Modern approaches to the construction and use of recombinant viruses

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Abstract

The review describes certain viral vectors and considers various methods for constructing recombinant viruses with special attention paid to the homologous recombination and CRISPR/Cas9 system, and also describes the capabilities of using various cloning vectors (different plasmids, BAC etc.). The review also presents a comparative analysis of the effectiveness and safety of using various viral vectors, both for creating recombinant vaccines and for obtaining oncolytic viruses, as well as medicines for gene therapy.

About the authors

Polina V. Prokhorova

Federal Scientific Center – All-Russian Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko of the Russian Academy of Sciences

Author for correspondence.
Email: appoliproh@yandex.ru
ORCID iD: 0009-0009-7278-5541

Research Assistant in the Working Group (Department) for the Implementation of the State Assignment in the Field of Infectious Pathology of Animals

Russian Federation, Moscow, 109428

Natalia N. Vlasova

Federal Scientific Center – All-Russian Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko of the Russian Academy of Sciences

Email: vlanany@yandex.ru
ORCID iD: 0000-0001-8707-7710

Dr. Sci. (Biol), Senior Researcher, Principal Researcher of the Laboratory of Biochemistry and Molecular Biology

Russian Federation, Moscow, 109428

Anton G. Yuzhakov

Federal Scientific Center – All-Russian Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko of the Russian Academy of Sciences

Email: anton_oskol@mail.ru
ORCID iD: 0000-0002-0426-9678

Ph.D. (Biol), Head of the Laboratory of Biochemistry and Molecular Biology

Russian Federation, Moscow, 109428

Alexey M. Gulyukin

Federal Scientific Center – All-Russian Research Institute of Experimental Veterinary Medicine named after K.I. Skryabin and Ya.R. Kovalenko of the Russian Academy of Sciences

