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Sathyamangalam Swaminathan, Navin Khanna
India is home to nearly a third of the global population at risk of dengue, a viral disease caused by four antigenically and genetically distinct dengue viruses. Clinical illness following dengue virus infection could either be mild and self-limiting dengue fever or severe dengue hemorrhagic fever/dengue shock syndrome, with potentially fatal consequences. A live attenuated vaccine known as Dengvaxia, developed by Sanofi, was licensed in 2015. Following this, long-term follow-up of Sanofi's phase III efficacy trial participants has revealed potential safety concerns...
January 23, 2019: International Journal of Infectious Diseases: IJID
Laura Lazo, Iris Valdes, Gerardo Guillén, Lisset Hermida, Lázaro Gil
Dengue fever remains a health problem worldwide. Although the vaccine developed by Sanofi Pasteur, Dengvaxia®, has been registered in several countries, the results following the immunization of thousands of people suggest an increased risk in non-immune persons and children younger than 9 years old. No other vaccine is registered so far, therefore the development of a safe and effective dengue vaccine continues to be a priority for the World Health Organization and the scientific community. Areas covered: This work reviews the main structural and antigenic properties of the capsid protein of dengue virus, along with the results of studies performed to assess the immunogenicity and protective capacity of vaccine candidates based on this viral protein in animals...
January 24, 2019: Expert Review of Vaccines
Robert Luo, Noah Fongwen, Cassandra Kelly-Cirino, Eva Harris, Annelies Wilder-Smith, Rosanna Peeling
OBJECTIVES: Vaccination for dengue with the live attenuated tetravalent CYD-TDV vaccine (Dengvaxia®) is only recommended in individuals who have had prior dengue virus (DENV) infection. Rapid diagnostic tests (RDT) for past DENV infection would offer a convenient method for pre-vaccination screening at point-of-care. A systematic review was conducted to evaluate the performance of current dengue rapid diagnostic tests (RDTs) for determining dengue serostatus, using IgG antibodies against DENV as a marker of past infection...
January 18, 2019: Clinical Microbiology and Infection
Eakachai Prompetchara, Chutitorn Ketloy, Stephen J Thomas, Kiat Ruxrungtham
The first licensed dengue vaccine, CYD-TDV (Dengvaxia®), has received regulatory approval in a number of countries. However, this vaccine has some limitations. Its efficacy against DENV2 was consistently lower than other serotypes. Protective efficacy also depended on prior dengue sero-status of the vaccinees. Lower efficacy was observed in children with < 9 years old and dengue-na?ve individuals. More importantly, risk of hospitalization and severe dengue was increased in the youngest vaccine recipients (2-5 years) compared to controls...
January 13, 2019: Asian Pacific Journal of Allergy and Immunology
Siew Pheng Lim
In the context of the only available vaccine (DENGVAXIA) that was marketed in several countries, but poses higher risks to unexposed individuals, the development of antivirals for dengue virus (DENV), whilst challenging, would bring significant benefits to public health. Here recent progress in the field of DENV drug discovery made in academic laboratories and industry is reviewed. Characteristics of an ideal DENV antiviral molecule, given the specific immunopathology provoked by this acute viral infection, are first described...
December 28, 2018: Antiviral Research
Rahul Shukla, Viswanathan Ramasamy, Ravi Kant Rajpoot, Upasana Arora, Ankur Poddar, Richa Ahuja, Hemalatha Beesetti, Sathyamangalam Swaminathan, Navin Khanna
A safe and efficacious vaccine for dengue continues to be an unmet public health need. The recent licensing of a dengue vaccine (Dengvaxia) developed by Sanofi has brought to the fore the safety issue of vaccine-induced infection-enhancement. Areas covered: This article focuses on two new yeast-produced tetravalent dengue envelope domain III-displaying virus-like particulate vaccine candidates reported in early 2018 and reviews the rationale underlying their design, and pre-clinical data which suggest that these may offer promising alternate options...
December 27, 2018: Expert Review of Vaccines
André van Eerde, Johanna Gottschamel, Ralph Bock, Kristine Eraker Aasland Hansen, Hetron Mweemba Munang'andu, Henry Daniell, Jihong Liu Clarke
Dengue fever is a mosquito (Aedes aegypti) -transmitted viral disease that is endemic in more than 125 countries around the world. There are four serotypes of the dengue virus (DENV 1-4) and a safe and effective dengue vaccine must provide protection against all four serotypes. To date, the first vaccine, Dengvaxia (CYD-TDV), is available after many decades' efforts, but only has moderate efficacy. More effective and affordable vaccines are hence required. Plants offer promising vaccine production platforms and food crops offer additional advantages for the production of edible human and animal vaccines, thus eliminating the need for expensive fermentation, purification, cold storage and sterile delivery...
