Journal: Heliyon

Article Title: The clinical impact of mRNA therapeutics in the treatment of cancers, infections, genetic disorders, and autoimmune diseases

doi: 10.1016/j.heliyon.2024.e26971

Figure Lengend Snippet: Some mRNA-therapeutics candidates investigating in trials. a

Article Snippet: 1 , NCT04956575 , mRNA-1010 , A Study of mRNA-1010 Seasonal Influenza Vaccine in Healthy Adults , Phase 1/2 , Completed , ModernaTX, Inc..

Techniques: Vaccines, Modification, Immunopeptidomics

Journal: Frontiers in Immunology

Article Title: mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV

doi: 10.3389/fimmu.2023.1172691

Figure Lengend Snippet: Structure, function and in vitro synthesis of vaccine mRNA. (A) mRNA are single stranded nucleic acids composed of an open reading frame (ORF) encoding the gene of interest, flanked by untranslated regions (UTRs) implicated in translation regulation, a cap at the 5’ end consisting of a N7-methylated guanosine residue, important for translation initiation and immune detection, and a poly(A) tail at the 3’ end, participating in the stability of the mRNA, as well as the stabilisation of the translation initiation complex. (B) In vitro synthesis of mRNA is often performed from a linearised plasmid template. The gene of interest is encoded in the plasmid template downstream of a promoter sequence. E. coli are transformed with the plasmid and cultured in liquid medium containing an antibiotic for which the plasmid encodes a resistance gene, thereby allowing the selection of bacteria that express the plasmid. The plasmid is then purified from the culture and digested using restriction enzymes to obtain a linear DNA template. In vitro transcription of mRNA is performed in the presence of the DNA template, an RNA polymerase and nucleotides triphosphates (NTPs). The capping can be performed by directly adding a cap analogue in the IVT reaction mix (1-step reaction), or alternatively by an enzymatic capping reaction after the IVT. If the poly(A) tail is not encoded in the plasmid, an additional step of polyadenylation is required. Created with BioRender.com .

Article Snippet: , Quadrivalent Influenza mRNA Vaccine CVSQIV (CureVac) , NCT05252338 , Phase 1 , 20222 , Recruiting.

Techniques: In Vitro, Methylation, Residue, Plasmid Preparation, Sequencing, Transformation Assay, Cell Culture, Selection, Bacteria, Purification

Journal: Frontiers in Immunology

Article Title: mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV

doi: 10.3389/fimmu.2023.1172691

Figure Lengend Snippet: Mechanism of action and immune response induced by mRNA vaccines. 1) mRNA vaccines enter the cells through different mechanisms depending on the nature and size of the nanoparticles, such as clathrin-, caveolin- and receptor-mediated endocytosis, micropinocytosis, phagocytosis or diffusion across the cell membrane . 2) After reaching the cytoplasm, mRNAs are translated by the ribosomes into the encoded protein. 3) The protein is processed by the proteasome into small antigenic peptides. 4) The peptides are presented at the surface of the antigen presenting cell by major histocompatibility complex (MHC) molecules to prime CD4+ and CD8+ T cells through, respectively, MHC-II or MHC-I interaction with the T cell receptor (TCR), to activate humoral and cellular adaptive responses. 5) Exogenous mRNAs can be detected by the innate immune system through binding to pattern recognition receptors (PRRs) localised at the endosomal membrane or in the cytosol, inducing the transcription and translation (6) of proinflammatory factors, such as type 1 interferons (IFN-I), IFN-stimulated genes (ISGs) and RNases. NF-κB, nuclear factor κB. Created with BioRender.com .

Article Snippet: , Quadrivalent Influenza mRNA Vaccine CVSQIV (CureVac) , NCT05252338 , Phase 1 , 20222 , Recruiting.

Techniques: Vaccines, Diffusion-based Assay, Membrane, Immunopeptidomics, Binding Assay

Journal: Frontiers in Immunology

Article Title: mRNA vaccines: a new opportunity for malaria, tuberculosis and HIV

doi: 10.3389/fimmu.2023.1172691

Figure Lengend Snippet: list of clinical trials evaluating mRNA vaccines against infectious diseases.