Email: admin@viev.ru
ORCID iD: 0000-0003-2160-4770

D. Sci. (Vet), Corresponding Member RAS, Director

Russian Federation, Moscow, 109428

References

  1. Travieso T., Li J., Mahesh S., Mello J.D.F.R.E., Blasi M. The use of viral vectors in vaccine development. NPJ Vaccines. 2022; 7(1): 75. https://doi.org/10.1038/s41541-022-00503-y
  2. Jogi H.R., Smaraki N., Rajak K.K., Yadav A.K., Bhatt M., Einstien C., et al. Revolutionizing Veterinary Health with Viral Vector-Based Vaccines. Indian J. Microbiol. 2024; 64(3): 867–78. https://doi.org/10.1007/s12088-024-01341-3
  3. Brisse M., Vrba S.M., Kirk N., Liang Y., Ly H. Emerging concepts and technologies in vaccine development. Front. Immunol. 2020; 11: 583077. https://doi.org/10.3389/fimmu.2020.583077
  4. Choi K.S. Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines. Clin. Exp. Vaccine Res. 2017; 6(2): 72. https://doi.org/10.7774/cevr.2017.6.2.72
  5. Mendell J.R., Al-Zaidy S., Shell R., Arnold W.D., Rodino-Klapac L.R., Prior T.W., et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N. Engl. J. Med. 2017; 377(18): 1713–22. https://doi.org/10.1056/NEJMoa1706198
  6. Ogbonmide T., Rathore R., Rangrej S.B., Hutchinson S., Lewis M., Ojilere S., et al. Gene Therapy for Spinal Muscular Atrophy (SMA): a review of current challenges and safety considerations for onasemnogene abeparvovec (zolgensma). Cureus. 2023; 15(3): e36197. https://doi.org/10.7759/cureus.36197
  7. Ozelo M.C., Mahlangu J., Pasi K.J., Giermasz A., Leavitt A.D., Laffan M., et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. N. Engl. J. Med. 2022; 386(11): 1013–25. https://doi.org/10.1056/NEJMoa2113708
  8. Testa F., Bacci G., Falsini B., Iarossi G., Melillo P., Mucciolo D.P., et al. Voretigene neparvovec for inherited retinal dystrophy due to RPE65 mutations: a scoping review of eligibility and treatment challenges from clinical trials to real practice. Eye (Lond.). 2024; 38(13): 2504–15. https://doi.org/10.1038/s41433-024-03065-6
  9. Link E.K., Tscherne A., Sutter G., Smith E.R., Gurwith M., Chen R.T., et al. A Brighton collaboration standardized template with key considerations for a benefit/risk assessment for a viral vector vaccine based on a non-replicating modified vaccinia virus Ankara viral vector. Vaccine. 2025; 43(Pt. 1): 126521. https://doi.org/10.1016/j.vaccine.2024.126521
  10. Wang S., Liang B., Wang W., Li L., Feng N., Zhao Y., et al. Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases. Signal Transduct. Target Ther. 2023; 8(1): 149. https://doi.org/10.1038/s41392-023-01408-5
  11. Zhan W., Muhuri M., Tai P.W.L., Gao G. Vectored immunotherapeutics for infectious diseases: can rAAVs be the game changers for fighting transmissible pathogens? Front. Immunol. 2021; 12: 673699. https://doi.org/10.3389/fimmu.2021.673699
  12. Nascimento I.P., Leite L.C.C. Recombinant vaccines and the development of new vaccine strategies. Braz. J. Med. Biol. Res. 2012; 45(12): 1102–11. https://doi.org/10.1590/s0100-879x2012007500142
  13. Tukhvatulin A.I., Dolzhikova I.V., Dzharullaeva A.S., Grousova D.M., Kovyrshina A.V., Zubkova O.V., et al. Safety and immunogenicity of rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine against SARS-CoV-2 in healthy adolescents: an open-label, non-randomized, multicenter, phase 1/2, dose-escalation study. Front. Immunol. 2023; 14: 1228461. https://doi.org/10.3389/fimmu.2023.1228461
  14. de Pinho Favaro M.T., Atienza-Garriga J., Martínez-Torró C., Parladé E., Vázquez E., Corchero J.L., et al. Recombinant vaccines in 2022: a perspective from the cell factory. Microb. Cell Fact. 2022; 21(1): 203. https://doi.org/10.1186/s12934-022-01929-8
  15. Valencia S., Gill R.B., Dowdell K.C., Wang Y., Hornung R., Bowman J.J., et al. Comparison of vaccination with rhesus CMV (RhCMV) soluble gB with a RhCMV replication-defective virus deleted for MHC class I immune evasion genes in a RhCMV challenge model. Vaccine. 2019; 37(2): 333–42. https://doi.org/10.1016/j.vaccine.2018.08.043
  16. Rasmussen T.B., Risager P.C., Fahnøe U., Friis M.B., Belsham G.J., Höper D., et al. Efficient generation of recombinant RNA viruses using targeted recombination-mediated mutagenesis of bacterial artificial chromosomes containing full-length cDNA. BMC Genomics. 2013; 14: 819. https://doi.org/10.1186/1471-2164-14-819
