The DOI matches its Crossref record; 84 of the 90 references it cites were found in a registry or an index; 1 of the 134 sources its claims cite were checked for support.
The dawn of mRNA vaccines: The COVID-19 case
Open accessAbstract
In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-1273, were granted the first historic authorization for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing. The COVID-19 mRNA vaccines represent a new class of vaccine products, which consist of synthetic mRNA strands encoding the SARS-CoV-2 Spike glycoprotein, packaged in lipid nanoparticles to deliver mRNA to cells. This review digs deeper into the scientific breakthroughs of the last decades that laid the foundations for the rapid rise of mRNA vaccines during the COVID-19 pandemic. As well as providing momentum for mRNA vaccines, SARS-CoV-2 represents an ideal case study allowing to compare design-activity differences between the different mRNA vaccine candidates. Therefore, a detailed overview of the composition and (pre)clinical performance of the three most advanced mRNA vaccines is provided and the influence of choices in their structural design on to their immunogenicity and reactogenicity profile is discussed in depth. In addition to the new fundamental insights in the mRNA vaccines' mode of action highlighted here, we also point out which unknowns remain that require further investigation and possibly, optimization in future mRNA vaccine development.
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TL;DR
This review explains how decades of mRNA, innate-immunity, and lipid-nanoparticle research enabled the rapid COVID-19 mRNA vaccines, and compares BNT162b2, mRNA-1273, and CVnCoV. It concludes that mRNA vaccines are highly efficacious and generally safe, but important unknowns remain about innate immune effects, durability, and which vaccine components drive differences in immunogenicity and reactogenicity.
Key findings
- All three most advanced vaccines encode full-length SARS-CoV-2 Spike with K986P/V987P proline substitutions; BNT162b2 uses 30 μg mRNA two doses 21 days apart, mRNA-1273 uses 100 μg two doses 28 days apart, and CVnCoV uses 12 μg two doses 28 days apart. BNT162b2 and mRNA-1273 use N1-methylpseudouridine-modified mRNA plus dsRNA removal, whereas CVnCoV uses unmodified, sequence-engineered mRNA.
- Efficacy was high: BNT162b2 showed up to 95% efficacy in phase 3, mRNA-1273 conferred 94.1% protection against symptomatic COVID-19, and real-world Israeli data for BNT162b2 estimated 97% effectiveness against symptomatic/severe disease and 94% against asymptomatic infection.
- CVnCoV at 12 μg induced neutralizing antibody titers in all participants comparable to convalescent individuals, while BNT162b2 and mRNA-1273 generally surpassed convalescent titers, even in elderly trial groups. BNT162b2 elicited S-specific CD8+ T cell responses in 91.9% of participants, compared with low or undetectable levels for mRNA-1273.
- Reactogenicity differed: fever after second mRNA-1273 dose occurred in 40% at 100 μg and 57% at 250 μg, but none at 25 μg; BNT162b2 fever after second 30 μg dose was 8% in ages 18–55 and 17% in ages 65–85; CVnCoV fever was reported by 57% after the first dose. Rare anaphylaxis after mRNA-1273 or BNT162b2 was estimated at approximately 1 in 100,000.
Methods
- Narrative review synthesizing three decades of mRNA vaccine research, innate immune sensing of RNA, lipid nanoparticle delivery, coronavirus Spike antigen design, and (pre)clinical data for BNT162b2, mRNA-1273, and CVnCoV.
- Compares vaccine composition in Table 1 and discusses design features, immunogenicity, reactogenicity, efficacy, and safety using published preclinical studies, phase 1/2/3 trials, real-world data, and preprints.
- No new primary data, systematic search strategy, or meta-analysis is described.
Limitations
- The paper states remaining unknowns: how innate immune responses to mRNA-LNPs affect translation, immunogenicity, and reactogenicity; how long immunity lasts; whether mRNA or the LNP vehicle drives the innate immune signature; and whether further optimization is possible.
- The paper notes that direct comparisons between vaccine candidates require caution because of differences in test populations, study designs, vaccination approaches, and potential efficacy differences; it also states that no public data exist on the Acuitas LNPs used in CVnCoV and BNT162b2, and that it cannot pinpoint which components cause differential CD8+ T cell responses.
- Evident from the text: the review relies heavily on early clinical reports, preprints, and manufacturer disclosures, and some LNP ratios and structural elements are described as not yet confirmed for the COVID-19 vaccines.
