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Dengue vaccine

Sineewanlaya Wichit, Pauline Ferraris, Valérie Choumet, Dorothée Missé
Arboviruses such as Dengue, Chikungunya, and Zika viruses represent a major public health problem due to globalization and propagation of susceptible vectors worldwide. Arthropod vector-derived salivary factors have the capacity to modulate human cells function by enhancing or suppressing viral replication and, therefore, modify the establishment of local and systemic viral infection. Here, we discuss how mosquito saliva may interfere with Dengue virus (DENV) infection in humans. Identification of saliva factors that enhance infectivity will allow the production of vector-based vaccines and therapeutics that would interfere with viral transmission by targeting arthropod saliva components...
October 19, 2016: Current Opinion in Virology
Stefan W Metz, Shaomin Tian, Gabriel Hoekstra, Xianwen Yi, Michelle Stone, Katie Horvath, Michael J Miley, Joseph DeSimone, Chris J Luft, Aravinda M de Silva
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year. Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes...
October 2016: PLoS Neglected Tropical Diseases
Marie Louise Landry, Kirsten St George
CONTEXT: -The rapid and accurate diagnosis of Zika virus infection is an international priority. OBJECTIVE: -To review current recommendations, methods, limitations, and priorities for Zika virus testing. DATA SOURCES: -Sources include published literature, public health recommendations, laboratory procedures, and testing experience. CONCLUSIONS: -Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited...
October 20, 2016: Archives of Pathology & Laboratory Medicine
Laura Rivino, Mei Qiu Lim
Dengue (DENV) and Zika viruses (ZIKV) are rapidly emerging mosquito-borne flaviviruses which represent a public health concern. Understanding host protective immunity to these viruses is critical for the design of optimal vaccines. Over a decade of research has highlighted a significant contribution of the T cell response to both protection and/or disease enhancement during dengue infection, the latter being mainly associated with sub-optimal cross-reactive T cell responses during secondary infections. Phase IIb/III clinical trials of the first licensed tetravalent dengue vaccine highlight increased vaccine efficacy in dengue-immune as opposed to dengue-naïve vaccinees, suggesting a possible immunoprotective role of pre-existing DENV-specific T cells that are boosted upon vaccination...
October 20, 2016: Immunology
Yuka Saito, Meng Ling Moi, Nozomi Takeshita, Chang-Kweng Lim, Hajime Shiba, Kuniaki Hosono, Masayuki Saijo, Ichiro Kurane, Tomohiko Takasaki
BACKGROUND: Dengue virus (DENV) and Japanese encephalitis virus (JEV) belong to the genus Flavivirus, and infection with a virus within this genus induces antibodies that are cross-reactive to other flaviviruses. Particularly in DENV infection, antibodies to DENV possess two competing activities: neutralizing activity and infection-enhancing activity. These antibody activities are considered central in modulating clinical outcomes of DENV infection. Here, we determined the neutralizing and infection-enhancing activity of DENV cross-reactive antibodies in adults before and after JE vaccination...
October 18, 2016: BMC Infectious Diseases
Takashi Suzuki, Joseph H Osei, Akihiro Sasaki, Michelle Adimazoya, Maxwell Appawu, Daniel Boakye, Nobuo Ohta, Samuel Dadzie
BACKGROUND: Dengue is one of the emerging diseases that can mostly only be controlled by vector control since there is no vaccine for the disease. Although, Dengue has not been reported in Ghana, movement of people from neighbouring countries where the disease has been reported can facilitate transmission of the disease. OBJECTIVE: This study was carried on the University of Ghana campus to determine the risk of transmission of viral haemorrhagic fevers and the insecticide susceptibility status of Ae...
September 2016: Ghana Medical Journal
Sean Ekins, John Liebler, Bruno J Neves, Warren G Lewis, Megan Coffee, Rachelle Bienstock, Christopher Southan, Carolina H Andrade
The Zika virus (ZIKV) is a flavivirus of the family Flaviviridae, which is similar to dengue virus, yellow fever and West Nile virus. Recent outbreaks in South America, Latin America, the Caribbean and in particular Brazil have led to concern for the spread of the disease and potential to cause Guillain-Barré syndrome and microcephaly. Although ZIKV has been known of for over 60 years there is very little in the way of knowledge of the virus with few publications and no crystal structures. No antivirals have been tested against it either in vitro or in vivo...
