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Cited by 347Immunotherapy and Immune ResponsesRNA Interference and Gene DeliverySARS-CoV-2 and COVID-19 Research

Three decades of messenger RNA vaccine development

Open access
Verbeke, Rein, Lentacker, Ine, De Smedt, Stefaan C., Dewitte, Heleen·2019·Nano Today
DOI 10.1016/j.nantod.2019.100766
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Verified 2026-10-10 · 1 reference not checked yet

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review traces three decades of mRNA vaccine development, from early liposomal and naked mRNA expression studies to lipid-nanoparticle-formulated clinical candidates. It argues that the central challenge is balancing mRNA translation capacity against the mRNA self-adjuvant type I IFN response to achieve safe and effective immunity.

Key findings

  • Early work showed mRNA could be delivered in vivo: liposomal mRNA transfected eukaryotic cells, and intramuscular naked mRNA produced encoded protein for a couple of days; mRNA encoding influenza nucleoprotein elicited virus-specific CTLs, and mRNA encoding carcinoembryonic antigen induced anti-tumoral antibody responses.
  • mRNA is intrinsically immunostimulatory via endosomal TLR3/7/8 and cytosolic RIG-I/MDA5, inducing type I IFN and pro-inflammatory cytokines; this self-adjuvant effect supports DC maturation and T cell activation but also inhibits mRNA translation and antigen expression.
  • Nucleoside-modified mRNA improves stability and translation—e.g., 25% thio-uridine and 25% 5-methylcytidine mRNA encoding Epo gave five times higher Epo levels than untreated mice two weeks after i.m. administration—but can reduce CTL responses due to lower type I IFN; unmodified mRNA may favor CTL responses while modified mRNA favors antibody responses.
  • Delivery route and formulation matter: in rhesus macaques, i.d. delivery of ionizable LNP with nucleoside-modified mRNA gave earlier skin DC activation, more efficient migration to draining LNs, prolonged antigen availability, and superior antibody titers and CD4+ T cell activation versus i.m.; nanoparticles up to 200 nm can enter lymphatic vessels, and a <50 nm calcium-phosphate/DOTAP/DSPE-PEG mRNA system showed mRNA in draining LN as early as 4 h after s.c. injection.

Methods

  • Narrative review synthesizing historical, immunological, delivery, and clinical literature on mRNA vaccines; no primary experimental data are reported.
  • Data include published preclinical and clinical studies, with a table summarizing selected clinical trial results across CureVac, BioNTech, Moderna, and eTheRNA platforms.
  • Main analysis is qualitative: it discusses mRNA pharmacology, innate immune sensing, nanoparticle design, administration routes, type I IFN effects, and combination with checkpoint inhibitors.

Limitations

  • Stated in the paper: clinical patient numbers are still limited; detailed studies on biomolecular corona formation and dynamics on LNPs are still very limited; how type I IFN signaling relates to mRNA vaccine design requires further investigation.
  • Evident from the text: as a narrative review, it lacks systematic search/selection criteria and quantitative synthesis; Table 1 combines heterogeneous platforms, doses, routes, and trial phases, limiting direct comparisons.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.nantod.2019.100766

Cites

218 of 219 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 187 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    In a phase I/IIa trial of a RNactive-based vaccine for non-small cell lung carcinoma, common diagnostic indicators for autoimmunity were elevated in up to 20% of patients after a RNactive schedule of five intradermal injections (dose 400-1600 μg).

    “In a phase I/IIa trial of a RNactive ® -based vaccine for non-small cell lung carcinoma (NSCLC), common diagnostic indicators for autoimmunity were found to be elevated up to 20% of the patients after a RNactive ® schedule of five intradermal injections (dose of 400-1600 µg) [187].”
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  • Findingcitation

    In a study testing the safety and immunogenicity of the RNactive platform as a prophylactic vaccine against rabies, a moderate case of Bell's palsy occurred one week after a second i.m. administration of the highest dose of 640 μg (1/37 patients).

    “Another study testing the safety and immunogenicity of the RNactive ® platform as prophylactic vaccine against rabies, elicited a moderate case of Bell's palsy one week after a second i.m. administration of the highest dose of 640 µg (1/37 patients).”
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  • Premisecitation

    In 1989, Vical demonstrated that mRNA packaged within a liposomal nanoparticle could successfully transfect mRNA into a variety of eukaryotic cells.

    “They demonstrated that mRNA packaged within a liposomal nanoparticle could successfully transfect mRNA into a variety of eukaryotic cells [1].”
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  • Interpretationreasoning

    The early Vical and Wolff data provided the first evidence that in vitro transcribed mRNA could deliver genetic information to produce proteins within living tissue.

    “These preliminary data provided the first evidence that in vitro transcribed (IVT) mRNA could deliver the genetic information to produce proteins within living tissue.”
    Quote in the paperSubstantial claim
  • Premisecitation

    Martinon et al. showed that liposomes containing mRNA encoding the influenza virus nucleoprotein elicited virus-specific cytotoxic T lymphocytes.

    “As pioneers, Martinon et al. showed that liposomes containing mRNA encoding the influenza virus nucleoprotein elicited virus-specific cytotoxic T lymphocytes (CTLs) [3].”
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    Findingcitation

    In a proof-of-concept study, nucleoside-modified mRNA co-delivered with the clinically approved TLR agonist MPLA achieved functional CTL responses like unmodified mRNA, but with strongly reduced type I IFN responses.