December 22, 2018: Plant Biotechnology Journal
Adib Afandi Abdullah, Yean Kee Lee, Sek Peng Chin, See Khai Lim, Vannajan Lee, Rozana Othman, Shatrah Othman, Noorsaadah Abdul Rahman, Rohana Yusof, Choon Han Heh
To date, there is still no approved anti-dengue agent to treat dengue infection in the market. Although the only licensed dengue vaccine, Dengvaxia is available, its protective efficacy against serotypes 1 and 2 of dengue virus was reported to be lower than serotypes 3 and 4. Moreover, according to WHO, the risk of being hospitalized and having severe dengue increased in seronegative individuals after they received Dengvaxia vaccination. Nevertheless, various studies had been carried out in search of dengue virus inhibitors...
December 4, 2018: Current Medicinal Chemistry
Khunsha Fatima, Najah Irfan Syed
No abstract text is available yet for this article.
December 2018: Journal of Global Health
Jih-Jin Tsai, Ching-Kuan Liu, Wen-Yang Tsai, Li-Teh Liu, Jasmine Tyson, Ching-Yi Tsai, Ping-Chang Lin, Wei-Kung Wang
Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. In this study, we investigated the seroprevalence of DENV infection in two districts of Kaohsiung City, a metropolis in southern Taiwan, where major dengue outbreaks have occurred in the past three decades. We enrolled 1,088 participants from the Sanmin and Nanzih districts after the dengue outbreak of 2015, the largest in Taiwan since World War II, and found an overall DENV seroprevalence of 12.4% (95% confidence interval: 10...
October 2018: PLoS Neglected Tropical Diseases
Heidi J Larson, Kenneth Hartigan-Go, Alexandre de Figueiredo
In November 2017, it was announced that the new dengue vaccine ("Dengvaxia") had risks for those not previously exposed to dengue. While some countries proceeded with adjusting guidance accordingly, the Philippines reacted with outrage and political turmoil with naming and shaming of government officials involved in purchasing the vaccine, as well as scientists involved in the vaccine trials and assessment. The result was broken public trust around the dengue vaccine as well heightened anxiety around vaccines in general...
October 12, 2018: Human Vaccines & Immunotherapeutics
Sandra Bos, Gilles Gadea, Philippe Despres
Dengue disease is the most prevalent mosquito-borne viral infection in humans. At least one half of the global population is estimated at risk of infection and an estimated 390 million people are infected each year. Over the past few years, dengue burden continued to increase, mainly impacting developing countries. Alarming changes in dengue epidemiology were observed highlighting a spread from tropical to subtropical regions as well as urban to rural areas. An increase in the co-infections with the four serotypes has also been noticed, involving a shift in the targeted population from pediatric to adult...
September 14, 2018: Pathogens and Global Health
Nagesh K Tripathi, Ambuj Shrivastava
Recombinant proteins are gaining enormous importance these days due to their wide application as biopharmaceutical products and proven safety record. Various recombinant proteins of therapeutic and prophylactic importance have been successfully produced in microbial and higher expression host systems. Since there is no specific antiviral therapy available against dengue, the prevention by vaccination is the mainstay in reducing the disease burden. Therefore, efficacious vaccines are needed to control the spread of dengue worldwide...
2018: Frontiers in Immunology
Wen-Yang Tsai, Hui-Ling Chen, Jih-Jin Tsai, Wanwisa Dejnirattisai, Amonrat Jumnainsong, Juthathip Mongkolsapaya, Gavin Screaton, James E Crowe, Wei-Kung Wang
The four serotypes of dengue virus (DENV) cause the most important mosquito-borne viral disease in humans. The envelope (E) protein is the major target of neutralizing antibodies and contains 3 domains (domain I [DI], DII, and DIII). Recent studies reported that human monoclonal antibodies (MAbs) recognizing DIII, the D1/DII hinge, the E-dimer epitope, or a quaternary epitope involving DI/DII/DIII are more potently neutralizing than those recognizing the fusion loop (FL) of DII. Due to inefficient cleavage of the premembrane protein, DENV suspensions consist of a mixture of mature, immature, and partially immature particles...
