the etiologic agent of Zika Congenital Syndrome in babies born to infected pregnant women. To prevent future ZIKV outbreaks and protect persons at risk for severe disease, we developed two live-attenuated vaccine (LAV) candidates containing 10- or 20-nucleotide deletions in the 3'UTR of the viral genome (Δ10 and Δ20). After a single-dose immunization, both Δ10 and Δ20 LAVs protected mice and non-human primates against ZIKV infection. Here, we characterized the stability, safety, and efficacy of the LAVs after continuously culturing th...
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research
ard Hildt Infection with Zika virus (ZIKV) came first to public attention after it was found to be associated with congenital microcephaly during the outbreak in Brazil (2015–2016). Diagnosis of ZIKV suffers from extensive cross-reactivity with other Flaviviruses, which are circulating in many ZIKV epidemic areas. Due to the fatal outcome of ZIKV infection during pregnancy, detailed knowledge about neutralizing and non-neutralizing epitopes is crucial for the development of robust detection systems of protective antibodies. Therefore, additional information about ZIKV immunogenicity and antibody response is requi...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Conclusion We found no differences in pregnancy or neonatal outcomes between women who tested positive and presumed positive for Zika virus during pregnancy. Testing of infants and placenta tissue after delivery was largely inconclusive. Improvement in testing for Zika virus infection is needed to determine which pregnancies are at risk for congenital anomalies. Further research is still needed to determine which children are at risk for poor neurodevelopmental outcomes related to Zika virus and how to best coordinate care among the immigrant population during a new disease epidemic. [...] Thieme Medical Publishers 33...
Source: American Journal of Perinatology - Category: Perinatology & Neonatology Authors: Tags: Original Article Source Type: research
Pregnant women &vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response. Vaccine. 2019 May 03;: Authors: Krubiner CB, Faden RR, Karron RA, Little MO, Lyerly AD, Abramson JS, Beigi RH, Cravioto AR, Durbin AP, Gellin BG, Gupta SB, Kaslow DC, Kochhar S, Luna F, Saenz C, Sheffield JS, Tindana PO, PREVENT Working Group Abstract Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely - and at times uniquely - affect the health interests of pregnant women and their offspring. These examples also hig...
Source: Vaccine - Category: Allergy & Immunology Authors: Tags: Vaccine Source Type: research
This study characterizes the contribution of household transmission in ZIKV epidemics and demonstrates the benefits of integrating multiple datasets to gain more insights on epidemic dynamics. PMID: 30995296 [PubMed - as supplied by publisher]
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
In this study, we exposed apically well-differentiated human NECs cultured at the ALI to the related flaviviruses ZIKV, JEV, WNV, and Usutu virus (USUV). We selected these viruses due to the recent increasing evidences of potential threat to humans (Cadar et al., 2017; Simonin et al., 2018). We show that NECs are particularly susceptible to JEV and WNV infection and to other flaviviruses included in this study. Infection with each virus led to shedding of infectious virus particles through the apical and basolateral surfaces and triggered host mechanisms at the level of inflammatory and antiviral mediators. Given...
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
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