    “In a proof-of-concept study, we demonstrated that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist MPLA, achieving functional CTL responses like unmodified mRNA, but with strongly reduced type I IFN responses [157].”
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    Findingcitation

    By dual antigen signalling to both conventional T cells and NKT cells, mRNA Galsomes induced a relatively higher tumor influx of antigen-specific CTLs, NKT and NK cells, and reduced the tumor presence of immunosuppressive myeloid cells, compared to mice treated with type I IFN inducing LNPs formulated with unmodified mRNA.

    “By the dual”
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    Premisereasoning

    mRNA molecules only need to reach the cytosol to be translated at ribosomes, so they avert the risk of integration into the host genome.

    “Indeed, as the mRNA molecules only have to reach the cytosol in order to be translated at the ribosomes, they avert the risk of being integrated into the host genome.”
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    Premisecitation

    Unmodified mRNA evoked substantial immune activation but produced no significant changes in Epo levels.

    “In contrast, no significant changes were detected with unmodified mRNA, which only evoked a substantial immune activation [44].”
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    Interpretationreasoning

    Because preparing a new mRNA construct tailored to a specific disease can be done in a straightforward and fast way, mRNA is an ideal candidate to trigger immunity against infectious diseases.

    “The fact that preparing a new mRNA construct tailored to a specific disease can be done in a straightforward and fast way, makes mRNA also an ideal candidate to trigger immunity against infectious diseases.”
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    Premisecitation

    Karikó and colleagues observed that ex vivo human dendritic cells tolerated mammalian mRNA, while strong inflammatory cytokine responses were detected upon delivery of mRNA derived from bacteria, necrotic mammalian cells and IVT mRNA.

    “In 2004, Karikó and colleagues observed, while exposing ex vivo human DCs to mRNA from different sources, that these cells tolerated mammalian mRNA, while strong inflammatory cytokine responses were detected upon the delivery of mRNA derived from bacteria, necrotic mammalian cells and IVT mRNA [39,40].”
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    Premisenone given

    mRNA can code full-length proteins, avoiding restrictions concerning a patient's MHC haplotype.

    “For one, mRNA can code full-length proteins, thus avoiding restrictions concerning a patient's MHC haplotype.”
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    Premisecitation

    The MHC class II pathway can be targeted using mRNA as a source of antigen after secretion and recycling of mRNA-expressed proteins or via direct shuttling of antigens from the cytosol to lysosomes, for example by incorporating a lysosomal targeting sequence.

    “Interestingly, also the MHC class II pathway can be targeted using mRNA as a source of antigen: this either after the secretion and recycling of the mRNA expressed proteins, or via direct shuttling of antigens from the cytosol to the lysosomes, e.g., promoted by the incorporation of a lysosomal targeting sequence in the mRNA construct [9,10].”
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    Interpretationreasoning

    Using antigen-encoding mRNA provides an easy way to evoke MHC-I presentation and elicit CTL responses.

    “One of the key advantages of using antigen-encoding mRNA, is that it provides an easy way to evoke MHC-I presentation and elicit CTL responses.”
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    Premisecitation

    Type I IFNs bind autocrine or paracrine receptors, activating the JAK-STAT pathway, which regulates expression of hundreds of proteins involved in antiviral immunity.

    “In turn, type I IFNs bind autocrine or paracrine receptors, activating the Janus kinase-signal transducer activator of transcription (JAK-STAT) pathway, which regulates the gene expression of hundreds of proteins involved in antiviral immunity [35,36].”
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    Premisecitation

    Antigen signalling by dendritic cells can originate from the cytoplasm via MHC class I molecules or from lysosomes via MHC class II molecules.

    “Antigen signalling by DCs can either originate from the cytoplasm, which involves the presentation of antigenic peptides in major histocompatibility complex (MHC) class I molecules, or alternatively from the lysosomes that harbour fragments of endo-or phagocytized antigens which are loaded into MHC class II.”
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    Premisecitation

    Dendritic cells are specialized in the uptake, processing and presentation of protein antigens to lymphocytes, linking innate and adaptive immune responses.

    “DCs are specialized in the uptake, processing and presentation of protein antigens to lymphocytes, which links innate and adaptive immune responses.”
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    Premisecitation

    A first-in-human trial demonstrated clinical feasibility and safety of personalized mRNA cancer vaccines for advanced melanoma, with all vaccinated patients developing CD4+ and CD8+ T cell responses against selected antigens and some showing objective antitumor responses.

    “A first-in-human trial demonstrated the clinical feasibility and safety of this approach for advanced melanoma cancers: all vaccinated patients developed CD4 + and CD8 + T cell responses against the selected antigens, with some patients showing objective antitumor responses [15].”
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    Premisecitation

    Antireverse cap modifications ensure correct cap orientation at the 5' end, yielding almost complete fractions of mRNA that can efficiently bind ribosomes.

    “Antireverse cap (ARCA) modifications can ensure the correct cap orientation at the 5' end, which yields almost complete fractions of mRNA that can efficiently bind the ribosomes [54].”
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    Premisecitation

    CureVac AG found that stabilizing mRNA with either a phosphorothioate backbone or precipitation with cationic protein protamine diminished antigen expression but produced stronger immune-stimulating capacities.

