scholarly journals Two Complex, Adenovirus-Based Vaccines That Together Induce Immune Responses to All Four Dengue Virus Serotypes

2006 ◽  
Vol 14 (2) ◽  
pp. 182-189 ◽  
Author(s):  
David H. Holman ◽  
Danher Wang ◽  
Kanakatte Raviprakash ◽  
Nicholas U. Raja ◽  
Min Luo ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Vaccine Development ◽  
De Novo ◽  
Natural Infection ◽  
Hemorrhagic Fever ◽  
Virus Infections ◽  
Dengue Vaccine ◽  
Membrane Antigens ◽  
Dengue Virus Serotypes

ABSTRACT Dengue virus infections can cause hemorrhagic fever, shock, encephalitis, and even death. Worldwide, approximately 2.5 billion people live in dengue-infested regions with about 100 million new cases each year, although many of these infections are believed to be silent. There are four antigenically distinct serotypes of dengue virus; thus, immunity from one serotype will not cross-protect from infection with the other three. The difficulties that hamper vaccine development include requirements of the natural conformation of the envelope glycoprotein to induce neutralizing immune responses and the necessity of presenting antigens of all four serotypes. Currently, the only way to meet these requirements is to use a mixture of four serotypes of live attenuated dengue viruses, but safety remains a major problem. In this study, we have developed the basis for a tetravalent dengue vaccine using a novel complex adenovirus platform that is capable of expressing multiple antigens de novo. This dengue vaccine is constructed as a pair of vectors that each expresses the premembrane and envelope genes of two different dengue virus serotypes. Upon vaccination, the vaccine expressed high levels of the dengue virus antigens in cells to mimic a natural infection and induced both humoral and cellular immune responses against multiple serotypes of dengue virus in an animal model. Further analyses show the humoral responses were indeed neutralizing against all four serotypes. Our studies demonstrate the concept of mimicking infections to induce immune responses by synthesizing dengue virus membrane antigens de novo and the feasibility of developing an effective tetravalent dengue vaccine by vector-mediated expression of glycoproteins of the four serotypes.

scholarly journals Dengue Vaccine Development at the Dengue virus serotypes

2019 ◽  
Vol 1 (1) ◽  
pp. 9-15
Author(s):  
Adinda Desi Irawati ◽  
Hotimah Masdan Salim
Keyword(s):  
Dengue Virus ◽  
Vaccine Development ◽  
Hemorrhagic Fever ◽  
Severe Dengue ◽  
Vaccine Recombinant ◽  
Dengue Vaccine ◽  
Live Attenuated Vaccine ◽  
Virus Particles ◽  
Dengue Virus Serotypes ◽  
Official Data

Dengue hemorrhagic fever (DHF) is a disease caused by dengue virus (DENV1-4) and is transmitted by the Aedes aegypti mosquito. However, in 2015, official data from the member countries, WHO reported more than 3.2 million cases, including 10,200 severe dengue cases and 1181 deaths. The protein encoded by the genome of dengue virus. Major structural and non structural proteins making up the genome of dengue. From genomic data several studies found that mechanism of vaccine that can use in dengue virus. Several vaccines was establish in the world for example Live attenuated Vaccine, Chimera Vaccine, Subunit Vaccine, DNA vaccines DENV, Activated DENV Vaccine  - Whole Virus Particles, Activated  DENV Vaccine - Recombinant Subunit DENV, and DENV Vaccine 5.

scholarly journals A Tetravalent Dengue Vaccine Based on a Complex Adenovirus Vector Provides Significant Protection in Rhesus Monkeys against All Four Serotypes of Dengue Virus

2008 ◽  
Vol 82 (14) ◽  
pp. 6927-6934 ◽  
Author(s):  
Kanakatte Raviprakash ◽  
Danher Wang ◽  
Dan Ewing ◽  
David H. Holman ◽  
Karla Block ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dengue Virus ◽  
Rhesus Macaques ◽  
High Titer ◽  
Adenovirus Vector ◽  
Significant Protection ◽  
Dengue Vaccine ◽  
Live Virus ◽  
Dengue Viruses ◽  
Dengue Virus Serotypes

