A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation

Hannaman, Drew; Dupuy, Lesley C.; Ellefsen, Barry; Schmaljohn, Connie S.

doi:10.1016/j.vaccine.2016.04.077

Cited by 55 publications

(44 citation statements)

References 11 publications

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“…Hannaman et al studied a DNA vaccine targeting the E3-E2-6K-E1 genes of the VEEV subtype IAB envelope and compared intradermal versus intramuscular electroporation (EP) at various doses in a small number of human subjects. In this study high dose intramuscular EP resulted in the development of VEEV neutralizing antibodies in all subjects while intradermal-EP promoted neutralizing antibody at lower levels and in fewer subjects [9]. T cell responses were not reported in this study.…”

Section: Clinical Review Of Recent Dna Vaccinescontrasting

confidence: 53%

DNA vaccines: prime time is now

Gary

Weiner

2020

Current Opinion in Immunology

144

118

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Recently newer synthetic DNA vaccines have been rapidly advanced to clinical study and have demonstrated an impressive degree of immune potency and tolerability. Improvements in DNA delivery over prior needle and syringe approaches include jet delivery, gene gun delivery, among others. Among the most effective of these new delivery methods, advanced electroporation (EP), combined with other advances, induces robust humoral and cellular immunity in both preventative as well as therapeutic studies. Advancements in the design of the DNA inserts include leader sequence changes, RNA and codon optimizations, improved insert designs, increased concentrations of DNA, and skin delivery, appear to complement newer delivery strategies. These advances also provide a framework for the in vivo production of synthetic DNA biologics. In this review, we focus on recent studies of synthetic DNA vaccines in the clinic for the prevention or treatment of infectious diseases with a focus on adaptive electroporation for delivery, and briefly summarize novel preclinical data advancing the in vivo delivery of DNAencoded antibody-like biologics.

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Section: Clinical Review Of Recent Dna Vaccinescontrasting

confidence: 53%

DNA vaccines: prime time is now

Gary

Weiner

2020

Current Opinion in Immunology

144

118

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“…Currently, numerous DNA vaccine based clinical trials are underway worldwide [51, 60–62] and EP remains the most promising method of DNA vaccine delivery until an alternative DNA delivery method capable of matching immunogenicity enhancements is developed. Significant boosting of antibody titers as well as functional responses in all DNA immunization groups by E. coli produced recombinant Pfs48/45 [23] also support a heterologous prime-boost regimen for Pfs48/45 DNA vaccine delivery.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation

Datta

Bansal

Gerloff

et al. 2017

Vaccine

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Pfs48/45 and Pfs25 are leading candidates for the development of Plasmodium falciparum transmission blocking vaccines (TBV). Expression of Pfs48/45 in the erythrocytic sexual stages and presentation to the immune system during infection in the human host also makes it ideal for natural boosting. However, it has been challenging to produce a fully folded, functionally active Pfs48/45, using various protein expression platforms. In this study, we demonstrate that full-length Pfs48/45 encoded by DNA plasmids is able to induce significant transmission reducing immune responses. DNA plasmids encoding Pfs48/45 based on native (WT), codon optimized (SYN), or codon optimized and mutated (MUT1 and MUT2), to prevent any asparagine (N)-linked glycosylation were compared with or without intramuscular electroporation (EP). EP significantly enhanced antibody titers and transmission blocking activity elicited by immunization with SYN Pfs48/45 DNA vaccine. Mosquito membrane feeding assays also revealed improved functional immunogenicity of SYN Pfs48/45 (N-glycosylation sites intact) as compared to MUT1 or MUT2 Pfs48/45 DNA plasmids (all N-glycosylation sites mutated). Boosting with recombinant Pfs48/45 protein after immunization with each of the different DNA vaccines resulted in significant boosting of antibody response and improved transmission reducing capabilities of all four DNA vaccines. Finally, immunization with a combination of DNA plasmids (SYN Pfs48/45 and SYN Pfs25) also provides support for the possibility of combining antigens targeting different life cycle stages in the parasite during transmission through mosquitoes.

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“…During the plasmid design, low-frequency eukaryotic codons in the foreign DNA backbone are identified and replaced for high-frequency codons, while still maintaining their respective coded amino acids [130][131][132]. There has been recent progress in terms of enhancing the immunogenicity in mice and chicken primed with such codon-optimized DNA vaccines [133][134][135].…”

Section: Codon Optimizationmentioning

confidence: 99%

Engineering DNA vaccines against infectious diseases

et al. 2018

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Engineering vaccine-based therapeutics for infectious diseases is highly challenging, as trial formulations are often found to be nonspecific, ineffective, thermally or hydrolytically unstable, and/or toxic. Vaccines have greatly improved the therapeutic landscape for treating infectious diseases and have significantly reduced the threat by therapeutic and preventative approaches. Furthermore, the advent of recombinant technologies has greatly facilitated growth within the vaccine realm by mitigating risks such as virulence reversion despite making the production processes more cumbersome. In addition, seroconversion can also be enhanced by recombinant technology through kinetic and nonkinetic approaches, which are discussed herein. Recombinant technologies have greatly improved both amino acid-based vaccines and DNA-based vaccines. A plateau of interest has been reached between 2001 and 2010 for the scientific community with regard to DNA vaccine endeavors. The decrease in interest may likely be attributed to difficulties in improving immunogenic properties associated with DNA vaccines, although there has been research demonstrating improvement and optimization to this end. Despite improvement, to the extent of our knowledge, there are currently no regulatory body-approved DNA vaccines for human use (four vaccines approved for animal use). This article discusses engineering DNA vaccines against infectious diseases while discussing advantages and disadvantages of each, with an emphasis on applications of these DNA vaccines. STATEMENT OF SIGNIFICANCE: This review paper summarizes the state of the engineered/recombinant DNA vaccine field, with a scope entailing "Engineering DNA vaccines against infectious diseases". We endeavor to emphasize recent advances, recapitulating the current state of the field. In addition to discussing DNA therapeutics that have already been clinically translated, this review also examines current research developments, and the challenges thwarting further progression. Our review covers: recombinant DNA-based subunit vaccines; internalization and processing; enhancing immune protection via adjuvants; manufacturing and engineering DNA; the safety, stability and delivery of DNA vaccines or plasmids; controlling gene expression using plasmid engineering and gene circuits; overcoming immunogenic issues; and commercial successes. We hope that this review will inspire further research in DNA vaccine development.

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A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation

Cited by 55 publications

References 11 publications

DNA vaccines: prime time is now

DNA vaccines: prime time is now

Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation

Engineering DNA vaccines against infectious diseases

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