  17. Zhan X., Lee M., Xiao J., Liu F. Construction and characterization of murine cytomegaloviruses that contain transposon insertions at open reading frames m09 and M83. J. Virol. 2000; 74(16): 7411–21. https://doi.org/10.1186/1471-2164-14-819
  18. Urnov F.D., Miller J.C., Lee Y.L., Beausejour C.M., Rock J.M., Augustus S., et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature. 2005; 435(7042): 646–51. https://doi.org/10.1038/nature03556
  19. Sakuma T., Hosoi S., Woltjen K., Suzuki K.I., Kashiwagi K., Wada H., et al. Efficient TALEN construction and evaluation methods for human cell and animal applications. Genes Cells. 2013; 18(4): 315–26. https://doi.org/10.1111/gtc.12037
  20. Kuo L., Godeke G.J., Raamsman M.J., Masters P.S., Rottier P.J. Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier. J. Virol. 2000; 74(3): 1393–406. https://doi.org/10.1128/jvi.74.3.1393-1406.2000
  21. Edmonds J., van Grinsven E., Prow N., Bosco-Lauth A., Brault A.C., Bowen R.A., et al. A novel bacterium-free method for generation of flavivirus infectious DNA by circular polymerase extension reaction allows accurate recapitulation of viral heterogeneity. J. Virol. 2013; 87(4): 2367–72. https://doi.org/10.1128/JVI.03162-12
  22. Sedova E.S., Shcherbinin D.N., Migunov A.I., Smirnov Yu.A., Logunov D.Yu., Shmarov M.M., et al. Recombinant influenza vaccines. Acta Naturae. 2012; 4(4): 17–27.
  23. Walsh E.P., Baron M.D., Rennie L.F., Monaghan P., Anderson J., Barrett T. Recombinant rinderpest vaccines expressing membrane-anchored proteins as genetic markers: evidence of exclusion of marker protein from the virus envelope. J. Virol. 2000; 74(21): 10165–75. https://doi.org/10.1128/jvi.74.21.10165-10175.2000
  24. Supotnitskiy M.V. Genotherapeutic vector systems based on viruses. Biopreparats (Biopharmaceuticals). 2011; (3): 15–26.
  25. Blasi M., Wescott E.C., Baker E.J., Mildenberg B., LaBranche C., Rountree W., et al. Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques. NPJ Vaccines. 2020; 5(1): 36. https://doi.org/10.1038/s41541-020-0186-5
  26. Blasi M., Negri D., LaBranche C., Alam S.M., Baker E.J., Brunner E.C., et al. IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells. Commun. Biol. 2018; 1: 134. https://doi.org/10.1038/s42003-018-0131-6
  27. Wang D., Wang X.W., Peng X.C., Xiang Y., Song S.B., Wang Y.Y., et al. CRISPR/Cas9 genome editing technology significantly accelerated herpes simplex virus research. Cancer Gene Ther. 2018; 25(5-6): 93–105. https://doi.org/10.1038/s41417-018-0016-3
  28. Chen J.S., Dagdas Y.S., Kleinstiver B.P., Welch M.M., Sousa A.A., Harrington L.B., et al. Enhanced proofreading governs CRISPR-Cas9 targeting accuracy. Nature. 2017; 550(7676): 407–10. https://doi.org/10.1038/nature24268
  29. Liu M., Rehman S., Tang X., Gu K., Fan Q., Chen D., et al. Methodologies for improving HDR efficiency. Front. Genet. 2018; 9: 691. https://doi.org/10.3389/fgene.2018.00691
  30. Tomita A., Sasanuma H., Owa T., Nakazawa Y., Shimada M., Fukuoka T., et al. Inducing multiple nicks promotes interhomolog homologous recombination to correct heterozygous mutations in somatic cells. Nat. Commun. 2023; 14(1): 5607. https://doi.org/10.1038/s41467-023-41048-5
  31. Nora L.C., Westmann C.A., Martins-Santana L., Alves L.F., Monteiro L.M.O., Guazzaroni M.E., et al. The art of vector engineering: towards the construction of next-generation genetic tools. Microb. Biotechnol. 2019; 12(1): 125–47. https://doi.org/10.1111/1751-7915.13318
  32. Julin D. Plasmid cloning vectors. In: Bell E., ed. Molecular Life Sciences. New York: Springer; 2014. https://doi.org/10.1007/978-1-4614-6436-5_86-1
  33. Helinski D.R. A brief history of plasmids. EcoSal Plus. 2022; 10(1): eESP00282021. https://doi.org/10.1128/ecosalplus.esp-0028-2021
  34. Zhou Y., Li C., Ren C., Hu J., Song C., Wang X., et al. One-step assembly of a porcine epidemic diarrhea virus infectious cDNA clone by homologous recombination in yeast: rapid manipulation of viral genome with CRISPR/Cas9 gene-editing technology. Front. Microbiol. 2022; 13: 787739. https://doi.org/10.3389/fmicb.2022.787739