ABSTRACT Nearly a third of the human population is at risk of infection with the four serotypes of dengue viruses, and it is estimated that more than 100 million infections occur each year. A licensed vaccine for dengue viruses has become a global health priority. A major challenge to developing a dengue vaccine is the necessity to produce fairly uniform protective immune responses to all four dengue virus serotypes. We have developed two bivalent dengue virus vaccines, using a complex adenovirus vector, by incorporating the genes expressing premembrane (prM) and envelope (E) proteins of dengue virus types 1 and 2 (dengue-1 and -2, respectively) (CAdVax-Den12) or dengue-3 and -4 (CAdVax-Den34). Rhesus macaques were vaccinated by intramuscular inoculation of a tetravalent dengue vaccine formulated by combining the two bivalent vaccine constructs. Vaccinated animals produced high-titer antibodies that neutralized all four serotypes of dengue viruses in vitro. The ability of the vaccine to induce rapid, as well as sustained, protective immune responses was examined with two separate live-virus challenges administered at 4 and 24 weeks after the final vaccination. For both of these virus challenge studies, significant protection from viremia was demonstrated for all four dengue virus serotypes in vaccinated animals. Viremia from dengue-1 and dengue-3 challenges was completely blocked, whereas viremia from dengue-2 and dengue-4 was significantly reduced, as well as delayed, compared to that of control-vaccinated animals. These results demonstrate that the tetravalent dengue vaccine formulation provides significant protection in rhesus macaques against challenge with all four dengue virus serotypes.

scholarly journals Dengue Fever: Causes, Complications, and Vaccine Strategies

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Niyati Khetarpal ◽  
Ira Khanna
Keyword(s):  
Dengue Virus ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Hemorrhagic Fever ◽  
Dengue Vaccine ◽  
Dengue Disease ◽  
The Public ◽  
Limited Application ◽  
Demographic Distribution ◽  
The Impact

Dengue is a highly endemic infectious disease of the tropical countries and is rapidly becoming a global burden. It is caused by any of the 4 serotypes of dengue virus and is transmitted within humans through femaleAedesmosquitoes. Dengue disease varies from mild fever to severe conditions of dengue hemorrhagic fever and shock syndrome. Globalization, increased air travel, and unplanned urbanization have led to increase in the rate of infection and helped dengue to expand its geographic and demographic distribution. Dengue vaccine development has been a challenging task due to the existence of four antigenically distinct dengue virus serotypes, each capable of eliciting cross-reactive and disease-enhancing antibody response against the remaining three serotypes. Recently, Sanofi Pasteur’s chimeric live-attenuated dengue vaccine candidate has been approved in Mexico, Brazil, and Philippines for usage in adults between 9 and 45 years of age. The impact of its limited application to the public health system needs to be evaluated. Simultaneously, the restricted application of this vaccine candidate warrants continued efforts in developing a dengue vaccine candidate which is additionally efficacious for infants and naïve individuals. In this context, alternative strategies of developing a designed vaccine candidate which does not allow production of enhancing antibodies should be explored, as it may expand the umbrella of efficacy to include infants and naïve individuals.

scholarly journals Analysis of cell-mediated immune responses in support of dengue vaccine development efforts

Vaccine ◽  
2015 ◽  
Vol 33 (50) ◽  
pp. 7083-7090 ◽  
Author(s):  
Alan L. Rothman ◽  
Jeffrey R. Currier ◽  
Heather L. Friberg ◽  
Anuja Mathew
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Dengue Vaccine

scholarly journals Overview of Plant-Derived Vaccine Antigens: Dengue Virus

2011 ◽  
Vol 14 (3) ◽  
pp. 400 ◽  
Author(s):  
Ravindra B Malabadi ◽  
Advaita Ganguly ◽  
Jaime A Teixeira da Silva ◽  
Archana Parashar ◽  
Mavanur R Suresh ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Low Cost ◽  
Current Status ◽  
Human Immune Deficiency Virus ◽  
Dengue Vaccine ◽  
New Methods ◽  
Vaccine Antigens