2016: F1000Research
Annie Elong Ngono, Hui-Wen Chen, William W Tang, Yunichel Joo, Kevin King, Daniela Weiskopf, John Sidney, Alessandro Sette, Sujan Shresta
Infection with one of the four dengue virus serotypes (DENV1-4) presumably leads to lifelong immunity against the infecting serotype but not against heterotypic reinfection, resulting in a greater risk of developing Dengue Hemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) during secondary infection. Both antibodies and T cell responses have been implicated in DHF/DSS pathogenesis. According to the T cell-based hypothesis termed "original antigenic sin," secondary DENV infection is dominated by non-protective, cross-reactive T cells that elicit an aberrant immune response...
October 7, 2016: EBioMedicine
David S Younger
Zika virus is an arbovirus belonging to the Flaviviridae family known to cause mild clinical symptoms similar to those of dengue and chikungunya. Zika is transmitted by different species of Aedes mosquitoes. Nonhuman primates and possibly rodents play a role as reservoirs. Direct interhuman transmission has also been reported. Human cases have been reported in Africa and Asia, Easter Island, the insular Pacific region, and Brazil. Its clinical profile is that of a dengue-like febrile illness, but recently associated Guillain-Barre syndrome and microcephaly have appeared...
November 2016: Neurologic Clinics
Angela Ferreira Lopes de Teive E Argolo, Valéria Christina de Rezende Féres, Marli Tenório Cordeiro, Lucimeire Antonelli da Silveira, Adriana Oliveira Guilarde, Ernesto Torres de Azevedo Marques, Wayner Vieira de Souza, Celina Maria Turchi Martelli
BACKGROUND: This study aims to identify dengue neutralizing antibody response in patients with dengue from a well-characterized cohort during an outbreak in central Brazil, 2012-2013. METHODS: We analyzed paired samples from 40 patients with severe dengue and 20 patients with dengue. Eligibility criteria were: IgM, NS1Ag and/or RT-PCR positivity and positive IgG result. Plaque reduction neutralization test (PRNT50) from DENV-1 to DENV-4 was performed to identify serotype-specific NAbs response...
October 7, 2016: BMC Infectious Diseases
David C Chang, Long T Hoang, Ahmad Nazri Mohamed Naim, Hongping Dong, Mark J Schreiber, Martin L Hibberd, Min Jie Alvin Tan, Pei-Yong Shi
Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5' cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2'-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection...
October 4, 2016: Virology
Meihui Xu, Roland Züst, Ying Xiu Toh, Jennifer M Pfaff, Kristen M Kahle, Edgar Davidson, Benjamin J Doranz, Sumathy Velumani, Farhana Tukijan, Cheng-I Wang, Katja Fink
Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue-specific antibodies that are produced by plasmablasts a few days after natural secondary infection...
October 5, 2016: Journal of Virology
Giovanni Benelli, Claire L Jeffries, Thomas Walker
Mosquitoes represent the major arthropod vectors of human disease worldwide transmitting malaria, lymphatic filariasis, and arboviruses such as dengue virus and Zika virus. Unfortunately, no treatment (in the form of vaccines or drugs) is available for most of these diseases andvectorcontrolisstillthemainformofprevention. Thelimitationsoftraditionalinsecticide-based strategies, particularly the development of insecticide resistance, have resulted in significant efforts to develop alternative eco-friendly methods...
October 3, 2016: Insects
Gokul Swaminathan, Elizabeth A Thoryk, Kara S Cox, Jeffrey S Smith, Jayanthi J Wolf, Marian E Gindy, Danilo R Casimiro, Andrew J Bett
Dengue virus has emerged as an important arboviral infection worldwide. As a complex pathogen, with four distinct serotypes, the development of a successful Dengue virus vaccine has proven to be challenging. Here, we describe a novel Dengue vaccine candidate that contains truncated, recombinant, Dengue virus envelope protein from all four Dengue virus serotypes (DEN-80E) formulated with ionizable cationic lipid nanoparticles (LNPs). Immunization studies in mice, Guinea pigs, and in Rhesus macaques, revealed that LNPs induced high titers of Dengue virus neutralizing antibodies, with or without co-administration or encapsulation of a Toll-Like Receptor 9 agonist...
