Non-Human Primate Models of Dengue Virus Infection: A Comparison of Viremia Levels and Antibody Responses during Primary and Secondary Infection among Old World and New World Monkeys

Due to the global burden of dengue disease, a vaccine is urgently needed. One of the key points in vaccine development is the development of a robust and reliable animal model of dengue virus infection. Characteristics including the ability to sustain viral replication, demonstration of clinical signs, and immune response that resemble those of human dengue virus infection are vital in animal models. Preclinical studies in vaccine development usually include parameters such as safety evaluation, induction of viremia and antigenemia, immunogenicity, and vaccine effectiveness. Although mice have been used as a model, non-human primates have an advantage over mice because of their relative similarity to humans in their genetic composition and immune responses. This review compares the viremia kinetics and antibody responses of cynomolgus macaques (Macaca fasicularis), common marmosets (Callithrix jacchus), and tamarins (Saguinus midas and Saguinus labitus) and summarize the perspectives and the usefulness along with challenges in dengue vaccine development.

Download Full-text

Imunocompetent Mice Model for Dengue Virus Infection

The Scientific World JOURNAL ◽

10.1100/2012/525947 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Denise Gonçalves ◽

Rafael de Queiroz Prado ◽

Eric Almeida Xavier ◽

Natália Cristina de Oliveira ◽

Paulo Marcos da Matta Guedes ◽

...

Keyword(s):

Animal Model ◽

Virus Infection ◽

Dengue Virus ◽

Viral Disease ◽

Mice Model ◽

Rt Pcr ◽

Dengue Virus Infection ◽

Dengue Disease ◽

The Family ◽

The World

Dengue fever is a noncontagious infectious disease caused by dengue virus (DENV). DENV belongs to the familyFlaviviridae, genusFlavivirus, and is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis. In our study, we have found that immunocompetent C57BL/6 mice infected intraperitoneally with DENV-1 presented some signs of dengue disease such as thrombocytopenia, spleen hemorrhage, liver damage, and increase in production of IFNγand TNFαcytokines. Moreover, the animals became viremic and the virus was detected in several organs by real-time RT-PCR. Thus, this animal model could be used to study mechanism of dengue virus infection, to test antiviral drugs, as well as to evaluate candidate vaccines.

Download Full-text

Immunoglobulin A Antibody Responses in Dengue Patients: a Useful Marker for Serodiagnosis of Dengue Virus Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.10.1235-1237.2005 ◽

2005 ◽

Vol 12 (10) ◽

pp. 1235-1237 ◽

Cited By ~ 14

Author(s):

M. Nawa ◽

T. Takasaki ◽

M. Ito ◽

S. Inoue ◽

K. Morita ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Immunoglobulin A ◽

Antibody Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Virus Infections ◽

Serum Samples ◽

Dengue Virus Infection ◽

Iga Antibody ◽

Antibody Capture

ABSTRACT We determined the usefulness of an immunoglobulin A (IgA) antibody-capture enzyme-linked immunosorbent assay for serodiagnosis of dengue virus infections. The results indicate that the presence of IgA and IgM in serum samples assures recent primary dengue virus infection even with a single serum sample.

Download Full-text

Roles for Endothelial Cells in Dengue Virus Infection

Advances in Virology ◽

10.1155/2012/840654 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 30

Author(s):

Nadine A. Dalrymple ◽

Erich R. Mackow

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Capillary Permeability ◽

Virus Disease ◽

Dengue Shock Syndrome ◽

Hemorrhagic Fever ◽

Dengue Virus Infection ◽

Barrier Functions ◽

Dengue Disease ◽

Primary Fluid

Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC) barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease.

Download Full-text

Protective Capacity of the Human Anamnestic Antibody Response during Acute Dengue Virus Infection

Journal of Virology ◽

10.1128/jvi.01096-16 ◽

2016 ◽

Vol 90 (24) ◽

pp. 11122-11131 ◽

Cited By ~ 9

Author(s):

Meihui Xu ◽

Roland Züst ◽

Ying Xiu Toh ◽

Jennifer M. Pfaff ◽

Kristen M. Kahle ◽

...

Keyword(s):

