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Geographic distribution of dengue virus endemic areas in 2011 with permission WHO 2012, http://who.int/ith/en/, Accessed 17 Feb 2012.
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Monika Simmons1, Nimfa Teneza-Mora1, Robert Putnak21Viral and Rickettsial Diseases Department, Naval Medical Research Center, 2Division of Viral Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USAAbstract: Dengue fever is caused by the mosquito-borne dengue virus (DENV) serotypes 1–4, and is the most common arboviral infection...
Context in source publication
Context 1
... the last decade, there has been intensified dis- ease transmission due to ineffective vector control. Figure 2 illustrates the geographic regions in which dengue infection is now endemic. Retrospective studies and use of serologi- cal surveys in mammals have demonstrated the presence of epizootics among Erythrocebus patas monkeys in Senegal. ...
Citations
... In this case, it is difficult to predict which type of dengue is prevalent in the particular geographical region for conducting vaccination program to prevent dengue. At present, tetravalent vaccine formulation is in progress for which monovalent vaccine identification for all the four dengue serotypes are essential [50] . Therefore, in the present study, the monovalent vaccine candidate, T cell epitope for each dengue serotype, was predicted from whole antigen through B cell epitope prediction. ...
Reverse vaccinology method was used to predict the monovalent peptide vaccine candidate to produce antibodies for therapeutic purpose and to predict tetravalent vaccine candidate to act as a common vaccine to cover all the fever dengue virus serotypes. Envelope (E)-proteins of DENV-1-4 serotypes were used for vaccine prediction using NCBI, Uniprot/Swissprot, Swiss-prot viewer, VaxiJen V2.0, TMHMM, BCPREDS, Propred-1, Propred and MHC Pred,. E-proteins of DENV-1-4 serotypes were identified as antigen from which T cell epitopes, through B cell epitopes, were predicted to act as peptide vaccine candidates. Each selected T cell epitope of E-protein was confirmed to act as vaccine and to induce complementary antibody against particular serotype of dengue virus. Chimeric tetravalent vaccine was formed by the conjugation of four vaccines, each from four dengue serotypes to act as a common vaccine candidate for all the four dengue serotypes. It can be justifiably concluded that the monovalent 9-mer T cell epitope for each DENV serotypes can be used to produce specific antibody agaomst dengue virus and a chimeric common tetravalent vaccine candidate to yield a comparative vaccine to cover any of the four dengue virus serotype. This vaccine is expected to act as highly immunogenic against preventing dengue fever.
... The dengue viruses (DENVs), which consist of four antigenically distinct serotypes, DENV 1, 2, 3, and 4, in the family Flaviviridae are estimated to cause up to 100 million symptomatic infections each year and 50,000 deaths due to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). [1][2][3] There are currently no antiviral drugs or methods for dengue disease prophylaxis. Tetravalent live attenuated vaccine (TLAV) candidates currently in clinical trials may require three doses administered over 9-12 months to confer protective immunity. ...
Passive immunization with anti-dengue virus (DENV) immune serum globulin (ISG) or monoclonal antibodies (Mabs) may serve to supplement or replace vaccination for short-term dengue immune prophylaxis. In the present study, we sought to establish proof-of-concept by evaluating several DENV-neutralizing antibodies for their ability to protect rhesus macaques against viremia following live virus challenge, including human anti-dengue ISG, and a human Mab (Mab11/wt) and its genetically engineered variant (Mab11/mutFc) that is unable to bind to cells with Fc gamma receptors (Fc?R) and potentiate antibody-dependent enhancement (ADE). In the first experiment, groups of animals received ISG or Mab11/wt at low doses (3-10 mg/kg) or a saline control followed by challenge with DENV-2 at day 10 or 30. After passive immunization, only low-titered circulating virus-neutralizing antibody titers were measured in both groups, which were undetectable by day 30. After challenge at day 10, a reduction in viremia duration compared with the control was seen only in the ISG group (75%). However, after a day 30 challenge, no reduction in viremia was observed in both immunized groups. In a second experiment to test the effect of higher antibody doses on short-term protection, groups received either ISG, Mab11/wt, Mab11/mutFc (each at 25 mg/kg) or saline followed by challenge with DENV-2 on day 10. Increased virus-neutralizing antibody titers were detected in all groups at day 5 postinjection, with geometric mean titers (GMTs) of 464 (ISG), 313 (Mab11/wt), and 309 (Mab11/mutFc). After challenge, there was complete protection against viremia in the group that received ISG, and a reduction in viremia duration of 89% and 83% in groups that received Mab11/wt and Mab11/mutFc, respectively. An in vitro ADE assay in Fc? receptor-bearing K562 cells with sera collected immediately before challenge showed increased DENV-2 infection levels in the presence of both ISG and Mab11/wt, which peaked at a serum dilution of 1:90, but not in Mab11/mutFc containing sera. The results suggest that antibody prophylaxis for dengue might be beneficial in eliminating or reducing viral loads thereby minimizing disease progression. Our results also suggest that blocking Fc?R interactions through Mab11 Fc engineering may further prevent ADE.
