scholarly journals Fast Tracks and Roadblocks for Zika Vaccines

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 77 ◽  
Author(s):  
Khairunnisa Ghaffar ◽  
Lisa Ng ◽  
Laurent Renia
Keyword(s):  
Clinical Trials ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Immunological Factors

In early 2014, a relatively obscure virus, the Zika virus, made headlines worldwide following an increase in the number of congenital malformations. Since then, research on Zika virus, treatment and vaccines have progressed swiftly with various drugs being repurposed and vaccines heading into clinical trials. Nonetheless, the need for a vaccine is crucial in order to eradicate this re-emerging arthropod-borne virus which remained silent since its first discovery in 1947. In this review, we focused on how the inconspicuous virus managed to spread, the key immunological factors required for a vaccine and the various vaccine platforms that are currently being studied.

scholarly journals Pregnancy and Zika virus

2020 ◽  
Vol 14 (2) ◽  
pp. 229-238
Author(s):  
T. V. Startseva ◽  
N. N. Kanshina ◽  
M. V. Tretyakova ◽  
V. O. Bitsadze ◽  
J. Kh. Khizroeva ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Asymptomatic Carrier ◽  
Clinical Signs ◽  
Neurological Complications ◽  
Zikv Infection ◽  
Coronavirus Infection ◽  
Novel Coronavirus ◽  
Urban Cycle

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the Flaviviridae family. In 1947 and 1948 ZIKV was first isolated from a nonhuman primate as well as from mosquitoes in Africa, respectively. For half a century, ZIKV infections in human were sporadic prior to 2015–2016 pandemic spreading. Transmission of ZIKV from mother to fetus can occur in any trimester of pregnancy, even if mother was an asymptomatic carrier. The clinical signs of ZIKV infection are nonspecific and can be misdiagnosed as some other infectious diseases, especially those caused by arboviruses such as Dengue and Chikungunya. ZIKV infection was solely associated with mild illness prior to the large French Polynesian and Brazil outbreaks, when severe neurological complications, Guillain–Barre syndrome and dramatically increased rate of severe congenital malformations (including microcephaly) were reported. The adaptation of ZIKV to an urban cycle in endemic areas suggests that the incidence of ZIKV infections may be underestimated. The pandemic of novel coronavirus infection (COVID-19) demonstrates that lessons from ZIKV pandemic propagation has not been learned properly.

scholarly journals Animal Models of Zika Virus Infection, Pathogenesis, and Immunity

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Thomas E. Morrison ◽  
Michael S. Diamond
Keyword(s):  
Animal Models ◽  
Virus Infection ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Scientific Community ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Rapid Testing ◽  
Zikv Infection ◽  
Male Reproductive Tract

ABSTRACT Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis.

scholarly journals Antibodies Elicited by an NS1-Based Vaccine Protect Mice against Zika Virus

mBio ◽  
2019 ◽  
Vol 10 (2) ◽  
Author(s):  
Mark J. Bailey ◽  
Felix Broecker ◽  
James Duehr ◽  
Fortuna Arumemi ◽  
Florian Krammer ◽  
...  
Keyword(s):  
Virus Vaccine ◽  
Zika Virus ◽  
Envelope Glycoprotein ◽  
Congenital Malformations ◽  
Ns1 Protein ◽  
Specific Antibodies ◽  
Antibody Dependent Enhancement ◽  
Effector Functions ◽  
Protective Antibodies ◽  
Infected Cells