Article Snippet: , Quadrivalent Influenza mRNA Vaccine CVSQIV (CureVac) , NCT05252338 , Phase 1 , 20222 , Recruiting.

Techniques: Clinical Proteomics, Vaccines, Modification, Virus

Journal: Vaccines

Article Title: From Design to Clinical Use: mRNA Vaccines for Infectious Diseases and Cancer

doi: 10.3390/vaccines14030202

Figure Lengend Snippet: The structure of mRNA and circular RNA.

Article Snippet: Pfizer’s quadrivalent mRNA vaccine completed Phase III trials in individuals aged 65 and over, demonstrating 73.1% efficacy in preventing severe influenza, and no serious adverse reactions were reported [ ].

Techniques:

Journal: Vaccines

Article Title: From Design to Clinical Use: mRNA Vaccines for Infectious Diseases and Cancer

doi: 10.3390/vaccines14030202

Figure Lengend Snippet: Construction and mechanism of mRNA vaccine.

Article Snippet: Pfizer’s quadrivalent mRNA vaccine completed Phase III trials in individuals aged 65 and over, demonstrating 73.1% efficacy in preventing severe influenza, and no serious adverse reactions were reported [ ].

Techniques:

Journal: NPJ Vaccines

Article Title: Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection

doi: 10.1038/s41541-023-00752-5

Figure Lengend Snippet: Protein expression of 293T cells transfected with modified and unmodified mRNA encoding the HA of A/California/07/2009 was analyzed via Western blot; detection of GAPDH was used as a control.

Article Snippet: The studies presented here add to this growing body of work by demonstrating that quadrivalent influenza mRNA vaccines targeting HA from four seasonal subtypes produced by GreenLight Biosciences (GLB) are potently immunogenic and protective following challenge in the mouse model.

Techniques: Expressing, Transfection, Modification, Western Blot, Control

Journal: NPJ Vaccines

Article Title: Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection

doi: 10.1038/s41541-023-00752-5

Figure Lengend Snippet: 6–8-week-old mice were vaccinated with 5 or 30 µg of modified or unmodified mRNA encoding A/California/07/2009 on days 0 and 21 for antibody analysis. LNP and saline were used as controls. Bleeds were taken at days 0 (pre-boost) and 42 (post-boost). Mice were challenged with A/California/04/2009 at day 42. a Anti-HA antibody titers of each vaccine group pre-boost. b Anti-HA antibody titers of each vaccine group post-boost. c Kaplan–Meier survival curve of each vaccine group following CA09 challenge. d Percent bodyweight loss of each vaccine group following CA09 challenge. Error bars represent standard deviation. Statistical analyses were performed using rank-based Mann–Whitney tests with Holm- Šidάk for multiple comparisons. LoD limit of detection; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: The studies presented here add to this growing body of work by demonstrating that quadrivalent influenza mRNA vaccines targeting HA from four seasonal subtypes produced by GreenLight Biosciences (GLB) are potently immunogenic and protective following challenge in the mouse model.

Techniques: Modification, Saline, Standard Deviation, MANN-WHITNEY

Journal: NPJ Vaccines

Article Title: Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection

doi: 10.1038/s41541-023-00752-5

Figure Lengend Snippet: 6–8-week-old mice were vaccinated with 30 µg of monovalent seasonal HA mRNA or quadrivalent seasonal HA mRNA (120 µg total) on days 0 and 21. LNP and saline were used as controls. Bleeds were taken at days 0 (pre-boost) and 42 (post-boost) for antibody analysis. Mice were challenged with A/California/04/2009 at day 42. a CA09 anti-HA antibody titers of each vaccine group pre- and post-boost. b HK14 anti-HA antibody titers of each vaccine group pre- and post-boost. c BBris anti-HA antibody titers of each vaccine group pre- and post-boost. d BPhu anti-HA antibody titers of each vaccine group pre- and post-boost. e Kaplan–Meier survival curve of CA09 and quadrivalent vaccine groups following CA09 challenge. f Percent bodyweight loss of CA09 and quadrivalent vaccine groups following CA09 challenge. Error bars represent standard deviation. Statistical analyses were performed using rank-based Mann–Whitney tests with Holm–Šidάk for multiple comparisons. LoD limit of detection; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: The studies presented here add to this growing body of work by demonstrating that quadrivalent influenza mRNA vaccines targeting HA from four seasonal subtypes produced by GreenLight Biosciences (GLB) are potently immunogenic and protective following challenge in the mouse model.