    “The company CureVac AG found that by stabilizing the mRNA with either a phosphorothioate backbone, or by its precipitation with the cationic protein protamine, antigen expression was diminished, but stronger immune-stimulating capacities could be obtained [62,63].”
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    Premisecitation

    Correlations exist between elongation of the poly(A) tail of mRNA and duration of expression, and specific 3' UTR modifications can slow down decay of the poly(A) tail by deadenylation.

    “Correlations were found between the elongation of the poly(A) tail of mRNA and the duration of expression, and specific modifications at the 3' UTR were reported that can slow-down the decay of the poly(A) tail by deadenylation [57,58].”
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    Interpretationcitation

    The findings support a paradigm for mRNA vaccine design with one strategy using mRNA fully optimized for a strong adjuvant effect and another using modified mRNA with high translation capacity and improved antigen bioavailability.

    “Taken together, these findings resulted in a paradigm of the design of mRNA formulations for vaccination.One strategy is to use mRNA which is fully optimized to obtain a strong adjuvant effect, another is to work with 'modified' mRNA with high translation capacity, and thus improved antigen bio-availability [43,62].”
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    Premisereasoning

    The cytosolic presence of a few mRNA molecules can ensure extensive antigen presentation to CTLs, whereas proteins rely on less efficient cross-presentation pathways.

    “As such, the cytosolic presence of a few mRNA molecules can ensure extensive antigen presentation to CTLs, while proteins have to rely on less efficient cross-presentation pathways.”
    Quote in the paperSubstantial claim

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    Premisenone given

    Binding of mRNA molecules to danger sensors leads to downstream signalling via MyD88 for TLR7/8 and TRIF for TLR3, resulting in production of type I IFN and pro-inflammatory cytokines such as IL-6 and TNF-alpha.

    “The binding of mRNA molecules to these danger sensors leads to downstream signalling via specific adaptor molecules (i.e.MyD88 for TLR7/8 and TRIF for TLR3), eventually resulting in the production of type I IFN and other pro-inflammatory cytokines (e.g., IL-6 and TNF-α).”
    Quote in the paperSubstantial claim

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    Premisecitation

    Paunovska et al. tested hundreds of LNPs for nucleic acid delivery to macrophages or endothelial cells after intravenous delivery and found almost no in vitro-in vivo correlations.

    “Moreover, using a high throughput system, Paunovska et al. were able to test hundreds of LNPs for the nucleic acid delivery to macrophages or endothelial cells after i.v.delivery, but found almost no in vitro-in vivo correlations [91].”
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    Premisecitation

    Ionizable lipids with pKa less than 7 have a neutral to mildly cationic charge under physiological pH conditions and are associated with reduced toxicity and prolonged blood circulation lifetime compared with permanently charged lipids.

    “These ionizable lipids (pKa < 7), originally optimized for siRNA delivery, have a neutral to mildly cationic charge under physiological pH conditions.This offers certain benefits over the permanently-charged lipids, the foremost of which is that ionizable lipids have been associated with a reduced toxicity and a prolonged blood circulation lifetime [100,101].”
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    Premisecitation

    Intradermal injections of GM-CSF contributed to infiltration of monocytes and migration of mRNA-transfected, matured dendritic cells to lymph nodes.

    “Intradermal injections of granulocyte-macrophage colony-stimulating factor (GM-CSF) contributed to the infiltration of monocytes, and to the migration of mRNA-transfected, matured DCs to the LNs [86,87].”
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    Premisecitation

    Skin-resident dendritic cells can engulf naked mRNA via macropinocytosis and trigger T cell immunity in mice.

    “Only years later, the involvement of immune cells in the uptake of unformulated mRNA was identified: skin-resident DCs were capable of engulfing naked mRNA via macropinocytosis and could trigger T cell immunity in mice [78].”
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    Premisecitation

    The addition of saturated phospholipids such as DPPC and DSPC increases the phase transition temperature of cationic liposomes and supports the formation of a lamellar lipid bilayer structure.

    “The addition of saturated phospholipids, such as DPPC and DSPC, increases the phase transition temperature of the cationic liposomes and supports the formation of such a lamellar lipid bilayer structure [102].”
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    Premisecitation

    Upon intradermal application of the RNActive vaccine, both sequence-engineered mRNA and protamine-complexed mRNA were taken up by immune and non-immune cells, with highest frequencies in macrophages, dendritic cells and neutrophils.

    “Upon i.d.application, both vaccine components, sequence-engineered mRNA and protamine-complexed mRNA, were taken up by both immune cells and non-immune cells, with the highest frequencies detected within macrophages, DCs and neutrophils [79].”
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    Premisecitation

    Lazzaro et al. concluded that APCs take up antigens produced by transfected muscle cells and that cross-presentation of myocyte-expressed antigens is the mechanism leading to induction of CTL responses.

    “They concluded that APCs could take up antigens that were produced by the transfected muscle cells, and that cross-presentation of the myocyte-expressed antigens was the mechanism leading to the induction of CTL responses [85].”
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    Premisecitation

    The earliest studies explored intramuscular, subcutaneous and intradermal routes, showing detectable protein expression at the injection site and adaptive immune responses.

    “The earliest studies have explored the i.m., subcutaneous (s.c.), and intradermal (i.d.) routes, showing detectable protein expression levels at the injection site, which also resulted in adaptive immune responses [4,51,75].”
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  • May combine two claims.

    Interpretationreasoning

    The chosen injection route plays a major role in the cell types that contact mRNA and in the potency of the evoked immune response.

