Development of a novel DNA SynCon™ tetravalent dengue vaccine that elicits immune responses against four serotypes

Ramanathan, Mathura P.; Kuo, Yuan-Chia; Selling, Bernard; Li, Qianjun; Sardesai, Niranjan Y.; Kim, J. Joseph; Weiner, David B.

doi:10.1016/j.vaccine.2009.06.061

Cited by 43 publications

(36 citation statements)

References 27 publications

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“…Although there are a number of studies describing DNA vaccines against dengue Azevedo et al, 2011;Galula et al, 2014;Khanam et al, 2006;Konishi et al, 2006;Ocazionez Jimenez & Lopes da Fonseca, 2000;Prompetchara et al, 2014;Ramanathan et al, 2009;Raviprakash et al, 2001Raviprakash et al, , 2006, to date there has been only one human clinical trial for a dengue DNA vaccine involving a Phase 1 study of a plasmid expressing the PrM and E proteins of DENV1 . In all cases, these vaccines have been proved to be safe and well-tolerated in humans, although low immunogenicity is still a concern associated with genetic vaccines in general (Coban et al, 2011;Danko et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Slon-Campos

Poggianella

Marchese

et al. 2015

Journal of General Virology

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Dengue virus (DENV) is currently among the most important human pathogens and affects millions of people throughout the tropical and subtropical regions of the world. Although it has been a World Health Organization priority for several years, there is still no efficient vaccine available to prevent infection. The envelope glycoprotein (E), exposed on the surface on infective viral particles, is the main target of neutralizing antibodies. For this reason it has been used as the antigen of choice for vaccine development efforts. Here we show a detailed analysis of factors involved in the expression, secretion and folding of E ectodomain from all four DENV serotypes in mammalian cells, and how this affects their ability to induce neutralizing antibody responses in DNA-vaccinated mice. Proper folding of E domain II (DII) is essential for efficient E ectodomain secretion, with DIII playing a significant role in stabilizing soluble dimers. We also show that the level of protein secreted from transfected cells determines the strength and efficiency of antibody responses in the context of DNA vaccination and should be considered a pivotal feature for the development of E-based DNA vaccines against DENV.

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Section: Discussionmentioning

confidence: 99%

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Slon-Campos

Poggianella

Marchese

et al. 2015

Journal of General Virology

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“…Dengue viruses that can be transmitted among humans by mosquitos (17), are popular throughout tropical areas of the world including China (18). For the high mortality and morbidity resulting from dengue infection, dengue has been a serious healthy concern (19).…”

Section: Discussionmentioning

confidence: 99%

“…The phenomenon of antibody dependent-enhancement (ADE) may be occur in VLPs-immunized mice, which is known as that different types of virus infection can increase the risk of development serious disease (17). The ADE activity of the monovalent and bivalent DENV VLPs was not assayed and this is a limitation in this paper.…”

Section: Discussionmentioning

confidence: 99%

Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

2015

Microbiology and Immunology

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We aimed to systematically analyze the immunological properties of monovalent and bivalent dengue virus-like particles (DENV VLPs) prepared in our study and provided basis for the development of DENV VLPs as a promising non-infectious candidate vaccine for dengue infection. The DENV-1/2 VLPs were prepared in the GAP promoter-based P.pastoris expression system using α-factor secretion signal. Groups of mice were immunized by monovalent and bivalent VLPs compared with inactivated virions and PBS. Then, the humoral immune response in mice were tested by ELISA, immunofluorescence and neutralization assay. ELISA and Enzyme linked immunospot assay were performed for investigating cytokines production after virus challenge in vivo and in vitro, respectively. Besides, the protection ability of VLPs was assessed by passive protection assay in suckling mice. The recombinant DENV-1/2 VLPs were successfully expressed with α-factor secretion signal. Sera of mice immunized with monovalent and bivalent VLPs elevated the specific antibodies level comparable to inactivated virions group. The monovalent and bivalent VLPs induced specific cellular immune response as confirmed by ELISPOT. The PRNT 50 titers of monovalent and bivalent VLPs sera against DENV-1/2 were different ranging from 16 to 64. Moreover, anti-monovalent and anti-bivalent DENV VLPs sera displayed protective capacity in survival rate and morbidity. Monovalent and bivalent VLPs showed attracting vaccine effect for dengue virus. The multivalent VLPs may be promising for preventing different types of dengue virus.

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“…In combined immunization, this advantage should overcome the dose quantity [81]. Although DNA vaccine are easy to manufacture and maintain however weak immunogenicity should be addressed.…”

Section: Discussionmentioning

confidence: 99%

Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

Atif

Raheel

Imran

et al. 2016

JHVRV

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Dengue virus infections are a major cause of mortality and morbidity in Southeast Asia, South and Central America with 24'000 deaths annually. Two factors are accountable for the severe outcomes of Dengue Hemorrhagic Fever (DHF); one is the virulence of the virus and second is the cross-reactivity of various dengue serotypes with the immune system of the host. Rapid rise in the levels of various cytokines, particularly Tumor Necrosis Factor-alpha (TNF-α), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interleukin-8 (IL-8) have a major role in inducing distinctive clinical presentations of DHF. These range from simple plasma leakage to hemorrhagic problems and even shock. Another hallmark of DHF is the presence of cross reactive primary antibodies which produce an intense immune response in secondary infection resulting in immune mediated pathology seen in DHF. There have been many attempts made in the past for the development of a suitable vaccine for dengue fever. Vaccination using plasmid DNA against dengue fever is an active area of research. In this review the role of different cells in the multiplication of dengue virus and viral interactions with the immune system have been discussed. Special emphasis is given to the nature of DNA vaccines in general developmental efforts of a dengue fever vaccine.

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Development of a novel DNA SynCon™ tetravalent dengue vaccine that elicits immune responses against four serotypes

Cited by 43 publications

References 27 publications

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Secretion of dengue virus envelope protein ectodomain from mammalian cells is dependent on domain II serotype and affects the immune response upon DNA vaccination

Retracted: Immunological properties reveal the monovalent and bivalent recombinant dengue virus‐like particles as candidate vaccine for dengue

Dengue Virus: Host-Pathogen Interactions and Emerging Role of DNA Vaccines

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