DNA Vaccines: Regulatory Considerations and Safety Aspects

Myhr, Anne Ingeborg

doi:10.21775/cimb.022.079

Cited by 57 publications

(33 citation statements)

References 15 publications

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“…After two decades of research, DNA vaccine technology is gaining maturity—several veterinary DNA vaccines are currently licensed for West Nile virus and melanoma ( 111 ), and significantly, the first commercial DNA vaccine against H5N1 in chickens has recently been conditionally approved by the USDA ( 112 ). In addition, ongoing large animal trials of DNA vaccines against other diseases such as against HIV ( 6 , 113 , 114 ), hepatitis ( 115 , 116 ), and Zika virus ( 117 , 118 ) offer valuable insights that can be applied to influenza DNA vaccine design.…”

Section: Future Prospectsmentioning

confidence: 99%

A Review of DNA Vaccines Against Influenza

2018

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The challenges of effective vaccination against influenza are gaining more mainstream attention, as recent influenza seasons have reported low efficacy in annual vaccination programs worldwide. Combined with the potential emergence of novel influenza viruses resulting in a pandemic, the need for effective alternatives to egg-produced conventional vaccines has been made increasingly clear. DNA vaccines against influenza have been in development since the 1990s, but the initial excitement over success in murine model trials has been tempered by comparatively poor performance in larger animal models. In the intervening years, much progress has been made to refine the DNA vaccine platform—the rational design of antigens and expression vectors, the development of novel vaccine adjuvants, and the employment of innovative gene delivery methods. This review discusses how these advances have been applied in recent efforts to develop an effective influenza DNA vaccine.

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Section: Future Prospectsmentioning

confidence: 99%

A Review of DNA Vaccines Against Influenza

2018

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“…Although DNA vaccines provide a high level of protection, their mechanism is not understood well. Moreover, only a few DNA vaccines have been approved for commercial use (Myhr, 2016). So far, there is no DNA vaccine against the ERM disease.…”

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confidence: 99%

The repeat structure of two paralogous genes, Yersinia ruckeri invasin (yrInv) and a “Y. ruckeri invasin-like molecule”, (yrIlm) sheds light on the evolution of adhesive capacities of a fish pathogen

Wróbel

Ottoni

Leo

et al. 2018

Journal of Structural Biology

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Inverse autotransporters comprise the recently identified type Ve secretion system and are exemplified by intimin from enterohaemorrhagic Escherichia coli and invasin from enteropathogenic Yersiniae. These proteins share a common domain architecture and promote bacterial adhesion to host cells. Here, we identified and characterized two putative inverse autotransporter genes in the fish pathogen Yersinia ruckeri NVH_3758, namely yrInv (for Y. ruckeri invasin) and yrIlm (for Y. ruckeri invasin-like molecule). When trying to clone the highly repetitive genes for structural and functional studies, we experienced problems in obtaining PCR products. PCR failures and the highly repetitive nature of inverse autotransporters prompted us to sequence the genome of Y. ruckeri NVH_3758 using PacBio sequencing, which produces some of the longest average read lengths available in the industry at this moment. According to our sequencing data, YrIlm is composed of 2603 amino acids (7812bp) and has a molecular mass of 256.4kDa. Based on the new genome information, we performed PCR analysis on four non-sequenced Y. ruckeri strains as well as the sequenced. Y. ruckeri type strain. We found that the genes are variably present in the strains, and that the length of yrIlm, when present, also varies. In addition, the length of the gene product for all strains, including the type strain, was much longer than expected based on deposited sequences. The internal repeats of the yrInv gene product are highly diverged, but represent the same bacterial immunoglobulin-like domains as in yrIlm. Using qRT-PCR, we found that yrIlm and yrInv are differentially expressed under conditions relevant for pathogenesis. In addition, we compared the genomic context of both genes in the newly sequenced Y. ruckeri strain to all available PacBio-sequenced Y. ruckeri genomes, and found indications of recent events of horizontal gene transfer. Taken together, this study demonstrates and highlights the power of Single Molecule Real-Time technology for sequencing highly repetitive proteins, and sheds light on the genetic events that gave rise to these highly repetitive genes in a commercially important fish pathogen.

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“…DNA vaccines are currently restricted to veterinary clinics. However, clinical trials are ongoing for human use and hope to offer protection against malaria, HIV, influenza, tuberculosis and Ebola [7].…”

Section: Therapeutic Nucleic Acidsmentioning

confidence: 99%

RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs

Bajan

Hutvágner

2020

Cells

294

211

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The first therapeutic nucleic acid, a DNA oligonucleotide, was approved for clinical use in 1998. Twenty years later, in 2018, the first therapeutic RNA-based oligonucleotide was United States Food and Drug Administration (FDA) approved. This promises to be a rapidly expanding market, as many emerging biopharmaceutical companies are developing RNA interference (RNAi)-based, and RNA-based antisense oligonucleotide therapies. However, miRNA therapeutics are noticeably absent. miRNAs are regulatory RNAs that regulate gene expression. In disease states, the expression of many miRNAs is measurably altered. The potential of miRNAs as therapies and therapeutic targets has long been discussed and in the context of a wide variety of infections and diseases. Despite the great number of studies identifying miRNAs as potential therapeutic targets, only a handful of miRNA-targeting drugs (mimics or inhibitors) have entered clinical trials. In this review, we will discuss whether the investment in finding potential miRNA therapeutic targets has yielded feasible and practicable results, the benefits and obstacles of miRNAs as therapeutic targets, and the potential future of the field.

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DNA Vaccines: Regulatory Considerations and Safety Aspects

Cited by 57 publications

References 15 publications

A Review of DNA Vaccines Against Influenza

A Review of DNA Vaccines Against Influenza

The repeat structure of two paralogous genes, Yersinia ruckeri invasin (yrInv) and a “Y. ruckeri invasin-like molecule”, (yrIlm) sheds light on the evolution of adhesive capacities of a fish pathogen

RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs

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