DNA vaccine technologies: design and delivery

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The COVID-19 pandemic has triggered the development of new directions in vaccine development, among which DNA- and mRNA-based technologies are particularly noteworthy. The platform based on DNA vaccines is developing particularly intensively due to their high stability at ambient temperature and the ability to activate both humoral and cellular immunity. The full cycle of DNA vaccine creation, which includes the construction of plasmid DNA, obtaining a producer strain, fermentation and purification, takes 2‒4 weeks. In addition, the production technology of such vaccines does not require working with dangerous pathogens, which significantly simplifies the process of their production and reduces the overall cost. Over more than 30 years of rapid development, DNA vaccine technology continues to undergo changes. Currently, there is a licensed DNA vaccine for the prevention of COVID-19, and many candidate prophylactic vaccines against viral and bacterial diseases are in clinical trials. The review covers not only the principles of constructing plasmid DNA vaccines, but also new technologies for obtaining DNA constructs, such as minicircular DNA, MIDGE DNA and DoggyboneTM DNA. New types of DNA vaccines are interesting because they consist only of the most essential elements for activating the immune response. Such constructs completely lack the sequences necessary for the production of plasmid DNA in bacterial cells — for example, the antibiotic resistance gene. One of the key problems in the development of a DNA vaccine is the method of its delivery to target cells. Currently, various delivery methods are used, both chemical and physical, which are rapidly developing and have already proven themselves to be reliable and effective. The characteristics of some of the most promising methods are also presented in the review.

Full Text

Restricted Access

About the authors

A. A. Fando

State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Author for correspondence.
Email: nastyafando@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region

A. A. Ilyichev

State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: nastyafando@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region

V. R. Litvinova

State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: nastyafando@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region

N. B. Rudometova

State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: nastyafando@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region

L. I. Karpenko

State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: nastyafando@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region

A. P. Rudometov

State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: nastyafando@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region