    “Over the years, it became clear that the chosen injection route plays a major role regarding the cell types that come in contact with the mRNA and the potency of the evoked immune response.”
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    Premisecitation

    After intratumoral injection in different subcutaneous murine tumor models, tumor-infiltrating CD8a+ cross-presenting dendritic cells were mainly responsible for mRNA uptake, resulting in mRNA expression for more than 5 days.

    “Indeed, tumor-infiltrating CD8a + cross-presenting DCs were mainly responsible for mRNA uptake after injection in different subcutaneous murine tumor models, resulting in mRNA expression for >5 days [83,84].”
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    Premisecitation

    An intranodally administered TriMix mRNA vaccine was safe and well tolerated in a dose-escalation clinical study against HIV-1 infection, obtaining moderate HIV-specific T cell responses at high doses (total mRNA dose of 1.2 mg).

    “Recently, an i.n.administered TriMix mRNA vaccine was shown to be safe and well tolerated in a doseescalation clinical study against HIV-1 infection, while obtaining moderate HIV-specific T cell responses at high doses (total mRNA dose of 1.2 mg) [89].”
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    Interpretationcitation

    The potency of the self-adjuvant effect of mRNA must be weighed against the risk of adverse reactions inherent to it, including inflammation reactions and auto-immune events.

    “Notwithstanding, the potency of this self-adjuvant effect of mRNA must be weighed against the risk of any adverse reaction inherent to it, including inflammation reactions and auto-immune events [68].”
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    Premisereasoning

    Because mRNAs are large and polyanionic, they cannot passively diffuse across the cell membrane and rely on active transportation via endocytic uptake mechanisms.

    “Since mRNAs are large and polyanionic molecules, they cannot passively diffuse across the cell membrane.Therefore, mRNA molecules rely on active transportation via endocytic uptake mechanisms.”
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    Premisecitation

    Physicochemical and structural characteristics of mRNA LNPs depend on lipid composition, the ratio of mRNA to total cationic lipids, and LNP synthesis.

    “Note that the physicochemical and structural characteristics of mRNA LNPs will depend on the lipid composition, the ratio of mRNA to the total amount of (cationic) lipids, and the LNP synthesis (for a detailed review on these parameters also see [107]).”
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    Premisecitation

    In the rapid-mixing step at acidic pH, empty small liposomal structures and loaded larger electron-dense particles are formed.

    “They proposed that in the rapid-mixing step at acidic pH, (”
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    Interpretationreasoning

    Depending on the administration route, specific extracellular barriers might be encountered, which prompts specific particle optimizations.

    “Importantly, depending on the administration route, specific extracellular barriers might be encountered which prompts specific particle optimizations.”
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    Premisecitation

    Although all recruited cell types internalize mRNA LNPs, only monocytes and myeloid DCs show high translation of the mRNA.

    “Although all of these cell types were able to internalize mRNA LNPs, only monocytes and myeloid DCs showed high translation of the mRNA.”
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    Premisecitation

    Prior reports have linked the occurrence of cholesterol nanocrystals to improved transfection efficiency.

    “Although this was not further investigated in this study, prior reports have linked the occurrence of cholesterol nanocrystals to an improved transfection efficiency [114,115].”
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    Premisecitation

    Bench-top microfluidic mixing devices are available for production of unloaded liposomes or mRNA LNPs via the ethanol-dilution principle, with potential to be scaled up for clinical or industrial purposes.

    “Notably, bench-top microfluidic mixing devices are available for the production of unloaded liposomes or mRNA LNPs via this ethanol-dilution principle, with the potential to be scaled up for clinical or industrial purposes [116].”
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    Premisecitation

    mRNA LNPs based on D-Lin-MC3-DMA, DSPC, cholesterol and a PEG-lipid exhibit a disordered inverse hexagonal phase containing D-Lin-MC3-DMA, cholesterol, water and mRNA.

    “In another study, Yanez Arteta et al. indicated that the structural arrangement of mRNA LNPs based on D-Lin-MC3-DMA, DSPC, cholesterol and a PEG-lipid exhibited a disordered inverse hexagonal phase containing D-Lin-MC3-DMA, cholesterol, water and mRNA.”
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    Premisecitation

    The mechanism of formation of ionizable LNP systems with different nucleic acid payloads has recently been elucidated by Kulkarni and colleagues.

    “The mechanism of the formation of these ionizable LNP systems (with different nucleic acid payloads) has recently been elucidated by Kulkarni and colleagues [111,112].”
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    Premisecitation

    i.d. delivery results in earlier activation of skin DCs, more efficient migration to draining LNs, and prolonged antigen availability at the injection site compared to i.m. delivery.

    “With respect to the resulting immune response, they showed that i.d.delivery resulted in an earlier activation of skin DCs and a more efficient migration to draining LNs, as well as a prolonged antigen availability at the injection site.”
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    Premisecitation

    Rapid screening of novel lipid libraries has helped continually optimize lipid compositions and supported discovery of new lead ionizable lipids with greatly improved potency and safety for mRNA transfection.

    “Furthermore, this has also supported the discovery of new lead ionizable lipids holding greatly improved potency and safety for mRNA transfection [117][118][119].”
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    Premisecitation

    i.d. delivery results in superior immunogenicity compared to i.m. delivery, with the highest antibody titers and CD4+ T cell activation.