Virus Infection ◽

Antibody Response ◽

Dengue Virus ◽

Secondary Infection ◽

Immune Memory ◽

Protective Capacity ◽

Dengue Virus Infection ◽

Immune Correlates

ABSTRACT Half of the world's population is exposed to the risk of dengue virus infection. Although a vaccine for dengue virus is now available in a few countries, its reported overall efficacy of about 60% is not ideal. Protective immune correlates following natural dengue virus infection remain undefined, which makes it difficult to predict the efficacy of new vaccines. In this study, we address the protective capacity of dengue virus-specific antibodies that are produced by plasmablasts a few days after natural secondary infection. Among a panel of 18 dengue virus-reactive human monoclonal antibodies, four groups of antibodies were identified based on their binding properties. While antibodies targeting the fusion loop of the glycoprotein of dengue virus dominated the antibody response, two smaller groups of antibodies bound to previously undescribed epitopes in domain II of the E protein. The latter, largely serotype-cross-reactive antibodies, demonstrated increased stability of binding at pH 5. These antibodies possessed weak to moderate neutralization capacity in vitro but were the most efficacious in promoting the survival of infected mice. Our data suggest that the cross-reactive anamnestic antibody response has a protective capacity despite moderate neutralization in vitro and a moderate decrease of viremia in vivo . IMPORTANCE Antibodies can protect from symptomatic dengue virus infection. However, it is not easy to assess which classes of antibodies provide protection because in vitro assays are not always predictive of in vivo protection. During a repeat infection, dengue virus-specific immune memory cells are reactivated and large amounts of antibodies are produced. By studying antibodies cloned from patients with heterologous secondary infection, we tested the protective value of the serotype-cross-reactive “recall” or “anamnestic” response. We found that results from in vitro neutralization assays did not always correlate with the ability of the antibodies to reduce viremia in a mouse model. In addition, a decrease of viremia in mice did not necessarily improve survival. The most protective antibodies were stable at pH 5, suggesting that antibody binding in the endosomes, after the antibody-virus complex is internalized, might be important to block virus spread in the organism.

Download Full-text

Upaya Pencegahan dan Pengendalian Demam Berdarah Dengue dalam Bentuk Peta Tematik di Kecamatan Rappocini

bionature ◽

10.35580/bionature.v19i2.9724 ◽

2019 ◽

Vol 19 (2) ◽

Author(s):

Suci Wulandhani ◽

A. Bida Purnamasari ◽

Ryan Humardani Syam Pratomo

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Hemorrhagic Fever ◽

Viral Disease ◽

High Rate ◽

Dengue Virus Infection ◽

Dengue Disease ◽

Keywords Prevention ◽

Short Time ◽

And Control

Abstract. Dengue hemorrhagic fever (DHF) is a disease caused by dengue virus infection. One symptom of dengue virus infection is high fever and headache. Dengue virus is a virus from the genus Flavivirus, family of Flaviviridae. This dengue fever is a dangerous viral disease because it can cause sufferers to die in a very short time / several days. The existence and population density are often associated with transmission, endemicity and Extraordinary Events (EE) of DHF. Disease mapping by utilizing digital technology to support epidemiological investigations and also as a tool to monitor regional conditions for dengue disease. The purpose of this study was to determine efforts to prevent and control dengue disease by mapping. The results of the study show that mapping can be seen as increasing and decreasing the number of cases of dengue disease so that it can assist in data management and reporting of information to monitor areas at risk of contracting dengue disease. Suggestions given need to do further research using other variables that are the cause of the high rate of dengue cases, so that it can be utilized by related agencies as the basis of the information system supporting the decision on preventive measures to combat dengue. Keywords: prevention and control, DHF, mapping.

Download Full-text

Clinical Evaluation of a Rapid Immunochromatographic Test for the Diagnosis of Dengue Virus Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.5.3.407-409.1998 ◽

1998 ◽

Vol 5 (3) ◽

pp. 407-409 ◽

Cited By ~ 20

Author(s):

Chew Theng Sang ◽

Lim Siew Hoon ◽

Andrea Cuzzubbo ◽

Peter Devine

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Secondary Infection ◽

Rapid Test ◽

Immunoglobulin M ◽

Immunochromatographic Test ◽

Dengue Virus Infection ◽

Hemagglutination Inhibition Assay ◽

Specific Immunoglobulin ◽

Paired Serum

ABSTRACT A rapid immunochromatographic test was compared to the hemagglutination inhibition assay for separate determinations of dengue virus-specific immunoglobulin M (IgM) and IgG levels in paired serum specimens from 92 patients (34 with primary dengue virus infection, 35 with secondary dengue virus infection, and 23 without dengue virus infection). The rapid test showed 99% sensitivity in the diagnosis of dengue virus infection. The majority (30 of 34 [88%]) of patients with primary infection showed positive IgM but negative IgG, while 34 of 35 (97%) patients with secondary infection showed positive IgG with or without IgM. Specificity in nonflavivirus infections was 96% (1 of 23 positive). The rapid test should be a useful aid in rapid diagnosis of dengue virus infection.

Download Full-text

Adaptive Immunity to Dengue Virus: Slippery Slope or Solid Ground for Rational Vaccine Design?

