CoChat
Sign Up
Cited by 190Immunotherapy and Immune ResponsesRNA Interference and Gene DeliveryMicrobial Inactivation Methods

DNA vaccines: prime time is now

Open access
Gary, Ebony N, Weiner, David B·2020·Current Opinion in Immunology
DOI 10.1016/j.coi.2020.01.006PMC PMC7195337
Open this paper in CoChat — free accountOpen PDF

Abstract

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 DNA-encoded antibody-like biologics.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.coi.2020.01.006

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Concerns on immunogenicity and safety of DNA vaccines remain.

    “however, the concerns on their immunogenicity and safety still remain (Gary and Weiner, 2020).”

    From Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2 (2020) · cites this paper as Gary and Weiner, 2020

    The Introduction (page not available) describes a highly consistent safety record, and the Clinical review of recent DNA vaccines (page not available) says all the constructs it reports were safe and immunogenic in clinical studies. Rather than stating that concerns about both properties still remain, the paper presents recent results as evidence of improved immunogenicity and tolerability. (LLM, conf=0.87)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • The DNA vaccine is easy to produce and stable for storage with limited recovery or residual toxicity.

    “The DNA vaccine is easy to be produced and is stable for storage with limited recovery or residual toxicity”

    From Development of an Inactivated Vaccine Candidate, BBIBP-CorV, with Potent Protection against SARS-CoV-2 (2020) · cites this paper as Gary and Weiner, 2020

    The Introduction describes synthetic DNA vaccines as rapidly synthesized and scalable, and says the platform addresses goals of temperature stability and consistent manufacture. It also reports a consistent safety record, but does not establish the more specific claim of limited recovery or residual toxicity. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 39