ABSTRACTZika virus is a mosquito-borne flavivirus which can cause severe disease in humans, including microcephaly and other congenital malformations in newborns and Guillain-Barré syndrome in adults. There are currently no approved prophylactics or therapeutics for Zika virus; the development of a safe and effective vaccine is an urgent priority. Preclinical studies suggest that the envelope glycoprotein can elicit potently neutralizing antibodies. However, such antibodies are implicated in the phenomenon of antibody-dependent enhancement of disease. We have previously shown that monoclonal antibodies targeting the Zika virus nonstructural NS1 protein are protective without inducing antibody-dependent enhancement of disease. Here, we investigated whether the NS1 protein itself is a viable vaccine target. Wild-type mice were vaccinated with an NS1-expressing DNA plasmid followed by two adjuvanted protein boosters, which elicited high antibody titers. Passive transfer of the immune sera was able to significantly protect STAT2 knockout mice against lethal challenge by Zika virus. In addition, long-lasting NS1-specific IgG responses were detected in serum samples from patients in either the acute or the convalescent phase of Zika virus infection. These NS1-specific antibodies were able to functionally engage Fcγ receptors. In contrast, envelope-specific antibodies did not activate Fc-mediated effector functions on infected cells. Our data suggest that the Zika virus NS1 protein, which is expressed on infected cells, is critical for Fc-dependent cell-mediated immunity. The present study demonstrates that the Zika virus NS1 protein is highly immunogenic and can elicit protective antibodies, underscoring its potential for an effective Zika virus vaccine.IMPORTANCEZika virus is a global public health threat that causes microcephaly and congenital malformations in newborns and Guillain-Barré syndrome in adults. Currently, no vaccines or treatments are available. While antibodies targeting the envelope glycoprotein can neutralize virus, they carry the risk of antibody-dependent enhancement of disease (ADE). In contrast, antibodies generated against the NS1 protein can be protective without eliciting ADE. The present study demonstrates the effectiveness of an NS1-based vaccine in eliciting high titers of protective antibodies against Zika virus disease in a mouse model. Sera generated by this vaccine can elicit Fc-mediated effector functions against Zika virus-infected cells. Lastly, we provide human data suggesting that the antibody response against the Zika virus NS1 protein is long-lasting and functionally active. Overall, our work will inform the development of a safe and effective Zika virus vaccine.

scholarly journals Insulin Glulisine in Pregnancy – Experience from Clinical Trials and Post-marketing Surveillance

2015 ◽  
Vol 11 (1) ◽  
pp. 17 ◽  
Author(s):  
Zoran Doder ◽  
Demi Vanechanos ◽  
Manfred Oster ◽  
Wolfgang Landgraf ◽  
Stephen Lin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Congenital Malformations ◽  
Safety Data ◽  
Live Births ◽  
Post Marketing Surveillance ◽  
Increased Risk ◽  
Post Marketing ◽  
Insulin Glulisine ◽  
In Pregnancy

Pregnancies complicated by gestational diabetes or pre-existing type 1 or type 2 diabetes mellitus are associated with a higher rate of adverse outcomes compared with pregnancies in the background population. These outcomes include miscarriage, pre-term delivery, pre-eclampsia, perinatal mortality and congenital malformations. Insulin glulisine (ApidraR, Sanofi) is a rapid-acting insulin analogue indicated for the treatment of adults, adolescents and children 6 years or older with diabetes mellitus where treatment with insulin is required. Here, all post-marketing and clinical trials safety data with insulin glulisine in pregnancy available to Sanofi up to June 2014 are summarised together with the findings of a comprehensive literature search. Cumulatively, a total of 303 pregnancy exposures to insulin glulisine were received. Of these 303 pregnancy exposures, there were 116 live births, 12 spontaneous abortions, two late foetal intra-uterine deaths (>28 weeks), three elective abortions and 170 cases without a known pregnancy outcome. There were six cases of congenital malformations; of these, there were five live births; in the other case a live birth was not confirmed. The congenital malformations reported to date do not reveal a pattern of defects. In conclusion, the evidence to date does not suggest a causal association between insulin glulisine and an increased risk of pregnancy complications or congenital malformations.

scholarly journals Prevalence of microcephaly: the Latin American Network of Congenital Malformations 2010–2017

2021 ◽  
Vol 5 (1) ◽  
pp. e001235
Author(s):  
Joan Morris ◽  
Ieda M Orioli ◽  
Adriana Benavides-Lara ◽  
María de la Paz Barboza-Arguello ◽  
Maria Aurora Canessa Tapia ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Latin American ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Random Effect ◽  
Individual Case ◽  
Poisson Models ◽  
Still Births ◽  
Level Data ◽  
Congenital Zika Syndrome