  35. Dix T.C., Lassota A., Brauer U., Haussmann I.U., Soller M. Gap-repair recombineering for efficient retrieval of large DNA fragments from BAC clones and manipulation of large high-copy number plasmids. BMC Methods. 2024; 1(1): 11. https://doi.org/10.1186/s44330-024-00011-6
  36. Hao M., Tang J., Ge S., Li T., Xia N. Bacterial-artificial-chromosome-based genome editing methods and the applications in herpesvirus research. Microorganisms. 2023; 11(3): 589. https://doi.org/10.3390/microorganisms11030589.
  37. Chen F., Li Y.Y., Yu Y.L., Dai J., Huang J.L., Lin J. Simplified plasmid cloning with a universal MCS design and bacterial in vivo assembly. BMC Biotechnol. 2021; 21(1): 24. https://doi.org/10.1186/s12896-021-00679-6
  38. Li C., Wen A., Shen B., Lu J., Huang Y., Chang Y. FastCloning: a highly simplified, purification-free, sequence- and ligation-independent PCR cloning method. BMC Biotechnol. 2011; 11: 92. https://doi.org/10.1186/1472-6750-11-92
  39. Walhout A.J., Temple G.F., Brasch M.A., Hartley J.L., Lorson M.A., van den Heuvel S., et al. GATEWAY recombinational cloning: application to the cloning of large numbers of open reading frames or ORFeomes. Methods Enzymol. 2000; 328: 575–92. https://doi.org/10.1016/s0076-6879(00)28419-x
  40. Motohashi K. A simple and efficient seamless DNA cloning method using SLiCE from Escherichia coli laboratory strains and its application to SLiP site-directed mutagenesis. BMC Biotechnol. 2015; 15: 47. https://doi.org/10.1186/s12896-015-0162-8
  41. Engler C., Gruetzner R., Kandzia R., Marillonnet S. Golden gate shuffling: a one-pot DNA shuffling method based on type IIs restriction enzymes. PLoS One. 2009; 4(5): e5553. https://doi.org/10.1371/journal.pone.0005553
  42. Koskela E.V., Frey A.D. Homologous recombinatorial cloning without the creation of single-stranded ends: exonuclease and ligation-independent cloning (ELIC). Mol. Biotechnol. 2015; 57(3): 233–40. https://doi.org/10.1007/s12033-014-9817-2
  43. Li M.Z., Elledge S.J. Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC. Nat. Methods. 2007; 4(3): 251–6. https://doi.org/10.1038/nmeth1010
  44. Tan L., Strong E.J., Woods K., West N.P. Homologous alignment cloning: a rapid, flexible and highly efficient general molecular cloning method. PeerJ. 2018; 6: e5146. https://doi.org/10.7717/peerj.5146
  45. Jeong J.Y., Yim H.S., Ryu J.Y., Lee H.S., Lee J.H., Seen D.S., et al. One-step sequence- and ligation-independent cloning as a rapid and versatile cloning method for functional genomics studies. Appl. Environ. Microbiol. 2012; 78(15): 5440–3. https://doi.org/10.1128/AEM.00844-12
  46. Zhu B., Cai G., Hall E.O., Freeman G.J. In-fusion assembly: seamless engineering of multidomain fusion proteins, modular vectors, and mutations. Biotechniques. 2007; 43(3): 354–9. https://doi.org/10.2144/000112536
  47. Zhou D., Zhou X., Bian A., Li H., Chen H., Small J.C., et al. An efficient method of directly cloning chimpanzee adenovirus as a vaccine vector. Nat. Protoc. 2010; 5(11): 1775–85. https://doi.org/10.1038/nprot.2010.134
  48. Davison A.J., Benkő M., Harrach B. Genetic content and evolution of adenoviruses. J. Gen. Virol. 2003; 84(Pt. 11): 2895–908. https://doi.org/10.1099/vir.0.19497-0
  49. Davis A.R., Wivel N.A., Palladino J.L., Tao L., Wilson J.M. Construction of adenoviral vectors. Mol. Biotechnol. 2001; 18(1): 63–70. https://doi.org/10.1385/MB:18:1:63
  50. Elkashif A., Alhashimi M., Sayedahmed E.E., Sambhara S., Mittal S.K. Adenoviral vector-based platforms for developing effective vaccines to combat respiratory viral infections. Clin. Transl. Immunology. 2021; 10(10): e1345. https://doi.org/10.1002/cti2.1345
  51. Gray G., Buchbinder S., Duerr A. Overview of STEP and Phambili trial results: two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine. Curr. Opin. HIV AIDS. 2010; 5(5): 357–61. https://doi.org/10.1097/COH.0b013e32833d2d2b
  52. Logunov D.Y., Dolzhikova I.V., Shcheblyakov D.V., Tukhvatulin A.I., Zubkova O.V., Dzharullaeva A.S., et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet. 2021; 397(10275): 671–81. https://doi.org/10.1016/S0140-6736(21)00386-X
