The Marburg virus(MARV),belonging to the Filoviridae family,poses a significant global health threat,emphasizing the urgency to develop Marburg virus-like particle(VLP)vaccines for outbreak mitigation.The virus's ...The Marburg virus(MARV),belonging to the Filoviridae family,poses a significant global health threat,emphasizing the urgency to develop Marburg virus-like particle(VLP)vaccines for outbreak mitigation.The virus's menacing traits accentuate the need for such vaccines,which can be addressed by VLPs that mimic its structure safely,potentially overcoming past limitations.Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section,followed by an exploration of VLPs as transformative tools,capable of eliciting immune responses without conventional risks.Noteworthy milestones and achievements in Marburg VLP vaccine development,seen through preclinical and clinical trials,indicate potential cross-protection.Ongoing challenges,encompassing durability,strain diversity,and equitable distribution,are addressed,with proposed innovations like novel adjuvant,mRNA technology,and structure-based design poised to enhance Marburg VLP vaccines.This review highlights the transformative potential of Marburg VLPs in countering the virus,showcasing global collaboration,regulatory roles,and health equity for a safer future through the harmonious interplay of science,regulation,and global efforts.展开更多
The tremendous success of mRNA vaccine during the COVID-19 pandemic has captured attention globally and highlighted the transformative potential of mRNA technology in addressing infectious diseases[1].In comparison to...The tremendous success of mRNA vaccine during the COVID-19 pandemic has captured attention globally and highlighted the transformative potential of mRNA technology in addressing infectious diseases[1].In comparison to conventional protein antibody-based therapies,the delivery of mRNA-encoding antibod-ies presents a cost-effective and versatile approach with several advantages.These include eliminating the laborious process of in vitro protein expression,enabling flexible manufacturing processes,and eliciting rapid therapeutic responses[2-4].However,the clinical application of mRNA-encoded antibodies for infectious diseases remains limited to date,only one such construct-mRNA-1944-has been assessed in non-human primates and approved for phase I clinical trial[5,6].Several challenges hampered the broader clinical application of mRNA-encoded antibody therapies,including the requirement for higher dosages for intravenous administration,limited pharmacodynamic and pharmacokinetics data,as well as the lack of safety and efficacy profiles in non-human primates[7].展开更多
Background While mRNA vaccines represent a transformative platform for infectious disease control,their efficacy in antigen-presenting cells(APCs)remains vulnerable to endogenous regulatory networks,particularly micro...Background While mRNA vaccines represent a transformative platform for infectious disease control,their efficacy in antigen-presenting cells(APCs)remains vulnerable to endogenous regulatory networks,particularly microRNA(miR)-mediated translational suppression.This study addresses a critical gap in current vaccine design paradigms by systematically investigating host miR interference-an understudied barrier to robust antigen production.Main text APCs express cell-type-specific miR repertoires capable of binding vaccine mRNAs through conserved seed sequences,as evidenced by synthesis of experimental data from 67 studies demonstrating miR-mediated repression of exogenous transcripts.To decode these inhibitory interactions,the commentary proposes an inte-grated multi-omics framework combining Argonaute immunoprecipitation with crosslinking-based miR-mRNA interactome sequencing,enabling precise mapping of miR-vaccine mRNA binding events in vaccine-transfected APCs.Furthermore,the commentary suggests two actionable strategies for evading miR interference:(1)Synony-mous codon optimization at seed-match regions,achieving binding energy reduction while preserving antigenic-ity through degeneracy of genetic coding;(2)Targeted co-delivery of miR inhibitors.By bridging host RNA biology and vaccine engineering,this work provides a blueprint for developing miR-resistant mRNA vaccines for public health interventions.Conclusions miRs may inhibit mRNA vaccine translation in APCs,potentially reducing antigen production and weak-ening the resulting immune response.To address this,next-generation mRNA vaccines should incorporate"miR-proofing"strategies during design to avoid miR interference.展开更多
文摘The Marburg virus(MARV),belonging to the Filoviridae family,poses a significant global health threat,emphasizing the urgency to develop Marburg virus-like particle(VLP)vaccines for outbreak mitigation.The virus's menacing traits accentuate the need for such vaccines,which can be addressed by VLPs that mimic its structure safely,potentially overcoming past limitations.Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section,followed by an exploration of VLPs as transformative tools,capable of eliciting immune responses without conventional risks.Noteworthy milestones and achievements in Marburg VLP vaccine development,seen through preclinical and clinical trials,indicate potential cross-protection.Ongoing challenges,encompassing durability,strain diversity,and equitable distribution,are addressed,with proposed innovations like novel adjuvant,mRNA technology,and structure-based design poised to enhance Marburg VLP vaccines.This review highlights the transformative potential of Marburg VLPs in countering the virus,showcasing global collaboration,regulatory roles,and health equity for a safer future through the harmonious interplay of science,regulation,and global efforts.
