Short noncoding DNA fragments improve the immune potency of electroporation-mediated HBV DNA vaccination

Peng, Jianping; Shi, Shuyang; Zhou, Yang; Ding, Qi; Wang, Hai; Tang, Haoneng; Yang, Yunqi; Bernstein, Jeff; Peyda, P; Xu, Yuhong

doi:10.1038/gt.2014.44

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…In the duck hepatitis B virus model, EP-mediated vaccination increased the production of neutralizing HBV-specific antibodies, expanded the spectrum of targeted epitopes[ 46 ] and resulted in T helper type 1 polarization[ 47 ]. Short non-coding DNA fragments appear to increase the immunopotency of EP-mediated HBV DNA vaccination[ 48 ]. DNA vaccine platforms based on EP show an enhanced ability to activate both arms of adaptive immunity and thus represent an important tool to overcome immunological exhaustion in CHB.…”

Section: Electroporation-mediated Deliverymentioning

confidence: 99%

Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure

Tsounis¹,

Mouzaki²,

Triantos³

2021

WJG

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Although a prophylactic vaccine is available, hepatitis B virus (HBV) remains a major cause of liver-related morbidity and mortality. Current treatment options are improving clinical outcomes in chronic hepatitis B; however, true functional cure is currently the exception rather than the rule. Nucleic acid vaccines are among the emerging immunotherapies that aim to restore weakened immune function in chronically infected hosts. DNA vaccines in particular have shown promising results in vivo by reducing viral replication, breaking immune tolerance in a sustained manner, or even decimating the intranuclear covalently closed circular DNA reservoir, the hallmark of HBV treatment. Although DNA vaccines encoding surface antigens administered by conventional injection elicit HBV-specific T cell responses in humans, initial clinical trials failed to demonstrate additional therapeutic benefit when administered with nucleos(t)ide analogs. In an attempt to improve vaccine immunogenicity, several techniques have been used, including codon/promoter optimization, coadministration of cytokine adjuvants, plasmids engineered to express multiple HBV epitopes, or combinations with other immunomodulators. DNA vaccine delivery by electroporation is among the most efficient strategies to enhance the production of plasmid-derived antigens to stimulate a potent cellular and humoral anti-HBV response. Preliminary results suggest that DNA vaccination via electroporation efficiently invigorates both arms of adaptive immunity and suppresses serum HBV DNA. In contrast, the study of mRNA-based vaccines is limited to a few in vitro experiments in this area. Further studies are needed to clarify the prospects of nucleic acid vaccines for HBV cure.

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Section: Electroporation-mediated Deliverymentioning

confidence: 99%

Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure

Tsounis¹,

Mouzaki²,

Triantos³

2021

WJG

View full text Add to dashboard Cite

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“…DNA, itself, through binding to cellular receptors can activate innate immune pathways. A recent study found that a short noncoding DNA fragment of ∼300bp improved electroporation-mediated gene transfer in vivo [110], and the immune potency of a HBV vaccine [111].…”

Section: Plasmid-encoded Signalling Moleculesmentioning

confidence: 99%

Molecular mechanisms for enhanced DNA vaccine immunogenicity

Petrovsky

2015

Expert Review of Vaccines

252

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Summary In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclinical models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or molecular adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.

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Present and future DNA vaccines for chronic hepatitis B treatment

Cova

2016

Expert Opinion on Biological Therapy

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With at least 240 million hepatitis B virus (HBV) carriers worldwide, being at a high risk of cirrhosis and hepatocellular carcinoma (HCC), chronic hepatitis B remains a major public health issue. Because current antiviral treatments are only virostatic, there is an urgent need for the development of innovative anti-HBV strategies leading to the functional cure. In this context, DNA-based vaccines appear as a promising approach. Area covered: In this review, the authors summarize the pertinent features of DNA vaccines for chronic hepatitis B therapy. They review several technologies that improve DNA vaccines efficacy evaluated in animal models of hepadnaviral infection. They also discuss the clinical trials of therapeutic DNA vaccination initiated in HBV-carrier patients. Expert opinion: Preclinical studies in HBV transgenic mice, DHBV-carrier ducks and WHV-infected woodchucks, have clearly demonstrated a benefit of DNA vaccine-based combination therapies for chronic hepatitis B treatment. However, the results of clinical trials conducted in HBV patients were rather disappointing and frustrating, as DNA-vaccines have not shown the same efficacy in patients as in animal models. We are convinced that the design of innovative clinical trials based on strategies able to increase DNA vaccine immunogenicity will allow to advance in this challenging field.

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Short noncoding DNA fragments improve the immune potency of electroporation-mediated HBV DNA vaccination

Cited by 3 publications

References 40 publications

Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure

Nucleic acid vaccines: A taboo broken and prospect for a hepatitis B virus cure

Molecular mechanisms for enhanced DNA vaccine immunogenicity

Present and future DNA vaccines for chronic hepatitis B treatment

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