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Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection
The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting t...
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| Published in: | Journal of nanobiotechnology 2024-05, Vol.22 (1), p.295-295, Article 295 |
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| container_end_page | 295 |
| container_issue | 1 |
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| container_title | Journal of nanobiotechnology |
| container_volume | 22 |
| creator | Zhang, Yupei Zhai, Songhui Huang, Hai Qin, Shugang Sun, Min Chen, Yuting Lan, Xing Li, Guohong Huang, Zhiying Wang, Denggang Luo, Yaoyao Xiao, Wen Li, Hao He, Xi Chen, Meiwan Peng, Xingchen Song, Xiangrong |
| description | The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines. |
| doi_str_mv | 10.1186/s12951-024-02488-3 |
| format | article |
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However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.</description><identifier>ISSN: 1477-3155</identifier><identifier>EISSN: 1477-3155</identifier><identifier>DOI: 10.1186/s12951-024-02488-3</identifier><identifier>PMID: 38807131</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Antibodies, Viral - immunology ; Antigens ; Antigens, Viral - chemistry ; Antigens, Viral - genetics ; Antigens, Viral - immunology ; B cells ; COVID-19 - immunology ; COVID-19 - prevention & control ; COVID-19 Vaccines - immunology ; Female ; Health aspects ; Humans ; Immune response ; Immunity, Cellular ; Immunity, Humoral ; Messenger RNA ; Mice ; Mice, Inbred BALB C ; mRNA Vaccines ; Peptides ; Pharmaceutical research ; Protein Sorting Signals ; RNA sequencing ; RNA, Messenger - genetics ; SARS-CoV-2 - immunology ; Signal sequence ; Simulation methods ; SRP ; Vaccines ; Vaccines, Synthetic - immunology ; Virus</subject><ispartof>Journal of nanobiotechnology, 2024-05, Vol.22 (1), p.295-295, Article 295</ispartof><rights>2024. The Author(s).</rights><rights>COPYRIGHT 2024 BioMed Central Ltd.</rights><rights>The Author(s) 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c451t-d2049206fd9ab68c9d644deb343f1d59b950628d5b4cee110501c908771290ec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134928/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11134928/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,37013,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38807131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Yupei</creatorcontrib><creatorcontrib>Zhai, Songhui</creatorcontrib><creatorcontrib>Huang, Hai</creatorcontrib><creatorcontrib>Qin, Shugang</creatorcontrib><creatorcontrib>Sun, Min</creatorcontrib><creatorcontrib>Chen, Yuting</creatorcontrib><creatorcontrib>Lan, Xing</creatorcontrib><creatorcontrib>Li, Guohong</creatorcontrib><creatorcontrib>Huang, Zhiying</creatorcontrib><creatorcontrib>Wang, Denggang</creatorcontrib><creatorcontrib>Luo, Yaoyao</creatorcontrib><creatorcontrib>Xiao, Wen</creatorcontrib><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>He, Xi</creatorcontrib><creatorcontrib>Chen, Meiwan</creatorcontrib><creatorcontrib>Peng, Xingchen</creatorcontrib><creatorcontrib>Song, Xiangrong</creatorcontrib><title>Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection</title><title>Journal of nanobiotechnology</title><addtitle>J Nanobiotechnology</addtitle><description>The signal sequence played a crucial role in the efficacy of mRNA vaccines against virus pandemic by influencing antigen translation. However, limited research had been conducted to compare and analyze the specific mechanisms involved. In this study, a novel approach was introduced by substituting the signal sequence of the mRNA antigen to enhance its immune response. Computational simulations demonstrated that various signal peptides differed in their binding capacities with the signal recognition