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Claims the paper makes
85 Not checked yet · 20 Own interpretation · 14 Sources not found · 1 Partly supported · 1 No basis given · accuracy not yet measured
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In the paper
“For Moderna's LNP formulation, Hassett et al. reported that the SM-102 lipid was selected based on its improved tolerability profile in non-human primates, as evidenced by a reduced local reactogenicity (e.g., edema and erythema) and lowest induction of systemic cytokine responses (e.g., IL-6) [13]”
§ The dawn of mRNA vaccines: The COVID-19 case > The mode of action of mRNA vaccines
What the sources say
- Partly supportedcites [13] Hassett K.J. Benenato K.E. Jacquinet E. Lee A. Woods A. Yuzhakov O. Himansu S. Deterling J. Geilich B.M. Ketova T. Optimization of lipid nanoparticles forintramuscular administration of mRNA vaccines Mol. Ther. Nucleic Acids 15 2019 1 11 30785039 PMC6383180 sourceExperimental — accuracy not yet measured
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In the paper
“by incorporating naturally occurring modified nucleotides into the IVT mRNA, its innate immune activity could be drastically reduced [6,7]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [6] Andries O. Mc Cafferty S. De Smedt S.C. Weiss R. Sanders N.N. Kitada T. N-1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice J. Control. Release 217 2015 337 344 26342664 source
- Not checked yetcites [7] Durbin A.F. Wang C. Marcotrigiano J. Gehrke L. RNAs containing modified nucleotides fail to trigger RIG-I conformational changes for innate immune signaling Mbio 7 2016 PMC5030355 27651356 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the identification of Toll-like receptors (TLRs) by Jules Hoffman and Bruce Beutler elucidated how the mammalian immune system could recognize highly conserved patterns associated with the presence of pathogens or damage [3]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [3] O’Neill L.A.J. Golenbock D. Bowie A.G. The history of toll-like receptors - redefining innate immunity Nat. Rev. Immunol. 13 2013 453 460 23681101 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additional efforts to remove double-stranded (ds)RNA contaminants even further ablated IVT RNA's immunostimulatory activity [8,9]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [8] Baiersdorfer M. Boros G. Muramatsu H. Mahiny A. Vlatkovic I. Sahin U. Kariko K. A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA Mol. Ther. Nulceic Acids 15 2019 26 35 PMC6444222 30933724 source
- Not checked yetcites [9] Kariko K. Muramatsu H. Ludwig J. Weissman D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA Nucleic Acids Res. 39 2011 e142 PMC3241667 21890902 source
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In the paper
“the many modifications observed in natural mRNA are in fact a way to avoid immune recognition, allowing the immune system to distinguish self from non-self RNA [5]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [5] Kariko K. Buckstein M. Ni H.P. Weissman D. Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA Immunity 23 2005 165 175 16111635 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Precedent work by Moderna and the NIH National Institute for Allergy and Infectious Diseases (NIAID) demonstrated that the membrane-bound MERS-CoV 2P S mRNA elicited more potent neutralizing antibody responses as compared to secreted MERS-CoV 2P S, or wild-type S mRNA”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > Antigen target
What the sources say
- Not matchedcites [27] Corbett K.S. Edwards D.K. Leist S.R. Abiona O.M. Boyoglu-Barnum S. Gillespie R.A. Himansu S. Schäfer A. Ziwawo C.T. DiPiazza A.T. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness Nature 586 2020 567 571 32756549 PMC7581537
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In the paper
“Codon optimization in the mRNA sequence to e.g., match host transfer (t)RNA abundances, or as a determinant of introducing secondary structures, can drastically impact the protein synthesis rate and ribosome dwell time (i.e. mRNA functional half-life) [33,34]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > mRNA design and modifications
What the sources say
- Not checked yetcites [33] Presnyak V. Alhusaini N. Chen Y.H. Martin S. Morris N. Kline N. Olson S. Weinberg D. Baker K.E. Graveley B.R. Codon optimality is a major determinant of mRNA stability Cell 160 2015 1111 1124 25768907 PMC4359748 source