References

  1. Wolff J.A., Malone R.W., Williams P., Chong W., Acsadi G., Jani, A., Felgner P.L. (1990) Direct gene transfer into mouse muscle in vivo. Science. 247, 1465‒1468.
  2. Tang D.C., DeVit M., Johnston S.A. (1992) Genetic immunization is a simple method for eliciting an immune response. Nature. 356, 152‒154.
  3. Ulmer J.B., Donnelly J.J., Parker S.E., Rhodes G.H., Felgner P.L., Dwarki V.J., Gromkowski S.H., Deck R.R., DeWitt C.M., Friedman A., Hawe L.A., Leander K.R., Martinez D., Perry H.C., Shiver J.W., Montgomery D.L., Liu M.A. (1993) Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 259, 1745‒1749.
  4. Shafaati M., Saidijam M., Soleimani M., Hazrati F., Mirzaei R., Amirheidari B., Tanzadehpanah H., Karampoor S., Kazemi S., Yavari B., Mahaki H., Safaei M., Rahbarizadeh F., Samadi P., Ahmadyousefi Y. (2022) A brief review on DNA vaccines in the era of COVID-19. Future Virol. 17, 49‒66.
  5. Mallapaty S. (2021) India’s DNA COVID vaccine is a first — more are coming. Nature. 597, 161‒162.
  6. Momin T., Kansagra K., Patel H., Sharma S., Sharma B., Patel J., Mittal R., Sanmukhani J., Maithal K., Dey A., Chandra H., Rajanathan C.T., Pericherla H.P., Kumar P., Narkhede A., Parmar D. (2021) Safety and immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India. EClinicalMedicine. 38, 101020.
  7. Maslow J. N., Kwon I., Kudchodkar S. B., Kane D., Tadesse A., Lee H., Tadesse A., Lee H., Park Y.K., Muthumani K., Roberts C.C. (2023) DNA vaccines for epidemic preparedness: SARS-CoV-2 and beyond. Vaccines (Basel). 11, 1016.
  8. Baghban R., Ghasemian A., Mahmoodi S. (2023) Nucleic acid-based vaccine platforms against the coronavirus disease 19 (COVID-19). Arch. Microbiol. 205, 150.
  9. Jahanafrooz Z., Baradaran B., Mosafer J., Hashemzaei M., Rezaei T., Mokhtarzadeh A., Hamblin M.R. (2020) Comparison of DNA and mRNA vaccines against cancer. Drug Discov. Today. 25, 552‒560.
  10. Tang J., Li M., Zhao C., Shen D., Liu L., Zhang X., Wei L. (2022) Therapeutic DNA vaccines against HPV-related malignancies: promising leads from clinical trials. Viruses. 14, 239.
  11. Robertson J., Ackland J., Holm A. (2007) Guidelines for assuring the quality and nonclinical safety evaluation of DNA vaccines. WHO Tech. Rep. Ser. 941, 57‒81. https://www.who.int/publications/m/item/annex-1-trs941-dna-vax
  12. Sheets R., Kang H.N., Meyer H., Knezevic I. (2020) WHO informal consultation on the guidelines for evaluation of the quality, safety, and efficacy of DNA vaccines, Geneva, Switzerland, December 2019. NPJ Vaccines. 5, 52.
  13. Beasley D.W. (2020) New international guidance on quality, safety and efficacy of DNA vaccines. NPJ Vaccines. 5, 53.
  14. Ghaffarifar F. (2018) Plasmid DNA vaccines: where are we now? Drugs Today (Barc.). 54(5), 315‒333.
  15. Pagliari S., Dema B., Sanchez-Martinez A., Flores G.M.Z., Rollier C.S. (2023) DNA vaccines: history, molecular mechanisms and future perspectives. J. Mol. Biol. 453, 168297.
  16. Xia W., Bringmann P., McClary J., Jones P.P., Manzana W., Zhu Y., Wang S., Liu Y., Harvey S., Madlansacay M.R., McLean K., Rosser M.P., MacRobbie J., Olsen C.L., Cobb R.R. (2006) High levels of protein expression using different mammalian CMV promoters in several cell lines. Protein Expr. Purif. 45, 115‒124.
  17. Johari Y.B., Scarrott J.M., Pohle T.H., Liu P., Mayer A., Brown A.J., James D.C. (2022) Engineering of the CMV promoter for controlled expression of recombinant genes in HEK293 cells. Biotechnol. J. 17, 2200062.