  53. Wu S., Huang J., Zhang Z., Wu J., Zhang J., Hu H., et al. Safety, tolerability, and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults: preliminary report of an open-label and randomised phase 1 clinical trial. Lancet Infect. Dis. 2021; 21(12): 1654–64. https://doi.org/10.1016/S1473-3099(21)00396-0
  54. Zhu F.C., Li Y.H., Guan X.H., Hou L.H., Wang W.J., Li J.X., et al. Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial. Lancet. 2020; 395(10240): 1845–54. https://doi.org/10.1016/S0140-6736(20)31208-3
  55. Xu J.W., Wang B.S., Gao P., Huang H.T., Wang F.Y., Qiu W., et al. Safety and immunogenicity of heterologous boosting with orally administered aerosolized bivalent adenovirus type-5 vectored COVID-19 vaccine and B.1.1.529 variant adenovirus type-5 vectored COVID-19 vaccine in adults 18 years and older: a randomized, double blinded, parallel controlled trial. Emerg. Microbes. Infect. 2024; 13(1): 2281355. https://doi.org/10.1080/22221751.2023.2281355
  56. See I., Su J.R., Lale A., Woo E.J., Guh A.Y., Shimabukuro T.T., et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021; 325(24): 2448–56. https://doi.org/10.1001/jama.2021.7517
  57. Sadoff J., Gray G., Vandebosch A., Cárdenas V., Shukarev G., Grinsztejn B., et al. Safety and efficacy of single-dose Ad26.COV2.S vaccine against COVID-19. N. Engl. J. Med. 2021; 384(23): 2187–201. https://doi.org/10.1056/NEJMoa2101544
  58. Bos R., Rutten L., van der Lubbe J.E.M., Bakkers M.J.G., Hardenberg G., Wegmann F., et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines. 2020; 5: 91. https://doi.org/10.1038/s41541-020-00243-x
  59. Zhu F.C., Hou L.H., Li J.X., Wu S.P., Liu P., Zhang G.R., et al. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet. 2015; 385(9984): 2272–9. https://doi.org/10.1016/S0140-6736(15)60553-0
  60. Zhang Z., Zhao Z., Wang Y., Wu S., Wang B., Zhang J., et al. Comparative immunogenicity analysis of intradermal versus intramuscular immunization with a recombinant human adenovirus type 5 vaccine against Ebola virus. Front. Immunol. 2022; 13: 963049. https://doi.org/10.3389/fimmu.2022.963049
  61. Anywaine Z., Whitworth H., Kaleebu P., Praygod G., Shukarev G., Manno D., et al. Safety and immunogenicity of a 2-dose heterologous vaccination regimen with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines: 12-month data from a phase 1 randomized clinical trial in Uganda and Tanzania. J. Infect. Dis. 2019; 220(1): 46–56. https://doi.org/10.1016/S1473-3099(21)00128-6
  62. Schultz N.H., Sørvoll I.H., Michelsen A.E., Munthe L.A., Lund-Johansen F., Ahlen M.T., et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N. Engl. J. Med. 2021; 384(22): 2124–30. https://doi.org/10.1056/NEJMoa2104882
  63. Greinacher A., Selleng K., Palankar R., Wesche J., Handtke S., Wolff M., et al. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood. 2021; 138(22): 2256–68. https://doi.org/10.1182/blood.2021013231
  64. Baker A.T., Boyd R.J., Sarkar D., Teijeira-Crespo A., Chan C.K., Bates E., et al. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Sci. Adv. 2021; 7(49): eabl8213. https://doi.org/10.1126/sciadv.abl8213
  65. Ewer K., Rampling T., Venkatraman N., Bowyer G., Wright D., Lambe T., et al. A monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA. N. Engl. J. Med. 2016; 374(17): 1635–46. https://doi.org/10.1056/NEJMoa1411627
  66. Warimwe G.M., Lorenzo G., Lopez-Gil E., Reyes-Sandoval A., Cottingham M.G., Spencer A.J., et al. Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice. Virol. J. 2013; 10: 349. https://doi.org/10.1186/1743-422X-10-349
  67. Manning W.C., Paliard X., Zhou S., Pat Bland M., Lee A.Y., Hong K., et al. Genetic immunization with adeno-associated virus vectors expressing herpes simplex virus type 2 glycoproteins B and D. J. Virol. 1997; 71(10): 7960–2. https://doi.org/10.1128/JVI.71.10.7960-7962
  68. Derkaev A.A., Ryabova E.I., Esmagambetov I.B., Shcheblyakov D.V., Godakova S.A., Vinogradova I.D., et al. rAAV expressing recombinant neutralizing antibody for the botulinum neurotoxin type A prophylaxis. Front. Microbiol. 2022; 13: 960937. https://doi.org/10.3389/fmicb.2022.960937