- Not checked yetcites [34] Mao Y. Liu H. Liu Y. Tao S. Deciphering the rules by which dynamics of mRNA secondary structure affect translation efficiency in Saccharomyces cerevisiae Nucleic Acids Res. 42 2014 4813 4822 24561808 PMC4005662 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“A major advantage of the mRNA approach, is that the proteins are produced by the host cells as they would be in case of a natural infection with the virus. As a result, the produced proteins will undergo the same post-translational processing, including glycosylation, subunit cleavage and proper protein folding.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > Antigen target
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the rapid development of the COVID-19 vaccines did not come out of the blue at all, the current COVID-19 pandemic merely provided momentum for mRNA vaccines to speed up their progress to approval”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“most of the MERS-CoV and SARS-CoV-1 neutralizing antibodies were directed to the S protein, in particular to its receptor-binding domain (RBD) [18,19]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [18] Du L.Y. Yang Y. Zhou Y.S. Lu L. Li F. Jiang S.B. MERS-CoV spike protein: a key target for antivirals Expert. Opin. Ther. Tar. 21 2017 131 143 PMC5457961 27936982 source
- Not checked yetcites [19] Tang X.C. Agnihothram S.S. Jiao Y.J. Stanhope J. Graham R.L. Peterson E.C. Avnir Y. Tallarico A.S. Sheehan J. Zhu Q. Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution Proc. Natl. Acad. Sci. USA 111 2014 (pp. 6863–6863) PMC4024880 24778221 source
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 7
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In the paper
“not only viral RNA, but also endogenous mRNA associated with apoptotic cells as well as in vitro transcribed (IVT) mRNA could bind and activate TLR3, TLR7 and TLR8 [4,5]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [4] Kariko K. Ni H.P. Capodici J. Lamphier M. Weissman D. mRNA is an endogenous ligand for toll-like receptor 3 J. Biol. Chem. 279 2004 12542 12550 14729660 source
- Not checked yetcites [5] Kariko K. Buckstein M. Ni H.P. Weissman D. Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA Immunity 23 2005 165 175 16111635 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In less than one year since the outbreak of the COVID-19 pandemic, two mRNA-based vaccines, BNT162b2 and mRNA-1273, were granted the first historic authorization for emergency use, while another mRNA vaccine, CVnCoV, progressed to phase 3 clinical testing.”
§ The dawn of mRNA vaccines: The COVID-19 case > Abstract
What the sources say
- Not matchedcites [23] European Medicines Agency EMA Recommends First COVID-19 Vaccine for Authorisation in the EU https://www.ema.europa.eu/en/news/ema-recommends-first-covid-19-vaccine-authorisation-eu 2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24] EMA Recommends COVID-19 Vaccine Moderna for Authorisation in the EU https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-moderna-authorisation-eu 2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [25] FDA Briefing Document - BNT162b2 https://www.fda.gov/media/144245/download 2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The COVID-19 mRNA vaccines represent a new class of vaccine products, which consist of synthetic mRNA strands encoding the SARS-CoV-2 Spike glycoprotein, packaged in lipid nanoparticles to deliver mRNA to cells.”
§ The dawn of mRNA vaccines: The COVID-19 case > Abstract
What the sources say
- Not checked yetcites [48] Vogel A.B. Kanevsky I. Che Y. Swanson K.A. Muik A. Vormehr M. Kranz L.M. Walzer K.C. Hein S. Güler A. Immunogenic BNT162b vaccines protect rhesus macaques from SARS-CoV-2 Nature 2021 33524990 source
- Not matchedcites [49] Walsh E.E. Frenck R.W. Falsey A.R. Kitchin N. Absalon J. Gurtman A. Lockhart S. Neuzil K. Mulligan M.J. Bailey R. Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates N. Engl. J. Med. 383 2020 2439 2450 33053279 PMC7583697
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [50] Sahin U. Muik A. Vogler I. Derhovanessian E. Kranz L.M. Vormehr M. Quandt J. Bidmon N. Ulges A. Baum A. BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans medRxiv 2020 (Preprint)
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plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This review digs deeper into the scientific breakthroughs of the last decades that laid the foundations for the rapid rise of mRNA vaccines during the COVID-19 pandemic.”
