Evaluation of protective efficacy using a nonstructural protein NS1 in DNA vaccine&amp;ndash;loaded microspheres against dengue 2 virus

Huang, Shih-shiung; Li, I‐Hsun; Hong, Po‐Da; Yeh, Ming–Kung

doi:10.2147/ijn.s49972

Cited by 11 publications

(4 citation statements)

References 22 publications

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“…However, some experimental studies have shown that ZIKV and DENV prototype NS1 vaccines can prevent the development of lethal infections in experimental conditions, 20 , 46 , 47 possibly due to FcR-mediated complement activation or antibody-dependent, cell-mediated cytotoxicity (ADCC) induced by NS1-specific antibodies elicited by NS1 protein vaccines. 48 , 49 We observed that E80-mRNA+NS1-mRNA elicited a lower titer of NS1-specific antibody than NS1-mRNA did, probably due to antigenic competition between E80 and NS1 proteins, as reported in some studies. 50 , 51 Although the incorporation of NS1-mRNA did not significantly enhance the protective efficacy of the DENV-2 E80-mRNA vaccine in our study, it apparently reduced ADE response to DENV-2 and altered IgG subclass distribution.…”

Section: Discussionsupporting

confidence: 75%

Modified mRNA-LNP Vaccines Confer Protection against Experimental DENV-2 Infection in Mice

Zhang

Jin

et al. 2020

Molecular Therapy - Methods & Clinical Development

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Dengue virus (DENV) infection is a major global public health concern, and there is no effective vaccine for it. In this study, we describe the design and characterization of three nucleotide-modified mRNA vaccines (prME-mRNA, E80-mRNA, and NS1-mRNA) for DENV-2. Our results showed that vaccination with E80-mRNA alone or a combination of E80-mRNA and NS1-mRNA can induce high levels of neutralizing antibodies and antigen-specific T cell responses; furthermore, these vaccines confer complete protection against DENV-2 challenge in immunocompetent mice. These data provide foundations for further development of a tetravalent DENV vaccine based on nucleotide-modified mRNA.

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Section: Discussionsupporting

confidence: 75%

Modified mRNA-LNP Vaccines Confer Protection against Experimental DENV-2 Infection in Mice

Zhang

Jin

et al. 2020

Molecular Therapy - Methods & Clinical Development

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“…Another plasmid DNA vaccine encoding prM and E proteins of dengue virus 3 was utilized to immunize mice which produced neutralizing antibodies that protected mice against lethal challenge ( 72 ). Evaluation of another NS1 based DNA vaccine loaded on PLGA/PEG microspheres in BALB/c mice resulted in the greatest survival of mice upon challenge study ( 131 ). In yet another approach, a DNA vaccine construct containing prM and E genes of dengue virus 4 was generated using a mammalian expression plasmid (pCI).…”

Section: Dna Vaccine Candidates For Dengue Virusmentioning

confidence: 99%

Recent Developments in Recombinant Protein–Based Dengue Vaccines

Tripathi

Shrivastava

2018

Front. Immunol.

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Recombinant proteins are gaining enormous importance these days due to their wide application as biopharmaceutical products and proven safety record. Various recombinant proteins of therapeutic and prophylactic importance have been successfully produced in microbial and higher expression host systems. Since there is no specific antiviral therapy available against dengue, the prevention by vaccination is the mainstay in reducing the disease burden. Therefore, efficacious vaccines are needed to control the spread of dengue worldwide. Dengue is an emerging viral disease caused by any of dengue virus 1–4 serotypes that affects the human population around the globe. Dengue virus is a single stranded RNA virus encoding three structural proteins (capsid protein, pre-membrane protein, and envelope protein) and seven non-structural proteins (NS1, NS2a, NS2b, NS3, NS4a, NS4b, NS5). As the only licensed dengue vaccine (Dengvaxia) is unable to confer balanced protection against all the serotypes, therefore various approaches for development of dengue vaccines including tetravalent live attenuated, inactivated, plasmid DNA, virus-vectored, virus-like particles, and recombinant subunit vaccines are being explored. These candidates are at different stages of vaccine development and have their own merits and demerits. The promising subunit vaccines are mainly based on envelope or its domain and non-structural proteins of dengue virus. These proteins have been produced in different hosts and are being investigated for development of a successful dengue vaccine. Novel immunogens have been designed employing various strategies like protein engineering and fusion of antigen with various immunostimulatory motif to work as self-adjuvant. Moreover, recombinant proteins can be formulated with novel adjuvants to enhance the immunogenicity and thus conferring better protection to the vaccinees. With the advent of newer and safer host systems, these recombinant proteins can be produced in a cost effective manner at large scale for vaccine studies. In this review, we summarize recent developments in recombinant protein based dengue vaccines that could lead to a good number of efficacious vaccine candidates for future human use and ultimately alternative dengue vaccine candidates.

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“…Dengue virus (DENV) causes hemorrhagic fever and shock syndrome and represents a public health threat in Southeast Asia and Central and South America. A Dengue vaccine consisting of PLGA/PEG NPs loaded with viral nonstructural protein 1 (NS1) in the absence of adjuvants was shown to be effective in mice [52]. Subsequently, Metz et al tested the efficacy of immunization with a tetravalent recombinant envelope (rE) protein subunit vaccine adsorbed into the PLGA-NP surface.…”

Section: Protein-based Plga Viral Vaccinesmentioning

confidence: 99%

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

et al. 2021

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The first vaccines ever made were based on live-attenuated or inactivated pathogens, either whole cells or fragments. Although these vaccines required the co-administration of antigens with adjuvants to induce a strong humoral response, they could only elicit a poor CD8+ T-cell response. In contrast, next-generation nano/microparticle-based vaccines offer several advantages over traditional ones because they can induce a more potent CD8+ T-cell response and, at the same time, are ideal carriers for proteins, adjuvants, and nucleic acids. The fact that these nanocarriers can be loaded with molecules able to modulate the immune response by inducing different effector functions and regulatory activities makes them ideal tools for inverse vaccination, whose goal is to shut down the immune response in autoimmune diseases. Poly (lactic-co-glycolic acid) (PLGA) and liposomes are biocompatible materials approved by the Food and Drug Administration (FDA) for clinical use and are, therefore, suitable for nanoparticle-based vaccines. Recently, another candidate platform for innovative vaccines based on extracellular vesicles (EVs) has been shown to efficiently co-deliver antigens and adjuvants. This review will discuss the potential use of PLGA-NPs, liposomes, and EVs as carriers of peptides, adjuvants, mRNA, and DNA for the development of next-generation vaccines against endemic and emerging viruses in light of the recent COVID-19 pandemic.

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Evaluation of protective efficacy using a nonstructural protein NS1 in DNA vaccine–loaded microspheres against dengue 2 virus

Cited by 11 publications

References 22 publications

Modified mRNA-LNP Vaccines Confer Protection against Experimental DENV-2 Infection in Mice

Modified mRNA-LNP Vaccines Confer Protection against Experimental DENV-2 Infection in Mice

Recent Developments in Recombinant Protein–Based Dengue Vaccines

Nano-Microparticle Platforms in Developing Next-Generation Vaccines

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