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Compared with conventional mRNA, RepRNA vaccines induce broad, durable humoral and cellular responses, shown to protect across models of infectious diseases and cancer. The article reviews design, delivery, immune activation mechanisms, preclinical infectious- and tumor-focused studies, and related clinical trials on safety and immunogenicity.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/replicon-rna-vaccines-design-delivery-and-immunogenicity-in-infectious-diseases-and-cancer/371423/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/replicon-rna-vaccines-design-delivery-and-immunogenicity-in-infectious-diseases-and-cancer/371423.png","ImageObject",300,407,{"name":42,"@type":43},"Rhys","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What makes Replicon RNA (RepRNA) different from conventional mRNA vaccines?","Question",{"text":63,"@type":64},"RepRNA can self-replicate in host cells, producing more RNA and antigen, and it generates double-stranded RNA that activates innate immunity, leading to broader and more durable humoral and cellular responses.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do RepRNA vectors induce immune responses?",{"text":68,"@type":64},"Replication-driven amplification increases antigen production for adaptive immunity, while RNA replication products such as double-stranded RNA stimulate innate immune responses as an immunological adjuvant.",{"name":70,"@type":61,"acceptedAnswer":71},"What is the article’s scope regarding RepRNA vaccines?",{"text":72,"@type":64},"It covers RepRNA vaccine design and delivery, mechanisms of immune activation, preclinical studies for infectious diseases and tumors, and related clinical trials focusing on safety and immunogenicity.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},371423,1790469177,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Tang et al. Journal of Hematology & Oncology (2025) 18:43 [https://doi.org/10.1186/s13045-025-01694-2](https://doi.org/10.1186/s13045-025-01694-2)  \nJournal of Hematology & Oncology  \n REVIEW Open Access  \nReplicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer  \nLirui Tang1, Haiying Que1, Yuquan Wei1, Ting Yang2*, Aiping Tong1* and Xiawei Wei1*  \nAbstract  \nReplicon RNA (RepRNA) represents a cutting-edge technology in the field of vaccinology, fundamentally transforming vaccine design and development. This innovative approach facilitates the induction of robust immune responses against a range of infectious diseases and cancers. RepRNA vaccines leverage the inherent capabilities of RNAdependent RNA polymerase associated with self-replicating repRNA, allowing for extreme replication within host cells. This process enhances antigen production and subsequently stimulates adaptive immunity. Additionally, the generation of double-stranded RNA during RNA replication can activate innate immune responses. Numerous studies have demonstrated that repRNA vaccines elicit potent humoral and cellular immune responses that are broader and more durable than those generated by conventional mRNA vaccines. These significant immune responses have been shown to provide protection in various models for infectious diseases and cancers. This article will explore the design and delivery of RepRNA vaccines, the mechanisms of immune activation, preclinical studies addressing infectious diseases and tumors, and related clinical trials that focus on safety and immunogenicity.  \nKeywords RNA replicon, Immune responses, Cancer therapy, Infectious diseases  \nBackground  \nReplicon RNA (repRNA) has received public attention since the COVID-19 pandemic due to the urgent need to develop an effective vaccine. In the face of major  \n†Lirui Tang and Haiying Que have contributed equally.  \n*Correspondence:  \nTing Yang [yangting8506@qq.com](yangting8506@qq.com)[ ](yangting8506@qq.com)Aiping Tong[aipingtong@scu.edu.cn](aipingtong@scu.edu.cn)[ ](aipingtong@scu.edu.cn)Xiawei Wei [xiaweiwei@scu.edu.cn](xiaweiwei@scu.edu.cn)  \n1 Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, Sichuan, People’s Republic of China  \n2 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, People’s Republic of China  \nepidemics, replicon vaccines have already been put into emergency use, including a VSV-based Ebola virus (EBOV) vaccine, ERVEBO®, approved by the US Food and Drug Administration (FDA) [1] and GEMCOVACOM approved in India [2] . RNA replicons derived from positive sense/negative sense, single-stranded RNA viruses are deployed for vaccine development due to the RNA-dependent RNA polymerase (RdRp) activity, which induces approximately 106 copies per cell after the subgenomic RNA translocates into the cytoplasm [3] . Alphaviruses, flaviviruses, Nodamura virus (NoV)(positive-strand RNA virus), Paramyxoviruses, andrhabdoviruses (negative-strand RNA virus) are applied for repRNA vaccine vectors [4, 5] . By replacing the structural genes of the viral genome with the gene of interest (GOI), and preserving the non-structural genes that encode RdRp, repRNAs can induce massive RNA amplification and protein expression when used at low  \n© The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not hav","cbCain7GHg77moxC","https://ap.wps.com/l/cbCain7GHg77moxC","pdf",9002497,37,"English","# Abstract\n# Background\n## Replicon RNA and vaccine attention since COVID-19\n## RepRNA vectors and RNA-dependent RNA polymerase replication\n## Antigen expression and innate immune activation\n## Comparison with conventional nucleic acid vaccine approaches","[{\"question\":\"What makes Replicon RNA (RepRNA) different from conventional mRNA vaccines?\",\"answer\":\"RepRNA can self-replicate in host cells, producing more RNA and antigen, and it generates double-stranded RNA that activates innate immunity, leading to broader and more durable humoral and cellular responses.\"},{\"question\":\"How do RepRNA vectors induce immune responses?\",\"answer\":\"Replication-driven amplification increases antigen production for adaptive immunity, while RNA replication products such as double-stranded RNA stimulate innate immune responses as an immunological adjuvant.\"},{\"question\":\"What is the article’s scope regarding RepRNA vaccines?\",\"answer\":\"It covers RepRNA vaccine design and delivery, mechanisms of immune activation, preclinical studies for infectious diseases and tumors, and related clinical trials focusing on safety and immunogenicity.\"}]","Replicon RNA vaccines - design, delivery, and immunogenicity in infectious diseases and cancer | PDF",1790192037,93]