October 5, 2016: Scientific Reports
Neil M Ferguson, Isabel Rodríguez-Barraquer, Ilaria Dorigatti, Luis Mier-Y-Teran-Romero, Daniel J Laydon, Derek A T Cummings
The first approved dengue vaccine has now been licensed in six countries. We propose that this live attenuated vaccine acts like a silent natural infection in priming or boosting host immunity. A transmission dynamic model incorporating this hypothesis fits recent clinical trial data well and predicts that vaccine effectiveness depends strongly on the age group vaccinated and local transmission intensity. Vaccination in low-transmission settings may increase the incidence of more severe "secondary-like" infection and, thus, the numbers hospitalized for dengue...
September 2, 2016: Science
Mahesha N Nadugala, Prasad H Premaratne, Charitha L Goonasekara
B-cell epitopes on the envelope (E) and premembrane (prM) proteins of dengue virus (DENV) were predicted using bioinformatics tools, BepiPred, Ellipro, and SVMTriP. Predicted epitopes, 32 and 17 for E and prM proteins, respectively, were then characterized for their level of conservations. The epitopes, EP4/E (48-55), epitope number 4 of E protein at amino acids 48-55, EP9/E (165-182), EP11/E (218-233), EP20/E (322-349), EP21/E (326-353), EP23/E (356-365), and EP25/E (380-386), showed a high intraserotype conservancy with very low pan-serotype conservancy, demonstrating a potential target as serotype specific diagnostic markers...
2016: Advances in Bioinformatics
Lázaro Gil, Karem Cobas, Laura Lazo, Ernesto Marcos, Laura Hernández, Edith Suzarte, Alienys Izquierdo, Iris Valdés, Aracelys Blanco, Pedro Puentes, Yaremis Romero, Yusleidi Pérez, María G Guzmán, Gerardo Guillén, Lisset Hermida
Despite the considerable effort that has been invested in elucidating the mechanisms of protection and immunopathogenesis associated with dengue virus infections, a reliable correlate of protection against the disease remains to be found. Neutralizing Abs, long considered the prime component of a protective response, can exacerbate disease severity when present at subprotective levels, and a growing body of data is challenging the notion that their titers are positively correlated with disease protection. Consequently, the protective role of cell-mediated immunity in the control of dengue infections has begun to be studied...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Alex Michael Ward, Meredith E K Calvert, Leah R Read, Seokyoung Kang, Brandt E Levitt, George Dimopoulos, Shelton S Bradrick, Jayantha Gunaratne, Mariano A Garcia-Blanco
Dengue virus (DENV) is a mosquito-borne Flavivirus classified into four serotypes (DENV-1-4) that causes Dengue fever (DF), Dengue hemorrhagic Fever (DHF) or Dengue shock syndrome (DSS). An estimated 390 million people are at risk for infection with DENV and there are no effective vaccines or therapeutics. We utilized RNA chromatography coupled with quantitative mass spectrometry (qMS) to identify host RNA binding proteins (RBPs) that interact with DENV-2 RNA. We identified ERI3 (also PRNPIP and PINT1), a putative 3'-5' RNA exonuclease, which preferentially associates with DENV-2 genomic RNA via interactions with dumbbell structures in the 3' UTR...
September 29, 2016: Scientific Reports
Ipsita Mohanty, Animesha Rath, Namita Mahapatra, Rupenangshu K Hazra
Vector-borne diseases particularly those transmitted by mosquitoes like Dengue are among the leading causes of mortality and morbidity in human population. There are no effective vaccines or treatment against dengue fever till date and the control methods are limited. So, new approaches are urgently in need to reverse these trends. Vector control is currently the primary intervention tool. Strategies that reduce or block pathogen transmission by mosquitoes have been proposed as a means of augmenting current control measures to reduce the growing burden of vector-borne diseases...
July 2016: Journal of Vector Borne Diseases
Indra Vythilingam, Jamal I-C Sam, Yoke F Chan, Loke T Khaw, Wan Y Wan Sulaiman
Zika virus (ZIKV) has now become a global public health concern. The vectors for ZIKV are Aedes aegypti and A. albopictus. Both these mosquitoes are predominant in Southeast Asia and are also responsible for the spread of other arboviral diseases like dengue virus and chikungunya virus. The incidence of dengue has been increasing over the years and this is of concern to public health workers. Simple laboratory tools for the detection of ZIKV is also lacking. In the absence of drugs and vaccine for these arboviral diseases, vector control is the main option for surveillance and control...
2016: Frontiers in Microbiology
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