Therapeutic vaccines: challenges of chronic viral infections

Sällberg, Matti; Weiland, Malin; Frelin, Lars

doi:10.1016/j.ddstr.2008.02.004

Cited by 5 publications

(8 citation statements)

References 150 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA Immunization has been shown to elicit suitable immune response against a number of viral antigens especially HCV and is currently used even for vaccine trials in humans (3,7). The vectors expressing partial or full length of core and NS3 genes from HCV have been exploited for vaccine purposes routinely due to their suitable immunogenicity and high homology among HCV genotypes (3,7,33,34). Recent publications reported significant controversy regarding to usefulness of full length core protein as vaccine antigen (20,21,24,26,29,35).…”

Section: Discussionmentioning

confidence: 99%

“…DNA immunization methods are growing for prophylactic or therapeutic purposes in HCV infection. Two DNA vaccine candidates have already reached clinical evaluation, and are well tolerated and immunogenic in HCV-chronically infected individuals (5)(6)(7)(8)(9). Rather than the big advantages in comparison with other vaccine formulation, the ability to introduce virus antigen to the host immune system, enabling it to elicit strong Th1 type CD4+ T cells and CD8+ cytotoxic T cells, is an important feature of DNA immunization (5,9).…”

Section: Introductionmentioning

confidence: 99%

“…Rather than the big advantages in comparison with other vaccine formulation, the ability to introduce virus antigen to the host immune system, enabling it to elicit strong Th1 type CD4+ T cells and CD8+ cytotoxic T cells, is an important feature of DNA immunization (5,9). In DNA immunization procedure, by intracellular expression of recombinant HCV proteins, antigens would be endogenously synthesized and processed via MHC class I pathway and presented on the cell surface similar to that of natural infection (7,10). Non-structural protein 3 (NS3) is a relatively conserved protein with both protease and RNA helicase enzymatic activities (11).…”

Section: Introductionmentioning

confidence: 99%

“…Previous publications showed that HCV specific cellular immune responses against NS3 is associated with viral clearance in acute infection, whereas absence of T cell response leads to viral persistence (12). Thus, NS3 is an important option for the purpose of anti-HCV vaccine design (4,6,7,10,13,14). Theoretically, endogenously expressed NS3 protein may disrupt the functional integrity of antigen presenting cells (APCs) due to its protease and/or helicase enzymatic activity (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

et al. 2010

View full text Add to dashboard Cite

Background and Aims: DNA constructs containing HCV antigens have become one of the vaccine candidates for induction of anti-HCV cellular and humoral immunity. In this study, we constructed a novel expressing vector harboring a fusion sequence derived from an overlapping fragment in the middle of NS3 and a truncated core fragment to avoid troubles reported to be associated with full gene expression. Methods: The partial NS3 (pNS3) and core genes were amplified by RT-PCR method using serum of HCV infected patient harboring genotype 1a of virus. After purification and cloning the genes into TA-cloning vector, they were evaluated by sequencing and restriction digestion analysis. The resultant pNS3 and core gene subcloned into expression vector separately followed by expression evaluation using RT-PCR and western blotting. The core expressing vector exploited for amplification of a new truncated core (50-160aa) sequence using PCR. Truncated core fragment was first cloned into TA vector at a natural restriction site downstream of pNS3 fragment. The resulting fused sequence was cut and subcloned into expression vector. The integrity and ability of expression of this fused sequence was evaluated by sequencing followed by RT-PCR analysis after DNA transfection into 293 cells. Results: The repeated sequencing data showed sequence integrity among the gene fragments as well as homology among them and reference 1a sequences. The colony-PCR, RT-PCR and western blotting confirmed insertion of genes into expressing vector, expression of genes in 293 cell line and production of protein in 293 respectively. Conclusion: This new expressing vector harboring a novel fused fragments of NS3 and core genes may overcome shortcomings in vaccine design in the setting of HCV disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Potent new direct acting antivirals (DAAs) have dramatically improved the success rates in disruption of the viral replication; however, high costs, side effects, and treatment failures still remain the main issues, underscoring the importance of developing therapeutic/prophylactic vaccines [25]. Several studies have shown that NS3 protein is a promising antigen for the purpose of anti-HCV vaccine development [26,27].…”

Section: Discussionmentioning

confidence: 99%

Synthesis and characterization of physicochemical and immunological properties of recombinant NS3-G2 dendrimer conjugate

Javadi

Rahimi

Modaressi

et al. 2015

vacres

View full text Add to dashboard Cite

Introduction: An effective vaccine against HCV infection is not available. The non-structural protein 3 (NS3) of the virus as an important immunogenic candidate has been utilized in various modules. Nanostructured polymers have been recently used for efficient vaccine and drug delivery. The aim of the current study was the synthesis of rNS3-G2 conjugate and preliminary evaluation of its immunogenicity. Methods: The dendrimer was synthesized and conjugated with purified recombinant NS3 (rNS3) protein. The physicochemical properties of the conjugate were evaluated by Zeta potential, FT-IR spectra and confirmed by atomic force microscopy (AFM). Immunogenicity of the conjugate was assessed in BALB/c mice. Results: Synthesis and conjugation of dendrimer G2 with the protein were confirmed and immunological assays showed that the conjugated form of the antigen induced higher titer of IgG compared to rNS3 antigen alone. Conclusion: The results showed that the antigenic structure of rNS3 was maintained when conjugated with the biodegradable and biocompatible G2 dendrimers and the immunogenic properties of the antigen were enhanced. Therefore the new formulation may have potential as a vaccine candidate.

show abstract

Postconditioning Hormesis Put in Perspective: An Overview of Experimental and Clinical Studies

2010

View full text Add to dashboard Cite

A beneficial effect of applying mild stress to cells or organisms, that were initially exposed to a high dose of stress, has been referred to as 'postconditioning hormesis'. The initial high dose of stress activates intrinsic self-recovery mechanisms. Modulation of these endogenous adaptation strategies by administration of a subsequent low dose of stress can confer effects that are beneficial to the biological system. Owing to its potentially therapeutic applications, postconditioning hormesis is subject to research in various scientific disciplines. This paper presents an overview of the dynamics of postconditioning hormesis and illustrates this phenomenon with a number of examples in experimental and clinical research.

show abstract

Therapeutic vaccines: challenges of chronic viral infections

Cited by 5 publications

References 150 publications

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

Construction of an Expression Vector Containing a Novel Fusion Sequence from Middle Region of NS3 and Truncated Core Genes of Hepatitis C Virus

Synthesis and characterization of physicochemical and immunological properties of recombinant NS3-G2 dendrimer conjugate

Postconditioning Hormesis Put in Perspective: An Overview of Experimental and Clinical Studies

Contact Info

Product

Resources

About