Top Down Computational Approach: A Vaccine Development Step to Find Novel Superantigenic HLA Binding Epitopes from Dengue Virus Proteome

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.

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

Clinical and Vaccine Immunology ◽

10.1128/cvi.00330-06 ◽

2006 ◽

Vol 14 (2) ◽

pp. 182-189 ◽

Cited By ~ 32

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.

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Epitopes based drug design for dengue virus envelope protein: A computational approach

Computational Biology and Chemistry ◽

10.1016/j.compbiolchem.2017.10.008 ◽

2017 ◽

Vol 71 ◽

pp. 152-160 ◽

Cited By ~ 12

Author(s):

Abdul Wadood ◽

Aamir Mehmood ◽

Huma Khan ◽

Muhammad Ilyas ◽

Ayaz Ahmad ◽

...

Keyword(s):

Drug Design ◽

Dengue Virus ◽

Envelope Protein ◽

Protein A ◽

Computational Approach ◽

Virus Envelope ◽

Virus Envelope Protein

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Vertically transmitted chikungunya, Zika and dengue virus infections: The pathogenesis from mother to fetus and the implications of co-infections and vaccine development

International Journal of Pediatrics and Adolescent Medicine ◽

10.1016/j.ijpam.2019.05.004 ◽

2020 ◽

Vol 7 (3) ◽

pp. 107-111

Author(s):

Tracy Evans-Gilbert

Keyword(s):

Dengue Virus ◽

Vaccine Development ◽

Virus Infections

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

Journal of Virology ◽

10.1128/jvi.01992-17 ◽

2018 ◽

Vol 92 (7) ◽

Cited By ~ 16

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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Dengue Virus Vaccine Development

Advances in Virus Research ◽

10.1016/b978-0-12-800098-4.00007-6 ◽

2014 ◽

pp. 315-372 ◽

Cited By ~ 43

Author(s):

Lauren E. Yauch ◽

Sujan Shresta

Keyword(s):

Dengue Virus ◽

Virus Vaccine ◽

Vaccine Development

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Enhanced Prokaryotic Expression of Dengue Virus Envelope Protein

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3pc80 ◽

2013 ◽

Vol 16 (4) ◽

pp. 609 ◽

Cited By ~ 5

Author(s):

Advaita Ganguly ◽

Ravindra B. Malabadi ◽

Dipankar Das ◽

Mavanur R. Suresh ◽

Hoon H Sunwoo

Keyword(s):

Dengue Virus ◽

Envelope Protein ◽

Vaccine Development ◽

Virus Envelope ◽

E Coli ◽

C Terminus ◽

Virus Envelope Protein ◽

Biological Functionality ◽

Dengue Diagnostics

Purpose. To highlight the expression and purification of the recombinant dengue virus type-1 antigen exploiting the codon optimized full length envelope for increased yield in E. coli. Methods. A 6x His tag was inserted at the C terminus to facilitate purification. The purified protein was recognized in Western blot by Monoclonal antibody specific for the tag. The in vitro refolded recombinant protein was used to immunize mice for the development of hybridomas and also analyzed for its biological functionality with heparan sulfate binding assay. Results. The polyclonal anti-sera from the immunized mice were found to recognize the envelope protein thereby establishing the immunogenicity of the protein. Conclusion. The purified envelope protein could potentially be used towards dengue diagnostics and vaccine development efforts. 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.

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Genotypic Differences in Dengue Virus Neutralization Are Explained by a Single Amino Acid Mutation That Modulates Virus Breathing

mBio ◽

10.1128/mbio.01559-15 ◽

2015 ◽

Vol 6 (6) ◽

Cited By ~ 35

Author(s):

Kimberly A. Dowd ◽

Christina R. DeMaso ◽

Theodore C. Pierson

Keyword(s):

Amino Acid ◽

Dengue Virus ◽

Vaccine Development ◽

Antibody Binding ◽

Single Amino Acid ◽

Genotypic Differences ◽

Conformational Ensembles ◽

Single Amino Acid Residue ◽

Virus Serotype ◽

Serotype 1

ABSTRACTFlaviviruses sample an ensemble of virion conformations resulting from the conformational flexibility of their structural proteins. To investigate how sequence variation among strains impacts virus breathing, we performed studies with the monoclonal antibody (MAb) E111, which binds an inaccessible domain III envelope (E) protein epitope of dengue virus serotype 1 (DENV1). Prior studies indicated that an observed ~200-fold difference in neutralization between the DENV1 strains Western Pacific-74 (West Pac-74) and 16007 could not be explained by differences in the affinity of MAb E111 for each strain. Through neutralization studies with wild-type and variant viruses carrying genes encoding reciprocal mutations at all 13 amino acid differences between the E proteins of West Pac-74 and 16007, we found that E111 neutralization susceptibility mapped solely to the presence of a lysine or arginine at E domain II residue 204, located distally from the E111 epitope. This same residue correlated with neutralization differences observed for MAbs specific for epitopes distinct from E111, suggesting that this amino acid dictates changes in the conformational ensembles sampled by the virus. Furthermore, an observed twofold difference in the stability of infectious West Pac-74 versus 16007 in solution also mapped to E residue 204. Our results demonstrate that neutralization susceptibility can be altered in an epitope-independent manner by natural strain variation that influences the structures sampled by DENV. That different conformational ensembles of flaviviruses may affect the landscape available for antibody binding, as well as virus stability, has important implications for functional studies of antibody potency, a critical aspect of vaccine development.IMPORTANCEThe global burden of dengue virus (DENV) is growing, with recent estimates of ~390 million human infections each year. Antibodies play a crucial role in protection from DENV infection, and vaccines that elicit a robust antibody response are being actively pursued. We report here the identification of a single amino acid residue in the envelope protein of DENV serotype 1 that results in global changes to virus structure and stability when it is changed. Our results indicate that naturally occurring variation at this particular site among virus strains impacts the ensemble of structures sampled by the virus, a process referred to as virus breathing. The finding that such limited and conservative sequence changes can modulate the landscape available for antibody binding has important implications for both vaccine development and the study of DENV-reactive antibodies.

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