Prospects for a dengue virus vaccine

Whitehead, Stephen S.; Blaney, Joseph E.; Durbin, Anna P.; Murphy, Brian R.

doi:10.1038/nrmicro1690

Cited by 550 publications

(487 citation statements)

References 95 publications

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“…Por otro lado, un mecanismo de reacción cruzada de las células T de memoria y la producción de sustancias inductoras de inflamación aumentaron la permeabilidad capilar en el endotelio vascular (24,(41)(42)(43).…”

Section: Discussionunclassified

Prevalencia y curso clínico de la infección por dengue en adultos mayores con cuadro febril agudo en un hospital de alta complejidad en Cali, Colombia

Rosso¹,

Vanegas

Rodríguez

et al. 2016

biomedica

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Contribución de los autores:Róbinson Pacheco y Fernando Rosso: desarrollo de la idea, diseño del estudio y revisión crítica del contenido Sarita Rodríguez: creación de la base de datos, análisis de la información, revisión crítica del contenido Sara Vanegas: revisión de la literatura, diseño del estudio, recolección de datos y análisis de la información Todos los autores participaron en la redacción del manuscrito.Prevalencia y curso clínico de la infección por dengue en adultos mayores con cuadro febril agudo en un hospital de alta complejidad en Cali, Colombia Introducción. Hay pocas series de casos publicadas sobre la prevalencia y el curso clínico del dengue en adultos mayores con síndrome febril, habitantes en zonas endémicas para la infección. Se cree que tales casos presentan una baja prevalencia pero revisten mayor gravedad, y más complicaciones y mortalidad. Objetivos. Describir la prevalencia y el curso clínico del dengue en adultos mayores atendidos por síndrome febril agudo en un hospital de alta complejidad de una zona endémica de la enfermedad. Introduction: Little is known about the prevalence and clinical course of dengue infection in elderly patients living in endemic areas; it is presumed that there is a lower prevalence but higher severity, complications and mortality. Objective: To describe the prevalence and clinical course of dengue infection in elderly patients who were admitted to a referral care center for infectious diseases in an endemic region. Materials and methods:We conducted an observational and descriptive study between 2011 and 2014, using a cohort of elderly patients with serological diagnosis of dengue.Results: A total of 235 febrile elderly patients were assessed, of which 43 patients (18.3%) were found to have dengue. The median age was 71 years; 48.7% were female, and 89% of patients had at least one comorbid condition. According to the serological tests, 51.4% of cases were positive for NS1 Ag, 27% for IgM and 54.1% for IgG, while 64.8% were secondary infections. Dengue was diagnosed in 13 patients (35%), dengue with warning signs in 16 cases (43%), and severe dengue in 8 cases (22%). Nearly 56.7% of patients were admitted to hospital and 21.6%, to the intensive care unit. None died. 180Biomédica 2016;36(Supl.2):179-86 Rosso F, Pacheco R, Rodríguez S, Vanegas S Conclusion: We found dengue infection to be more frequent than expected in this sample of elderly patients, due to acute febrile syndrome. Elderly patients also required higher rate of hospitalization and had more complications, however there were no deaths due to good management.

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Section: Discussionunclassified

Prevalencia y curso clínico de la infección por dengue en adultos mayores con cuadro febril agudo en un hospital de alta complejidad en Cali, Colombia

Rosso¹,

Vanegas

Rodríguez

et al. 2016

biomedica

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“…Reverse genetics has proven to be a very valuable tool to introduce attenuating mutations into dengue viruses to produce live attenuated DENV vaccine candidates [18,31]. Specifically, modification of the 3'-UTR as a means to attenuate DENV has resulted in the development of several promising live attenuated vaccine candidates [19,22,32,33].…”

Section: Discussionmentioning

confidence: 99%

Dengue virus type 3 vaccine candidates generated by introduction of deletions in the 3′ untranslated region (3′-UTR) or by exchange of the DENV-3 3′-UTR with that of DENV-4

