Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice
<b>Background:</b> Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve...
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2025-01-01
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| author | Denis N. Kisakov Larisa I. Karpenko Lyubov A. Kisakova Sergey V. Sharabrin Mariya B. Borgoyakova Ekaterina V. Starostina Oleg S. Taranov Elena K. Ivleva Oleg V. Pyankov Anna V. Zaykovskaya Elena V. Dmitrienko Vladimir A. Yakovlev Elena V. Tigeeva Irina Alekseevna Bauer Svetlana I. Krasnikova Nadezhda B. Rudometova Andrey P. Rudometov Artemiy A. Sergeev Alexander A. Ilyichev |
| author_facet | Denis N. Kisakov Larisa I. Karpenko Lyubov A. Kisakova Sergey V. Sharabrin Mariya B. Borgoyakova Ekaterina V. Starostina Oleg S. Taranov Elena K. Ivleva Oleg V. Pyankov Anna V. Zaykovskaya Elena V. Dmitrienko Vladimir A. Yakovlev Elena V. Tigeeva Irina Alekseevna Bauer Svetlana I. Krasnikova Nadezhda B. Rudometova Andrey P. Rudometov Artemiy A. Sergeev Alexander A. Ilyichev |
| author_sort | Denis N. Kisakov |
| collection | DOAJ |
| description | <b>Background:</b> Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution. <b>Methods:</b> In the first part of the study, the optimal conditions providing low traumatization and high expression of the model mRNA-GFP molecule in the tissues of laboratory animals were determined. Then, we used the selected protocol to immunize BALB/c mice with mRNA-RBD encoding the SARS-CoV-2 receptor-binding domain (RBD). It was demonstrated that mice vaccinated with naked mRNA-RBD developed a high level of specific antibodies with virus-neutralizing activity. The vaccine also induced a strong RBD-specific T-cell response and reduced the viral load in the lungs of the animals after infection with the SARS-CoV-2 virus. The level of immune response in mice immunized with mRNA-RBD using a spring-loaded jet injector was comparable to that in animals immunized with mRNA-RBD encapsulated in LNPs. <b>Results:</b> In this study, the efficacy of an inexpensive, simple, and safe method of mRNA delivery using a spring-loaded jet injector was evaluated and validated. <b>Conclusions:</b> Our findings suggest that the jet injection method may be a possible alternative to LNPs for delivering mRNA vaccines against SARS-CoV-2 infection. |
| format | Article |
| id | doaj-art-829b09024e724a0983b717fad54d4412 |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Vaccines |
| spelling | doaj-art-829b09024e724a0983b717fad54d44122025-01-24T13:51:49ZengMDPI AGVaccines2076-393X2025-01-011316510.3390/vaccines13010065Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in MiceDenis N. Kisakov0Larisa I. Karpenko1Lyubov A. Kisakova2Sergey V. Sharabrin3Mariya B. Borgoyakova4Ekaterina V. Starostina5Oleg S. Taranov6Elena K. Ivleva7Oleg V. Pyankov8Anna V. Zaykovskaya9Elena V. Dmitrienko10Vladimir A. Yakovlev11Elena V. Tigeeva12Irina Alekseevna Bauer13Svetlana I. Krasnikova14Nadezhda B. Rudometova15Andrey P. Rudometov16Artemiy A. Sergeev17Alexander A. Ilyichev18State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090 Novosibirsk, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, RussiaState Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor, World-Class Genomic Research Center for Biological Safety and Technological Independence, Federal Scientific and Technical Program on the Development of Genetic Technologies, 630559 Koltsovo, Russia<b>Background:</b> Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution. <b>Methods:</b> In the first part of the study, the optimal conditions providing low traumatization and high expression of the model mRNA-GFP molecule in the tissues of laboratory animals were determined. Then, we used the selected protocol to immunize BALB/c mice with mRNA-RBD encoding the SARS-CoV-2 receptor-binding domain (RBD). It was demonstrated that mice vaccinated with naked mRNA-RBD developed a high level of specific antibodies with virus-neutralizing activity. The vaccine also induced a strong RBD-specific T-cell response and reduced the viral load in the lungs of the animals after infection with the SARS-CoV-2 virus. The level of immune response in mice immunized with mRNA-RBD using a spring-loaded jet injector was comparable to that in animals immunized with mRNA-RBD encapsulated in LNPs. <b>Results:</b> In this study, the efficacy of an inexpensive, simple, and safe method of mRNA delivery using a spring-loaded jet injector was evaluated and validated. <b>Conclusions:</b> Our findings suggest that the jet injection method may be a possible alternative to LNPs for delivering mRNA vaccines against SARS-CoV-2 infection.https://www.mdpi.com/2076-393X/13/1/65mRNA vaccinesneedle-free jet injectionlipid nanoparticlesRBDSARS-CoV-2immune response |
| spellingShingle | Denis N. Kisakov Larisa I. Karpenko Lyubov A. Kisakova Sergey V. Sharabrin Mariya B. Borgoyakova Ekaterina V. Starostina Oleg S. Taranov Elena K. Ivleva Oleg V. Pyankov Anna V. Zaykovskaya Elena V. Dmitrienko Vladimir A. Yakovlev Elena V. Tigeeva Irina Alekseevna Bauer Svetlana I. Krasnikova Nadezhda B. Rudometova Andrey P. Rudometov Artemiy A. Sergeev Alexander A. Ilyichev Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice Vaccines mRNA vaccines needle-free jet injection lipid nanoparticles RBD SARS-CoV-2 immune response |
| title | Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice |
| title_full | Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice |
| title_fullStr | Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice |
| title_full_unstemmed | Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice |
| title_short | Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice |
| title_sort | jet injection of naked mrna encoding the rbd of the sars cov 2 spike protein induces a high level of a specific immune response in mice |
| topic | mRNA vaccines needle-free jet injection lipid nanoparticles RBD SARS-CoV-2 immune response |
| url | https://www.mdpi.com/2076-393X/13/1/65 |
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