Advances in COVID-19 mRNA vaccine development

In the paper

“Nucleoside-modified mRNA can reduce the activation of TLRs, retinoic acid-inducible gene I (RIG-I), protein kinase R (PKR), and 2′-5′-oligoadenylate synthetase (OAS). Additionally, nucleoside modification increases translation activity and resistance against RNase L-mediated degradation.54,81,173–176”

What the sources say

• Not checked yetcites [54] Hornung, V. et al. 5′-Triphosphate RNA is the ligand for RIG-I. Science 314, 994–997 (2006). source
• Not checked yetcites [81] Karikó, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005). source
• Not checked yetcites [173] Andries, O. et al. N1-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Control. Rel. 217, 337–344 (2015). source
• Partly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [174] Anderson, B. R. et al. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res 38, 5884–5892 (2010). sourceExperimental — accuracy not yet measured
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [175] Anderson, B. R. et al. Nucleoside modifications in RNA limit activation of 2′-5′-oligoadenylate synthetase and increase resistance to cleavage by RNase L. Nucleic Acids Res 39, 9329–9338 (2011). source
• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [176] Svitkin, Y. V. et al. N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res 45, 6023–6036 (2017). source

In the paper

“Codon preference varies extensively in different organisms,249 therefore adjusting the balance between codon usage frequency and host tRNA availability can significantly improve translation efficiency and in vivo expression of the target antigen.250,251”

What the sources say

• Supported

  Citation 249 is attached to the first clause only. The Introduction states that synonymous codon usage is partly species- or taxon-specific and describes comparisons between organisms; the later claim about tRNA availability and antigen expression is attached to citations 250 and 251, not this source. (LLM, conf=0.93)

  cites [249] Sharp, P. M. & Li, W. H. The codon Adaptation Index–a measure of directional synonymous codon usage bias, and its potential applications. Nucl. Acids Res 15, 1281–1295 (1987). source
• Partly supported

  The Discussion reports a relationship between codon optimality and tRNA abundance, and the Results report higher fluorescence from an optimal-codon reporter than a non-optimal one in human cells (pages not provided). The paper does not show that balancing host tRNA availability against codon usage improves translation efficiency or in vivo expression of a target antigen. Its cross-species comparison suggests some differences in codon regulation, but also reports substantial similarity between humans and zebrafish, rather than extensive variation across organisms. (LLM, conf=0.83)

  cites [250] Wu, Q. et al. Translation affects mRNA stability in a codon-dependent manner in human cells. elife 8, e45396 (2019). sourceExperimental — accuracy not yet measured
• Not checked yetcites [251] Gustafsson, C., Govindarajan, S. & Minshull, J. Codon bias and heterologous protein expression. Trends Biotechnol. 22, 346–353 (2004). source

In the paper

“indicated that the incidence of anaphylaxis after BNT162b2 vaccination in Japan was higher, which points towards considering race-related adverse effects401 whose underlying causes are still unknown.”

What the sources say

• Supported

  The discussion compares estimated anaphylaxis rates after BNT162b2 vaccination in Japan with a lower US rate, while noting that the reasons for the difference are unknown. The conclusion says incidence may be higher in certain populations, such as the Japanese, and calls for further safety studies that account for ethnicity and race. The cited claim reflects those findings and the recommendation, not an established racial cause. (LLM, conf=0.88)

  cites [401] Hashimoto, T. et al. High anaphylaxis rates following vaccination with the Pfizer BNT162b2 mRNA vaccine against COVID-19 in Japanese healthcare workers: a secondary analysis of initial post-approval safety data. J. Travel Med. 28, taab090 (2021). source

In the paper

“BioNTech/Pfizer proceeded with BNT162b2 in global phase II/III clinical trials on July 27, 2020, which received EUA by the US government on December 11, 2020379,380 as well as the European Union conditional marketing authorization (CMA) on December 21, 2020.381,382”

What the sources say

• Partly supported

  The Scientific Summary (Protective Efficacy; page not supplied) describes the multinational phase II/III trial but does not date its start to July 27, 2020. The Introduction confirms EU conditional marketing authorization on December 21, and its References list a US FDA emergency-use-authorization announcement dated December 11, 2020. (LLM, conf=0.86)

  cites [379] Lamb, Y. N. BNT162b2 mRNA COVID-19 Vaccine: First Approval. Drugs 81, 495-501, https://doi.org/10.1007/s40265-021-01480-7 sourceExperimental — accuracy not yet measured
• Not checked yetcites [380] FDA takes key action in fight against COVID-19 by issuing emergency use authorization for first COVID-19 Vaccine, https://www.fda.gov/news-events/press-announcements/fda-takes-key-action-fight-against-covid-19-issuing-emergency-use-authorization-first-covid-19 (2020).
• Not checked yetcites [381] Pfizer and BioNTech receive authorization in the European Union for COVID-19 vaccine, https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-receive-authorization-european-union (2020).
• Supported