  69. Liao G., Lau H., Liu Z., Li C., Xu Z., Qi X., et al. Single-dose rAAV5-based vaccine provides long-term protective immunity against SARS-CoV-2 and its variants. Virol. J. 2022; 19(1): 212. https://doi.org/10.1186/s12985-022-01940-w
  70. Pipe S.W., Leebeek F.W.G., Recht M., Key N.S., Castaman G., Miesbach W., et al. Gene therapy with etranacogene dezaparvovec for hemophilia B. N. Engl. J. Med. 2023; 388(8): 706–18. https://doi.org/10.1056/NEJMoa2211644
  71. Ertl H.C.J. Immunogenicity and toxicity of AAV gene therapy. Front. Immunol. 2022; 13: 975803. https://doi.org/10.3389/fimmu.2022.975803
  72. Pantaleo G., Janes H., Karuna S., Grant S., Ouedraogo G.L., Allen M., et al. Safety and immunogenicity of a multivalent HIV vaccine comprising envelope protein with either DNA or NYVAC vectors (HVTN 096): a phase 1b, double-blind, placebo-controlled trial. Lancet HIV. 2019; 6(11): e737–49. https://doi.org/10.1016/S2352-3018(20)30002-3
  73. Mastrangelo M.J., Eisenlohr L.C., Gomella L., Lattime E.C. Poxvirus vectors: orphaned and underappreciated. J. Clin. Invest. 2000; 105(8): 1031–4. https://doi.org/10.1172/JCI9819
  74. Draper S.J., Cottingham M.G., Gilbert S.C. Utilizing poxviral vectored vaccines for antibody induction-progress and prospects. Vaccine. 2013; 31(39): 4223–30.
  75. Ura T., Okuda K., Shimada M. Developments in viral vector-based vaccines. Vaccines. 2014; 2(3): 624–41. https://doi.org/10.1016/j.vaccine.2013.05.091
  76. Chen Z., Zhang L., Qin C., Ba L., Yi C.E., Zhang F., et al. Recombinant modified vaccinia virus Ankara expressing the spike glycoprotein of severe acute respiratory syndrome coronavirus induces protective neutralizing antibodies primarily targeting the receptor binding region. J. Virol. 2005; 79(5): 2678–88. https://doi.org/10.1128/JVI.79.5.2678-2688.2005
  77. Gönczöl E., Berensci K., Pincus S., Endresz V., Méric C., Paoletti E., et al. Preclinical evaluation of an ALVAC (canarypox) – human cytomegalovirus glycoprotein B vaccine candidate. Vaccine. 1995; 13(12): 1080–5. https://doi.org/10.1016/0264-410x(95)00048-6
  78. Naberezhnaya E.R., Soboleva A.V., Vorobyev P.O., Vadekhina V.V., Yusubalieva G.M., Isaeva I.V., et al. Interferon type I-expressing recombinant vaccinia virus as a platform for selective immunotherapy of glioblastoma and melanoma. Bulletin of Russian State Medical University. 2024; (6): 18–26. https://doi.org/10.24075/brsmu.2024.072 https://elibrary.ru/rgazed
  79. Kuligina E.V., Richter V.A., Vlassov V.V. Antitumor drug based on the gene-modified vaccinia virus VV-GMCSF-lact. (in Russian)
  80. Open multi-cohort study of the first phase of safety of a drug based on double recombinant vaccinia virus VV-GMCSF-Lact; 2025. Available at: https://clinicaltrials.gov/study/NCT05376527?%20cond=cancer&intr=lactaptin&rank=1
  81. Shakiba Y., Naberezhnaya E.R., Kochetkov D.V., Yusubalieva G.M., Vorobyev P.O., Chumakov P.M., et al. Comparison of the oncolytic activity of recombinant vaccinia virus strains LIVP-RFP and MVA-RFP against solid tumors. Bulletin of Russian State Medical University. 2023; (2): 4–11. https://doi.org/10.24075/brsmu.2023.010 (in Russian)
  82. Su D., Han L., Shi C., Li Y., Qian S., Feng Z., et al. An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application. Virulence. 2024; 15(1): 2425744. https://doi.org/10.1080/21505594.2024.2425744
  83. Ingusci S., Goins W.F., Cohen J.B., Miyagawa Y., Knipe D.M., Glorioso J.C. Next-generation replication-defective HSV vectors for delivery of large DNA payloads. Mol. Ther. 2025; 33(5): 2205–16. https://doi.org/10.1016/j.ymthe.2025.03.055
  84. Kaliberdenko V.B., Aramyan E.E., Zinchenko M.S. Features of oncolytic virotherapy and its application for the treatment of glioblastoma. Klinicheskii razbor v obshchei meditsine. 2024; 5(12): 51–4. https://doi.org/10.47407/kr2024.5.12.00537 (in Russian)
  85. Gubanova N.V., Gaitan A.S., Razumov I.A., Mordvinov V.A., Krivoshapkin A.L., Netsesov S.V., et al. Oncolytic viruses in the treatment of gliomas. Mol. Biol. 2012; 46(6): 780–9. https://elibrary.ru/rgnuux
