Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection

Vaccines remain one of the most effective tools in combating infectious diseases, though traditional platforms are constrained by limitations including suboptimal immunogenicity, safety concerns, and manufacturing complexity. Circular RNA (circRNA) vaccines have recently emerged as a novel vaccine m...

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Main Authors: Ying Zhang, Shumei Jin, Zan Zuo, Shujing Liu, Juan Xu, Chongyi Yang, Ping Wan, Linting Xun, Mei Luo, Fan Yang, Wenjie Chen, Zhengji Song, Jialong Qi
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/6/563
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author Ying Zhang
Shumei Jin
Zan Zuo
Shujing Liu
Juan Xu
Chongyi Yang
Ping Wan
Linting Xun
Mei Luo
Fan Yang
Wenjie Chen
Zhengji Song
Jialong Qi
author_facet Ying Zhang
Shumei Jin
Zan Zuo
Shujing Liu
Juan Xu
Chongyi Yang
Ping Wan
Linting Xun
Mei Luo
Fan Yang
Wenjie Chen
Zhengji Song
Jialong Qi
author_sort Ying Zhang
collection DOAJ
description Vaccines remain one of the most effective tools in combating infectious diseases, though traditional platforms are constrained by limitations including suboptimal immunogenicity, safety concerns, and manufacturing complexity. Circular RNA (circRNA) vaccines have recently emerged as a novel vaccine modality, demonstrating unique advantages including high stability, low innate immunogenicity, and sustained antigen expression. Although early research has predominantly focused on viral targets, accumulating evidence now supports the application potential of circRNA vaccines against diverse pathogens, particularly antibiotic-resistant bacteria. Through encoding critical antigens or virulence factors, these circRNA vaccines demonstrate capability to induce protective immune responses, presenting a viable alternative to conventional antimicrobial strategies. This review highlights recent advances in circRNA vaccine development, spanning synthetic circularization techniques, delivery approaches, and immunological mechanisms. We emphasize their potential against viral, bacterial, fungal, and parasitic infections, while addressing current challenges and future research directions of this emerging platform. Collectively, these insights underscore circRNA’s multifaceted versatility and its expanding relevance in next-generation vaccine innovation.
format Article
id doaj-art-00d3e18f05ab44ceb8a50004195a71b1
institution Kabale University
issn 2076-393X
language English
publishDate 2025-05-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj-art-00d3e18f05ab44ceb8a50004195a71b12025-08-20T03:26:56ZengMDPI AGVaccines2076-393X2025-05-0113656310.3390/vaccines13060563Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen InfectionYing Zhang0Shumei Jin1Zan Zuo2Shujing Liu3Juan Xu4Chongyi Yang5Ping Wan6Linting Xun7Mei Luo8Fan Yang9Wenjie Chen10Zhengji Song11Jialong Qi12Yunnan Provincial Key Laboratory of Clinical Virology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, ChinaYunnan Institute of Food and Drug Supervision and Control, Medical Products Administration of Yunnan Province, Kunming 650032, ChinaYunnan Provincial Key Laboratory of Clinical Virology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, ChinaSchool of Pharmacy, Mudanjiang Medical University, Mudanjiang 157011, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming 650504, ChinaYunnan Institute of Food and Drug Supervision and Control, Medical Products Administration of Yunnan Province, Kunming 650032, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming 650504, ChinaYunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Kunming 650032, ChinaYunnan Digestive Endoscopy Clinical Medical Center, Department of Gastroenterology, The First People’s Hospital of Yunnan Province, Kunming 650032, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming 650504, ChinaGuangdong-Hongkong-Macao Joint Laboratory of Respiratory Infectious Disease, State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou 510182, ChinaSchool of Medicine, Kunming University of Science and Technology, Kunming 650504, ChinaYunnan Provincial Key Laboratory of Clinical Virology, The First People’s Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650032, ChinaVaccines remain one of the most effective tools in combating infectious diseases, though traditional platforms are constrained by limitations including suboptimal immunogenicity, safety concerns, and manufacturing complexity. Circular RNA (circRNA) vaccines have recently emerged as a novel vaccine modality, demonstrating unique advantages including high stability, low innate immunogenicity, and sustained antigen expression. Although early research has predominantly focused on viral targets, accumulating evidence now supports the application potential of circRNA vaccines against diverse pathogens, particularly antibiotic-resistant bacteria. Through encoding critical antigens or virulence factors, these circRNA vaccines demonstrate capability to induce protective immune responses, presenting a viable alternative to conventional antimicrobial strategies. This review highlights recent advances in circRNA vaccine development, spanning synthetic circularization techniques, delivery approaches, and immunological mechanisms. We emphasize their potential against viral, bacterial, fungal, and parasitic infections, while addressing current challenges and future research directions of this emerging platform. Collectively, these insights underscore circRNA’s multifaceted versatility and its expanding relevance in next-generation vaccine innovation.https://www.mdpi.com/2076-393X/13/6/563circRNA vaccinecircular RNApathogens infectionRNA delivery
spellingShingle Ying Zhang
Shumei Jin
Zan Zuo
Shujing Liu
Juan Xu
Chongyi Yang
Ping Wan
Linting Xun
Mei Luo
Fan Yang
Wenjie Chen
Zhengji Song
Jialong Qi
Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection
Vaccines
circRNA vaccine
circular RNA
pathogens infection
RNA delivery
title Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection
title_full Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection
title_fullStr Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection
title_full_unstemmed Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection
title_short Rational Design and Immunological Mechanisms of Circular RNA-Based Vaccines: Emerging Frontiers in Combating Pathogen Infection
title_sort rational design and immunological mechanisms of circular rna based vaccines emerging frontiers in combating pathogen infection
topic circRNA vaccine
circular RNA
pathogens infection
RNA delivery
url https://www.mdpi.com/2076-393X/13/6/563
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