Blaney

Sathe

Goddard

et al. 2008

Vaccine

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The dengue virus type 3 (DENV-3) vaccine candidate, rDEN3Δ30, was previously found to be underattenuated in both SCID-HuH-7 mice and rhesus monkeys. Herein, two strategies have been employed to generate attenuated rDEN3 vaccine candidates which retain the full complement of structural and nonstructural proteins of DENV-3 and thus are able to induce humoral or cellular immunity to each of the DENV-3 proteins. First, using the predicted secondary structure of the 3' untranslated region (3'-UTR) of DENV-3 to design novel deletions, nine deletion mutant viruses were engineered and found to be viable. Four of nine deletion mutants replicated efficiently in Vero cells and were genetically stable. Second, chimeric rDENV-3 viruses were generated by replacement of the 3'-UTR of the rDENV-3 cDNA clone with that of rDENV-4 or rDEN4Δ30 yielding the rDEN3-3'D4 and rDEN3-3'D4Δ30 viruses, respectively. Immunization of rhesus monkeys with either of two deletion mutant viruses, rDEN3Δ30/31 and rDEN3Δ86, or with rDEN3-3'D4Δ30 resulted in infection without detectable viremia, with each virus inducing a strong neutralizing antibody response capable of conferring protection from DENV-3 challenge. The rDEN3Δ30/31 virus showed a strong host range restriction phenotype with complete loss of replication in C6/36 mosquito cells despite robust replication in Vero cells. In addition, rDEN3Δ30/31 had reduced replication in Toxorynchites mosquitoes following intrathoracic inoculation. The results are discussed in the context of vaccine development and the physical structure of the DENV 3'-UTR.

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“…The ideal dengue vaccine should be free of important reactogenicity, induce life-long protection against infection with any of the four DENV serotypes and be affordable 126,127 . Vaccine candidates should be evaluated in population-based efficacy trials in several at-risk populations in different geographical settings including Asia and the Americas, which experience different patterns of dengue transmission intensity and dengue virus circulation 122 .…”

Section: Vaccine Developmentmentioning

confidence: 99%

Dengue: a continuing global threat

et al. 2010

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Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.Dengue is the most important arthropod-borne viral infection of humans. Worldwide, an estimated 2.5 billion people are at risk of infection, approximately 975 million of whom live in urban areas in tropical and sub-tropical countries in Southeast Asia, the Pacific and the Americas 1 . Transmission also occurs in Africa and the Eastern Mediterranean, and rural Europe PMC Funders GroupAuthor Manuscript Nat Rev Microbiol. Author manuscript; available in PMC 2015 February 19. Published in final edited form as:Nat Rev Microbiol. 2010 December ; 8(12 0): S7-16. doi:10.1038/nrmicro2460. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts communities are increasingly being affected. It is estimated that more than 50 million infections occur each year, including 500,000 hospitalizations for dengue haemorrhagic fever, mainly among children, with the case fatality rate exceeding 5% in some areas [1][2][3][4] . The geographical areas in which dengue transmission occurs have expanded in recent years (FIG. 1), and all four dengue virus serotypes (DENV-1-4) are now circulating in Asia, Africa and the Americas, a dramatically different scenario from that which prevailed 20 or 30 years ago (FIG. 2). The molecular epidemiology of these serotypes has been studied in an attempt to understand their evolutionary relationships 11 .This Review will provide an update on our understanding of the pathogenesis of this successful pathogen, how we diagnose and control infection and the progress that has been made in vaccine development. Dengue virus pathogenesisDengue viruses belong to the genus flavivirus within the Flaviviridae family. DENV-1-4 evolved in non-human primates from a common ancestor and each entered the urban cycle independently an estimated 500-1,000 years ago 12 . The virion comprises a spherical particle, 40-50 nm in diameter, with a lipopolysaccharide envelope. The positive singlestrand RNA genome (FIG. 3), which is approximately 11 kb in length, has a single open reading frame that encodes three structural proteins -the capsid (C), membrane (M) and envelope (E) glycoproteins -and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5 [18][19][20] . ADE occurs when mononuclear phagocytes are infected through their Fc receptors by immune complexes that form between DE...

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Prospects for a dengue virus vaccine

Cited by 550 publications

References 95 publications

Prevalencia y curso clínico de la infección por dengue en adultos mayores con cuadro febril agudo en un hospital de alta complejidad en Cali, Colombia

Prevalencia y curso clínico de la infección por dengue en adultos mayores con cuadro febril agudo en un hospital de alta complejidad en Cali, Colombia

Dengue virus type 3 vaccine candidates generated by introduction of deletions in the 3′ untranslated region (3′-UTR) or by exchange of the DENV-3 3′-UTR with that of DENV-4

Dengue: a continuing global threat

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