  86. Senzer N.N., Kaufman H.L., Amatruda T., Nemunaitis M., Reid T., Daniels G., et al. Phase II Clinical trial of a granulocyte-macrophage colony-stimulating factor – encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma. JCO. 2009; 27(34): 5763–71. https://doi.org/10.1200/JCO.2009.24.367
  87. Guide S.V., Gonzalez M.E., Bağcı I.S., Agostini B., Chen H., Feeney G., et al. Trial of Beremagene Geperpavec (B-VEC) for dystrophic epidermolysis bullosa. N. Engl. J. Med. 2022; 387(24): 2211–9. https://doi.org/10.1056/NEJMoa2206663
  88. Ollmann Saphire E. A vaccine against Ebola Virus. Cell. 2020; 181(1): 6. https://doi.org/10.1016/j.cell.2020.03.011
  89. Munis A.M., Bentley E.M., Takeuchi Y. A tool with many applications: vesicular stomatitis virus in research and medicine. Expert Opin. Biol. Ther. 2020; 20(10): 1187–201. https://doi.org/10.1080/14712598.2020.1787981
  90. Mire C.E., Geisbert J.B., Agans K.N., Satterfield B.A., Versteeg K.M., Fritz E.A., et al. Durability of a vesicular stomatitis virus-based Marburg virus vaccine in nonhuman primates. PLoS One. 2014; 9(4): e94355. https://doi.org/10.1371/journal.pone.0094355
  91. Stein D.R., Warner B.M., Soule G., Tierney K., Frost K.L., Booth S., et al. A recombinant vesicular stomatitis-based Lassa fever vaccine elicits rapid and long-term protection from lethal Lassa virus infection in guinea pigs. NPJ Vaccines. 2019; 4: 8. https://doi.org/10.1038/s41541-019-0104-x
  92. Hamilton A.M., Foster P.J., Ronald J.A. Evaluating nonintegrating lentiviruses as safe vectors for noninvasive reporter-based molecular imaging of multipotent mesenchymal stem cells. Hum. Gene Ther. 2018; 29(10): 1213–25. https://doi.org/10.1089/hum.2018.111
  93. Dong W., Kantor B. Lentiviral vectors for delivery of gene-editing systems based on CRISPR/Cas: current state and perspectives. Viruses. 2021; 13(7): 1288. https://doi.org/10.3390/v13071288
  94. Apolonia L. The old and the new: prospects for non-integrating lentiviral vector technology. Viruses. 2020; 12(10): 1103. https://doi.org/10.3390/v12101103
  95. Negri D.R.M., Rossi A., Blasi M., Michelini Z., Leone P., Chiantore M.V., et al. Simian immunodeficiency virus-Vpx for improving integrase defective lentiviral vector-based vaccines. Retrovirology. 2012; 9: 69. https://doi.org/10.1186/1742-4690-9-69
  96. Gallinaro A., Borghi M., Bona R., Grasso F., Calzoletti L., Palladino L., et al. Integrase defective lentiviral vector as a vaccine platform for delivering influenza antigens. Front. Immunol. 2018; 9: 171. https://doi.org/10.3389/fimmu.2018.00171
  97. Fontana J.M., Christos P.J., Michelini Z., Negri D., Cara A., Salvatore M. Mucosal immunization with integrase-defective lentiviral vectors protects against influenza virus challenge in mice. PLoS One. 2014; 9(5): e97270. https://doi.org/10.1371/journal.pone.0097270
  98. Chen Z. Parainfluenza virus 5-vectored vaccines against human and animal infectious diseases. Rev. Med. Virol. 2018; 28(2): e1965. https://doi.org/10.1002/rmv.1965
  99. An D., Li K., Rowe D.K., Diaz M.C.H., Griffin E.F., Beavis A.C., et al. Protection of K18-hACE2 mice and ferrets against SARS-CoV-2 challenge by a single-dose mucosal immunization with a parainfluenza virus 5-based COVID-19 vaccine. Sci. Adv. 2021; 7(27): eabi5246. https://doi.org/10.1016/j.isci.2021.103379
  100. Liang B., Ngwuta J.O., Herbert R., Swerczek J., Dorward D.W., Amaro-Carambot E., et al. Packaging and prefusion stabilization separately and additively increase the quantity and quality of Respiratory Syncytial Virus (RSV)-neutralizing antibodies induced by an RSV fusion protein expressed by a parainfluenza virus vector. J. Virol. 2016; 90(21): 10022–38. https://doi.org/10.1128/JVI.01196-16
  101. Lingemann M., Liu X., Surman S., Liang B., Herbert R., Hackenberg A.D., et al. Attenuated human parainfluenza virus type 1 expressing Ebola virus glycoprotein GP administered intranasally is immunogenic in African green monkeys. J. Virol. 2017; 91(10): e02469-16. https://doi.org/10.1128/JVI.02469-16
  102. Brandler S., Tangy F. Recombinant vector derived from live attenuated measles virus: potential for flavivirus vaccines. Comp. Immunol. Microbiol. Infect. Dis. 2008; 31(2-3): 271–91. https://doi.org/10.1016/j.cimid.2007.07.012