§ The dawn of mRNA vaccines: The COVID-19 case > Abstract
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In the paper
“research into the use of mRNA as a source of protein has been around for three decades [1]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [1] Verbeke R. Lentacker I. De Smedt S.C. Dewitte H. Three decades of messenger RNA vaccine development Nano Today 28 2019 100766 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“although it has been employed for various therapeutic targets, its use as a source of antigen in vaccination approaches is by far the most popular [2]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [2] Pardi N. Hogan M.J. Porter F.W. Weissman D. mRNA vaccines - a new era in vaccinology Nat. Rev. Drug Discov. 17 2018 261 279 29326426 PMC5906799 source
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In the paper
“modified and purified IVT mRNA enables much higher protein expression and has a more favorable safety profile, as it drastically reduces the production of pro-inflammatory type I IFNs [6]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [6] Andries O. Mc Cafferty S. De Smedt S.C. Weiss R. Sanders N.N. Kitada T. N-1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice J. Control. Release 217 2015 337 344 26342664 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In their final COVID-19 vaccines, both BioNTech and Moderna have made use of a highly-purified and N1-methyl-pseudouridine (1mΨ) modified mRNA. In contrast, CureVac has applied its “unmodified” mRNA vaccine technology”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [10] Thess A. Grund S. Mui B.L. Hope M.J. Baumhof P. Fotin-Mleczek M. Schlake T. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals Mol. Ther. 23 2015 1456 1464 26050989 PMC4817881 source
- Not checked yetcites [11] Lutz J. Lazzaro S. Habbeddine M. Schmidt K.E. Baumhof P. Mui B.L. Tam Y.K. Madden T.D. Hope M.J. Heidenreich R. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines npj Vaccines 2 2017 PMC5648897 29263884 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“1mΨ nucleotide-modifications were shown to provide additional base pair stability, giving rise to a high degree of secondary structure which significantly improves the mRNA translation [35]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > mRNA design and modifications
What the sources say
- Not checked yetcites [35] Mauger D.M. Cabral B.J. Presnyak V. Su S.V. Reid D.W. Goodman B. Link K. Khatwani N. Reynders J. Moore M.J. mRNA structure regulates protein expression through changes in functional half-life Proc. Natl. Acad. Sci. U. S. A. 116 2019 24075 31712433 PMC6883848 source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“isolation of neutralizing antibodies from the serum of COVID-19 patients confirmed the strong immunogenicity of the S protein, but showed an equal immunogenicity of the RBD and the N-terminal domain (NTD)”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > Antigen target
What the sources say
- Not checked yetcites [28] Liu L. Wang P. Nair M.S. Yu J. Rapp M. Wang Q. Luo Y. Chan J.F.W. Sahi V. Figueroa A. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike Nature 584 2020 450 456 32698192 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“When the new SARS-CoV-2 virus was identified, detailed investigations into the structure and dynamics of the SARS-CoV-2 S protein revealed large homology to the SARS-CoV-1 S protein, which allowed the major players in vaccine development to immediately turn to the S protein as vaccine target [20,21]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not matchedcites [20] Cai Y.F. Zhang J. Xiao T.S. Peng H.Q. Sterling S.M. Walsh R.M. Rawson S. Rits-Volloch S. Chen B. Distinct conformational states of SARS-CoV-2 spike protein Science 369 2020 1586 1592 32694201 PMC7464562
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not checked yetcites [21] Wrapp D. Wang N.S. Corbett K.S. Goldsmith J.A. Hsieh C.L. Abiona O. Graham B.S. McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Science 367 2020 1260 1263 32075877 PMC7164637 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This protein mediates viral entry by first binding to its cellular receptor (i.e. angiotensin-converting enzyme 2, ACE2 for SARS-CoV-1 or dipeptidyl peptidase 4, DPP4/CD26 for MERS-CoV). Upon interaction, the S protein undergoes structural changes resulting in the fusion of viral and host cell membranes.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [18] Du L.Y. Yang Y. Zhou Y.S. Lu L. Li F. Jiang S.B. MERS-CoV spike protein: a key target for antivirals Expert. Opin. Ther. Tar. 21 2017 131 143 PMC5457961 27936982 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“All mRNA vaccines target the same SARS-CoV-2 antigen and incorporate mRNA encoding the full-length, transmembrane anchored S protein. The genetic sequence is slightly altered to stabilize the prefusion conformation of the glycoprotein using two proline (2P) substitutions (K986P and V987P mutations) (Fig. 2a) [21]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > Antigen target
