Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a novel LPP-de...
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MDPI AG
2025-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/13/1/93 |
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| author | Xuchang Shan Ruiwen Han Xueting Cheng Jialuo Bing Zhenyong Qi Shucai Sun Tangqi Wang Qiaohong Chu Yao Deng Desheng Zhai Wenjie Tan |
| author_facet | Xuchang Shan Ruiwen Han Xueting Cheng Jialuo Bing Zhenyong Qi Shucai Sun Tangqi Wang Qiaohong Chu Yao Deng Desheng Zhai Wenjie Tan |
| author_sort | Xuchang Shan |
| collection | DOAJ |
| description | Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a novel LPP-delivered mRNA vaccine that expresses the respiratory syncytial virus prefusion protein (RSV pre-F) to evaluate its immunogenicity and protective effect in a mouse model. We synthesized mRNAs with gene modification for RSV pre-F and prepared mRNA vaccines using the LPP delivery platform, referred to as RSV pre-F LPP-mRNA. RSV pre-F protein expression in mRNA vaccines was characterized in vitro. Then, we evaluated the effects of the immune response and protection of this mRNA vaccine in mice up to 24 weeks post-vaccination. Following booster immunization, robust and long-lasting RSV pre-F-specific IgG antibodies were detected in the serum of mice, which exhibited Th1/Th2 balanced IgG response and cross-neutralizing antibodies against different subtypes (RSV A2, B18537, and clinical isolate hRSV/C-Tan/BJ 202301), with a clear dose–response relationship observed. RSV pre-F-specific IgG antibodies were maintained in the mice for an extended period, lasting up to 18 weeks post-immunization. Concurrently, multifunctional RSV F-specific CD8<sup>+</sup> T cells (IFN–γ, IL-2, and TNF-α) were detected in the mice. After RSV A2 challenge, the RSV pre-F LPP-mRNA vaccine led to a significant reduction in viral replication, while reduced pathological damage was observed in lung tissue. The LPP-delivered mRNA vaccine expressing RSV pre-F induces a robust and long-lasting immune response and protection, indicating good prospects for further development and application. |
| format | Article |
| id | doaj-art-c6fbcb3f86fe4dc4ad8cf4629b8b92ea |
| institution | Kabale University |
| issn | 2076-393X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj-art-c6fbcb3f86fe4dc4ad8cf4629b8b92ea2025-01-24T13:51:55ZengMDPI AGVaccines2076-393X2025-01-011319310.3390/vaccines13010093Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial VirusXuchang Shan0Ruiwen Han1Xueting Cheng2Jialuo Bing3Zhenyong Qi4Shucai Sun5Tangqi Wang6Qiaohong Chu7Yao Deng8Desheng Zhai9Wenjie Tan10School of Public Health, Xinxiang Medical University, Xinxiang 453003, ChinaZhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaSchool of Public Health, Xinxiang Medical University, Xinxiang 453003, ChinaSchool of Public Health, Xinxiang Medical University, Xinxiang 453003, ChinaDepartment of Nuclear Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang 050004, ChinaZhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaSchool of Public Health, Xinxiang Medical University, Xinxiang 453003, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, China CDC, 155 Changbai Road, Beijing 102206, ChinaRespiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and children. mRNA vaccines based on the lipopolyplex (LPP) platform have been previously reported, but they remain unapplied in RSV vaccine development. In this study, we developed a novel LPP-delivered mRNA vaccine that expresses the respiratory syncytial virus prefusion protein (RSV pre-F) to evaluate its immunogenicity and protective effect in a mouse model. We synthesized mRNAs with gene modification for RSV pre-F and prepared mRNA vaccines using the LPP delivery platform, referred to as RSV pre-F LPP-mRNA. RSV pre-F protein expression in mRNA vaccines was characterized in vitro. Then, we evaluated the effects of the immune response and protection of this mRNA vaccine in mice up to 24 weeks post-vaccination. Following booster immunization, robust and long-lasting RSV pre-F-specific IgG antibodies were detected in the serum of mice, which exhibited Th1/Th2 balanced IgG response and cross-neutralizing antibodies against different subtypes (RSV A2, B18537, and clinical isolate hRSV/C-Tan/BJ 202301), with a clear dose–response relationship observed. RSV pre-F-specific IgG antibodies were maintained in the mice for an extended period, lasting up to 18 weeks post-immunization. Concurrently, multifunctional RSV F-specific CD8<sup>+</sup> T cells (IFN–γ, IL-2, and TNF-α) were detected in the mice. After RSV A2 challenge, the RSV pre-F LPP-mRNA vaccine led to a significant reduction in viral replication, while reduced pathological damage was observed in lung tissue. The LPP-delivered mRNA vaccine expressing RSV pre-F induces a robust and long-lasting immune response and protection, indicating good prospects for further development and application.https://www.mdpi.com/2076-393X/13/1/93respiratory syncytial virusprefusion proteinmRNA vaccinelipopolyplex platformimmune protection |
| spellingShingle | Xuchang Shan Ruiwen Han Xueting Cheng Jialuo Bing Zhenyong Qi Shucai Sun Tangqi Wang Qiaohong Chu Yao Deng Desheng Zhai Wenjie Tan Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus Vaccines respiratory syncytial virus prefusion protein mRNA vaccine lipopolyplex platform immune protection |
| title | Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus |
| title_full | Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus |
| title_fullStr | Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus |
| title_full_unstemmed | Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus |
| title_short | Robust and Long-Lasting Immunity and Protection in Mice Induced by Lipopolyplex-Delivered mRNA Vaccines Expressing the Prefusion Protein of Respiratory Syncytial Virus |
| title_sort | robust and long lasting immunity and protection in mice induced by lipopolyplex delivered mrna vaccines expressing the prefusion protein of respiratory syncytial virus |
| topic | respiratory syncytial virus prefusion protein mRNA vaccine lipopolyplex platform immune protection |
| url | https://www.mdpi.com/2076-393X/13/1/93 |
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