  The cited paper states that the European Commission granted conditional marketing authorisation to BNT162b2 on Dec 21, 2020 (opening section; page not provided). The US EUA and trial-start dates are outside the EU-authorisation clause supported by this citation. (LLM, conf=0.95)

  cites [382] Cavaleri, M., Enzmann, H., Straus, S. & Cooke, E. The European Medicines Agency’s EU conditional marketing authorisations for COVID-19 vaccines. Lancet. (2021). source

In the paper

“Phase I clinical data showed that CVnCoV has acceptable tolerance and high immunogenicity.29,427”

What the sources say

• Supported

  The Discussion reports an acceptable reactogenicity profile in the phase 1 trial. The Abstract Results report strong immune responses at the 12 μg dose, including 100% seroconversion for S-protein or RBD antibodies and responses comparable to convalescent sera. The immunogenicity finding is strongest for that dose, rather than all doses equally. (LLM, conf=0.91)

  cites [29] Kremsner, P. G. et al. Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-CoV-2: A phase 1 randomized clinical trial. Wien. Klin. Wochenschr. 133, 931–941 (2021). source
• ?Could not verify

  The introduction reports human Phase 2b/3 efficacy results, not Phase I tolerability or immunogenicity. The Vaccine Immunogenicity section reports responses in cynomolgus macaques, so it cannot establish what Phase I clinical data showed. Searches for Phase I tolerability and immunogenicity found no passage addressing the claim. (LLM, conf=0.75)

  cites [427] Gebre, M. et al. Optimization of non-coding regions improves protective efficacy of an mRNA SARS-CoV-2 vaccine in nonhuman primates. BioRxiv, https://doi.org/10.1101/2021.08.13.456316 (2021). sourceExperimental — accuracy not yet measured

In the paper

“mRNA vaccines can be categorized as non-replicating mRNA, self-amplifying mRNA (saRNA) and circular RNA (circRNA) based on their genetic characteristics (Fig. 3).107”

What the sources say

• Not checked yetcites [107] Iavarone, C., O’hagan, D. T., Yu, D., Delahaye, N. F. & Ulmer, J. B. Mechanism of action of mRNA-based vaccines. Expert Rev. Vaccines 16, 871–881 (2017). source

In the paper

“Among these, the COVID-19 messenger RNA (mRNA) vaccine has been drawing increasing attention owing to its great application prospects and advantages, which include short development cycle, easy industrialization, simple production process, flexibility to respond to new variants, and the capacity to induce better immune response.”

In the paper

“Studies have shown that when poly(A) tail size increases to 120 bp, the expression level of the corresponding protein increases accordingly. However, when poly(A) tail size is greater than 120 bp, the expression level of the corresponding protein did not increase.152”

What the sources say

• Not checked yetcites [152] Kormann, M. S. et al. Expression of therapeutic proteins after deliveryof chemically modified mRNA in mice. Nat. Biotechnol. 29, 154–157 (2011). source

In the paper

“Since the cap1 structure has only been described to date in eukaryotic mRNAs, it can be used as a signature of self-RNA, thus reducing the activation of pattern recognition receptor (PRR) and consequently improving translation efficiency of mRNA in vivo.119”

What the sources say

• Not checked yetcites [119] Hyde, J. L. & Diamond, M. S. Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation. Virology 479, 66–74 (2015). source

In the paper

“The 5′-cap structure prevents mRNA from degradation by exonucleases, thereby maintaining mRNA stability and enabling translation initiation.115”

What the sources say

• Not checked yetcites [115] Kwon, H. et al. Emergence of synthetic mRNA: in vitro synthesis of mRNA and its applications in regenerative medicine. Biomaterials 156, 172–193 (2018). source

In the paper

“At present, the cap1 structure is most commonly applied for capping mRNA vaccines.”

In the paper

“Co-transcriptional capping is the most commonly used method in IVT for mRNA,115”

What the sources say

• Not checked yetcites [115] Kwon, H. et al. Emergence of synthetic mRNA: in vitro synthesis of mRNA and its applications in regenerative medicine. Biomaterials 156, 172–193 (2018). source

In the paper

“The advantages of non-replicating mRNA vaccines include the use of an RNA molecule of simple structure and shorter length. An optimized or modified mRNA can have greatly enhanced biological activity.”

