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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 350 million people annually leading to approximately 500,000 hospitali-zations 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 DENV infection represent a large, unmet medical need. Small mole-cules 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, but a shortage of target-based assays suitable for screening and medicinal chemistry studies has limited efforts in this area...
July 20, 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...
July 16, 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...
July 17, 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...
July 3, 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
Jung-Seok Lee, José Lourenço, Sunetra Gupta, Andrew Farlow
BACKGROUND: The dengue vaccination era began when Dengvaxia (CYD-TDV) became available in 2016. In addition, several second-generation vaccine candidates are currently in phase 3 trials, suggesting that a broader availability of dengue vaccines may be possible in the near future. Advancing on the recent WHO-SAGE recommendations for the safe and effective use of CYD-TDV at the regional level on average, this study investigates the vaccination impacts and cost-effectiveness of CYD-TDV and of a hypothetical new vaccine candidate (NVC) in a country-specific manner for three endemic countries: Vietnam, Thailand, and Colombia...
April 19, 2018: Vaccine
Bouchra Kitab, Michinori Kohara, Kyoko Tsukiyama-Kohara
Dengue is the most prevalent arboviral disease in humans and leads to significant morbidity and socioeconomic burden in tropical and subtropical areas. Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV1-4) and usually manifests as a mild febrile illness, but may develop into fatal dengue hemorrhagic fever and shock syndrome. There are no specific antiviral therapies against dengue because understanding of DENV biology is limited. A tetravalent chimeric dengue vaccine, Dengvaxia, has finally been licensed for use, but its efficacy was significantly lower against DENV-2 infections and in dengue-naïve individuals...
July 2018: Archives of Virology
Yu-Shi Tian, Yi Zhou, Tatsuya Takagi, Masanori Kameoka, Norihito Kawashita
The global occurrence of viral infectious diseases poses a significant threat to human health. Dengue virus (DENV) infection is one of the most noteworthy of these infections. According to a WHO survey, approximately 400 million people are infected annually; symptoms deteriorate in approximately one percent of cases. Numerous foundational and clinical investigations on viral epidemiology, structure and function analysis, infection source and route, therapeutic targets, vaccines, and therapeutic drugs have been conducted by both academic and industrial researchers...
2018: Chemical & Pharmaceutical Bulletin
Scott B Halstead
A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative...
February 26, 2018: Human Vaccines & Immunotherapeutics
Wei-Lian Tan, Yean Kee Lee, Yen Fong Ho, Rohana Yusof, Noorsaadah Abdul Rahman, Saiful Anuar Karsani
Dengue is endemic throughout tropical and subtropical regions of the world. Currently, there is no clinically approved therapeutic drug available for this acute viral infection. Although the first dengue vaccine Dengvaxia has been approved for use in certain countries, it is limited to those without a previous dengue infection while the safety and efficacy of the vaccine in those elderly and younger children still need to be identified. Therefore, it is becoming increasingly important to develop therapeutics/drugs to combat dengue virus (DENV) infection...
2018: PeerJ
Isabel N Kantor
Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar...
2018: Medicina
Eric Plennevaux, Annick Moureau, José L Arredondo-García, Luis Villar, Punnee Pitisuttithum, Ngoc H Tran, Matthew Bonaparte, Danaya Chansinghakul, Diana L Coronel, Maïna L'Azou, R Leon Ochiai, Myew-Ling Toh, Fernando Noriega, Alain Bouckenooghe
Background: We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments. Methods: We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2-16 years across 10 countries in Asia and Latin America...
April 3, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Antonio L Dans, Leonila F Dans, Mary Ann D Lansang, Maria Asuncion A Silvestre, Gordon H Guyatt
Severe life-threatening dengue fever usually occurs when a child is infected by dengue virus a second time. This is caused by a phenomenon called antibody-dependent enhancement (ADE). Since dengue vaccines can mimic a first infection in seronegative children (those with no previous infection), a natural infection later in life could lead to severe disease. The possibility that dengue vaccines can cause severe dengue through ADE has led to serious concern regarding the safety of mass vaccination programs. A published meta-analysis addressed this safety issue for a new vaccine against dengue fever-Dengvaxia...
March 2018: Journal of Clinical Epidemiology
Maíra Aguiar, Nico Stollenwerk
No abstract text is available yet for this article.
February 1, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Scott B Halstead
During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection...
November 7, 2017: Vaccine
Chye Sheng Gan, See Khai Lim, Chin Fei Chee, Rohana Yusof, Choon Han Heh
Dengvaxia® (CTD-TDV), the only licensed tetravalent dengue vaccine by Sanofi Pasteur, was made available since 2015. However, administration of CTD-TDV, in general, has not received the prequalification recommendation from the World Health Organization. Having a universal antidengue agent for treatment will therefore beneficial. Accordingly, the development of nucleoside inhibitors specific to dengue viral polymerase that perturb dengue infection has been studied by many. Alternatively, we have used a marketed anti-HCV prodrug sofosbuvir to study its in silico and in vitro effects against dengue...
February 2018: Chemical Biology & Drug Design
Kirsten Vannice, Liliana Chocarro, Michael Pfleiderer, Ahmed Bellah, Michael Ward, In-Kyu Yoon, Joachim Hombach
No abstract text is available yet for this article.
October 13, 2017: Vaccine
Scott B Halstead
The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1...
June 1, 2018: Cold Spring Harbor Perspectives in Biology
Gavin Screaton, Juthathip Mongkolsapaya
A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines...
June 1, 2018: Cold Spring Harbor Perspectives in Biology
Ruth Aralí Martínez-Vega, Gabriel Carrasquila, Expedito Luna, José Ramos-Castañeda
The vaccine against Dengue virus (DENV), Dengvaxia® (CYD), produced by Sanofi-Pasteur, has been registered by several national regulatory agencies; nevertheless, the performance and security of this vaccine have been challenged in a series of recent papers. In this work, we intend to contribute to the debate by analyzing the concept of an enhancing vaccine, presenting objections to the epidemiological model base of the concept and, likewise, presenting data that contradict that concept.
July 13, 2017: Vaccine
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