  18. Duan B., Cheng L., Gao Y., Yin F.X., Su G.H., Shen Q.Y., Liu K., Hu X., Liu X., Li G.P. (2012) Silencing of fat-1 transgene expression in sheep may result from hypermethylation of its driven cytomegalovirus (CMV) promoter. Theriogenology. 78, 793‒802.
  19. Franck C.O., Fanslau L., Bistrovic Popov A., Tyagi P., Fruk L. (2021) Biopolymer‐based carriers for DNA vaccine design. Angew. Chem. Int. Ed. Engl. 60, 13225‒13243.
  20. Krinner S., Heitzer A., Asbach B., Wagner R. (2015) Interplay of promoter usage and intragenic CpG content: impact on GFP reporter gene expression. Hum. Gene Ther. 26, 826‒840.
  21. Dean D.A., Dean B.S., Muller S., Smith L.C. (1999) Sequence requirements for plasmid nuclear import. Exp. Cell Res. 253, 713‒722.
  22. Li H.S., Yong L.I.U., Li D.F., Zhang R.R., Tang H.L., Zhang Y.W., Huang W., Liu Y., Peng H., Xu J., Hong K., Shao Y.M. (2007) Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer. Chin. Med. J. (Engl.). 120, 496‒502.
  23. Li L., Petrovsky N. (2016) Molecular mechanisms for enhanced DNA vaccine immunogenicity. Exp. Rev. Vaccines. 15, 313‒329.
  24. Sunita S.A., Singh Y., Shukla P. (2020) Computational tools for modern vaccine development. Hum. Vaccin. Immunother. 16, 723‒735.
  25. Dobaño C., Sedegah M., Rogers W.O., Kumar S., Zheng H., Hoffman S.L., Doolan D.L. (2009) Plasmodium: mammalian codon optimization of malaria plasmid DNA vaccines enhances antibody responses but not T cell responses nor protective immunity. Exp. Parasitol. 122, 112‒123.
  26. Varaldo P.B., Miyaji E.N., Vilar M.M., Campos A.S., Dias W.O., Armôa G.R., Tendler M., Leite L.C.C., McIntosh D. (2006) Mycobacterial codon optimization of the gene encoding the Sm14 antigen of Schistosoma mansoni in recombinant Mycobacterium bovis Bacille Calmette-Guérin enhances protein expression but not protection against cercarial challenge in mice. FEMS Immunol. Med. Microbiol. 48, 132‒139.
  27. Staudacher J., Rebnegger C., Dohnal T., Landes N., Mattanovich D., Gasser B. (2022) Going beyond the limit: increasing global translation activity leads to increased productivity of recombinant secreted proteins in Pichia pastoris. Metab. Eng. 70, 181‒195.
  28. Seymour B.J., Singh S., Certo H.M., Sommer K., Sather B.D., Khim S., Rawlings D.J. (2021) Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector. Mol. Ther. Methods Clin. Dev. 20, 635‒651.
  29. McCluskie M.J., Weeratna R.D., Davis H.L. (2000) The role of CpG in DNA vaccines. Springer Semin. Immunopathol. 22, 125‒132.
  30. Williams J.A. (2013) Vector design for improved DNA vaccine efficacy, safety and production. Vaccines (Basel). 1, 225‒249.
  31. von Heijne G. (1998) Life and death of a signal peptide. Nature. 396, 111‒113.
  32. Kovjazin R., Carmon L. (2014) The use of signal peptide domains as vaccine candidates. Hum. Vaccin. Immunother. 10, 2733‒2740.
  33. Liaci A.M., Förster F. (2021) Take me home, protein roads: structural insights into signal peptide interactions during ER translocation. Int. J. Mol. Sci. 22, 11871.
  34. Стародубова Е.С., Исагулянц М.Г., Карпов В.Л. (2010) Регуляция процессинга иммуногена: сигнальные последовательности и их использование для создания нового поколения ДНК-вакцин. Acta Naturae. 2, 59‒65.
  35. Reguzova A., Antonets D., Karpenko L., Ilyichev A., Maksyutov R., Bazhan S. (2015) Design and evaluation of optimized artificial HIV-1 poly-T cell-epitope immunogens. PloS One. 10, e0116412.
  36. Cheng M.A., Farmer E., Huang C., Lin J., Hung C.F., Wu T.C. (2018) Therapeutic DNA vaccines for human papillomavirus and associated diseases. Hum. Gene Ther. 29, 971‒996.
  37. Ильичев А.А., Орлова Л.А., Шарабрин С.В., Карпенко Л.И. (2020) Технология мРНК как одна из перспективных платформ для разработки вакцины против SARS-CoV-2. Вавиловский журнал генетики и селекции. 24, 802‒807.