  1. Jorritsma S. Gowans E. Grubor-Bauk B. Wijesundara D. Delivery methods to increase cellular uptake and immunogenicity of DNA vaccines Vaccine 34 2016 5488 5494 27742218
  2. [2]Khan A.S. Broderick K.E. Sardesai N.Y. Clinical development of intramuscular electroporation: providing a “boost” for DNA vaccines Electroporation Protocols 2014 Springer 279 289 24510832
  3. [3]Lambricht L. Lopes A. Kos S. Sersa G. Préat V. Vandermeulen G. Clinical potential of electroporation for gene therapy and DNA vaccine delivery Expert Opin Drug Deliv 13 2016 295 310 26578324
  4. Kutzler M.A. Weiner D.B. DNA vaccines: ready for prime time? Nat Rev Genet 9 2008 776 18781156 PMC4317294
  5. [5]Chattergoon M.A. Robinson T.M. Boyer J.D. Weiner D.B. Specific immune induction following DNA-based immunization through in vivo transfection and activation of macrophages/antigen-presenting cells J Immunol 160 1998 5707 5718 9637479
  6. [6]Akbari O. Panjwani N. Garcia S. Tascon R. Lowrie D. Stockinger B. DNA vaccination: transfection and activation of dendritic cells as key events for immunity J Exp Med 189 1999 169 178 9874573 PMC1887690
  7. [7]Sheets R.L. Stein J. Manetz T.S. Andrews C. Bailer R. Rathmann J. Gomez P.L. Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, severe acute respiratory syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts Toxicol Sci 91 2006 620 630 16569728 PMC2366098
  8. Kalams S.A. Parker S.D. Elizaga M. Metch B. Edupuganti S. Hural J. De Rosa S. Carter D.K. Rybczyk K. Frank I. Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery J Infect Dis 208 2013 818 829 23840043 PMC3733506
  9. [9]Hannaman D. Dupuy L.C. Ellefsen B. Schmaljohn C.S. A phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation Vaccine 34 2016 3607 3612 27206386
  10. [10]Muthumani K. Griffin B.D. Agarwal S. Kudchodkar S.B. Reuschel E.L. Choi H. Kraynyak K.A. Duperret E.K. Keaton A.A. Chung C. In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine npj Vaccines 1 2016 16021 29263859 PMC5707885
  11. [11]Griffin B.D. Muthumani K. Warner B.M. Majer A. Hagan M. Audet J. Stein D.R. Ranadheera C. Racine T. De La Vega M.-A. DNA vaccination protects mice against Zika virus-induced damage to the testes Nat Commun 8 2017 15743 PMC5467228 28589934
  12. Tebas P. Roberts C.C. Muthumani K. Reuschel E.L. Kudchodkar S.B. Zaidi F.I. White S. Khan A.S. Racine T. Choi H. Safety and immunogenicity of an anti–Zika virus DNA vaccine—preliminary report New Engl J Med 2017 10.1056/NEJMoa1708120 PMC6824915 34525286 · DOI
  13. [13]Gaudinski M.R. Houser K.V. Morabito K.M. Hu Z. Yamshchikov G. Rothwell R.S. Berkowitz N. Mendoza F. Saunders J.G. Novik L. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials Lancet 391 2018 552 562 29217376 PMC6379903
  14. [14]Patel A. Reuschel E.L. Kraynyak K.A. Racine T. Park D.H. Scott V.L. Audet J. Amante D. Wise M.C. Keaton A.A. Protective efficacy and long-term immunogenicity in cynomolgus macaques by Ebola virus glycoprotein synthetic DNA vaccines J Infect Dis 219 2018 544 555 30304515
  15. [15]Broderick K. Shen X. Soderholm J. Lin F. McCoy J. Khan A. Yan J. Morrow M. Patel A. Kobinger G. Prototype development and preclinical immunogenicity analysis of a novel minimally invasive electroporation device Gene Ther 18 2011 258 20962869
  16. Tebas P. Kraynyak K.A. Patel A. Maslow J.N. Morrow M.P. Sylvester A.J. Knoblock D. Gillespie E. Amante D. Racine T. Intradermal SynCon® Ebola GP DNA vaccine is temperature stable and safely demonstrates cellular and humoral immunogenicity advantages in healthy volunteers J Infect Dis 220.3 2019 400 410 30891607
  17. [17]Muthumani K. Falzarano D. Reuschel E.L. Tingey C. Flingai S. Villarreal D.O. Wise M. Patel A. Izmirly A. Aljuaid A. A synthetic consensus anti–spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates Sci Transl Med 7 2015 301ra132–301ra132 PMC4573558 26290414
  18. Modjarrad K. Roberts C.C. Mills K.T. Castellano A.R. Paolino K. Muthumani K. Reuschel E.L. Robb M.L. Racine T. M-d Oh Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial Lancet Infect Dis 19 2019 1013 1022 31351922 PMC7185789
  19. Houser K.V. Yamshchikov G.V. Bellamy A.R. May J. Enama M.E. Sarwar U. Larkin B. Bailer R.T. Koup R. Paskel M. DNA vaccine priming for seasonal influenza vaccine in children and adolescents 6 to 17 years of age: a phase 1 randomized clinical trial PLoS One 13 2018 e0206837 PMC6214651 30388160
  20. [21]Carter C. Houser K.V. Yamshchikov G.V. Bellamy A.R. May J. Enama M.E. Sarwar U. Larkin B. Bailer R.T. Koup R. Safety and immunogenicity of investigational seasonal influenza hemagglutinin DNA vaccine followed by trivalent inactivated vaccine administered intradermally or intramuscularly in healthy adults: an open-label randomized phase 1 clinical trial PLoS One 14 2019 PMC6750650 31532789
  21. [22]Serrano B. Brotons M. Bosch F.X. Bruni L. Epidemiology and burden of HPV-related disease Best Pract Res Clin Obstet Gynaecol 47 2018 14 26 29037457
  22. [23]Bagarazzi M.L. Yan J. Morrow M.P. Shen X. Parker R.L. Lee J.C. Giffear M. Pankhong P. Khan A.S. Broderick K.E. Immunotherapy against HPV16/18 generates potent TH1 and cytotoxic cellular immune responses Sci Transl Med 4 2012 155ra138–155ra138 PMC4317299 23052295