What the sources say
- Not checked yetcites [21] Wrapp D. Wang N.S. Corbett K.S. Goldsmith J.A. Hsieh C.L. Abiona O. Graham B.S. McLellan J.S. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation Science 367 2020 1260 1263 32075877 PMC7164637
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This implies that vaccinating against the entire S protein, rather than only one of its structural components, is expected to result in an improved response which will be less affected when the virus undergoes genetic drift [28]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > Antigen target
What the sources say
- Not checked yetcites [28] Liu L. Wang P. Nair M.S. Yu J. Rapp M. Wang Q. Luo Y. Chan J.F.W. Sahi V. Figueroa A. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike Nature 584 2020 450 456 32698192 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The promising COVID-19 vaccines rapidly received Fast Track designation by the FDA and EMA, resulting in their approval by both regulatory agencies before the end of 2020 for emergency use [[23], [24], [25], [26]]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not matchedcites [23] European Medicines Agency EMA Recommends First COVID-19 Vaccine for Authorisation in the EU https://www.ema.europa.eu/en/news/ema-recommends-first-covid-19-vaccine-authorisation-eu 2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [24] EMA Recommends COVID-19 Vaccine Moderna for Authorisation in the EU https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-moderna-authorisation-eu 2021
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [25] FDA Briefing Document - BNT162b2 https://www.fda.gov/media/144245/download 2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“During the mixing step, the pH of the formulation is kept low to protonate the ionizable lipid's amine function, enabling electrostatic complexation of the now positively charged lipids and the negatively charged mRNA. A dialysis or ultrafiltration is then performed to neutralize the pH, resulting in uncharged, solid-core LNPs that densely package the mRNA [14]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
What the sources say
- Not checked yetcites [14] Kulkarni J.A. Witzigmann D. Leung J. van der Meel R. Zaifman J. Darjuan M.M. Grisch-Chan H.M. Thöny B. Tam Y.Y.C. Cullis P.R. Fusion-dependent formation of lipid nanoparticles containing macromolecular payloads Nanoscale 11 2019 9023 9031 31021343 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Moderna claimed that with such an approach, both local and systemic innate immune effects upon mRNA (vaccine) administration can be limited to a bare minimum in mice [37]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > mRNA design and modifications
What the sources say
- Not checked yetcites [37] Nelson J. Sorensen E.W. Mintri S. Rabideau A.E. Zheng W. Besin G. Khatwani N. Su S.V. Miracco E.J. Issa W.J. Impact of mRNA chemistry and manufacturing process on innate immune activation Sci. Adv. 6 2020 (eaaz6893) PMC7314518 32637598 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“previous experience with the closely related SARS-CoV-1, showed that CD8+ and CD4+ memory T cells were detectable as late as 17 years post-infection, while neutralizing antibody titers had waned substantially by 1 year after infection [69,70]”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
What the sources say
- Not checked yetcites [69] Sariol A. Perlman S. Lessons for COVID-19 immunity from other coronavirus infections Immunity 53 2020 248 263 32717182 PMC7359787 source
- Not checked yetcites [70] Le Bert N. Tan A.T. Kunasegaran K. Tham C.Y.L. Hafezi M. Chia A. Chng M.H.Y. Lin M. Tan N. Linster M. SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls Nature 584 2020 457 462 32668444 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“the CVnCoV vaccine candidate contains an “unmodified” mRNA, which employs sequence engineering (e.g., reduction in uridine content), selected UTRs, and a stringent purification protocol to remove dsRNA fragments [11]”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 mRNA vaccines: Differences and similarities > mRNA design and modifications
What the sources say
- Not checked yetcites [11] Lutz J. Lazzaro S. Habbeddine M. Schmidt K.E. Baumhof P. Mui B.L. Tam Y.K. Madden T.D. Hope M.J. Heidenreich R. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines npj Vaccines 2 2017 PMC5648897 29263884 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the (local) induction of type IFNs and other inflammatory cytokines plays - in all likelihood - an important role in the reactogenicity of mRNA vaccines.”
