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Dengue vaccine

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https://www.readbyqxmd.com/read/28441781/dengue-virus-non-structural-protein-5
#1
REVIEW
Abbas El Sahili, Julien Lescar
The World Health Organization estimates that the yearly number of dengue cases averages 390 million. This mosquito-borne virus disease is endemic in over 100 countries and will probably continue spreading, given the observed trend in global warming. So far, there is no antiviral drug available against dengue, but a vaccine has been recently marketed. Dengue virus also serves as a prototype for the study of other pathogenic flaviviruses that are emerging, like West Nile virus and Zika virus. Upon viral entry into the host cell and fusion of the viral lipid membrane with the endosomal membrane, the viral RNA is released and expressed as a polyprotein, that is then matured into three structural and seven non-structural (NS) proteins...
April 24, 2017: Viruses
https://www.readbyqxmd.com/read/28435678/screening-for-immune-response-against-dengue-virus-in-vietnamese-non-human-primates-implications-for-vaccine-developers
#2
Laura Lazo Vázquez, Edith Suzarte Portal, Jorge Castro Velazco, Phuong Yen, Le Trung Dung, Lázaro Gil González, Iris Valdés Prado, Ernesto Marcos López, Karem Cobas Acosta, Nguyen Dang Hien, Gerardo Guillén Nieto, Lisset Hermida Cruz
One of the major problems faced for the development of a vaccine against Dengue virus is the lack of a suitable animal model. Although non-human primates do not show overt signs of disease, these animals develop viremia after the infection and are the best model to evaluate vaccine candidates against this pathogen. However, for that purpose, the screening of all animals is mandatory to discard those with previous natural immunity. The most common technique used in the screening is the plaque reduction neutralization test (PRNT)...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435428/in-silico-cd4-cd8-t-cell-and-b-cell-immunity-associated-immunogenic-epitope-prediction-and-hla-distribution-analysis-of-zika-virus
#3
Essam Mohammed Janahi, Anupam Dhasmana, Vandana Srivastava, Aditya Narayan Sarangi, Sana Raza, Jamal M Arif, Madan Lal Bramha Bhatt, Mohtashim Lohani, Mohammed Yahya Areeshi, Anand Murari Saxena, Shafiul Haque
Zika virus (ZIKV) is a mosquito-borne flavivirus distributed all over Africa, South America and Asia. The infection with the virus may cause acute febrile sickness that clinically resembles dengue fever, yet there is no vaccine, no satisfactory treatment, and no means of evaluating the risk of the disease or prognosis in the infected people. In the present study, the efficacy of the host's immune response in reducing the risk of infectious diseases was taken into account to carry out immuno-informatics driven epitope screening strategy of vaccine candidates against ZIKV...
2017: EXCLI journal
https://www.readbyqxmd.com/read/28432975/vaccination-strategies-against-zika-virus
#4
REVIEW
Estefania Fernandez, Michael S Diamond
The epidemic emergence of Zika virus (ZIKV) in 2015-2016 has been associated with congenital malformations and neurological sequela. Current efforts to develop a ZIKV vaccine build on technologies that successfully reduced infection or disease burden against closely related flaviviruses or other RNA viruses. Subunit-based (DNA plasmid and modified mRNA), viral vectored (adeno- and measles viruses) and inactivated viral vaccines are already advancing to clinical trials in humans after successful mouse and non-human primate studies...
April 19, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28430748/immunogenicity-of-the-inactivated-japanese-encephalitis-virus-vaccine-ixiaro%C3%A2-n-children-from-a-japanese-encephalitis-virus-endemic-region
#5
Katrin L Dubischar, Vera Kadlecek, Benjamin Sablan, Charissa Fay Borja-Tabora, Salvacion Gatchalian, Susanne Eder-Lingelbach, Sigrid Kiermayr, Martin Spruth, Kerstin Westritschnig
BACKGROUND: Japanese encephalitis (JE) is a major public health concern in Asia and poses a small, but potentially fatal threat to travelers from non-endemic countries, including children. No JE vaccine for pediatric use has been available in Europe and the USA. METHODS: Age-stratified cohorts of children between 2 months and 17 years received 2 doses of Vero cell-derived inactivated JE virus vaccine (IXIARO) administered 28 days apart (<3 years 0.25 mL [half adult dose], ≥3 years 0...
