scholarly journals Pre-Clinical Pregnancy Models for Evaluating Zika Vaccines

2019 ◽  
Vol 4 (2) ◽  
pp. 58 ◽  
Author(s):  
In-Jeong Kim ◽  
Marcia Blackman ◽  
Jr-Shiuan Lin
Keyword(s):  
Adult Animal ◽  
Clinical Importance ◽  
Clinical Pregnancy ◽  
Current Status ◽  
Zikv Infection ◽  
Term Infants ◽  
Developmental Abnormalities ◽  
Vaccine Candidates ◽  
Congenital Zika Syndrome ◽  
Phase I And Ii

Zika virus (ZIKV) infection during pregnancy can result in a variety of developmental abnormalities in the fetus, referred to as Congenital Zika Syndrome (CZS). The effects of CZS can range from the loss of the viable fetus to a variety of neurological defects in full-term infants, including microcephaly. The clinical importance of ZIKV-induced CZS has driven an intense effort to develop effective vaccines. Consequently, there are approximately 45 different ZIKV vaccine candidates at various stages of development with several undergoing phase I and II clinical trials. These vaccine candidates have been shown to effectively prevent infection in adult animal models, however, there has been less extensive testing for their ability to block vertical transmission to the fetus during pregnancy or prevent the development of CZS. In addition, it is becoming increasingly difficult to test vaccines in the field as the intensity of the ZIKV epidemic has declined precipitously, making clinical endpoint studies difficult. These ethical and practical challenges in determining efficacy of ZIKV vaccine candidates in preventing CZS have led to increased emphasis on pre-clinical testing in animal pregnancy models. Here we review the current status of pre-clinical pregnancy models for testing the ability of ZIKV vaccines to prevent CZS.

scholarly journals Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Genetic Variants ◽  
Educational Level ◽  
Congenital Anomalies ◽  
Family Income ◽  
First Trimester ◽  
In Utero ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

scholarly journals Current Status of Zika Virus Vaccines: Successes and Challenges

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 266 ◽  
Author(s):  
Aryamav Pattnaik ◽  
Bikash R. Sahoo ◽  
Asit K. Pattnaik
Keyword(s):  
Zika Virus ◽  
Viral Infections ◽  
Current Status ◽  
Effective Vaccine ◽  
Congenital Diseases ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Nucleic Acid Vaccines ◽  
Funding Agencies ◽  
Inactivated Vaccines

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs.

scholarly journals Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vertical Transmission ◽  
Birth Defects ◽  
Asian American ◽  
Zika Virus ◽  
French Polynesia ◽  
Transmission Model ◽  
Foreseeable Future ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

scholarly journals Zika Virus Pathogenesis: From Early Case Reports to Epidemics

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 886 ◽  
Author(s):  
Ryan D. Pardy ◽  
Martin J. Richer
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Case Reports ◽  
Viral Persistence ◽  
The Body ◽  
Therapeutic Approaches ◽  
Zikv Infection ◽  
Congenital Zika Syndrome ◽  
Early Case ◽  
The Impact

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 pregnancy have identified risk factors for CZS and the impact this syndrome has on early childhood. Understanding these outcomes and the factors that drive ZIKV pathogenesis are key to developing vaccination and therapeutic approaches to avoid these severe and potentially debilitating symptoms.

scholarly journals Congenital Zika syndrome is associated with maternal protein malnutrition

2020 ◽  
Vol 6 (2) ◽  
pp. eaaw6284 ◽  
Author(s):  
J. Barbeito-Andrés ◽  
P. Pezzuto ◽  
L. M. Higa ◽  
A. A. Dias ◽  
J. M. Vasconcelos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Size ◽  
Epidemiological Data ◽  
Protein Malnutrition ◽  
Rna Seq ◽  
Zikv Infection ◽  
Postnatal Brain ◽  
Low Protein ◽  
Congenital Zika Syndrome ◽  
Pregnant Mice

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.