particle (SRP) 54 M subunit, which positively correlated with antigen translation efficiency. Our data revealed that the signal sequences of tPA and IL-6-modified receptor binding domain (RBD) mRNA vaccines sequentially led to higher antigen expression and elicited more robust humoral and cellular immune protection against the SARS-CoV-2 compared to the original signal sequence. By highlighting the importance of the signal sequence, this research provided a foundational and safe approach for ongoing modifications in signal sequence-antigen design, aiming to optimize the efficacy of mRNA vaccines.</description><subject>Animals</subject><subject>Antibodies, Viral - immunology</subject><subject>Antigens</subject><subject>Antigens, Viral - chemistry</subject><subject>Antigens, Viral - genetics</subject><subject>Antigens, Viral - immunology</subject><subject>B cells</subject><subject>COVID-19 - immunology</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 Vaccines - immunology</subject><subject>Female</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity, Cellular</subject><subject>Immunity, Humoral</subject><subject>Messenger RNA</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>mRNA Vaccines</subject><subject>Peptides</subject><subject>Pharmaceutical research</subject><subject>Protein Sorting Signals</subject><subject>RNA sequencing</subject><subject>RNA, Messenger - genetics</subject><subject>SARS-CoV-2 - immunology</subject><subject>Signal sequence</subject><subject>Simulation methods</subject><subject>SRP</subject><subject>Vaccines</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Virus</subject><issn>1477-3155</issn><issn>1477-3155</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptkk9v1DAQxSMEoqXwBTggS1zoIcV_E-eEVlULK1UgFThbXnucdbWxl9i7Klc-Oc6mVF0JRVGSmd88Z55eVb0l-IIQ2XxMhHaC1Jjy6ZayZs-qU8LbtmZEiOdP3k-qVyndYUwpp_xldcKkxC1h5LT6c-WcNx5CRsn3QW9Qgl87CAZQdGi4_bpAe22MD5AQhLUujYTyGpAO2fcQENxvR0jJx4BynL50sAfAD8MuANqOMYPJU1_32oeU0d6P5Rwf3Fx_Xb1wepPgzcPzrPp5ffXj8kt98-3z8nJxUxsuSK4txbyjuHG206tGms42nFtYMc4csaJbdQI3VFqx4gaAECwwMR2WbVtswmDYWbWcdW3Ud2o7-kGPv1XUXh0KceyVHrM3G1CSlcMo1o4zzbFpNCW02GVbK3AnHRStT7PWdrcawJriX9npSPS4E_xa9XGvCCGsrCGLwocHhTEWw1NWg08GNhsdIO6SYrghrRRckoK-n9Fel38rvsUiaSZcLdpONLwhfKIu_kOVy8LgTQzgfKkfDZwfDRQmw33u9S4ltfx-e8zSmTVjTGkE97gqwWoKo5rDqEoQ1SGMipWhd09Nehz5lz72F3PH2cs</recordid><startdate>20240528</startdate><enddate>20240528</enddate><creator>Zhang, Yupei</creator><creator>Zhai, Songhui</creator><creator>Huang, Hai</creator><creator>Qin, Shugang</creator><creator>Sun, Min</creator><creator>Chen, Yuting</creator><creator>Lan, Xing</creator><creator>Li, Guohong</creator><creator>Huang, Zhiying</creator><creator>Wang, Denggang</creator><creator>Luo, Yaoyao</creator><creator>Xiao, Wen</creator><creator>Li, Hao</creator><creator>He, Xi</creator><creator>Chen, Meiwan</creator><creator>Peng, Xingchen</creator><creator>Song, Xiangrong</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20240528</creationdate><title>Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection</title><author>Zhang, Yupei ; 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| subjects | Animals Antibodies, Viral - immunology Antigens Antigens, Viral - chemistry Antigens, Viral - genetics Antigens, Viral - immunology B cells COVID-19 - immunology COVID-19 - prevention & control COVID-19 Vaccines - immunology Female Health aspects Humans Immune response Immunity, Cellular Immunity, Humoral Messenger RNA Mice Mice, Inbred BALB C mRNA Vaccines Peptides Pharmaceutical research Protein Sorting Signals RNA sequencing RNA, Messenger - genetics SARS-CoV-2 - immunology Signal sequence Simulation methods SRP Vaccines Vaccines, Synthetic - immunology Virus |
| title | Efficient signal sequence of mRNA vaccines enhances the antigen expression to expand the immune protection against viral infection |
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