... Currently, the disease is endemic in more than 100 countries, and is spreading throughout the world. Dengue disease is caused by four antigenically related distinct serotypes, namely, dengue virus (DENV)-1, DENV-2, DENV-3 and in which only DENV-2 and DENV-3 are mostly found in tropical countries [2,3]. The distinctions among the serotypes are based on their antigenicity and immunogenic property in the human body. ...
Objective: To find out the antigenic nature of envelop (E) and non-structural (NS) proteins
and their ability to induce specific antibodies, and to investigate specific antibody produced by
specific dengue virus (DENV) serotypes.
Methods: Amino acid sequences of E and NS proteins of dengue serotypes were analysed
by using VaxiJen antigen predicition server. The transmembrane of topology analyses were
conducted by using transmembrane prediction using hidden markov models. The Hex dock
server was used for docking.
Results: The antigenicity score and exomembrane potentiality of E and NS proteins were
calculated. All those proteins were antigenic; these antigens were made to interact with
antibodies such as immunoglobulin A, immunoglobulin G and immunoglobulin M. Higher
energy values of immunoglobulin M were found in DENV-1 and DENV-2, and more energy
values were found in immunoglobulin G of DENV-3, DENV-4, NS-1, NS-3 and NS-5.
Conclusions: In the present study, DENV-1 and DENV-2 are positive to immunoglobulin M and
involved in the primary infection. DENV 3, DENV 4 and all the NS proteins (NS-1, NS-3, NS-5)
which elicit immunoglobulin G are involved in the secondary infection.
... Symptoms range from mild to moderate undifferentiated febrile illness to more complex severe clinical manifestations which can lead to death. Despite life-long immunity to the infecting serotype and limited duration of cross-protection against other serotypes [3,4], severe dengue disease is more often associated with second or subsequent infection with heterologous dengue serotype, hypothesized to be due to antibody-dependent enhancement of infection by preexisting "cross-enhancing" antibodies [5]. ...
Background:
A tetravalent dengue vaccine was shown to be efficacious against symptomatic dengue in two phase III efficacy studies performed in five Asian and five Latin American countries. The objective here was to estimate key parameters of a dengue transmission model using the data collected during these studies.
Methods:
Parameter estimation was based on a Sequential Monte Carlo approach and used a cohort version of the transmission model. Serotype-specific basic reproduction numbers were derived for each country. Parameters related to serotype interactions included duration of cross-protection and level of cross-enhancement characterized by differences in symptomaticity for primary, secondary and post-secondary infections. We tested several vaccine efficacy profiles and simulated the evolution of vaccine efficacy over time for the scenarios providing the best fit to the data.
Results:
Two reference scenarios were identified. The first included temporary cross-protection and the second combined cross-protection and cross-enhancement upon wild-type infection and following vaccination. Both scenarios were associated with differences in efficacy by serotype, higher efficacy for pre-exposed subjects and against severe dengue, increase in efficacy with doses for naïve subjects and by a more important waning of vaccine protection for subjects when naïve than when pre-exposed. Over 20 years, the median reduction of dengue risk induced by the direct protection conferred by the vaccine ranged from 24% to 47% according to country for the first scenario and from 34% to 54% for the second.
Conclusion:
Our study is an important first step in deriving a general framework that combines disease dynamics and mechanisms of vaccine protection that could be used to assess the impact of vaccination at a population level.
... Currently, the disease is endemic in more than 100 countries, and is spreading throughout the world. Dengue disease is caused by four antigenically related distinct serotypes, namely, dengue virus (DENV)-1, DENV-2, DENV-3 and in which only DENV-2 and DENV-3 are mostly found in tropical countries [2,3]. The distinctions among the serotypes are based on their antigenicity and immunogenic property in the human body. ...
ability to induce specific antibodies, and to investigate specific antibody produced by specific
dengue virus (DENV) serotypes.
Methods: Amino acid sequences of E and NS proteins of dengue serotypes were analysed
by using VaxiJen antigen predicition server. The transmembrane of topology analyses using
transmembrane prediction using hidden markov models. The Hex dock server was used for
docking.
Results: The antigenicity score and exomembrane potentiality of E and NS proteins were
calculated. All those proteins were antigenic; these antigens were made to interact with
antibodies such as immunoglobulin A, immunoglobulin G and immunoglobulin M. Higher
energy values of immunoglobulin M were found in DENV-1 and DENV-2, and more energy
values were found in immunoglobulin G of DENV-3, DENV-4, NS-1, NS-3 and NS-5.