April 19, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28429036/a-review-of-zika-virus-infections-in-pregnancy-and-implications-for-antenatal-care-in-singapore
#6
Harvard Zhenjia Lin, Paul Anantharajah Tambyah, Eu Leong Yong, Arijit Biswas, Shiao-Yng Chan
Given the consensus that there is a causal relationship between Zika virus (ZIKV) infection in pregnancy and congenital Zika syndrome (CZS), clinicians must be prepared to manage affected patients despite the numerous gaps in current knowledge. The clinical course in pregnancy appears similar to that in non-pregnant women, although viraemia may be prolonged. ZIKV infection can be diagnosed by serum and urine reverse transcription-polymerase chain reaction, but commercially available serological tests are currently unreliable in dengue-endemic regions...
April 2017: Singapore Medical Journal
https://www.readbyqxmd.com/read/28427960/construct-and-expression-of-recombinant-domains-i-ii-of-dengue-virus-2-and-its-efficacy-to-evaluate-immune-response-in-endemic-area-possible-use-in-prognosis
#7
Alfredo Eduardo Montes-Gómez, Hector Vivanco-Cid, José Bustos-Arriaga, Mussaret Bano Zaidi, Jazmin Garcia Machorro, Benito Gutierrez-Castañeda, Leticia Cedillo-Barron
The envelope (E) protein from DENV, contain three functional and structural domains (DI, DII and DIII). Some studies suggest that neutralizing antibodies during natural DENV infection are predominantly against DI and DII, in contrast, low proportion of the antibodies were against DIII. Thus it is necessary to establish the proportion of human antibodies against DENV E protein that bind to DI and DII during the normal course of infection; as an indicator of the quality of the antibody response and to further design new vaccine candidates for DENV...
April 17, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28424472/temperature-dependent-folding-allows-stable-dimerization-of-secretory-and-virus-associated-e-proteins-of-dengue-and-zika-viruses-in-mammalian-cells
#8
J L Slon Campos, S Marchese, J Rana, M Mossenta, M Poggianella, M Bestagno, O R Burrone
Dengue and Zika are two of the most important human viral pathogens worldwide. In both cases, the envelope glycoprotein E is the main target of the antibody response. Recently, new complex quaternary epitopes were identified which are the consequence of the arrangement of the antiparallel E dimers on the viral surface. Such epitopes can be exploited to develop more efficient cross-neutralizing vaccines. Here we describe a successful covalent stabilization of E dimers from Dengue and Zika viruses in mammalian cells...
April 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424031/yellow-fever-from-angola-and-congo-a-storm-gathers
#9
Qanta A Ahmed, Ziad A Memish
In common with Zika, Chikungunya and Dengue, Yellow Fever (YF) is an arthropod-borne flavivirus. It is transmitted between humans and from monkeys by mosquitoes of the Aedes aegypti (its principal vector), haemogogus and albopictus varieties. Three cycles of transmission may occur: urban; sylvatic; and intermediate. Recently, sub-Saharan Africa has seen the resurgence of this neglected disease. The current YF outbreak in Angola began in December 2015 in the capital Luanda and by October 2016 there had been > 4300 suspected cases, with 376 deaths (case fatality rate = 8...
April 2017: Tropical Doctor
https://www.readbyqxmd.com/read/28423309/the-natural-product-cavinafungin-selectively-interferes-with-zika-and-dengue-virus-replication-by-inhibition-of-the-host-signal-peptidase
#10
David Estoppey, Chia Min Lee, Marco Janoschke, Boon Heng Lee, Kah Fei Wan, Hongping Dong, Philippe Mathys, Ireos Filipuzzi, Tim Schuhmann, Ralph Riedl, Thomas Aust, Olaf Galuba, Gregory McAllister, Carsten Russ, Martin Spiess, Tewis Bouwmeester, Ghislain M C Bonamy, Dominic Hoepfner
Flavivirus infections by Zika and dengue virus impose a significant global healthcare threat with no US Food and Drug Administration (FDA)-approved vaccination or specific antiviral treatment available. Here, we present the discovery of an anti-flaviviral natural product named cavinafungin. Cavinafungin is a potent and selectively active compound against Zika and all four dengue virus serotypes. Unbiased, genome-wide genomic profiling in human cells using a novel CRISPR/Cas9 protocol identified the endoplasmic-reticulum-localized signal peptidase as the efficacy target of cavinafungin...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28421694/molecular-engineering-and-plant-expression-of-an-immunoglobulin-heavy-chain-scaffold-for-delivery-of-a-dengue-vaccine-candidate
#11
Mi-Young Kim, Craig Van Dolleweerd, Alastair Copland, Matthew John Paul, Sven Hofmann, Gina R Webster, Emily Julik, Ivonne Ceballos-Olvera, Jorge Reyes-Del Valle, Moon-Sik Yang, Yong-Suk Jang, Rajko Reljic, Julian K Ma
In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a Polymeric Immunoglobulin G Scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells...