基金supported by the National Key Research and Development Project of China(2022YFC2304100 and 2021YFC2302400)the National Natural Science Foundation of China(82371833,82350801,and 82222041)+1 种基金Cheng-Feng Qin was supported by the National Science Fund for Distinguished Young Scholars(81925025)the Innovation Fund for Medical Sciences(2019-I2M-5-049)from the Chinese Academy of Medical Sciences.
文摘The tremendous success of mRNA vaccine during the COVID-19 pandemic has captured attention globally and highlighted the transformative potential of mRNA technology in addressing infectious diseases[1].In comparison to conventional protein antibody-based therapies,the delivery of mRNA-encoding antibod-ies presents a cost-effective and versatile approach with several advantages.These include eliminating the laborious process of in vitro protein expression,enabling flexible manufacturing processes,and eliciting rapid therapeutic responses[2-4].However,the clinical application of mRNA-encoded antibodies for infectious diseases remains limited to date,only one such construct-mRNA-1944-has been assessed in non-human primates and approved for phase I clinical trial[5,6].Several challenges hampered the broader clinical application of mRNA-encoded antibody therapies,including the requirement for higher dosages for intravenous administration,limited pharmacodynamic and pharmacokinetics data,as well as the lack of safety and efficacy profiles in non-human primates[7].
基金funded by the Provincial Natural Science Foundation of Jiangxi(Grant No.20224BAB206113)the National Natural Science Foundation of China(Grant No.82141214)+1 种基金the Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program(Grant No CXTD22011)the Top Discipline of Jiangxi Province,Discipline of Chinese and Western Integrative Medicine at Jiangxi University of Chinese Medicine(Grant No.zxyylxk20220103)to TLX。
文摘Background While mRNA vaccines represent a transformative platform for infectious disease control,their efficacy in antigen-presenting cells(APCs)remains vulnerable to endogenous regulatory networks,particularly microRNA(miR)-mediated translational suppression.This study addresses a critical gap in current vaccine design paradigms by systematically investigating host miR interference-an understudied barrier to robust antigen production.Main text APCs express cell-type-specific miR repertoires capable of binding vaccine mRNAs through conserved seed sequences,as evidenced by synthesis of experimental data from 67 studies demonstrating miR-mediated repression of exogenous transcripts.To decode these inhibitory interactions,the commentary proposes an inte-grated multi-omics framework combining Argonaute immunoprecipitation with crosslinking-based miR-mRNA interactome sequencing,enabling precise mapping of miR-vaccine mRNA binding events in vaccine-transfected APCs.Furthermore,the commentary suggests two actionable strategies for evading miR interference:(1)Synony-mous codon optimization at seed-match regions,achieving binding energy reduction while preserving antigenic-ity through degeneracy of genetic coding;(2)Targeted co-delivery of miR inhibitors.By bridging host RNA biology and vaccine engineering,this work provides a blueprint for developing miR-resistant mRNA vaccines for public health interventions.Conclusions miRs may inhibit mRNA vaccine translation in APCs,potentially reducing antigen production and weak-ening the resulting immune response.To address this,next-generation mRNA vaccines should incorporate"miR-proofing"strategies during design to avoid miR interference.
