Prototype LNP-mRNA vaccine candidates [SC_RNAseq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA853803 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV and MERS-CoV, and test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and Duplex LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV. Single cell RNA-seq profiled the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing systemic increase in activated B cells, and differential gene expression across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.
2025-07-30 | GSE207141 | GEO
Project description:Precise immunological mechanisms of mRNA vaccines have still not been fully elucidated, especially the initial immune responses at the injection site. Here, by constructing a single-cell atlas of injection site responses of mRNA vaccine, we show that stromal inflammatory responses and type I interferon responses dominate initial transcriptional reactions elicited by mRNA vaccines at the injection site. Tracking down the fates of the delivered mRNA revealed that injection site fibroblasts are highly enriched with the delivered mRNA, and they express IFN-β specifically in response to the mRNA component, not to the LNP. Accordingly, migratory dendritic cells highly expressing interferon stimulated genes (mDC_ISG) were found specifically in muscle and draining lymph nodes of mRNA vaccine injected mice, compared to the empty LNP injected mice. Co-administration of IFN-β and LNP robustly induced mDC_ISGs at the injection site and substantially enhanced antigen-specific CD8 T cell responses. Collectively, these data elucidate earliest mechanisms of the mRNA vaccine and highlight the underappreciated immunogenic role of the mRNA component in the mRNA vaccine.
2023-12-14 | GSE239574 | GEO
Project description:The result show that an mRNA/LNP vaccine induced significant numbers of differentially expressed genes (DEG). The analysis identified 123 DEGs between control PBS and mRNA/LNP vaccinated groups where 23 genes and 100 genes were upregulated and downregulated, respectively, in the mRNA/LNP group. To understand the biological changes from the transcriptomic data, gene set enrichment analysis (GSEA) was performed using the whole transcriptome data set. GSEA identified the biological pathways associated with interferon gamma response and protein secretion as the top two ‘Hallmark’ gene sets enriched in OVA mRNA/LNP group, compared to PBS group.
2024-11-06 | GSE267045 | GEO
Project description:Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNP is one approach to avoid these adverse reactions. Herein, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNP, including SS-cleavable and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNPssPalmO). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNP, mRNA-LNPssPalmO induced comparable antigen-specific antibodies and better IFN--producing Th1 responses in mice. Both mRNA-LNPssPalmO and conventional mRNA-LNP conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNPssPalmO showed better cross-protection against heterologous H5N1 virus challenge compared to conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNPssPalmO induced less inflammatory responses (e.g., inflammatory cytokine production and vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss and fever) compared with conventional mRNA-LNP. These results suggest that mRNA-LNPssPalmO would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy.
2025-03-05 | GSE279743 | GEO
Project description:Messenger RNA vaccines based on lipid nanoparticles (mRNA-LNPs) are promising vaccine modalities. However, mRNA-LNP vaccines frequently cause adverse reactions such as swelling and fever in humans, partly due to the inflammatory nature of LNP. Modification of the ionizable lipids used in LNP is one approach to avoid these adverse reactions. Herein, we report the development of mRNA-LNP vaccines with better protective immunity and reduced adverse reactions using LNP, including SS-cleavable and pH-activated lipid-like materials with oleic acid (ssPalmO) as an ionizable lipid (LNPssPalmO). We used mRNA expressing H5N1 subtype high-pathogenicity avian influenza virus-derived hemagglutinin or neuraminidase to generate mRNA-LNP vaccines against H5N1 influenza. Compared with conventional LNP, mRNA-LNPssPalmO induced comparable antigen-specific antibodies and better IFN--producing Th1 responses in mice. Both mRNA-LNPssPalmO and conventional mRNA-LNP conferred strong protection against homologous H5N1 virus challenge. In addition, mRNA-LNPssPalmO showed better cross-protection against heterologous H5N1 virus challenge compared to conventional mRNA-LNPs. Furthermore, we observed that mRNA-LNPssPalmO induced less inflammatory responses (e.g., inflammatory cytokine production and vascular hyperpermeability) and fewer adverse reactions (e.g., weight loss and fever) compared with conventional mRNA-LNP. These results suggest that mRNA-LNPssPalmO would be a safe alternative to conventional vaccines to overcome mRNA-LNP vaccine hesitancy.