April 19, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28418786/evaluation-in-mice-of-the-immunogenicity-of-a-tetravalent-subunit-vaccine-candidate-against-dengue-virus-using-mucosal-and-parenteral-immunization-routes
#12
Laura Lazo Vázquez, Lázaro Gil González, Ernesto Marcos López, Yusleidi Pérez Fuentes, Lázaro Cervetto de Armas, Enma Brown Richards, Iris Valdés Prado, Edith Suzarte Portal, Karem Cobas Acosta, Melyssa Yaugel Novoa, Yaremis Romero Fernández, Gerardo Guillén Nieto, Lisset Hermida Cruz
Our group has developed a subunit vaccine candidate against Dengue virus (DENV) based on two different viral regions, the domain III of the envelope protein and the capsid protein. The chimeric proteins for each serotype (DIIIC1-4), aggregated with the oligodeoxynucleotide 39 M, form the tetravalent formulation named Tetra DIIIC. Tetra DIIIC induces a protective immune response in mice when it is inoculated by intraperitoneal route. However, if children are the main targets for a DENV vaccine, then a needle-free route of administration should be attractive and advantageous...
April 18, 2017: Viral Immunology
https://www.readbyqxmd.com/read/28403438/current-status-of-dengue-therapeutics-research-and-development
#13
REVIEW
Jenny G H Low, Eng Eong Ooi, Subhash G Vasudevan
Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue...
March 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28396347/serotype-specific-interactions-among-functional-domains-of-dengue-virus-2-non-structural-proteins-ns-5-and-ns3-are-crucial-for-viral-rna-replication
#14
Tadahisa Teramoto, Anuradha Balasubramanian, Kyung H Choi, Radhakrishnan Padmanabhan
Four serotypes of mosquito-borne Dengue virus (DENV), evolved from a common ancestor, are human pathogens of global significance, and there is no vaccine or antiviral drug available. The N-terminal domain of DENV NS5 has guanylyltransferase and methyltransferase (MTase) and the C-terminal region has the polymerase (POL) which are important for 5'-capping and RNA replication. The crystal structure of NS5 showed it as a dimer but the functional evidence for NS5 dimer is lacking. The results of our studies show that the substitution of DENV2 NS5 MTase or POL with that of DENV4 NS5 within DENV2 RNA resulted in severe attenuation of replication in the transfected BHK-21 cells...
April 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28394300/computational-identification-of-antibody-epitopes-on-the-dengue-virus-ns1-protein
#15
Martina L Jones, Fiona S Legge, Kebaneilwe Lebani, Stephen M Mahler, Paul R Young, Daniel Watterson, Herbert R Treutlein, Jun Zeng
We have previously described a method to predict antigenic epitopes on proteins recognized by specific antibodies. Here we have applied this method to identify epitopes on the NS1 proteins of the four Dengue virus serotypes (DENV1-4) that are bound by a small panel of monoclonal antibodies 1H7.4, 1G5.3 and Gus2. Several epitope regions were predicted for these antibodies and these were found to reflect the experimentally observed reactivities. The known binding epitopes on DENV2 for the antibodies 1H7.4 and 1G5...
April 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28393598/-zika-virus-infection-in-pregnancy
#16
Gabriella Varjasi, Róbert Póka
The Zika virus is a flavivirus spread by mosquitoes. Its primary vectors are the Aedes aegypti and the Aedes albopictus. Before 2007 it sporadically caused benign morbidity. Since 2015, it started spreading "explosively" in America, especially in Brazil. In August 2016 they reported cases from New York and Poland, too. Most of the infections don't produce any symptoms, but can cause grave complications. The most important lesion is microcephalia that forms in fetuses. Microcephalia's most serious consequence is mental retardation, which puts great burden on both the family and the society...