  23. Trimble C.L. Morrow M.P. Kraynyak K.A. Shen X. Dallas M. Yan J. Edwards L. Parker R.L. Denny L. Giffear M. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial Lancet 386 2015 2078 2088 26386540 PMC4888059
  24. [26]Aggarwal C. Cohen R.B. Morrow M.P. Kraynyak K.A. Sylvester A.J. Knoblock D.M. Bauml J.M. Weinstein G.S. Lin A. Boyer J. Immunotherapy targeting HPV16/18 generates potent immune responses in HPV-associated head and neck cancer Clin Cancer Res 25 2019 110 124 30242022 PMC6320307
  25. [27]Ribas A. Wolchok J.D. Cancer immunotherapy using checkpoint blockade Science 359 2018 1350 1355 29567705 PMC7391259
  26. Perales-Puchalt A. Duperret E.K. Muthumani K. Weiner D.B. Simplifying checkpoint inhibitor delivery through in vivo generation of synthetic DNA-encoded monoclonal antibodies (DMAbs) Oncotarget 10 2019 13 30713599 PMC6343757
  27. Duperret E.K. Trautz A. Stoltz R. Patel A. Wise M.C. Perales-Puchalt A. Smith T. Broderick K.E. Masteller E. Kim J.J. Synthetic DNA-encoded monoclonal antibody delivery of Anti–CTLA-4 antibodies induces tumor shrinkage in vivo Cancer Res 78 2018 6363 6370 30287678 PMC6239932
  28. Perales-Puchalt A. Duperret E.K. Yang X. Hernandez P. Wojtak K. Zhu X. Jung S.-H. Tello-Ruiz E. Wise M.C. Montaner L.J. DNA-encoded bispecific T cell engagers and antibodies present long-term antitumor activity JCI Insight 4 2019 PMC6538381 30996140
  29. [31]Muthumani K. Flingai S. Wise M. Tingey C. Ugen K.E. Weiner D.B. Optimized and enhanced DNA plasmid vector based in vivo construction of a neutralizing anti-HIV-1 envelope glycoprotein Fab Hum Vaccin Immunother 9 2013 2253 2262 24045230 PMC3906412
  30. Xu Z. Wise M.C. Choi H. Perales-Puchalt A. Patel A. Tello-Ruiz E. Chu J.D. Muthumani K. Weiner D.B. Synthetic DNA delivery by electroporation promotes robust in vivo sulfation of broadly neutralizing anti-HIV immunoadhesin eCD4-Ig EBioMedicine 35 2018 97 105 30174283 PMC6161476
  31. Wise M.C. Xu Z. Tello-Ruiz E. Beck C. Trautz A. Patel A. Elliott S.T. Chokkalingam N. Kim S. Kerkau M.G. In vivo delivery of synthetic DNA–encoded antibodies induces broad HIV-1–neutralizing activity J Clin Invest 130 2020 PMC6994112 31697648
  32. [34]Elliott S.T. Kallewaard N.L. Benjamin E. Wachter-Rosati L. McAuliffe J.M. Patel A. Smith T.R. Schultheis K. Park D.H. Flingai S. DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections npj Vaccines 2 2017 18 29263874 PMC5627301
  33. [35]Andrews C.D. Luo Y. Sun M. Yu J. Goff A.J. Glass P.J. Padte N.N. Huang Y. Ho D.D. In vivo production of monoclonal antibodies by gene transfer via electroporation protects against lethal influenza and Ebola infections Mol Ther Methods Clin Dev 7 2017 74 82 29034261 PMC5633264
  34. [36]Flingai S. Plummer E.M. Patel A. Shresta S. Mendoza J.M. Broderick K.E. Sardesai N.Y. Muthumani K. Weiner D.B. Protection against dengue disease by synthetic nucleic acid antibody prophylaxis/immunotherapy Sci Rep 5 2015 12616 26220099 PMC4518257
  35. Muthumani K. Block P. Flingai S. Muruganantham N. Chaaithanya I.K. Tingey C. Wise M. Reuschel E.L. Chung C. Muthumani A. Rapid and long-term immunity elicited by DNA-encoded antibody prophylaxis and DNA vaccination against chikungunya virus J Infect Dis 214 2016 369 378 27001960 PMC4936642
  36. Esquivel R.N. Patel A. Kudchodkar S.B. Park D.H. Stettler K. Beltramello M. Allen J.W. Mendoza J. Ramos S. Choi H. In vivo delivery of a DNA-encoded monoclonal antibody protects non-human primates against Zika Virus Mol Ther 27 2019 974 985 30962164 PMC6520333
  37. [39]Patel A. Park D.H. Davis C.W. Smith T.R. Leung A. Tierney K. Bryan A. Davidson E. Yu X. Racine T. In vivo delivery of synthetic human DNA-encoded monoclonal antibodies protect against ebolavirus infection in a mouse model Cell Rep 25 2018 1982 1993 e1984 30428362 PMC6319964
  38. Patel A. DiGiandomenico A. Keller A.E. Smith T.R. Park D.H. Ramos S. Schultheis K. Elliott S.T. Mendoza J. Broderick K.E. An engineered bispecific DNA-encoded IgG antibody protects against Pseudomonas aeruginosa in a pneumonia challenge model Nat Commun 8 2017 637 PMC5608701 28935938
  39. [41]Wang Y. Esquivel R. Flingai S. Schiller Z.A. Kern A. Agarwal S. Chu J. Patel A. Sullivan K. Wise M.C. Anti-OspA DNA-encoded monoclonal antibody prevents transmission of spirochetes in tick challenge providing sterilizing immunity in mice J Infect Dis 219 2018 1146 1150 PMC6420172 30476132

Cited by

Sorted by citations

Authors
Gary, E. N., & Weiner, D. B.
Affiliations
The Wistar Institute (US)
Corresponding author
Weiner, David B
ORCID
Venue
Current Opinion in Immunology
Publisher
Elsevier BV
Published
2020-08
Volume
65
Pages
21-27
ISSN
0952-7915 (ISSN-L)
DOI
10.1016/j.coi.2020.01.006
PMC
PMC7195337
OpenAlex
W3014901343
Cited by
190
References
0
Citations by year
2026: 11 · 2025: 33 · 2024: 27 · 2023: 29 · 2022: 32 · 2021: 39 · 2020: 19
FWCI
2.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
Funders
  • Bill and Melinda Gates Foundation
  • Foundation for the National Institutes of Health
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
Keywords
DNA vaccine, electroporation, DNA delivery, gene gun, codon optimization, 5' untranslated region, skin delivery, humoral immunity, cell-mediated immunity, infectious disease prevention, therapeutic vaccines
MeSH terms
Animals, Communicable Diseases, Humans, Immunity, Cellular, Electroporation, Vaccines, DNA

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review