ObjectiveThe Latin American Network of Congenital Malformations: ReLAMC was established in 2017 to provide accurate congenital anomaly surveillance. This study used data from ReLAMC registries to quantify the prevalence of microcephaly from 2010 to 2017 (before, during and after the Zika virus epidemic).DesignNine ReLAMC congenital anomaly registries provided case-level data or aggregate data for any live births, still births or terminations of pregnancy with microcephaly. Births to pregnant women infected with Zika virus first occurred in Brazil in 2015, and in the remaining registry areas in 2016 with the exception of Chile that did not experience Zika virus. Therefore the prevalence of microcephaly for 2010–2014 and individual years 2015, 2016 and 2017 was estimated using multilevel random effect Poisson models. Clinical classification and characteristics of the cases were compared pre and post Zika for all centres providing individual case-level data.ResultsThe prevalence of microcephaly for all registries excluding Brazil was 2.3 per 10 000 (95% CI 2.0 to 2.6) for 2010–2014 rising to 5.4 (95% CI 4.8 to 6.0) in 2016 and 5.9 (95% CI 5.3 to 6.6) in 2017. Brazil had a prevalence of 0.6 per 10 000 (95% CI 0.5 to 0.6) in 2010–2014, rising to 5.8 (95% CI 5.6 to 6.1) in 2015, 8.0 (95% CI 7.6 to 8.3) in 2016 and then falling in 2017. Only 29 out of 687 cases of microcephaly were reported as congenital Zika syndrome in countries excluding Brazil.ConclusionsThe prevalence of microcephaly was influenced both by Zika causing congenital Zika syndrome and by increased reporting awareness.

scholarly journals Zika Virus Causing Encephalomyelitis Associated With Immunoactivation

2016 ◽  
Vol 3 (4) ◽  
Author(s):  
Rafael Mello Galliez ◽  
Mariana Spitz ◽  
Patricia Piazza Rafful ◽  
Marcelo Cagy ◽  
Claudia Escosteguy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Immune Activation ◽  
Zika Virus ◽  
Congenital Malformations ◽  
Neurological Impairment ◽  
Recovery Phase ◽  
Neurological Manifestations ◽  
Zikv Infection ◽  
Fluid Attenuated Inversion Recovery ◽  
Brain And Spinal Cord

Abstract Brazil has experienced a Zika virus (ZIKV) outbreak with increased incidence of congenital malformations and neurological manifestations. We describe a case of a 26-year-old Brazilian Caucasian man infected with ZIKV and diagnosed with encephalomyelitis. Brain and spinal cord images showed hyperintense lesions on T2 and fluid-attenuated inversion recovery (FLAIR), and levels of proinflammatory cytokines in the cerebrospinal fluid showed a remarkable increase of interleukin (IL)-6 and IL-8. The observed pattern suggests immune activation during the acute phase, along with the neurological impairment, with normalization in the recovery phase. This is the first longitudinal report of ZIKV infection causing encephalomyelitis with documented immune activation.

scholarly journals Clinical Trials and Administration of Zika Virus Vaccine in Pregnant Women: Lessons (that Should Have Been) Learned from Excluding Immunization with the Ebola Vaccine during Pregnancy and Lactation

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 81 ◽  
Author(s):  
David Schwartz
Keyword(s):  
Clinical Trials ◽  
Virus Infection ◽  
Pregnant Women ◽  
Zika Virus ◽  
Ebola Virus ◽  
Intrauterine Infection ◽  
Vaccine Safety ◽  
Zika Virus Infection ◽  
Pregnancy And Lactation ◽  
Torch Infection

As evidenced from recent epidemics, both Ebola and Zika virus infection are potentially catastrophic when occurring in pregnant women. Ebola virus causes extremely high rates of mortality in both mothers and infants; Zika virus is a TORCH infection that produces a congenital malformation syndrome and pediatric neurodevelopmental abnormalities. Production of efficacious vaccines has been a public health priority for both infections. Unfortunately, during the clinical trials and subsequent deployment of a vaccine for the Ebola virus, pregnant and lactating women were, and continue to be, excluded from receiving the life-saving vaccine. The most serious consequence of Zika virus infection, congenital Zika syndrome, results from fetal infection during pregnancy. Thus, pregnant women have a major stake in the ongoing development of a vaccine for Zika virus. The exclusion of pregnant women from the development, clinical trials and administration of a potential Zika vaccine unfairly deprives them and their infants of the protection they need against this potentially catastrophic intrauterine infection. When creating policy about these issues, it is important to critically evaluate vaccine safety in pregnancy in the context of the substantial risk of infection for the pregnant woman and her fetus in the absence of immunization.

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