ABSTRACT - This review highlights the advantages and current status of plant-derived vaccine development with special reference to the dengue virus. There are numerous problems involved in dengue vaccine development, and there is no vaccine against all four dengue serotypes. Dengue vaccine development using traditional approaches has not been satisfactory in terms of inducing neutralizing antibodies. Recently, these issues were addressed by showing a very good response to inducing neutralizing antibodies by plant-derived dengue vaccine antigens. This indicates the feasibility of using plant-derived vaccine antigens as a low-cost method to combat dengue and other infectious diseases. The application of new methods and strategies such as dendritic cell targeting in cancer therapy, severe acute respiratory syndrome, tuberculosis, human immune deficiency virus, and malaria might play an important role. These new methods are more efficient than traditional protocols. It is expected that in the near future, plant-derived vaccine antigens or antibodies will play an important role in the control of human infectious diseases. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Characterization of dengue virus infections in a sample of patients suggests unique clinical, immunological, and virological profiles that impact on the diagnosis of dengue and dengue hemorrhagic fever

2016 ◽  
Vol 88 (10) ◽  
pp. 1703-1710 ◽  
Author(s):  
Thamarasi Senaratne ◽  
Harith Wimalaratne ◽  
D. G. S. Alahakoon ◽  
Nirmali Gunawardane ◽  
Jillian Carr ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Dengue Hemorrhagic Fever ◽  
Hemorrhagic Fever ◽  
Virus Infections

scholarly journals Sustained Specific and Cross-Reactive T Cell Responses to Zika and Dengue Virus NS3 in West Africa

2018 ◽  
Vol 92 (7) ◽  
Author(s):  
Bobby Brooke Herrera ◽  
Wen-Yang Tsai ◽  
Charlotte A. Chang ◽  
Donald J. Hamel ◽  
Wei-Kung Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Dengue Virus ◽  
Zika Virus ◽  
Cell Response ◽  
Vaccine Development ◽  
T Cell Responses ◽  
T Cell Response ◽  
Zikv Infection ◽  
Cell Responses

ABSTRACT Recent studies on the role of T cells in Zika virus (ZIKV) infection have shown that T cell responses to Asian ZIKV infection are important for protection, and that previous dengue virus (DENV) exposure amplifies the protective T cell response to Asian ZIKV. Human T cell responses to African ZIKV infection, however, remain unexplored. Here, we utilized the modified anthrax toxin delivery system to develop a flavivirus enzyme-linked immunosorbent spot (ELISPOT) assay. Using human ZIKV and DENV samples from Senegal, West Africa, our results demonstrate specific and cross-reactive T cell responses to nonstructural protein 3 (NS3). Specifically, we found that T cell responses to NS3 protease are ZIKV and DENV specific, but responses to NS3 helicase are cross-reactive. Sequential sample analyses revealed immune responses sustained many years after infection. These results have important implications for African ZIKV/DENV vaccine development, as well as for potential flavivirus diagnostics based on T cell responses. IMPORTANCE The recent Zika virus (ZIKV) epidemic in Latin America and the associated congenital microcephaly and Guillain-Barré syndrome have raised questions as to why we have not recognized these distinct clinical diseases in Africa. The human immunologic response to ZIKV and related flaviviruses in Africa represents a research gap that may shed light on the mechanisms contributing to protection. The goal of our study was to develop an inexpensive assay to detect and characterize the T cell response to African ZIKV and DENV. Our data show long-term specific and cross-reactive human immune responses against African ZIKV and DENV, suggesting the usefulness of a diagnostic based on the T cell response. Additionally, we show that prior flavivirus exposure influences the magnitude of the T cell response. The identification of immune responses to African ZIKV and DENV is of relevance to vaccine development.

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