    “Together, this resulted in a superior immunogenicity compared to i.m. delivery, as i.d.injection resulted in the highest antibody titers and CD4 + T cell activation.”
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    Premisecitation

    The biomolecular corona may reduce the colloidal stability of mRNA LNPs, followed by aggregation of the particles and premature release of the mRNA cargo.

    “This may reduce the colloidal stability of the mRNA LNPs, followed by the aggregation of the particles and a premature release of the mRNA cargo [139,140].”
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    Premisecitation

    Vu et al. found that nanoparticles mediate complement activation quite universally over a range of clinically approved liposomes.

    “Recently, Vu et al. elucidated how nanoparticles mediate complement activation, and found this to be quite universal over a range of clinically approved liposomes [148].”
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    Premisecitation

    PEG-lipids with shorter acyl chains can gradually diffuse out of LNPs, temporarily confer stealth properties, and achieve higher transfection efficiencies compared to longer, persistent PEG-lipids.

    “These PEG-lipids can gradually diffuse out of the LNPs, and thus temporarily confer stealth properties to the LNP system, while achieving higher transfection efficiencies compared to the longer, persistent PEG-lipids [139,144].”
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    Premisecitation

    These mRNA nanoparticles have a relatively small particle size (<50 nm) and an uncharged, strongly PEGylated outer surface.

    “These mRNA nanoparticles had a relatively small particle size (<50 nm), and an uncharged, strongly PEGylated outer-surface.”
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    Premisecitation

    In cancer immunotherapy, it is essential to evoke a systemic immune response to obtain antitumor immunity, making i.v. delivery appealing for mRNA-based cancer vaccines.

    “In the specific case of cancer immunotherapy, it was proven essential to evoke a systemic immune response to obtain antitumor immunity, which makes i.v.delivery a highly appealing administration route for mRNA-based cancer vaccines [92,136,137].”
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    Premisenone given

    Merely a few surface-bound immunoglobulin molecules are sufficient to trigger complement activation.

    “Merely a few surface-bound immunoglobulin molecules are sufficient to trigger complement activation.”
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  • May combine two claims.

    Premisecitation

    Incorporation of PEGylated lipids provides a stealth effect, reduces overall protein adsorption, and improves colloidal stability of LNPs, but hampers LNP cellular uptake and transfection capacity.

    “Alternatively, the incorporation of PEGylated lipids is widely used to provide a”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [143]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    It is possible to tweak the serum stability of LNPs by modifying their helper lipid composition.

    “It is also possible to tweak the serum stability of LNPs by modifying their helper lipid composition.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    In patients with pre-existing anti-PEG antibodies, infusion of PEGylated LNPs is contra-indicated, as it could lead to stronger complement activation and accelerated blood clearance of PEGylated nanoparticles.

    “However, PEGylation also has its limitations: in patients with pre-existing anti-PEG antibodies, infusion of PEGylated LNPs is contra-indicated, as this could lead to an even stronger complement activation as well as an accelerated blood clearance of PEGylated nanoparticles.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [143]

      Not checked in the free run.

    • cites [148]

      Not checked in the free run.

    • cites [155]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nanoparticles up to 200 nm are able to enter the lymphatic vessels, whereas larger particles are withheld at the injection site.

    “Reports suggest that nanoparticles up to 200 nm are able to enter the lymphatic vessels, whereas larger particles are withheld at the injection site [128][129][130].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [128][129][130]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Recent findings suggest that nanoparticle-mediated infusion reactions are triggered by an acute intoxication of pulmonary intravascular macrophages.

    “However, recent findings suggest that these nanoparticle-mediated infusion reactions are triggered by an acute intoxication of pulmonary intravascular macrophages [152][153][154].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [152][153][154]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Perche et al. prepared mannosylated nanoparticles loaded with mRNA, which could be used as an active targeting strategy to enhance transfection of splenic DCs.

    “Perche et al. prepared mannosylated nanoparticles loaded with mRNA, which could be used as an active targeting strategy to enhance the transfection of splenic DCs [126].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [126]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The observed site-specific targeting could be attributed to LNP surface charge, but involvement of a different biomolecular corona cannot be excluded.

    “While it is possible that the observed site-specific targeting could be attributed to the LNP surface charge, the involvement of a different biomolecular corona cannot be excluded.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Chronic activation of the type I IFN pathway leads to induction of regulatory DCs, deletion of virus-specific B cells and strongly impaired T cell responses.

    “Here, it was found that chronic activation of the type I IFN pathway leads to the induction of regulatory DCs, the deletion of virus-specific B cells and strongly impaired T cells responses [180][181][182].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [180][181][182]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    If type I IFNs are produced after recognition of MHC-presented antigens by T cells, they act as a strong 3rd signal cytokine to stimulate T cell activation and proliferation.

    “If type I IFNs are produced after recognition of MHC-presented antigens by T cells, they act as a strong 3 rd signal cytokine to stimulate T cell activation and proliferation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Type I IFN signalling induces DC maturation, improved antigen processing and presentation, and enhances DC migration to enriched T cell zones (e.g., via CCR7).

    “Indeed, type I IFN signalling induces DC maturation, improved antigen processing and presentation, and enhances DC migration to enriched T cell zones (e.g., via CCR7) [172][173][174][175].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [172][173][174][175]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    By regulating other pro-inflammatory cytokines, type I IFNs are involved in the regulation of Natural Killer cell responses.