  38. Устьянцев И.Г., Голубчикова Ю.С., Бородулина О.Р., Крамеров Д.А. (2017) Каноническое и неканоническое полиаденилирование РНК. Молекуляр. биология. 51, 262‒273.
  39. Xu Z.L., Mizuguchi H., Ishii-Watabe A., Uchida E., Mayumi T., Hayakawa T. (2001) Optimization of transcriptional regulatory elements for constructing plasmid vectors. Gene. 272, 149‒156.
  40. Chen Z.Y., He C.Y., Ehrhardt A., Kay M.A. (2003) Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol. Ther. 8, 495‒500.
  41. Maniar L.E.G., Maniar J.M., Chen Z.Y., Lu J., Fire A.Z., Kay M.A. (2013) Minicircle DNA vectors achieve sustained expression reflected by active chromatin and transcriptional level. Mol. Ther. 21, 131‒138.
  42. Одонне К.-Ж., Жоливэ Э. (2015) Плазмида без устойчивости к антибиотику. Патент RU548809C2, бюлл. № 11 от 20.04.2015.
  43. Mignon C., Sodoyer R., Werle B. (2015) Antibiotic-free selection in biotherapeutics: now and forever. Pathogens. 4, 157‒181.
  44. Chen Z., Yao J., Zhang P., Wang P., Ni S., Liu T., Zhao Y., Tang K., Sun Y., Qian Q., Wang X. (2023) Minimized antibiotic-free plasmid vector for gene therapy utilizing a new toxin-antitoxin system. Metab. Eng. 79, 86‒96.
  45. Khalid K., Poh C.L. (2023) The development of DNA vaccines against SARS-CoV-2. Adv. Med. Sci. 68, 213‒226.
  46. Grunwald T., Ulbert S. (2015) Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases. Clin. Exp. Vaccine Res. 4, 1‒10.
  47. Dey A., Rajanathan T.C., Chandra H., Pericherla H.P., Kumar S., Choonia H.S., Bajpai M., Singh A., Sinha A., Saini G., Dalal P., Vandriwala S., Raheem M., Divate D., Navlani N., Sharma V., Parikh A., Prasath S., Rao M., Maithal K. (2021) Immunogenic potential of DNA vaccine candidate, ZyCoV-D against SARS-CoV-2 in animal models. Vaccine. 39, 4108‒4116.
  48. Khobragade A., Bhate S., Ramaiah V., Deshpande S., Giri K., Phophle H., Supe P., Godara I., Revanna R., Nagarkar R., Sanmukhani J., Dey A., Rajanathan C., Kansagra M., Koradia P. (2022) Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India. Lancet. 399, 1313‒1321.
  49. Ohlson J. (2020) Plasmid manufacture is the bottleneck of the genetic medicine revolution. Drug Discov. Today. 25, 1891‒1893.
  50. Monet L., Grandchamp N. (2020) The emergence of the next-generation vaccines. Arch. Clin. Biomed. Res. 4, 325‒348.
  51. Jiang Y., Gao X., Xu K., Wang J., Huang H., Shi C., Yang W., Kang Y., Curtiss R., Yang G., Wang C. (2019) A novel Cre recombinase-mediated in vivo minicircle DNA (CRIM) vaccine provides partial protection against Newcastle disease virus. Appl. Environ. Microbiol. 85, e00407-19.
  52. Almeida A.M., Queiroz J.A., Sousa F., Sousa Â. (2020) Minicircle DNA: the future for DNA-based vectors? Trends Biotechnol. 38, 1047‒1051.
  53. Gaspar V., Melo-Diogo D.D., Costa E., Moreira A., Queiroz J., Pichon C., Correia I., Sousa F. (2015) Minicircle DNA vectors for gene therapy: advances and applications. Expert Opin. Biol. Ther. 15, 353‒379.
  54. Munye M.M., Tagalakis A.D., Barnes J.L., Brown R.E., McAnulty R.J., Howe S.J., Hart S.L. (2016) Minicircle DNA provides enhanced and prolonged transgene expression following airway gene transfer. Sci. Rep. 6, 23125.
  55. Stenler S., Blomberg P., Smith C.E. (2014) Safety and efficacy of DNA vaccines: plasmids vs. minicircles. Hum. Vaccin. Immunother. 10, 1306‒1308.
  56. Darquet A.M., Rangara R., Kreiss P., Schwartz B., Naimi S., Delaere P., Crouzet J., Scherman D. (1999) Minicircle: an improved DNA molecule for in vitro and in vivo gene transfer. Gene Ther. 6, 209‒218.
