A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 16, 2024

Antibody-dependent enhancement (ADE) is a potential concern for the development of Zika virus (ZIKV) vaccines. Cross-reactive but poorly neutralizing antibodies, usually targeting viral pre-membrane or envelope (E) proteins, can potentially enhance dengue (DENV) infection. Although E domain III (EDIII) contains ZIKV-specific epitopes, its immunogenicity poor. Here, we show that dimeric EDIII, fused to human IgG1 Fc fragment (EDIII-Fc) and encoded by circular RNA (circRNA), induces better germinal center reactions higher antibodies compared circRNAs encoding monomeric trimeric EDIII. Two doses EDIII-Fc ZIKV nonstructural protein NS1, another protective antigen, prevent lethal infection in neonates born immunized C57BL/6 mice interferon-α/β receptor knockout adult mice. Importantly, single-dose optimized circRNA vaccine with improved antigen expression confers potent durable protection without inducing obvious DENV ADE mice, laying groundwork developing flavivirus vaccines based on NS1.

Язык: Английский

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Synthetic circRNA therapeutics: innovations, strategies, and future horizons

MedComm, Год журнала: 2024, Номер 5(11)

Опубликована: Ноя. 1, 2024

Abstract Small molecule drugs are increasingly emerging as innovative and effective treatments for various diseases, with mRNA therapeutics being a notable representative. The success of COVID‐19 vaccines has underscored the transformative potential in RNA therapeutics. Within family, there is another unique type known circRNA. This single‐stranded closed‐loop offers advantages over mRNA, including enhanced stability prolonged protein expression, which may significantly impact therapeutic strategies. Furthermore, circRNA plays pivotal role pathogenesis such cancers, autoimmune disorders, cardiovascular making it promising clinical intervention target. Despite these benefits, application settings remains underexplored. review provides comprehensive overview current state synthetic therapeutics, focusing on its synthesis, optimization, delivery, diverse applications. It also addresses challenges impeding advancement from bench to bedside. By summarizing aspects, aims equip researchers insights into ongoing developments future directions Highlighting both progress existing gaps research, this valuable perspectives advancing field guiding investigations.

Язык: Английский

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An mpox quadrivalent mRNA vaccine elicits sustained and protective immunity in mice against lethal vaccinia virus challenge

Emerging Microbes & Infections, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Assessing the long-term efficacy of MPXV vaccine candidates is crucial for global response to ongoing mpox epidemic. Built upon our previous study quadrivalent mRNA vaccine, herein we reported that MPXV-1103 could elicit sustained humoral and cellular immunity in mice, including induction A35/B6/A29/M1-specific IgG antibodies, VACV neutralizing antibodies activated cytotoxic CD8+T cells, which provides 100% protection against lethal challenge even at 280 days after first vaccination. Our results provide critical insights orthopoxvirus development.

Язык: Английский

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Expanding the Potential of Circular RNA (CircRNA) Vaccines: A Promising Therapeutic Approach

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(1), С. 379 - 379

Опубликована: Янв. 4, 2025

In recent years, circular RNAs (circRNAs) have garnered significant attention due to their unique structure and function, positioning them as promising candidates for next-generation vaccines. The circRNA vaccine, an RNA offers advantages in preventing infectious diseases by serving a vector protein expression through non-canonical translation. Notably, vaccines demonstrated enduring antigenic generate larger percentage of neutralizing antibodies compared mRNA administered at the same dosage. Furthermore, can elicit robust cellular humoral immunity, indicating potential tumor vaccine development. However, certain challenges must be addressed facilitate widespread use both disease prevention treatment. These include low efficiency linear circularization, suboptimal targeting delivery systems, assessment side effects. This work aims describe characteristics functions circRNAs, elucidate mechanism behind vaccines, discuss applications treatment tumors, along with future applications.