2025-03-05 | GSE279744 | GEO
Project description:The mRNA-LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory
| PRJNA704856 | ENA
Project description:mRNA vaccines are emerging as a powerful vaccine platform as they are well-tolerated and scalable. Modified non-replicating mRNA encoding Influenza hemagglutinin and encapsulated in lipid nanoparticles (LNP) induced robust antibody and CD4 T cell responses after intramuscular or intradermal delivery in rhesus macaques. We investigated the local innate immune responses modulating such vaccine-induced immunity at the sites of immunization (skeletal muscle and skin) and their draining lymph nodes (LNs). Rapid mobilization of antigen presenting cells was found at the LNP/mRNA-injection sites and LNs. Dendritic cells efficiently internalized the LNPs, translated the mRNA cargo and upregulated co-stimulatory molecules. In addition, several type I interferon-inducible genes were expressed at the immunization sites and draining LNs. The innate immune activation was transient and resulted in priming of antigen-specific CD4+ T cells exclusively in the vaccine-draining LNs. Collectively, mRNA-based vaccines induce type I interferon-polarized innate immunity and antigen production by antigen presenting cells, which resulted potent vaccine-specific responses.
2017-04-26 | GSE98211 | GEO
Project description:SARS-CoV2 mRNA vaccine-induced side effects have been extensively reported in the clinical field. However, the potential toxicity of mRNA vaccines has not been fully identified. We aimed to clarify mRNA vaccine-induced bone marrow toxicity. Six-week-old CrlOri:CD1(ICR) female mice were used. A SARS-CoV2 S protein coding nucleoside-modified mRNA vaccine candidate or D-PBS (Negative control) was intramuscularly injected at left side femoral muscle twice at 2-week intervals (100 ug/head). Mice were sacrificed at 2 days post-secondary injection, and the bulk RNA sequencing for bone marrow of left side femur was performed. Notably, the mRNA vaccine induced significant decrease of erythroid cells in bone marrow. The bone marrow suppression was mediated by the complete mRNA vaccine, but not by mRNA only or LNP only. The RNA sequencing revealed that interferon-stimulated genes (ISGs), cell death-related genes and proteolysis-related genes were significantly upregulated, while erythrocyte development-related genes, hematopoietic cell differentiation-related genes and cytoskeleton-related genes were downregulated, in the bone marrow tissue of mRNA vaccine-injected mice compared to that of only LNP-injected mice. These findings indicate that the mRNA template is mainly involved in the mRNA vaccine-induced bone marrow suppression. We confirmed that the mRNA vaccine can cause pathological changes in bone marrow tissue. Although the underlying mechanism needs to be clarified, our findings suggest that mRNA vaccine-induced bone marrow suppression should be cautiously considered in the pre-clinical developmental process.
2025-04-01 | GSE292262 | GEO
Project description:Listeria monocytogenes is a foodborne intracellular bacterial pathogen leading to human listeriosis. Despite a high mortality rate and increasing antibiotic resistance no clinically approved vaccine against Listeria is available. To identify antigens for this bacterial pathogen that can be encoded in mRNA vaccine formulations, we screened for Listeria epitopes presented on the surface of infected human cell lines by mass spectrometry-based immunopeptidomics. In between more than 15,000 human self-peptides, we detected 68 Listeria epitopes from 42 different bacterial proteins, including several known antigens. Peptide epitopes presented on different cell lines were often derived from the same bacterial surface proteins, classifying these antigens as potential vaccine candidates. Encoding these highly presented antigens in lipid nanoparticle mRNA vaccine formulations resulted in high levels of protection in vaccination challenge experiments in mice. Our results pave the way for the development of a clinical mRNA vaccine against Listeria and demonstrate the power of immunopeptidomics for next-generation bacterial vaccine development.
2022-09-26 | PXD031451 | Pride