Conclusions: In the present study, DENV-1 and DENV-2 are positive to immunoglobulin M and
involved in the primary infection. DENV 3, DENV 4 and all the NS proteins (NS-1, NS-3, NS-5)
which elicit immunoglobulin G are involved in the secondary infection
... Research into the development of dengue vaccines has produced various candidates in phase II and I clinical trials. In 2012, Sanofi-Pasteur developed the only vaccine candidate in phase III clinical trials (Simmons et al. 2012); however, because of some particularities of the virus, the search for an effective dengue vaccine is still a challenge. The exposure to just one serotype will cause only minor illness, but the subsequent exposure to a second dengue serotype will increase the probability of the illness progressing to the severe and sometimes fatal dengue hemorrhagic fever. ...
Citation: Marques AM, Kaplan MAC (2015) Active metabolites of the genus Piper against Aedes aegypti: natural alternative sources for dengue vector control. Universitas Scientiarum 20(Abstract The mosquito, Aedes aegypti, is the principal vector of the viruses responsible for dengue and dengue hemorrhagic fevers. The mosquito is widespread throughout tropical and sub-tropical regions; its prevalence makes dengue one of the most important mosquito-borne viral diseases in the world occurring annually in more than 100 endemic countries. Because blood is essential to their development cycle, the Aedes species maintains a close association with humans and their dwellings. Fittingly, the most widely adopted strategy to decrease the incidence of these diseases is the control of the mosquito larvae population. The emergence of insecticide-resistant mosquitoes has amplified the interest in finding natural products effective against Aedes aegypti adults, as well as larvae. Plant-derived compounds have played an important role in the discovery of new active entities for vector management as they are safer and have lower toxicity to humans in comparison to conventional insecticides. This review assesses a naturally occurring plant matrix and pure compounds of the Piper species, which have been shown to be active against Aedes aegypti.
... For that to happen, universal accessibility, as an important concern, must be a high priority in research and action agendas. Recent news about the development and clinical trials of a safe and effective vaccine against dengue are encouraging [26,27]. Yet, once again, some crucial issues are still pending. ...
Infectious diseases of poverty, also labeled tropical diseases or neglected tropical diseases (NTDs) and caused by pathogenic agents (viruses, bacteria, fungi, and other parasites), are viciously more prevalent among poor people. Though being preventable for the most part in a cost-effective way, they are devastating. These are, to name a few, Chagas disease, schistosomiasis, malaria, leprosy, visceral leishmaniasis, lymphatic filariasis, Buruli ulcer, and onchocerciasis. Besides the vicious circle these diseases maintain with dire conditions of poverty, an increased microbial resistance to some therapeutic drugs adds to the complexity of health disparities and human suffering among the socially disadvantaged, marginalized, and prejudiced against. Fostering virtuous circles (as opposed to vicious circles) against infections of poverty and putting the disenfranchised first are primary concerns for social scientists engaged with research into infectious diseases of poverty. The historical role of social science research into these diseases, its current impacts, substantial contributions, and opportunities and interests for future endeavors are the focus of this article. Persistent disruptions and their propensity to wholly hamper productivity, derail economic and social progress, and deny child development are part of the complex reality to look into. In forcing the displacement of populations and creating chaos, they increase the risk for the spread of infections and maintain the infected poor in a downward spiral of poverty through their capacity of securing the vicious relationship with NTDs. Rather than compassion for inequalities, vulnerabilities, deprivations and misery, or bad fate, foci such as social justice, preparedness, and empowerment are of utmost importance. The case for bridging the divide among scientific disciplines has been strongly made over the years by scholars and outside of academic institutions. Acknowledging the importance of interdisciplinary science and contemplating the need for funded multidisciplinary research is hopeful for broadening the expertise needed to tackle these multidimensional afflictions. However, it should also call for a cautious enthusiasm.
Objectives
Dengue virus surface proteins are often used in the development of vaccines that protect against dengue virus infection. However, the surface proteins on the four serotypes of dengue virus display high variation, which increases the difficulty of developing a vaccine that can protect against all viral strains. In this study, a polytope that is recognized by broadly neutralizing antibodies (bnAbs) was designed using conserved epitopes from the four serotypes.
Methods
We constructed a polytope using four conserved dengue virus epitopes such that two aligned epitopes were separated from the other two epitopes by a histidyl-tRNA synthetase spacer. The epitopes were selected based on our previous docking studies. We then performed molecular docking of the polytope with the four bnAbs.
Results
The polytope bound precisely to the four bnAbs—B7, C8, A11, and C10. Moreover, the polytope had a higher affinity for the bnAbs compared to the DENV2 antigen. The polytope and A11 antibody complex had the lowest binding energy relative to complexes between the polytope and the other three antibodies assessed. The highest total number of hydrogen bonds was found in the polytope and B7 antibody complex. The hydrogen bond length in all the complexes ranged from 2.07 to 3.03 Å, implying that hydrogen bonds stabilized the complexes.
Conclusion
The developed polytope interacted with four different bnAbs that recognize the four serotypes of dengue virus. The results of this study suggest that this polytope warrants further development for use in a broad-spectrum vaccine against dengue virus.