Язык: Английский

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现代疫苗学赋能新突发病毒性传染病疫苗的快速“智造”——以猴痘疫情为例

Chinese Science Bulletin (Chinese Version), Год журнала: 2025, Номер 70(7), С. 789 - 798

Опубликована: Фев. 11, 2025

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Development and Characterization of a miRNA-Responsive Circular RNA Expression System with Cell-Type Specificity

Molecular Therapy — Nucleic Acids, Год журнала: 2025, Номер 36(1), С. 102450 - 102450

Опубликована: Янв. 14, 2025

Язык: Английский

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Elucidating the Mechanism of VVTT Infection Through Machine Learning and Transcriptome Analysis

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 1203 - 1203

Опубликована: Янв. 30, 2025

The vaccinia virus (VV) is extensively utilized as a vaccine vector in the treatment of various infectious diseases, cardiovascular immunodeficiencies, and cancers. Tiantan strain (VVTT) has been instrumental an irreplaceable eradication smallpox China; however, it still presents significant adverse toxic effects. After WHO recommended that routine vaccination be discontinued, Chinese government stopped national program 1981. outbreak monkeypox 2022 focused people’s attention on Orthopoxvirus. However, there are limited reports safety side effects VVTT. In this study, we employed combination transcriptomic analysis machine learning-based feature selection to identify key genes implicated VVTT infection process. We four learning algorithms, including random forest (RF), minimum redundancy maximum relevance (MRMR), eXtreme Gradient Boosting (XGB), least absolute shrinkage operator cross-validation (LASSOCV), for selection. Among these, XGB was found most effective used further screening, resulting optimal model with ROC curve 0.98. Our revealed involvement pathways such spinocerebellar ataxia p53 signaling pathway. Additionally, identified three critical targets during infection—ARC, JUNB, EGR2—and validated these using qPCR. research elucidates mechanism by which infects cells, enhancing our understanding vaccine. This knowledge not only facilitates development new more vaccines but also contributes deeper comprehension viral pathogenesis. By advancing molecular mechanisms underlying infection, study lays foundation Such insights crucial strengthening global health security ensuring resilient response future pandemics.

Язык: Английский

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RNA vaccines: The dawn of a new age for tuberculosis?

Human Vaccines & Immunotherapeutics, Год журнала: 2025, Номер 21(1)

Опубликована: Фев. 27, 2025

Since 2019, there has been a growing focus on mRNA vaccines for infectious disease prevention, particularly following the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). offer advantages such as rapid production and ability to induce robust cellular antibody responses, which are essential combating infections that require cell-mediated immunity, including Tuberculosis (TB). This review explores recent progress in TB addresses several key areas: (1) urgent need new vaccines; (2) current advancements vaccine development, challenges technology; (3) design characteristics (4) immunological mechanisms (5) manufacturing processes (6) safety regulatory considerations. interdisciplinary aims provide insights researchers working address critical questions development.

Язык: Английский

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Roles of circRNAs in viral pathogenesis

Frontiers in Cellular and Infection Microbiology, Год журнала: 2025, Номер 15

Опубликована: Март 13, 2025

Circular RNAs (circRNAs) are a class of non-coding with covalently closed circular structure, lacking 5’-caps or 3’-poly(A) tails. They relatively conserved, highly stable, and often exhibit tissue- cell-specific production in eukaryotic cells. Based on the advances sequencing technologies bioinformatics, multiple reports have suggested that viruses other microorganisms may encode circRNA-like molecules, providing new insights into physiological pathological roles circRNAs. The innate immune system functions as body’s primary defense mechanism against viral infections. It detects pathogen-associated molecular patterns (PAMPs) activates signaling pathways to suppress replication limit their spread. CircRNAs involved regulation host play essential pathogenesis. has been shown circRNAs can regulate gene expression by acting miRNA sponges protein sponges, encoding small proteins specific cases. For example, previous studies revealed participate antiviral response through competitive endogenous RNA (ceRNA) network sponges. This review highlights research progress host- virus-encoded host-virus interactions, well potential diagnostic biomarkers therapeutic targets clinical applications.

Язык: Английский

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Unlocking the potential of circular RNA vaccines: a bioinformatics and computational biology perspective

EBioMedicine, Год журнала: 2025, Номер 114, С. 105638 - 105638

Опубликована: Март 19, 2025

Язык: Английский

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