    “By regulating other pro-inflammatory cytokines, type I IFNs are also involved in the regulation of other immune cell types, such as Natural Killer (NK) cell responses [179].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [179]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    For a self-amplifying mRNA LNP vaccine, antigen expression is dramatically enhanced in the absence of IFN-α/β, correlating with improved immunogenicity and IgG antibody responses.

    “For a self-amplifying mRNA LNP vaccine, Pepini et al. reported that the antigen expression was dramatically enhanced in the absence of IFN-α/β, which correlated with improved immunogenicity and IgG antibody responses [167].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [167]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nucleoside-modified mRNA LNPs outperform unmodified mRNA LNPs in translation capacity, but fail to elicit successful CTL responses due to drastically reduced production of type I IFNs.

    “Comparative studies performed by our research group and others demonstrated that nucleoside-modified mRNA LNPs outperformed unmodified mRNA LNPs in translation capacity, but failed to elicit successful CTL responses due to the drastically reduced production of type I IFNs [119,157].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [119]

      Not checked in the free run.

    • cites [157] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    The type I IFN response by mRNA vaccines might have dual effects on naïve T cells, depending on the duration and relative timing between type I IFN signalling and T cell priming.

    “In an opinion article, De Beuckelaer et al. suggested that the type I IFN response by mRNA vaccines might have dual effects on naïve T cells, depending on the duration and relative timing between type I IFN signalling and T cell priming [169].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [169]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    By lowering the lipid-to-mRNA ratio to a lower lipid content, DOTMA-DOPE mRNA LNPs become negatively charged and specifically target DCs in the spleen.

    “Interestingly, by lowering the lipid-to-mRNA ratio to a lower lipid content, Kranz et al. demonstrated that DOTMA-DOPE mRNA LNPs become negatively charged and specifically target DCs in the spleen [92,158].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [92] source

      Not checked in the free run.

    • cites [158]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    The early type I IFN response induced by an mRNA vaccine might not only limit mRNA-encoded antigen expression, but even exert deleterious effects on T cell responses.

    “This might explain why the early type I IFN response induced by an mRNA vaccine, might not only limit the mRNA-encoded antigen expression, but even exert deleterious effects on T cell responses [169].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [169]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In humoral immunity, type I IFNs promote the generation of long-lived antibody responses by indirect enhancement of helper T cell responses and by direct immune-stimulatory effects on B cells.

    “In humoral immunity, type I IFNs promote the generation of long-lived antibody responses by the indirect enhancement of helper T cell responses and by direct immune-stimulatory effects on B cells [177,178].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [177]

      Not checked in the free run.

    • cites [178]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Combining mRNA vaccines with PD-1 checkpoint inhibitor treatments is an opportunity.

    “As such, this sparks opportunity for combining mRNA vaccines with PD-1 checkpoint inhibitor treatments.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Breckpot and colleagues demonstrated reprogramming of DCs after intratumoral administration of TriMix mRNA (CD40L, caTLR4 and CD70), or using mRNA encoding a fusokine consisting of IFN-β and the ectodomain of the TGF-β receptor II.

    “Breckpot and colleagues demonstrated the reprogramming of DCs after the intratumoral administration of TriMix mRNA (i.e.CD40L, caTLR4 and CD70), or using mRNA encoding a fusokine consisting of IFN-β and the ectodomain of the TGF-β receptor II [84,202].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [84]

      Not checked in the free run.

    • cites [202]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Expression of MLKL provokes a type of immunogenic cell death called necroptosis, which enables release of tumor-specific antigens and natural DAMPs that trigger antitumor responses.

    “Indeed, the expression of the MLKL provokes a type of immunogenic cell death, called necroptosis, which enables the release of tumor-specific antigens and natural DAMPs that trigger antitumor responses.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [204]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    It is crucial to monitor immunosuppressive mechanisms that might hamper the evoked immunity.

    “In addition, it is of crucial importance to keep a close eye on several immunosuppressive mechanisms that might hamper the evoked immunity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Bell's palsy is a condition of temporary facial paralysis that has been linked to autoimmunity.

    “This is a condition of temporary facial paralysis, which has been linked to autoimmunity [188].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [188]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    By localized expression of these immunomodulatory molecules, this strategy was able to break DC tolerance and activate tumor-specific T cell responses.

    “By the localized expression of these immunomodulatory molecules, this strategy was able to break DC tolerance and to activate tumor-specific T cell responses.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [203] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Thran et al. evaluated an LNP formulation of sequence-engineered mRNA coding for prophylactic or therapeutic antibodies, which could provide protection against rabies infection, botulinum intoxication, and tumors.

    “To give two examples, Thran et al. evaluated an LNP formulation of sequence-engineered mRNA coding for prophylactic or therapeutic antibodies.This could provide protection against rabies infection, botulinum intoxication, and tumors [201].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [201] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Distinct mRNA vaccines, varying in mRNA design, formulation and administration route, will exhibit differences in kinetics and cell-specificity for both mRNA expression and innate immune activation.

    “There is, however no doubt that distinct mRNA vaccines, varying in mRNA design, formulation and administration route, will exhibit differences in kinetics and cell-specificity for both mRNA expression and innate immune activation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    These tools include transgenic reporter mouse strains, such as IFN-β reporter mice and Cre recombinase reporter mice, and fluorescent imaging mRNA probes that detect mRNA at high resolution.

