Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis
Toxoplasma gondii, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against T. gondii infection. Recently, mRNA vaccines have been rapidly developed, and their packagi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1161507/full |
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| author | Yizhuo Zhang Yizhuo Zhang Dan Li Dan Li Yu Shen Yu Shen Shiyu Li Shiyu Li Shaohong Lu Shaohong Lu Shaohong Lu Bin Zheng Bin Zheng Bin Zheng |
| author_facet | Yizhuo Zhang Yizhuo Zhang Dan Li Dan Li Yu Shen Yu Shen Shiyu Li Shiyu Li Shaohong Lu Shaohong Lu Shaohong Lu Bin Zheng Bin Zheng Bin Zheng |
| author_sort | Yizhuo Zhang |
| collection | DOAJ |
| description | Toxoplasma gondii, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against T. gondii infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from T. gondii, was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice via intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce T. gondii-specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after T. gondii challenge (P< 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively (P< 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against T. gondii infection. |
| first_indexed | 2024-04-09T18:08:26Z |
| format | Article |
| id | doaj.art-e96e47c8417143458af2c18b8039ee93 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T18:08:26Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-e96e47c8417143458af2c18b8039ee932023-04-14T05:30:35ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-04-011410.3389/fimmu.2023.11615071161507Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosisYizhuo Zhang0Yizhuo Zhang1Dan Li2Dan Li3Yu Shen4Yu Shen5Shiyu Li6Shiyu Li7Shaohong Lu8Shaohong Lu9Shaohong Lu10Bin Zheng11Bin Zheng12Bin Zheng13Institute of Parasitic Diseases, School of Basic Medicine and Forensics, Hangzhou Medical College, Hangzhou, ChinaEngineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaInstitute of Parasitic Diseases, School of Basic Medicine and Forensics, Hangzhou Medical College, Hangzhou, ChinaEngineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaInstitute of Parasitic Diseases, School of Basic Medicine and Forensics, Hangzhou Medical College, Hangzhou, ChinaEngineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaInstitute of Parasitic Diseases, School of Basic Medicine and Forensics, Hangzhou Medical College, Hangzhou, ChinaEngineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaInstitute of Parasitic Diseases, School of Basic Medicine and Forensics, Hangzhou Medical College, Hangzhou, ChinaEngineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Bio-tech Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaInstitute of Parasitic Diseases, School of Basic Medicine and Forensics, Hangzhou Medical College, Hangzhou, ChinaEngineering Research Center of Novel Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaKey Laboratory of Bio-tech Vaccine of Zhejiang Province, Hangzhou Medical College, Hangzhou, ChinaToxoplasma gondii, a specialized intracellular parasite, causes a widespread zoonotic disease and is a severe threat to social and economic development. There is a lack of effective drugs and vaccines against T. gondii infection. Recently, mRNA vaccines have been rapidly developed, and their packaging materials and technologies are well established. In this study, TGGT1_216200 (TG_200), a novel molecule from T. gondii, was identified using bioinformatic screening analysis. TG_200 was purified and encapsulated with a lipid nanoparticle (LNP) to produce the TG_200 mRNA-LNP vaccine. The immune protection provided by the new vaccine and its mechanisms after immunizing BABL/C mice via intramuscular injection were investigated. There was a strong immune response when mice were vaccinated with TG_200 mRNA-LNP. Elevated levels of anti-T. gondii-specific immunoglobulin G (IgG), and a higher IgG2a-to-IgG1 ratio was observed. The levels of interleukin-12 (IL-12), interferon-γ (IFN-γ), IL-4, and IL-10 were also elevated. The result showed that the vaccine induced a mixture of Th1 and Th2 cells, and Th1-dominated humoral immune response. Significantly increased antigen-specific splenocyte proliferation was induced by TG_200 mRNA-LNP immunization. The vaccine could also induce T. gondii-specific cytotoxic T lymphocytes (CTLs). The expression levels of interferon regulatory factor 8 (IRF8), T-Box 21 (T-bet), and nuclear factor kappa B (NF-κB) were significantly elevated after TG_200 mRNA-LNP immunization. The levels of CD83, CD86, MHC-I, MHC-II, CD8, and CD4 molecules were also higher. The results indicated that TG_200 mRNA-LNP produced specific cellular and humoral immune responses. Most importantly, TG_200 mRNA-LNP immunized mice survived significantly longer (19.27 ± 3.438 days) than the control mice, which died within eight days after T. gondii challenge (P< 0.001). The protective effect of adoptive transfer was also assessed, and mice receiving serum and splenocytes from mice immunized with TG_200 mRNA-LNP showed improved survival rates of 9.70 ± 1.64 days and, 13.40 ± 2.32 days, respectively (P< 0.001). The results suggested that TG_200 mRNA-LNP is a safe and promising vaccine against T. gondii infection.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1161507/fullToxoplasma gondiivaccinemRNAlipid nanoparticleimmune response |
| spellingShingle | Yizhuo Zhang Yizhuo Zhang Dan Li Dan Li Yu Shen Yu Shen Shiyu Li Shiyu Li Shaohong Lu Shaohong Lu Shaohong Lu Bin Zheng Bin Zheng Bin Zheng Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis Frontiers in Immunology Toxoplasma gondii vaccine mRNA lipid nanoparticle immune response |
| title | Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis |
| title_full | Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis |
| title_fullStr | Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis |
| title_full_unstemmed | Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis |
| title_short | Immunization with a novel mRNA vaccine, TGGT1_216200 mRNA-LNP, prolongs survival time in BALB/c mice against acute toxoplasmosis |
| title_sort | immunization with a novel mrna vaccine tggt1 216200 mrna lnp prolongs survival time in balb c mice against acute toxoplasmosis |
| topic | Toxoplasma gondii vaccine mRNA lipid nanoparticle immune response |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1161507/full |
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