§ The dawn of mRNA vaccines: The COVID-19 case > The mode of action of mRNA vaccines
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In COVID-19 patients, a coordinated adaptive immunity of CD4+ T cells, CD8+ T cells, and antibody responses was correlated to milder disease, whereas an uncoordinated response frequently failed to control disease [68]”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
What the sources say
- Not checked yetcites [68] Rydyznski Moderbacher C. Ramirez S.I. Dan J.M. Grifoni A. Hastie K.M. Weiskopf D. Belanger S. Abbott R.K. Kim C. Choi J. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity Cell 183 2020 996 1012 33010815 PMC7494270 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Similar to the more classical vaccine approaches, the COVID-19 mRNA vaccines are injected in the muscle, where they trigger localized and transient inflammation that recruits different immune cells to the injection site (Fig. 3 ) [11,41]”
§ The dawn of mRNA vaccines: The COVID-19 case > The mode of action of mRNA vaccines
What the sources say
- Not checked yetcites [11] Lutz J. Lazzaro S. Habbeddine M. Schmidt K.E. Baumhof P. Mui B.L. Tam Y.K. Madden T.D. Hope M.J. Heidenreich R. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines npj Vaccines 2 2017 PMC5648897 29263884 source
- Not checked yetcites [41] Liang F. Lindgren G. Lin A. Thompson E.A. Ols S. Röhss J. John S. Hassett K. Yuzhakov O. Bahl K. Efficient targeting and activation of antigen-presenting cells in vivo after modified mRNA vaccine administration in rhesus macaques Mol. Ther. 25 2017 2635 2647 28958578 PMC5768558 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“According to mechanistic studies on the fate of mRNA LNPs in rhesus monkeys, primarily monocytes and DC subsets translate the mRNA, likely involving ApoE dependent endocytosis [41]”
§ The dawn of mRNA vaccines: The COVID-19 case > The mode of action of mRNA vaccines
What the sources say
- Not checked yetcites [41] Liang F. Lindgren G. Lin A. Thompson E.A. Ols S. Röhss J. John S. Hassett K. Yuzhakov O. Bahl K. Efficient targeting and activation of antigen-presenting cells in vivo after modified mRNA vaccine administration in rhesus macaques Mol. Ther. 25 2017 2635 2647 28958578 PMC5768558 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the type I IFN activity of mRNA vaccines can prematurely stop mRNA-translation, thereby reducing antigen availability and diminishing the vaccine's efficacy to obtain adaptive immune responses [63,64]”
§ The dawn of mRNA vaccines: The COVID-19 case > The mode of action of mRNA vaccines
What the sources say
- Not checked yetcites [63] Pepini T. Pulichino A.M. Carsillo T. Carlson A.L. Sari-Sarraf F. Ramsauer K. Debasitis J.C. Maruggi G. Otten G.R. Geall A.J. Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design J. Immunol. 198 2017 4012 4024 28416600 PMC5421303 source
- Not checked yetcites [64] Van Hoecke L. Roose K. Ballegeer M. Zhong Z. Sanders N.N. De Koker S. Saelens X. Van Lint S. The opposing effect of type I IFN on the T cell response by non-modified mRNA-lipoplex vaccines is determined by the route of administration Mol. Ther. Nucleic Acids 22 2020 373 381 33230442 PMC7533292 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The COVID-19 mRNA vaccines are primarily focused on triggering B cells to promote the induction of neutralizing antibodies, but there are also good reasons to believe that CD8+ T cell and CD4+ T cell responses may contribute to the protection against SARS-CoV-2 [66]”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
What the sources say
- Not checked yetcites [66] Karlsson A.C. Humbert M. Buggert M. The known unknowns of T cell immunity to COVID-19 Sci. Immunol. 5 2020 (eabe8063) 33208380 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Since the type I IFN activity can be better controlled with 1mΨ-modified mRNA, resulting in higher maximal tolerable doses of the 1mΨ-modified mRNA vaccines, they might achieve a more durable protein expression and thus prolonged antigen availability.”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In GCs, B cells undergo affinity maturation and isotype switching. After rounds of clonal expansion, this gives rise to high affinity B cells and their differentiation into plasma cells and memory B cells, which eventually determines the quality and durability of the antibody response.”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“The vaccine efficacy of mRNA-1273 is in line with the outcome of BNT162b2, conferring 94.1% protection against symptomatic COVID-19 disease [54].”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
What the sources say