  57. Osborn M.J., McElmurry R.T., Lees C.J., DeFeo A.P., Chen Z.Y., Kay M.A., Naldini L., Freeman G., Tolar J., Blazar B.R. (2011) Minicircle DNA-based gene therapy coupled with immune modulation permits long-term expression of α-L-iduronidase in mice with mucopolysaccharidosis type I. Mol. Ther. 19, 450‒460.
  58. Wang Q., Jiang W., Chen Y., Liu P., Sheng C., Chen S., Zhang H., Pan C., Gao S., Huang W. (2014) In vivo electroporation of minicircle DNA as a novel method of vaccine delivery to enhance HIV-1-specific immune responses. J. Virol. 88, 1924‒1934.
  59. Dietz W.M., Skinner N.E., Hamilton S.E., Jund M.D., Heitfeld S.M., Litterman A.J., Hwu P., Chen Z., Salazar A., Ohlfest J., Blazar B., Pennell C., Osborn M.J. (2013) Minicircle DNA is superior to plasmid DNA in eliciting antigen-specific CD8+ T-cell responses. Mol. Ther. 21, 1526‒1535.
  60. Alves C.P., Prazeres D.M.F., Monteiro G.A. (2021) Minicircle biopharmaceuticals — an overview of purification strategies. Front. Chem. Eng. 2, 612594.
  61. Schakowski F., Gorschlueter M., Buttgereit P., Maerten A., Lilienfeld-Toal M.V., Junghans C., Schroff M., König-Merediz S., Ziske C., Strehl J., Sauerbruch T., Wittig B., Schmidt-Wolf I.G. (2007) Minimal size MIDGE vectors improve transgene expression in vivo. In Vivo. 21, 17‒23.
  62. Junghans C., Schroff M., Koenig‐Merediz S.A., Alfken J., Smith C., Sack F., Schirmbeck R., Wittig B. (2001) Form follows function: the design of minimalistic immunogenically defined gene expression (MIDGE®) constructs. In: Plasmids for Therapy and Vaccination. Ed. Schleef M. Wiley, 139‒146. https://doi.org/10.1002/9783527612833.ch08
  63. Moreno S., Lopez-Fuertes L., Vila-Coro A.J., Sack F., Smith C.A., Konig S.A., Timón M. (2004) DNA immunisation with minimalistic expression constructs. Vaccine. 22, 1709‒1716.
  64. Leutenegger C.M., Boretti F.S., Mislin C.N., Flynn J.N., Schroff M., Habel A., Lutz H. (2000) Immunization of cats against feline immunodeficiency virus (FIV) infection by using minimalistic immunogenic defined gene expression vector vaccines expressing FIV gp140 alone or with feline interleukin-12 (IL-12), IL-16, or a CpG motif. J. Virol. 74, 10447‒10457.
  65. Zheng C., Juhls C., Oswald D., Sack F., Westfehling I., Wittig B., Babiuk L.A. (2006) Effect of different nuclear localization sequences on the immune responses induced by a MIDGE vector encoding bovine herpesvirus-1 glycoprotein D. Vaccine. 24, 4625‒4629.
  66. Galling N., Kobelt D., Aumann J., Schmidt M., Wittig B., Schlag P.M., Walther W. (2012) Intratumoral dispersion, retention, systemic biodistribution, and clearance of a small-size tumor necrosis factor-α-expressing MIDGE vector after nonviral in vivo jet-injection gene transfer. Hum. Gene Ther. Methods. 23, 264‒270.
  67. Adie T., Orefo I., Kysh D., Kondas K., Thapa S., Extance J., Rothwell P.J. (2022) dbDNA™: an advanced platform for genetic medicines. Drug Discov. Today. 27, 374‒377.
  68. Scott V.L., Patel A., Villarreal D.O., Hensley S.E., Ragwan E., Yan J., Weiner D.B. (2015) Novel synthetic plasmid and Doggybone™ DNA vaccines induce neutralizing antibodies and provide protection from lethal influenza challenge in mice. Hum. Vaccin. Immunother. 11, 1972‒1982.
  69. Walters A.A., Kinnear E., Shattock R.J., McDonald J.U., Caproni L.J., Porter N., Tregoning J.S. (2014) Comparative analysis of enzymatically produced novel linear DNA constructs with plasmids for use as DNA vaccines. Gene Ther. 21, 645‒652.