Techniques: Saline, Standard Deviation, MANN-WHITNEY

Journal: NPJ Vaccines

Article Title: Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection

doi: 10.1038/s41541-023-00752-5

Figure Lengend Snippet: 6–8-week-old mice were vaccinated with quadrivalent vaccine containing 0.01–10 µg of mRNA encoding each HA subtype (0.04–40 µg total) or 1.5 µg of QIV on days 0 and 21. LNP and saline were used as controls. Bleeds were taken at days 0 (pre-boost) and 42 (post-boost) for antibody analysis. Mice were challenged with A/California/04/2009 at day 42. a CA09 anti-HA antibody titers of each vaccine group pre- and post-boost. b HK14 anti-HA antibody titers of each vaccine group pre- and post-boost. c BBris anti-HA antibody titers of each vaccine group pre- and post-boost. d BPhu anti-HA antibody titers of each vaccine group pre- and post-boost. e Kaplan–Meier survival curve of each vaccine group following CA09 challenge. f Percent bodyweight loss of each vaccine group following CA09 challenge. Error bars represent standard deviation. Statistical analyses were performed using rank-based Mann–Whitney tests with Holm–Šidάk for multiple comparisons. LoD limit of detection; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: The studies presented here add to this growing body of work by demonstrating that quadrivalent influenza mRNA vaccines targeting HA from four seasonal subtypes produced by GreenLight Biosciences (GLB) are potently immunogenic and protective following challenge in the mouse model.

Techniques: Saline, Standard Deviation, MANN-WHITNEY

Journal: NPJ Vaccines

Article Title: Seasonal quadrivalent mRNA vaccine prevents and mitigates influenza infection

doi: 10.1038/s41541-023-00752-5

Figure Lengend Snippet: 6–8-week-old mice were vaccinated with quadrivalent vaccine containing 10 µg of mRNA encoding each HA subtype (40 µg total) on day 0 (prime) or days 0 and 21 (prime-boost). LNP and saline were used as controls. Bleeds were taken at days 0 (pre-boost) and 42 (post-boost) for antibody analysis. Mice were challenged with A/California/04/2009 at day 42. a Anti-HA antibody titers against each antigen following one or two doses of mRNA vaccine. b Kaplan–Meier survival curve of each vaccine group following CA09 challenge. c Percent bodyweight loss of each vaccine group following CA09 challenge. Error bars represent standard deviation. Statistical analyses were performed using rank-based Mann–Whitney tests with Holm- Šidάk for multiple comparisons. LoD limit of detection; P-B prime-boost; * p < 0.05; ** p < 0.01; *** p < 0.001; **** p < 0.0001.

Article Snippet: The studies presented here add to this growing body of work by demonstrating that quadrivalent influenza mRNA vaccines targeting HA from four seasonal subtypes produced by GreenLight Biosciences (GLB) are potently immunogenic and protective following challenge in the mouse model.

Techniques: Saline, Standard Deviation, MANN-WHITNEY

Journal: International Journal of Molecular Sciences

Article Title: A Comprehensive Review of mRNA Vaccines

doi: 10.3390/ijms24032700

Figure Lengend Snippet: mRNA molecule structural components .

Article Snippet: Seasonal quadrivalent influenza mRNA vaccine CVSQIV , NA/Intramuscular injection , Influenza , NCT05252338 , 1 , CureVac AG , Recruiting.

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: A Comprehensive Review of mRNA Vaccines

doi: 10.3390/ijms24032700

Figure Lengend Snippet: mRNA lipid nanoparticles’ (mRNA-LNPs) site of intramuscular administration and modes of action of the mRNA-LNPs. mRNA-LNP vaccines can transfect muscle cells and transfect the tissue-resident antigen-presenting cells (APCs) near the injection site. Additionally, mRNA-LNP vaccines can flow into lymph nodes (LNs) and transfect the LN-resident cells, resulting in activation of T and B cells. Adapted with permission from .