    “This includes the generation of transgenic reporter mouse strains, such as the IFN-β reporter mice and Cre recombinase (mRNA) reporter mice, as well as the development of fluorescent imaging mRNA probes that allow to detect mRNA at high resolution [90,158,[192][193][194][195].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90,158,[192][193][194][195]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    This mRNA platform represented a valid alternative to classic mRNA cancer vaccines, providing a strong infiltration of T cells able to eliminate tumors in mice.

    “This mRNA platform represented a valid alternative to classic mRNA cancer vaccines, providing a strong infiltration of T cells able to eliminate tumors in mice.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [197] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    Adequate intracellular delivery of mRNA molecules, preferably by targeting APCs in vivo, is essential for mRNA vaccine success.

    “Firstly, it is essential to ensure adequate intracellular delivery of mRNA molecules, preferably by targeting APCs in vivo.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Two papers showed that intravenous administration of unmodified mRNA lipid nanoparticles triggered a rapid and systemic induction of type I IFNs, involving selective targeting of dendritic cells and macrophages and activation of the TLR7 pathway.

    “Two papers showed that the i.v.administration of unmodified mRNA LNPs triggered a rapid and systemic induction of type I IFNs, which involved the selective targeting of DCs and macrophages and the activation of the TLR7 pathway[92,136].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [92] source

      Not checked in the free run.

    • cites [136] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Both mRNA-encoded antigen expression and adequate immunostimulation are of crucial importance to the vaccine outcome.

    “Both parameters are of crucial importance to the vaccine outcome, but are inherently linked to the structural properties of the mRNA molecule itself.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationnone given

    More extended clinical experience is needed to know how patients respond to mRNA vaccines, including comparative research to select the best suited mRNA platform and administration route and to show clear therapeutic benefits over other vaccine strategies.

    “However, it is still waiting for a more extended clinical experience on how patients respond to mRNA vaccines, including more comparative research to select for the best suited mRNA platform and administration route, as well as to show clear therapeutic benefits over other vaccine strategies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationreasoning

    The design of mRNA lipid nanoparticles requires a multi-objective solving approach in which overall mRNA transfection capacity depends on trade-offs between requirements to cross extra- and intracellular barriers, while precautions are needed to prevent potential nanoparticle inherent immune toxicities.

    “We discussed that the design of these LNPs asks for a multi-objective solving approach in which the overall mRNA transfection capacity will depend on trade-offs between different requirements to cross the extra-and intracellular barriers, while precautions are needed to prevent potential nanoparticle inherent (immune) toxicities.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    mRNA represents an attractive source of antigen in vaccination approaches.

    “mRNA represents an attractive source of antigen in vaccination approaches”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    mRNA-encoded antigen expression and adequate immunostimulation are inherently linked to the structural properties of the mRNA molecule itself.

    “Both parameters are of crucial importance to the vaccine outcome, but are inherently linked to the structural properties of the mRNA molecule itself.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    There is currently a trend towards the use of lipid-based nanoparticles for both localized and systemic delivery of mRNA.

    “Nowadays, there appears to be a trend towards the use of lipid-based nanoparticles for both localized and systemic delivery of mRNA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Nanoformulation widens the administration and delivery options for mRNA vaccines.

    “Nanoformulation widens the administration and delivery options for mRNA vaccines”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Type I IFN activity of mRNA vaccines might vary depending on the mRNA formulation, administration route, individual patient, and intended therapeutic application.

    “Fundamental research should further focus on how to control the type I IFN activity of mRNA vaccines, which might vary depending on the mRNA formulation, administration route, the individual patient and the intended therapeutic application.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    For clinical translation of mRNA LNP systems, meeting pharmaceutical and regulatory product requirements, including scale-up GMP manufacturing, quality control, stability testing, and safety and efficacy assessments in relevant animal models, is critical.

    “For clinical translation of these mRNA LNP systems, it will also be critical to meet pharmaceutical-and regulatory product requirements, going from scale-up manufacturing under GMP conditions, quality control of these products, stability testing, and good safety and efficacy assessments during the pre-clinical stage in relevant animal models.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    A fairly large knowledge gap about the in vivo behaviour of mRNA has been filled, both after delivery of naked mRNA or when formulated in nanoparticles, and for various immunization routes.

    “Over the years, a fairly large knowledge gap about the in vivo behaviour of mRNA has been filled, both after the delivery of naked mRNA or when formulated in nanoparticles, and this for various immunization routes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Preclinical studies in non-human primates show accumulating evidence that mRNA vaccination is feasible, generally well-tolerated, and potentially beneficial over other traditional vaccine approaches.

    “For prophylactic mRNA vaccines against infectious diseases, (pre-)clinical studies (in non-human primates) show accumulating evidence that mRNA vaccination is feasible, generally well-tolerated, and potentially beneficial over other traditional vaccine approaches.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationnone given

    The mRNA-induced type I IFN response might add to the immunogenicity of the mRNA vaccine.

    “More specifically, although the mRNA-induced type I IFN response might add to the immunogenicity of the mRNA vaccine, it also interferes with the mRNA-encoded antigen expression and possibly even lead to deleterious immune effects.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The self-adjuvant effect of mRNA is a double-edged sword for vaccine efficacy.

    “The self-adjuvant effect of mRNA is a double-edged sword for vaccine efficacy”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    Each structural element of IVT mRNA can be optimized and modified to modulate the stability, translation capacity, and immune-stimulatory profile of mRNA.

    “Each of these elements can be optimized and modified in order to modulate the stability, translation capacity, and immune-stimulatory profile of mRNA.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Both unformulated and nanoparticulate mRNA are used for direct in vivo vaccination.