  70. Allen A., Wang C., Caproni L.J., Sugiyarto G., Harden E., Douglas L.R., Savelyeva N. (2018) Linear doggybone DNA vaccine induces similar immunological responses to conventional plasmid DNA independently of immune recognition by TLR9 in a pre-clinical model. Cancer Immunol. Immunother. 67, 627‒638.
  71. Mucker E.M., Brocato R.L., Principe L.M., Kim R.K., Zeng X., Smith J.M., Hooper J.W. (2022) SARS-CoV-2 Doggybone DNA vaccine produces cross-variant neutralizing antibodies and is protective in a COVID-19 animal model. Vaccines (Basel). 10, 1104.
  72. Bulcha J.T., Wang Y., Ma H., Tai P.W., Gao G. (2021) Viral vector platforms within the gene therapy landscape. Signal Transduct. Target. Ther. 6, 53.
  73. Ghosh S., Brown A.M., Jenkins C., Campbell K. (2020) Viral vector systems for gene therapy: a comprehensive literature review of progress and biosafety challenges. Appl. Biosafety. 25, 7‒18.
  74. Lundstrom K. (2021) Viral vectors for COVID-19 vaccine development. Viruses. 13, 317.
  75. Lu B., Lim J.M., Yu B., Song S., Neeli P., Sobhani N., Chai D. (2024) The next-generation DNA vaccine platforms and delivery systems: advances, challenges and prospects. Front. Immunol. 15, 1332939.
  76. Lim M., Badruddoza A.Z.M., Firdous J., Azad M., Mannan A., Al-Hilal T.A., Islam M.A. (2020) Engineered nanodelivery systems to improve DNA vaccine technologies. Pharmaceutics. 12, 30.
  77. Shah M.A.A., Ali Z., Ahmad R., Qadri I., Fatima K., He N. (2015) DNA mediated vaccines delivery through nanoparticles. J. Nanosci. Nanotechnol. 15, 41‒53.
  78. Patel R., Kaki M., Potluri V.S., Kahar P., Khanna D. (2022) A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson. Hum. Vaccin. Immunother. 18, 2002083.
  79. Tenchov R., Bird R., Curtze A.E., Zhou Q. (2021) Lipid nanoparticles‒from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano. 15, 16982‒17015.
  80. Khan M.S., Baskoy S.A., Yang C., Hong J., Chae J., Ha H., Choi J. (2023) Lipid-based colloidal nanoparticles for applications in targeted vaccine delivery. Nanoscale Adv. 5, 1853‒1869.
  81. Karunakaran B., Gupta R., Patel P., Salave S., Sharma A., Desai D., Kommineni N. (2023) Emerging trends in lipid-based vaccine delivery: a special focus on developmental strategies, fabrication methods, and applications. Vaccines (Basel). 11(3), 661.
  82. Saade F., Petrovsky N. (2012) Technologies for enhanced efficacy of DNA vaccines. Expert Rev. Vaccines. 11, 189‒209.
  83. Mahale N.B., Thakkar P.D., Mali R.G., Walunj D.R., Chaudhari S.R. (2012) Niosomes: novel sustained release nonionic stable vesicular systems–an overview. Adv. Colloid Interface Sci. 183, 46‒54.
  84. Ge X., Wei M., He S., Yuan W.E. (2019) Advances of non-ionic surfactant vesicles (niosomes) and their application in drug delivery. Pharmaceutics. 11, 55.
  85. Jain S., Singh P., Mishra V., Vyas S.P. (2005) Mannosylated niosomes as adjuvant–carrier system for oral genetic immunization against hepatitis B. Immunol. Lett. 101, 41‒49.
  86. Vyas S.P., Singh R. P., Jain S., Mishra V., Mahor S., Singh P., Dubey P. (2005) Non-ionic surfactant based vesicles (niosomes) for non-invasive topical genetic immunization against hepatitis B. Int. J. Pharm. 296, 80‒86.
  87. Pamornpathomkul B., Niyomtham N., Yingyongnarongkul B.E., Prasitpuriprecha C., Rojanarata T., Ngawhirunpat T., Opanasopit P. (2018) Cationic niosomes for enhanced skin immunization of plasmid DNA-encoding ovalbumin via hollow microneedles. AAPS PharmSciTech. 19, 481‒488.
  88. Hou X., Zaks T., Langer R., Dong Y. (2021) Lipid nanoparticles for mRNA delivery. Nat. Rev. Mat. 6, 1078‒1094.
  89. Garcia-Fuentes M., Alonso M.J. (2012) Chitosan-based drug nanocarriers: where do we stand? J. Control. Release. 161, 496‒504.