- Not checked yetcites [54] Baden L.R. El Sahly H.M. Essink B. Kotloff K. Frey S. Novak R. Diemert D. Spector S.A. Rouphael N. Creech C.B. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine N. Engl. J. Med. 384 2021 403 416 33378609 PMC7787219 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Both local and systemic AE occurred dose-dependently, were mostly mild to moderate and more common after boost vaccination.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [82] Mulligan M.J. Lyke K.E. Kitchin N. Absalon J. Gurtman A. Lockhart S. Neuzil K. Raabe V. Bailey R. Swanson K.A. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults Nature 586 2020 589 593 32785213 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“no more than 37% of the participants reported any (localized or systemic) AE after the second dose, with fever only reported by max. 5% of the participants (depending on the dosing and prime-boost schedule) [83].”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [83] Zhang Y. Zeng G. Pan H. Li C. Hu Y. Chu K. Han W. Chen Z. Tang R. Yin W. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial Lancet Infect. Dis. 21 2 2021 181 192 33217362 PMC7832443 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“AEs occurred more frequent when NVX-CoV2373 was combined with the adjuvant, and slightly more AEs were reported after the boost dose.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [84] Keech C. Albert A. Cho I. Robertson A. Reed P. Neal S. Plested J.S. Zhu M. Cloney-Clark S. Zhou H. Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine N. Engl. J. Med. 383 2020 2320 2332 32877576 PMC7494251 source
plaindirectn = 82- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“fever was reported by 57% of the participants after the first dose, but the incidence of this AE did not further increase after the boost vaccine [57].”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [57] Kremsner P. Mann P. Bosch J. Fendel R. Gabor J.J. Kreidenweiss A. Kroidl A. Leroux-Roels I. Leroux-Roels G. Schindler C. Phase 1 assessment of the safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers medRxiv 2020 (Preprint) PMC8354521 34378087 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The mRNA dose selected for phase 2b/3 clinical testing of CureVac's CVnCoV vaccine candidate was 12 μg, substantially lower than what is used in the nucleoside-modified mRNA vaccines.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [57] Kremsner P. Mann P. Bosch J. Fendel R. Gabor J.J. Kreidenweiss A. Kroidl A. Leroux-Roels I. Leroux-Roels G. Schindler C. Phase 1 assessment of the safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers medRxiv 2020 (Preprint) PMC8354521 34378087 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Because of its improved safety profile, together with the benefit of BNT162b2 to induce immunity against epitopes in S1 and S2 regions of the S antigen, while BNT162b1 is only restricted to epitopes inside the RBD region, made that BNT162b2 was selected as lead candidate for further advancement.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not matchedcites [49] Walsh E.E. Frenck R.W. Falsey A.R. Kitchin N. Absalon J. Gurtman A. Lockhart S. Neuzil K. Mulligan M.J. Bailey R. Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates N. Engl. J. Med. 383 2020 2439 2450 33053279 PMC7583697
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“Also local reactogenicity was less prominent for BNT162b2 and particularly in the older cohort, fewer severe systemic AEs were reported for this vaccine candidate.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not matchedcites [49] Walsh E.E. Frenck R.W. Falsey A.R. Kitchin N. Absalon J. Gurtman A. Lockhart S. Neuzil K. Mulligan M.J. Bailey R. Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates N. Engl. J. Med. 383 2020 2439 2450 33053279 PMC7583697
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
In the paper
“events also peaked at day 2 after dosing and were resolved by day 7.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [82] Mulligan M.J. Lyke K.E. Kitchin N. Absalon J. Gurtman A. Lockhart S. Neuzil K. Raabe V. Bailey R. Swanson K.A. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults Nature 586 2020 589 593 32785213 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Typical other systemic AEs that occurred in more than half of the dosed participants were fatigue, chills, myalgia and headache, which were all increasingly reported for higher dosages, particularly after the boost vaccine [53].”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [53] Jackson L.A. Anderson E.J. Rouphael N.G. Roberts P.C. Makhene M. Coler R.N. McCullough M.P. Chappell J.D. Denison M.R. Stevens L.J. An mRNA vaccine against SARS-CoV-2 - preliminary report N. Engl. J. Med. 383 2020 1920 1931 32663912 PMC7377258 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Despite the high incidence of systemic AEs after a single dosage, no major toxicities were reported and all AEs resolved within 2 days after dosing.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [57] Kremsner P. Mann P. Bosch J. Fendel R. Gabor J.J. Kreidenweiss A. Kroidl A. Leroux-Roels I. Leroux-Roels G. Schindler C. Phase 1 assessment of the safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers medRxiv 2020 (Preprint) PMC8354521 34378087 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Their exceptionally rapid development and production as well as high efficiency to prevent SARS-CoV-2 infection, demonstrate that mRNA-based therapeutics are ready for their place in the sun.”
§ The dawn of mRNA vaccines: The COVID-19 case > Conclusions and perspectives
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although this rapid pace was possible due to substantial pre-existing knowledge”
§ The dawn of mRNA vaccines: The COVID-19 case > Conclusions and perspectives
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
- Rests on an assumption: Two mRNA vaccines were granted authorization for emergency use in less than one year.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as they were demonstrated to be generally safe and very efficacious to prevent against symptomatic COVID-19 disease.”