Article Snippet: Seasonal quadrivalent influenza mRNA vaccine CVSQIV , NA/Intramuscular injection , Influenza , NCT05252338 , 1 , CureVac AG , Recruiting.

Techniques: Vaccines, Injection, Activation Assay

Journal: International Journal of Molecular Sciences

Article Title: A Comprehensive Review of mRNA Vaccines

doi: 10.3390/ijms24032700

Figure Lengend Snippet: Pharmacological mechanism of adaptive immune responses induced by mRNA-LNP vaccines. (1) In vitro transcribed mRNA is encapsulated into a lipid nanoparticle (LNP). (2) Transfection of mRNA-LNP vaccine molecules into the host cells, using specialized lipids on the surface of the LNPs. (3) Endocytosis of mRNA-LNP. (4) Endosomal escape of mRNA to the cytosol after endocytosis-mediated internalization. (5) Translation of the mRNA by the host cell ribosomes into the desired antigen protein intracellularly. (6) Antigenic protein released outside the cell, or the antigenic protein is degraded by a proteosome, exposing the antigenic sites. (7) Major histocompatibility complex I (MHC I) epitope presentation of the MHC I to the cell membrane for antigen presentation (APC). MHC I presents the epitope to CD8+ T cells. (9) The exogenous protein released earlier can get degraded and presented via MHC II epitopes. The extracellular antigen can get recognized by B cells, leading to B cell maturation .

Article Snippet: Seasonal quadrivalent influenza mRNA vaccine CVSQIV , NA/Intramuscular injection , Influenza , NCT05252338 , 1 , CureVac AG , Recruiting.

Techniques: Vaccines, In Vitro, Transfection, Immunopeptidomics, Membrane

Journal: International Journal of Molecular Sciences

Article Title: A Comprehensive Review of mRNA Vaccines

doi: 10.3390/ijms24032700

Figure Lengend Snippet: The steps and stages of an mRNA vaccine manufacturing process. mRNA vaccine production can be divided into three phases: upstream mRNA manufacturing, downstream mRNA purification, and formulation of mRNA lipid nanoparticles. mRNA production can be performed in a one-step co-transcriptional reaction, where a capping reagent is used, or in a two-step reaction, where the enzymatic capping is performed. mRNA purification process at a smaller lab scale consists of DNase I digestion enzyme followed by LiCl precipitation of the mRNA. Purification of mRNA at a large scale involves utilizing well-established chromatographic methods coupled with tangential flow filtration (TFF). Finally, the formulation of mRNA vaccines consists of mixing mRNA aqueous solution with lipid solution in a non-aqueous phase. This causes self-assembly of the lipid nanoparticles (LNPs) and encapsulates the negatively charged mRNA within the core of the LNPs. The mixing of the mRNA and the lipid molecules in a staggered herringbone micromixer (SHM) occurs in various cycles which results in the formation of the final mRNA-LNP vaccines. Adapted with permission from [ , ].

Article Snippet: Seasonal quadrivalent influenza mRNA vaccine CVSQIV , NA/Intramuscular injection , Influenza , NCT05252338 , 1 , CureVac AG , Recruiting.

Techniques: Purification, Formulation, Filtration, Vaccines

Journal: International Journal of Molecular Sciences

Article Title: A Comprehensive Review of mRNA Vaccines

doi: 10.3390/ijms24032700

Figure Lengend Snippet: Ongoing Clinical Trials With mRNA Vaccines (Excluding COVID-19 Vaccines).

Article Snippet: Seasonal quadrivalent influenza mRNA vaccine CVSQIV , NA/Intramuscular injection , Influenza , NCT05252338 , 1 , CureVac AG , Recruiting.

Techniques: Clinical Proteomics, Vaccines, Formulation, Injection, Virus, Infection, Amplification

Journal: Signal Transduction and Targeted Therapy

Article Title: Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications

doi: 10.1038/s41392-024-02002-z

Figure Lengend Snippet: Concurrently administered vaccines

Article Snippet: mRNA-1345 + influenza vaccine , RSV and influenza , 2023-09-25 , Phase III , Active, not recruiting , ModernaTX, Inc. , NCT06060457.

Techniques: Infection