scholarly journals Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins

2020 ◽  
Vol 14 (8) ◽  
pp. e0008424
Author(s):  
Murilo Sena Amaral ◽  
Ernesto Goulart ◽  
Luiz Carlos Caires-Júnior ◽  
David Abraham Morales-Vicente ◽  
Alessandra Soares-Schanoski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Zikv Infection ◽  
Congenital Zika Syndrome ◽  
Differential Gene ◽  
Discordant Twins

scholarly journals Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 352 ◽  
Author(s):  
Antoni Soriano-Arandes ◽  
Marie Antoinette Frick ◽  
Milagros García López-Hortelano ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
...  
Keyword(s):  
Zika Virus ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Child Pair ◽  
Referral Hospitals ◽  
Congenital Zika Syndrome ◽  
Endemic Areas ◽  
Neurodevelopmental Abnormalities ◽  
Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

scholarly journals Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins

2019 ◽  
Author(s):  
Murilo Sena Amaral ◽  
Ernesto Goulart ◽  
Luiz Carlos Caires-Júnior ◽  
David Abraham Morales-Vicente ◽  
Alessandra Soares-Schanoski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Genetic Background ◽  
Zikv Infection ◽  
Dizygotic Twins ◽  
Susceptibility Factors ◽  
Congenital Zika Syndrome ◽  
Host Genetic ◽  
Discordant Twins

AbstractZika virus (ZIKV) causes congenital Zika syndrome (CZS), which is characterized by fetal demise, microcephaly and other abnormalities. ZIKV in the pregnant woman circulation must cross the placental barrier that includes fetal endothelial cells and trophoblasts, in order to reach the fetus. CZS occurs in ∼1-40% of cases of pregnant women infected by ZIKV, suggesting that mothers’ infection by ZIKV during pregnancy is not deterministic for CZS phenotype in the fetus. Therefore, other susceptibility factors might be involved, including the host genetic background. We have previously shown that in three pairs of dizygotic twins discordant for CZS, neural progenitor cells (NPCs) from the CZS-affected twins presented differential in vitro ZIKV susceptibility compared with NPCs from the non-affected. Here, we analyzed human-induced-pluripotent-stem-cell-derived (hiPSC-derived) trophoblasts from these twins and compared by RNA-Seq the trophoblasts from CZS-affected and non-affected twins. Following in vitro exposure to a Brazilian ZIKV strain (ZIKVBR), trophoblasts from CZS-affected twins were significantly more susceptible to ZIKVBR infection when compared with trophoblasts from the non-affected. Transcriptome profiling revealed no differences in gene expression levels of ZIKV candidate attachment factors, IFN receptors and IFN in the trophoblasts, either before or after ZIKVBR infection. Most importantly, ZIKVBR infection caused, only in the trophoblasts from CZS-affected twins, the downregulation of genes related to extracellular matrix organization and to leukocyte activation, which are important for trophoblast adhesion and immune response activation. In addition, only trophoblasts from non-affected twins secreted significantly increased amounts of chemokines RANTES/CCL5 and IP10 after infection with ZIKVBR. Overall, our results showed that trophoblasts from non-affected twins have the ability to more efficiently activate genes that are known to play important roles in cell adhesion and in triggering the immune response to ZIKV infection in the placenta, and this may contribute to predict protection from ZIKV dissemination into fetuses’ tissues.Author summaryThe Zika virus (ZIKV) infection in adults is usually characterized by mild flu-like symptoms, with most cases remaining asymptomatic. However, in the last years, widespread ZIKV infection was shown for the first time to be associated with congenital Zika syndrome (CZS) and death of neonates. CZS is a very debilitating condition that includes microcephaly and mental retardation, leading to a strong social and health impact. This dramatic condition calls for a careful evaluation of the molecular mechanisms involved in ZIKV infection in the maternal-fetal interface. It is estimated that CZS occurs in ∼1-40% of cases of pregnant women infected by ZIKV, which suggests that different susceptibility factors might be involved, including the host genetic background. By analyzing trophoblast cells that recapitulate the placenta from three pairs of dizygotic twins discordant for CZS, we were able to show that trophoblasts from CZS-affected twins were significantly more susceptible to ZIKV infection when compared with trophoblasts from the non-affected twins. We also provide a detailed picture of genes differentially expressed by trophoblasts from the discordant twins after infection with ZIKV. These genes can be further investigated as possible therapeutic targets to avoid viral dissemination into developing fetus’ tissues.

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