    “Both unformulated and nanoparticulate mRNA are used for direct in vivo vaccination”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The choice of amino lipids (cationic or ionizable lipids) and helper lipids impacts the structural arrangement and functional properties of formulated mRNA lipid nanoparticles.

    “The choice of the amino lipids (cationic or ionizable lipids) and helper lipids will have an impact on the structural arrangement and functional properties of the formulated mRNA LNPs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    mRNA approaches that do not necessarily rely on the self-adjuvant effect of mRNA are on the rise, such as replacement of type I IFN responses by more controllable adjuvant systems or using mRNA for passive immunization approaches.

    “As such, mRNA approaches which do not necessarily rely on the self-adjuvant effect of mRNA are one the rise, such as the replacement of type I IFN responses by more controllable adjuvant systems, or using mRNA for passive immunization approaches.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The establishment of effective combination therapies that could increase the response rate of checkpoint inhibitors is an area of intensive investigation.

    “Therefore, the establishment of effective combination therapies that could increase the response rate of checkpoint inhibitors is an area of intensive investigation [220,221].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [220]

      Not checked in the free run.

    • cites [221]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Contradictory results have been reported about the role of type I IFN responses on the immunogenicity of mRNA vaccines.

    “Contradictory results have been reported about the role of type I IFN responses on the immunogenicity of mRNA vaccines (see also section 2.3).”
    Quote in the paperNot a substantial claim
97 of 97

  • The authors state this as an assumption.

    When mRNA LNPs are prepared by admixing mRNA with pre-formed monolamellar liposomes containing a permanently-charged lipid, the liposomes reorganize to form a multi-lamellar structure in which mRNA molecules are sandwiched between concentric lipid bilayers.

    “When mRNA LNPs are prepared by admixing mRNA with pre-formed (monolamellar) liposomes containing a permanently-charged lipid, it is assumed that the liposomes reorganize to form a multi-lamellar structure in which mRNA molecules are”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Modified nucleosides can be used to create mRNA vaccines with significantly improved translation efficiency.

    “The modified nucleosides escape the type interferons (IFNs) induced antiviral pathways and are targeted to break and block invading mRNA; therefore they can be used to create mRNA vaccines with significantly improved translation efficiency (Verbeke et al. 2019).”

    From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Verbeke et al. 2019

  • Modified nucleosides escape type interferons (IFNs) induced antiviral pathways and are targeted to break and block invading mRNA.

    “The modified nucleosides escape the type interferons (IFNs) induced antiviral pathways and are targeted to break and block invading mRNA; therefore they can be used to create mRNA vaccines with significantly improved translation efficiency (Verbeke et al. 2019).”

    From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Verbeke et al. 2019

  • The basic structure of mRNA is made up of a protein-encoding ORF, surrounded by 5′ and 3′ UTRs, a 7-methyl guanosine 5′ cap structure, and a 3′ poly(A) tail.

    “The basic structure of mRNA, same as eukaryotic mRNA, is made up of (i) protein encoding ORF, surrounded by (ii) 5′ and 3′ UTRs, and (iii) a 7-methyl guanosine 5′ cap structure and (iv) a 3′poly(A) tail at the end sides (Verbeke et al. 2019; Schlake et al. 2012; Sahin et al. 2014) (Fig. 1).”

    From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Verbeke et al. 2019

  • The shell of Arteta et al.'s mRNA-LNPs is a monolayer.

    “Another interesting finding by Arteta et al. is that the shell of their mRNA-LNPs is a monolayer (Yanez Arteta et al., 2018, Verbeke et al., 2019).”

    From mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability (2021) · cites this paper as Verbeke et al., 2019

  • Research into the use of mRNA as a source of protein has been around for three decades.

    “research into the use of mRNA as a source of protein has been around for three decades [1]”

    From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [1]

Cites

Flagged first, then by citations

Research works printed but not linked: 9

  1. Conry, 1995, Cancer Res., 55, 1397
  2. Devoldere, 2015, Drug Discov. Today
  3. Orlandini von Niessen, 2018, Mol. Ther., 271, 824
  4. Vu, 2019, Nat. Nanotechnol.
  5. Pepini, 2017, J. Immunol.
  6. Kirschman, 2017, Nucleic Acids Res.
  7. Verbeke, 2019, ACS Nano, 13, 1655
  8. Kübler, 2015, JITC, 3, 26
  9. Bazhin, 2018, Front. Immunol., 9

Cited by

Sorted by citations

Related

Authors
Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H.
Affiliations
  • Ghent University Hospital (BE)
  • Vrije Universiteit Brussel (BE)
ORCID
Venue
Nano Today
Publisher
Elsevier BV
Published
2019-10
Volume
28
Pages
100766
ISSN
1748-0132 (ISSN-L)
DOI
10.1016/j.nantod.2019.100766
OpenAlex
W2969814123
Cited by
342
References
218
Citations by year
2026: 50 · 2025: 45 · 2024: 48 · 2023: 61 · 2022: 55 · 2021: 69 · 2020: 14
FWCI
13.84
Type
journal article
Language
en
Open access
Licence
Locations
  • Nano Today (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
Funders
  • Agentschap voor Innovatie door Wetenschap en Technologie
  • Fonds Wetenschappelijk Onderzoek
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Keywords
mRNA vaccines, mRNA, vaccine design, vaccine safety and efficacy, vaccine administration

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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