  103. Ebenig A., Lange M.V., Mühlebach M.D. Versatility of live-attenuated measles viruses as platform technology for recombinant vaccines. NPJ Vaccines. 2022; 7(1): 119. https://doi.org/10.1038/s41541-022-00543-4
  104. Desprès P., Combredet C., Frenkiel M.P., Lorin C., Brahic M., Tangy F. Live measles vaccine expressing the secreted form of the West Nile virus envelope glycoprotein protects against West Nile virus encephalitis. J. Infect. Dis. 2005; 191(2): 207–14. https://doi.org/10.1086/426824
  105. Rossi S.L., Comer J.E., Wang E., Azar S.R., Lawrence W.S., Plante J.A., et al. Immunogenicity and efficacy of a measles virus-vectored chikungunya vaccine in nonhuman primates. J. Infect. Dis. 2019; 220(5): 735–42. https://doi.org/10.1093/infdis/jiz202
  106. Nürnberger C., Bodmer B.S., Fiedler A.H., Gabriel G., Mühlebach M.D. A measles virus-based vaccine candidate mediates protection against Zika virus in an allogeneic mouse pregnancy model. J. Virol. 2019; 93(3): e01485-18. https://doi.org/10.1128/JVI.01485-18
  107. Fournier P., Arnold A., Wilden H., Schirrmacher V. Newcastle disease virus induces pro-inflammatory conditions and type I interferon for counter-acting Treg activity. Int. J. Oncol. 2012; 40(3): 840–50. https://doi.org/10.3892/ijo.2011.1265
  108. Kim S.H., Samal S. Newcastle disease virus as a vaccine vector for development of human and veterinary vaccines. Viruses. 2016; 8(7): 183. https://doi.org/10.3390/v8070183
  109. Kuiken T., Buijs P., Van Run P., Van Amerongen G., Koopmans M., Van Den Hoogen B. Pigeon paramyxovirus type 1 from a fatal human case induces pneumonia in experimentally infected cynomolgus macaques (Macaca fascicularis). Vet. Res. 2017; 48(1): 80. https://doi.org/10.1186/s13567-017-0486-6
  110. Sun W., Liu Y., Amanat F., González-Domínguez I., McCroskery S., Slamanig S., et al. A Newcastle disease virus expressing a stabilized spike protein of SARS-CoV-2 induces protective immune responses. Nat. Commun. 2021; 12(1): 6197. https://doi.org/10.1038/s41467-021-26499-y
  111. DiNapoli J.M., Yang L., Samal S.K., Murphy B.R., Collins P.L., Bukreyev A. Respiratory tract immunization of non-human primates with a Newcastle disease virus-vectored vaccine candidate against Ebola virus elicits a neutralizing antibody response. Vaccine. 2010; 29(1): 17–25. https://doi.org/10.1016/j.vaccine.2010.10.024
  112. Gonçalves M.A. Adeno-associated virus: from defective virus to effective vector. Virol. J. 2005; 2(1): 43. https://doi.org/10.1186/1743-422X-2-43
  113. Somia N., Verma I.M. Gene therapy: trials and tribulations. Nat. Rev. Genet. 2000; 1(2): 91–9. https://doi.org/10.1038/35038533
  114. Schubert M., Harmison G.G., Meier E. Primary structure of the vesicular stomatitis virus polymerase (L) gene: evidence for a high frequency of mutations. J. Virol. 1984; 51(2): 505–14. https://doi.org/10.1128/JVI.51.2.505-514.1984
  115. An H.Y., Kim G.N., Wu K., Kang C.Y. Genetically modified VSVNJ vector is capable of accommodating a large foreign gene insert and allows high level gene expression. Virus Res. 2013; 171(1): 168–77. https://doi.org/10.1016/j.virusres.2012.11.007
  116. Kalidasan V., Ng W.H., Ishola O.A., Ravichantar N., Tan J.J., Das K.T. A guide in lentiviral vector production for hard-to-transfect cells, using cardiac-derived c-kit expressing cells as a model system. Sci. Rep. 2021; 11(1): 19265. https://doi.org/10.1038/s41598-021-98657-7
  117. Jenkins G.M., Pagel M., Gould E.A., de A Zanotto P.M., Holmes E.C. Evolution of base composition and codon usage bias in the genus Flavivirus. J. Mol. Evol. 2001; 52: 383. https://doi.org/10.1007/s002390010168
  118. Duffy S., Shackelton L.A., Holmes E.C. Rates of evolutionary change in viruses: patterns and determinants. Nat. Rev. Genet. 2008; 9: 267. https://doi.org/10.1038/nrg2323

Supplementary files

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2. Fig. 1. Synthesis of the target protein by cellular ribosomes.

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3. Fig. 2. The main methods for creating recombinant viruses. a – homologous recombination; b – CRISPR/Cas9 system.

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