April 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28393307/a-dose-response-study-in-mice-of-a-tetravalent-vaccine-candidate-composed-of-domain-iii-capsid-proteins-from-dengue-viruses
#17
Iris Valdés, Ernesto Marcos, Edith Suzarte, Yusleidi Pérez, Enma Brown, Laura Lazo, Karem Cobas, Melyssa Yaugel, Yadira Rodríguez, Lázaro Gil, Gerardo Guillén, Lisset Hermida
Tetra DIIIC is a subunit vaccine candidate based on domain III of the envelope protein and the capsid protein of the four serotypes of dengue virus. This vaccine preparation contains the DIIIC proteins aggregated with a specific immunostimulatory oligodeoxynucleotide (ODN 39M). Tetra DIIIC has already been shown to be immunogenic and protective in mice and monkeys. In this study, we evaluated the immunogenicity in mice of several formulations of Tetra DIIIC containing different amounts of the recombinant proteins...
April 9, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28393119/polytopic-vaccination-with-a-live-attenuated-dengue-vaccine-enhances-b-cell-and-t-cell-activation-but-not-neutralizing-antibodies
#18
Taweewun Hunsawong, Sineewanlaya Wichit, Thipwipha Phonpakobsin, Yongyuth Poolpanichupatam, Chonticha Klungthong, Napaporn Latthiwongsakorn, Butsaya Thaisomboonsuk, Rawiwan Im-Erbsin, In-Kyu Yoon, Damon W Ellison, Louis R Macareo, Anon Srikiatkhachorn, Robert V Gibbons, Stefan Fernandez
Dengue, caused by dengue viruses (DENVs), is the most common arboviral disease of humans. Several dengue vaccine candidates are at different stages of clinical development and one has been licensed. Inoculation with live-attenuated DENV constructs is an approach that has been used by vaccine developers. Unfortunately, the simultaneous injection of all four attenuated DENV serotypes (DENV1-4) into a single injection site (monotopic vaccination) has been postulated to result in interference in the replication of some serotypes in favor of others, an important obstacle in obtaining a balanced immune response against all serotypes...
March 2017: Heliyon
https://www.readbyqxmd.com/read/28389141/luteolin-restricts-dengue-virus-replication-through-inhibition-of-the-proprotein-convertase-furin
#19
Minhua Peng, Satoru Watanabe, Kitti Wing Ki Chan, Qiuyan He, Ya Zhao, Zhongde Zhang, Xiaoping Lai, Dahai Luo, Subhash G Vasudevan, Geng Li
The increasing prevalence of dengue fever in the Indian sub-continent and Southern China is a major public health concern. There is currently an approved tetravalent vaccine available in a handful of countries for protection from dengue infection, but its efficacy against dengue virus (DENV) serotype 2 is not ideal and its overall performance in children under 9 years of age is poor. In many of the dengue afflicted countries-traditional medicine is widely used as a panacea for illnesses and here we describe the systematic evaluation of a natural product, luteolin, originating from the "heat clearing" class of herbs...
April 4, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28381638/antibody-epitopes-identified-in-critical-regions-of-dengue-virus-nonstructural-1-protein-in-mouse-vaccination-and-natural-human-infections
#20
Tomer Hertz, P Robert Beatty, Zachary MacMillen, Sarah S Killingbeck, Chunling Wang, Eva Harris
Dengue is a global public health problem and is caused by four dengue virus (DENV) serotypes (DENV1-4). A major challenge in dengue vaccine development is that cross-reactive anti-DENV Abs can be protective or potentially increase disease via Ab-dependent enhancement. DENV nonstructural protein 1 (NS1) has long been considered a vaccine candidate as it avoids Ab-dependent enhancement. In this study, we evaluated survival to challenge in a lethal DENV vascular leak model in mice immunized with NS1 combined with aluminum and magnesium hydroxide, monophosphoryl lipid A + AddaVax, or Sigma adjuvant system+CpG DNA, compared with mice infected with a sublethal dose of DENV2 and mice immunized with OVA (negative control)...
April 5, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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