  90. Shae D., Postma A., Wilson J.T. (2016) Vaccine delivery: where polymer chemistry meets immunology. Ther. Deliv. 7, 193‒196.
  91. Buschmann M.D., Merzouki A., Lavertu M., Thibault M., Jean M., Darras V. (2013) Chitosans for delivery of nucleic acids. Adv. Drug Deliv. Rev. 65, 1234‒1270.
  92. Kumar M.N.V.R. (2000) A review of chitin and chitosan applications. React. Funct. Polym. 46, 1‒27.
  93. Ali A., Ahmed S. (2018) A review on chitosan and its nanocomposites in drug delivery. Int. J. Biol. Macromol. 109, 273‒286.
  94. Nanishi E., Dowling D.J., Levy O. (2020) Toward precision adjuvants: optimizing science and safety. Curr. Opin. Pediatr. 32, 125‒138.
  95. Li J., Cai C., Li J., Li J., Li J., Sun T., Yu G. (2018) Chitosan-based nanomaterials for drug delivery. Molecules. 23, 2661.
  96. Babaei M., Eshghi H., Abnous K., Rahimizadeh M., Ramezani M. (2017) Promising gene delivery system based on polyethylenimine-modified silica nanoparticles. Cancer Gene Ther. 24, 156‒164.
  97. Shen C., Li J., Zhang Y., Li Y., Shen G., Zhu J., Tao J. (2017) Polyethylenimine-based micro/nanoparticles as vaccine adjuvants. Int. J. Nanomedicine. 12, 5443‒5460.
  98. Torrieri-Dramard L., Lambrecht B., Ferreira H.L., Van den Berg T., Klatzmann D., Bellier B. (2011) Intranasal DNA vaccination induces potent mucosal and systemic immune responses and cross-protective immunity against influenza viruses. Mol. Ther. 19, 602‒611.
  99. Suk J.S., Xu Q., Kim N., Hanes J., Ensign L.M. (2016) PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Adv. Drug Deliv. Rev. 99, 28‒51.
  100. Ho J.K., White P.J., Pouton C.W. (2018) Self-crosslinking lipopeptide/DNA/PEGylated particles: a new platform for DNA vaccination designed for assembly in aqueous solution. Mol. Ther. Nucleic Acids. 12, 504‒517.
  101. Liu Y., Xu Y., Tian Y., Chen C., Wang C., Jiang X. (2014) Functional nanomaterials can optimize the efficacy of vaccines. Small. 10, 4505‒4520.
  102. Li X., Naeem A., Xiao S., Hu L., Zhang J., Zheng Q. (2022) Safety challenges and application strategies for the use of dendrimers in medicine. Pharmaceutics. 14, 1292.
  103. Bober Z., Bartusik-Aebisher D., Aebisher D. (2022) Application of dendrimers in anticancer diagnostics and therapy. Molecules. 27, 3237.
  104. Chis A.A., Dobrea C., Morgovan C., Arseniu A.M., Rus L.L., Butuca A., Frum A. (2020) Applications and limitations of dendrimers in biomedicine. Molecules. 25, 3982.
  105. Karpenko L.I., Apartsin E.K., Dudko S.G., Starostina E.V., Kaplina O.N., Antonets D.V., Bazhan S.I. (2020) Cationic polymers for the delivery of the Ebola DNA vaccine encoding artificial T-cell immunogen. Vaccines (Basel). 8, 718.
  106. Santos A., Veiga F., Figueiras A. (2019) Dendrimers as pharmaceutical excipients: synthesis, properties, toxicity and biomedical applications. Materials. 13, 65.
  107. Petrovici A.R., Pinteala M., Simionescu N. (2023) Dextran formulations as effective delivery systems of therapeutic agents. Molecules. 28, 1086.
  108. Sun G., Mao J.J. (2012) Engineering dextran-based scaffolds for drug delivery and tissue repair. Nanomedicine. 7, 1771‒1784.
  109. Hu Q., Lu Y., Luo Y. (2021) Recent advances in dextran-based drug delivery systems: from fabrication strategies to applications. Carbohydr. Polym. 264, 117999.
  110. Лебедев Л.Р., Карпенко Л.И., Порываева В.А., Азаев М.Ш., Рябчикова Е.И., Гилева И.П., Ильичев А.А. (2000) Конструирование вирусоподобных частиц, экспонирующих эпитопы ВИЧ-1. Молекуляр. биология. 34, 480‒485.