Pathogens ◽

10.3390/pathogens9060470 ◽

2020 ◽

Vol 9 (6) ◽

pp. 470 ◽

Cited By ~ 1

Author(s):

Lucas Wilken ◽

Guus F. Rimmelzwaan

Keyword(s):

Dengue Virus ◽

Vaccine Development ◽

Secondary Infection ◽

Severe Disease ◽

Structural Protein ◽

Dengue Vaccine ◽

Dengue Disease ◽

Generation Vaccine ◽

Virus Serotype ◽

Rational Vaccine Design

The four serotypes of dengue virus are the most widespread causes of arboviral disease, currently placing half of the human population at risk of infection. Pre-existing immunity to one dengue virus serotype can predispose to severe disease following secondary infection with a different serotype. The phenomenon of immune enhancement has complicated vaccine development and likely explains the poor long-term safety profile of a recently licenced dengue vaccine. Therefore, alternative vaccine strategies should be considered. This review summarises studies dissecting the adaptive immune responses to dengue virus infection and (experimental) vaccination. In particular, we discuss the roles of (i) neutralising antibodies, (ii) antibodies to non-structural protein 1, and (iii) T cells in protection and pathogenesis. We also address how these findings could translate into next-generation vaccine approaches that mitigate the risk of enhanced dengue disease. Finally, we argue that the development of a safe and efficacious dengue vaccine is an attainable goal.

Download Full-text

FEVER AS INDICATOR TO SECONDARY INFECTION IN DENGUE VIRAL INFECTION

Indonesian Journal of Tropical and Infectious Disease ◽

10.20473/ijtid.v7i1.5640 ◽

2018 ◽

Vol 7 (1) ◽

pp. 21

Author(s):

Soegeng Soegijanto ◽

Sufiandika Nuryandari ◽

Siti Churrotin ◽

Teguh Hari Sucipto

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Viral Infection ◽

Dengue Fever ◽

Clinical Manifestation ◽

Secondary Infection ◽

Salmonella Typhi ◽

Severe Dengue ◽

Concurrent Infection ◽

Dengue Virus Infection

Dengue Virus Infections are distributed in tropical and sub-tropical regions and transmitted by the mosquitoes such as Aedes aegypti and Aedes albopictus. Dengue virus can cause dengue fever, dengue hemorrhagic fever and dengue shock syndrome or dengue and severe dengue classified by World Health Organization. Beside it concurrent infection virus salmonella had been found some cases who showed fever more than 7 days. Concurrent infection with two agents can result in an illness having overlapping symptoms creating a diagnostic dilemma for treating physician, such as dengue fever with typhoid fever. The aim of this research is detection of dengue virus and secondary infection with Salmonella typhi in patients suspected dengue virus infection. Detection of dengue virus and Salmonella typhi using immunochromatography test such as NS1, IgG/IgM for dengue virus infection, and IgM/IgG Salmonella and blood culture. The fifty children with dengue virus infection came to Soerya hospital and 17 cases suspected dengue virus infection, five cases showed a positive NS1 on the second day of fever and one case concurrent with clinical manifestation of convulsi on the third days of fever there were five cases only showed positive. It was showed in this study that on the fourth to six day of fever in dengue virus infection accompanied by antibody IgM & IgG dengue. There were 12 cases showed the clinical manifestation of concurrent dengue viral infection and Salmonella, all of them showed a mild clinical manifestation and did not show plasma leakage and shock. In this study we found the length of stay of concurrent Dengue Virus Infection and Salmonella infection is more than 10 days. These patients were also more likely to have co-existing haemodynamic disturbances and bacterial septicaemia which would have required treatment with inotropes and antibiotics. This idea is very important to make update dengue viral management to decrease mortality in outbreak try to gain new prevention method before the occurrence of outbreak.

Download Full-text

Manifestation of thrombocytopenia in dengue-2-virus-infected mice

Journal of General Virology ◽

10.1099/0022-1317-81-9-2177 ◽

2000 ◽

Vol 81 (9) ◽

pp. 2177-2182 ◽

Cited By ~ 84

Author(s):

Kao-Jean Huang ◽

Shu-Yi J. Li ◽

Shiour-Ching Chen ◽

Hsiao-Sheng Liu ◽

Yee-Shin Lin ◽

...

Keyword(s):

Virus Infection ◽

Dengue Virus ◽

Secondary Infection ◽

Clinical Manifestations ◽

Dengue Shock Syndrome ◽

Dengue Virus Infection ◽

Platelet Antibody

Dengue virus infection causes dengue fever, dengue haemorrhagic fever and dengue shock syndrome. No animal model is available that mimics these clinical manifestations. In this study, the establishment is reported of a murine model for dengue virus infection that resembles the thrombocytopenia manifestation. Dengue-2 virus (dengue virus type 2) can infect murine cells either in vitro (primary cell culture) or in vivo. Viraemia detected by RT–PCR was found transiently at 2 days after intravenous injection of dengue-2 virus. Transient thrombocytopenia developed at 10–13 days after primary or secondary infection. Anti-platelet antibody was generated after dengue-2 virus infection. There was strain variation in dengue-2 virus infection; the A/J strain was more sensitive than BALB/c or B6 mice. This dengue-2-virus-infected mouse system accompanied by thrombocytopenia and anti-platelet antibody will be a valuable model to study the pathogenicity of dengue virus infection.

Download Full-text