December 1, 2018: Journal of Virology
Daniel Olson, Anne-Marie Rick, Steven Krager, Molly Lamb, Edwin J Asturias
BACKGROUND: Arboviruses including dengue (DENV), chikungunya (CHIKV) and Zika cause significant morbidity in Latin America. With multiple arbovirus vaccines in development, better understanding of community attitudes and acceptability for these vaccines is needed. METHODS: In September 2016, a cross-sectional survey assessed arbovirus knowledge, attitudes, vaccine demand and willingness-to-pay (WTP) at the conclusion of a DENV/norovirus surveillance study in rural Guatemala with high arbovirus endemicity...
November 2018: Pediatric Infectious Disease Journal
Wenlong Lian, Jaebong Jang, Supanee Potisopon, Pi-Chun Li, Amal Rahmeh, Jinhua Wang, Nicholas P Kwiatkowski, Nathanael S Gray, Priscilla L Yang
Dengue virus is a major human pathogen that infects over 390 million people annually leading to approximately 500 000 hospitalizations due to severe dengue. Since the only marketed vaccine, Dengvaxia, has recently been shown to increase disease severity in those lacking natural immunity, antivirals to prevent or treat dengue  infection represent a large, unmet medical need. Small molecules that target the dengue virus envelope protein, E, on the surface of the virion could act analogously to antibodies by engaging E extracellularly to block infection; however, a shortage of target-based assays suitable for screening and medicinal chemistry studies has limited efforts in this area...
September 14, 2018: ACS Infectious Diseases
Enahoro A Iboi, Abba B Gumel
A new mathematical model is designed and used to assess the impact of the newly-released Dengvaxia vaccine on the transmission dynamics of two co-circulating dengue strains (where strain 1 consists of dengue serotypes 1, 3 and 4; and strain 2 consists of dengue serotype 2). It is shown that the model exhibits the phenomenon of backward bifurcation when the disease-induced mortality in the host population exceeds a certain threshold value or if the vaccine does not provide perfect protection against infection with the two strains...
October 2018: Mathematical Biosciences
Hannah E Clapham, Bridget A Wills
The complex interaction between dengue viruses and the human immune system means that development of a safe, effective dengue vaccine was never going to be simple. The only currently licenced dengue vaccine (Dengvaxia®) does, indeed, have a complex immune profile depending on recipients' immune status, meaning that use of this vaccine is not straightforward. This commentary reviews the recommendations for vaccine use to date, and discusses issues and opportunities related to the implementation of vaccination programmes in light of these recommendations...
August 1, 2018: Transactions of the Royal Society of Tropical Medicine and Hygiene
Hugo C Turner, Bridget A Wills, Motiur Rahman, Hoang Quoc Cuong, Guy E Thwaites, Maciej F Boni, Hannah E Clapham
Background: After new analysis, Sanofi Pasteur now recommends their dengue vaccine (Dengvaxia) should only be given to individuals previously infected with dengue and the World Health Organization's recommendations regarding its use are currently being revised. As a result, the potential costs of performing large-scale individual dengue screening and/or dengue serosurveys have become an important consideration for decision making by policymakers in dengue-endemic areas. Methods: We used an ingredients-based approach to estimate the financial costs for conducting both a school-based dengue serosurvey and school-based individual dengue screening within a typical province in Vietnam, using an existing commercial indirect immunoglobulin G enzyme-linked immunosorbent assay kit...
August 1, 2018: Transactions of the Royal Society of Tropical Medicine and Hygiene
Jason E Coffman, Stefan W Metz, Alex Brackbill, Molly Paul, Michael J Miley, Joseph DeSimone, J Christopher Luft, Aravinda de Silva, Shaomin Tian
The dengue virus (DENV) causes over 350 million infections, resulting in ∼25,000 deaths per year globally. An effective dengue vaccine requires generation of strong and balanced neutralizing antibodies against all four antigenically distinct serotypes of DENV. The leading live-attenuated tetravalent dengue virus vaccine platform has shown partial efficacy, with an unbalanced response across the four serotypes in clinical trials. DENV subunit vaccine platforms are being developed because they provide a strong safety profile and are expected to avoid the unbalanced immunization issues associated with live multivalent vaccines...
May 16, 2018: Bioconjugate Chemistry
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