  111. Karpenko L.I., Rudometov A.P., Sharabrin S.V., Shcherbakov D.N., Borgoyakova M.B., Bazhan S.I., Ilyichev A.A. (2021) Delivery of mRNA vaccine against SARS-CoV-2 using a polyglucin: spermidine conjugate. Vaccines (Basel). 9, 76.
  112. Карпенко Л.И., Бажан С.И., Богрянцева М.П., Рындюк Н.Н., Гинько З.И., Кузубов В.И., Ильичев А.А. (2016) Комбинированная вакцина против ВИЧ-1 на основе искусственных полиэпитопных иммуногенов: результаты I фазы клинических испытаний. Биоорган. химия. 42, 191‒191.
  113. Sadeghian I., Heidari R., Sadeghian S., Raee M.J., Negahdaripour M. (2022) Potential of cell-penetrating peptides (CPPs) in delivery of antiviral therapeutics and vaccines. Eur. J. Pharm. Sci. 169, 106094.
  114. Kowalski P.S., Rudra A., Miao L., Anderson D.G. (2019) Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol. Ther. 27, 710‒728.
  115. Jorritsma S.H.T., Gowans E.J., Grubor-Bauk B., Wijesundara D.K. (2016) Delivery methods to increase cellular uptake and immunogenicity of DNA vaccines. Vaccine. 34, 5488‒5494.
  116. Kisakov D.N., Belyakov I.M., Kisakova L.A., Yakovlev V.A., Tigeeva E.V., Karpenko L.I. (2024) The use of electroporation to deliver DNA-based vaccines. Expert Rev. Vaccines. 23, 102‒123.
  117. Weniger B.G., Papania M.J. (2013) Alternative vaccine delivery methods. In: Vaccines (6th edition). Eds Plotkin S.A., Orenstein W.A., Offit P.A. 1200‒1231. doi: 10.1016/B978-1-4557-0090-5.00063-X
  118. Mitragotri S. (2006) Current status and future prospects of needle-free liquid jet injectors. Nat. Rev. Drug Discov. 5, 543‒548.
  119. Wang R., Bian Q., Xu Y., Xu D., Gao J. (2021) Recent advances in mechanical force-assisted transdermal delivery of macromolecular drugs. Int. J. Pharm. 602, 120598.
  120. Кисаков Д.Н., Кисакова Л.А., Шарабрин С.В., Яковлев В.А., Тигеева Е.В., Боргоякова М.Б., Старостина Е.В., Зайковская А.В., Рудометов А.П., Рудометова Н.Б., Карпенко Л.И., Ильичев А.А. (2023) Доставка экспериментальной мРНК-вакцины, кодируюшей RBD SARS-CoV-2, с помощью струйной инжекции. Бюллетень экспериментальной биологии и медицины. 176, 751‒756.
  121. Manam S., Ledwith B.J., Barnum A. B., Troilo P.J., Pauley C.J., Harper L.B., Nichols W.W. (2001) Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA. Intervirology. 43, 273‒281.
  122. Houser K.V., Chen G.L., Carter C., Crank M.C., Nguyen T.A., Burgos Florez M.C., Ledgerwood J.E. (2022) Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial. Nat. Med. 28, 383‒391.
  123. Pearton M., Saller V., Coulman S. A., Gateley C., Anstey A.V., Zarnitsyn V., Birchall J.C. (2012) Microneedle delivery of plasmid DNA to living human skin: formulation coating, skin insertion and gene expression. J. Control. Release. 160, 561‒569.
  124. Song J.M., Kim Y.C., Eunju O., Compans R.W., Prausnitz M.R., Kang S.M. (2012) DNA vaccination in the skin using microneedles improves protection against influenza. Mol. Ther. 20, 1472–1480.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Schematic representation of a plasmid DNA vaccine.

Download (208KB)
Indexing metadata
3. Fig. 2. Scheme of activation of humoral and cellular immunity in response to the introduction of a DNA vaccine. Designations: pDNA – plasmid DNA (here and below in the figures); CTL (cytotoxic T cells) – cytotoxic T-lymphocytes.

Download (549KB)
Indexing metadata
4. Fig. 3. Technology for obtaining minicircular DNA.

Download (125KB)
Indexing metadata
5. Fig. 4. Technology for obtaining MIDGE DNA.

Download (379KB)
Indexing metadata
6. Fig. 5. Technology for obtaining DoggyboneTM DNA.

Download (475KB)
Indexing metadata
7. Fig. 6. Methods of delivery of DNA vaccines.

Download (612KB)
Indexing metadata

Copyright (c) 2025 Russian Academy of Sciences