§ The dawn of mRNA vaccines: The COVID-19 case > Conclusions and perspectives
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The prime vaccine commonly caused fatigue and headache, but the incidence of these AEs could be significantly reduced by prophylactic paracetamol.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [85] Folegatti P.M. Ewer K.J. Aley P.K. Angus B. Becker S. Belij-Rammerstorfer S. Bellamy D. Bibi S. Bittaye M. Clutterbuck E.A. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial Lancet 396 2020 467 478 32702298 PMC7445431 source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is clear that all of the described vaccines are generally safe, commonly trigger local reactogenicity and that all AEs resolved within 2 days after dosing.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
boosteddirectn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In the limited subset of 10 participants who received a prime-boost vaccine, fever was exclusively reported after the prime dose in 40% of the subjects, but once again resolved after 2 days.”
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 vaccines: safety first
What the sources say
- Not checked yetcites [85] Folegatti P.M. Ewer K.J. Aley P.K. Angus B. Becker S. Belij-Rammerstorfer S. Bellamy D. Bibi S. Bittaye M. Clutterbuck E.A. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial Lancet 396 2020 467 478 32702298 PMC7445431 source
plainn = 10- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Two mRNA vaccines were granted authorization for emergency use in less than one year.
“In less than one year, two mRNA vaccines were granted authorization for emergency use”
The paper relies on this without support.
Neutralizing antibody levels above a certain threshold are protective against SARS-CoV-2.
“but remained above levels that are expected to be protective”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“mRNA is created via a cell-free enzymatic transcription reaction that enables rapid and scalable production, as illustrated by the current pandemic's rapid pursuit of RNA vaccines (Verbeke et al. 2021).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Verbeke et al. 2021
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“The COVID-19 vaccine candidates demonstrate the structurally modified mRNA approach allows for higher tolerated doses and may be more suitable for producing a fast antibody response (Verbeke et al. 2021).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Verbeke et al. 2021
In the citing paper
“Tfh cells further help activate CD8+ cytotoxic T cells that may specifically recognize and eliminate virus-infected cells (Figure 1).6,55, 56, 57”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [55]
In the citing paper
“Tfh cells recognize antigens on the APC surface and help to activate B cells, which in turn produce high-affinity virus-neutralizing antibodies.6,55, 56, 57”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [55]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The dawn of mRNA vaccines: The COVID-19 case > COVID-19 creates momentum for mRNA vaccines
“The promising COVID-19 vaccines rapidly received Fast Track designation by the FDA and EMA, resulting in their approval by both regulatory agencies before the end of 2020 for emergency use [[23], [24], [25], [26]].”
§ The dawn of mRNA vaccines: The COVID-19 case > References
“24. EMA Recommends COVID-19 Vaccine Moderna for Authorisation in the EU https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-moderna-authorisation-eu 2021”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
“In comparison, the nucleoside-modified mRNA vaccines BNT162b2 (30 μg mRNA dose) and mRNA-1273 (100 μg mRNA dose) generally surpassed the titers from convalescent COVID-19 patient samples, even in the elderly trial group, hinting towards potential stronger induction of humoral immunity to the unmodified mRNA vaccine CVnCoV [49,53].”
§ The dawn of mRNA vaccines: The COVID-19 case > Immune responses and protection induced by COVID-19 mRNA vaccines
“two vaccine doses of CVnCoV (12 μg mRNA dose) induced SARS-CoV-2 neutralizing antibody titers in all participants at levels that were comparable to those found in individuals who had recovered from natural infection [57].”
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Metadata
- Authors
- Verbeke, R., Lentacker, I., De Smedt, S. C., & Dewitte, H.
- Affiliations
- Ghent University (BE)
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2021-05
- Volume
- 333
- Pages
- 511-520
- ISSN
- 0168-3659 (ISSN-L)
- PMC
- PMC8008785
- OpenAlex
- W3143214431
- Semantic Scholar
- 625ba194b83ffb3092b932815a598844f28b3009
- Cited by
- 504
- References
- 90
- Citations by year
- 2026: 72 · 2025: 72 · 2024: 88 · 2023: 118 · 2022: 94 · 2021: 60
- FWCI
- 28.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- Funders
- Universiteit Gent (F2020/IOF-StarTT/039, FAF-C/2018/1213)
- Horizon 2020 European Innovation Council Fast Track to Innovation (810685)
- Horizon 2020
- FWO (G040319N, G016221N)
- Kom op tegen kanker
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- mRNA vaccines, COVID-19 pandemic, SARS-CoV-2 spike protein, lipid nanoparticles, BNT162b2, mRNA-1273, vaccine design, immunogenicity, reactogenicity, emergency use authorization
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Humans, RNA, Messenger, Vaccines, Pandemics
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.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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