In the paper

“The poly(A) tail plays an important role in maintaining mRNA stability and translation efficiency.116”

What the sources say

• Not checked yetcites [116] Gallie, D. R. The cap and poly (A) tail function synergistically to regulate mRNA translational efficiency. Genes Dev. 5, 2108–2116 (1991). source

In the paper

“At present, the 3′ UTR is mainly derived from hemoglobin subunit α (HBA) and subunit β (HBB) genes,140 but it can also be derived from albumin (ALB), heat-shock protein 70 (Hsp70), tyrosine hydroxylase (TH), and collagen alpha 1 (COL1A1) genes.141–143”

What the sources say

• Not checked yetcites [140] Wadhwa, A., Aljabbari, A., Lokras, A., Foged, C. & Thakur, A. Opportunities and challenges in the delivery of mRNA-based vaccines. Pharmaceutics 12, 102 (2020). source
• Not checked yetcites [141] Zhang, B. Vaccines and compositions based on S antigen protein of SARS-CoV-2. CN112480217A (2021).
• Not checked yetcites [142] Karikó, K., Muramatsu, H., Keller, J. M. & Weissman, D. Increased erythropoiesis in mice injected with submicrogram quantities of pseudouridine-containing mRNA encoding erythropoietin. Mol. Ther. 20, 948–953 (2012). source
• Not checked yetcites [143] Sepac, A. et al. Comparison of cardiomyogenic potential among human ESC and iPSC lines. Cell Transpl. 21, 2523–2530 (2012). source

In the paper

“In mammalian cells, actively translated mRNAs generally contain 100–250 adenosine residues.117,150”

What the sources say

• Not checked yetcites [117] To, K. K. & Cho, W. C. An overview of rational design of mRNA-based therapeutics and vaccines. Expert Opin. Drug Discov. 16, 1307–1317 (2021). source
• Not checked yetcites [150] Tang, T. T. & Passmore, L. A. Recognition of poly (A) RNA through its intrinsic helical structure. Cold Spring Harb. Symp. Quant. Biol. 84, 21–30 (2019). source

In the paper

“The 5′ UTR is mainly involved in translation of its downstream ORF sequence.132,133 The Kozak sequence is generally added after the 5′ UTR sequence to improve translation efficiency.134”

What the sources say

• Not checked yetcites [132] Balzer, Le,S., Onsager, I., Lorentzen, J. A. & Lale, R. Dual UTR-A novel 5′ untranslated region design for synthetic biology applications. Synth. Biol. 5, ysaa006 (2020). source
• Not checked yetcites [133] Leppek, K., Das, R. & Barna, M. Functional 5′ UTR mRNA structures in eukaryotic translation regulation and how to find them. Nat. Rev. Mol. Cell Biol. 19, 158–174 (2018). source
• Not checked yetcites [134] Nance, K. D. & Meier, J. L. Modifications in an emergency: the role of N1-Methylpseudouridine in COVID-19 vaccines. ACS Cent. Sci. 7, 748–756 (2021). source

In the paper

“The vaccinia capping enzyme (VCE) integrates the enzymatic activity of RTPase, GTase, and G-N7 MTase, which can be capped to generate a cap0 structure, and then 2′-O-MTase can be used to generate a methylated cap1 structure, thus reaching a capping efficiency of 100%.52”

What the sources say

• Not checked yetcites [52] Linares-Fernández, S., Lacroix, C., Exposito, J. Y. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends Mol. Med. 26, 311–323 (2019). source

In the paper

“Of note, it has been reported that the COVID-19 vaccine mRNA-1273 developed by Moderna employs the capping enzyme described above.28”

What the sources say

• Not checked yetcites [28] Corbett, K. S. et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 586, 567–571 (2020). source

In the paper

“A non-replicating mRNA contains an open reading frame (ORF) encoding the gene coding for the target antigen flanked by 5′ and 3′ UTR. The 5′ end contains a 7-methylguanosine cap structure (5′-cap, m7G), whereas the 3′ end contains a poly(A) tail structure.”

What the sources say

• Not checked yetcites [113] Schlake, T., Thess, A., Fotin-Mleczek, M. & Kallen, K.-J. Developing mRNA-vaccine technologies. RNA Biol. 9, 1319–1330 (2012). source
• Not checked yetcites [114] Youn, H. & Chung, J. K. Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy. Expert Opin. Biol. Ther. 15, 1–12 (2015). source

In the paper

“The poly(A) tail can also bind to multiple poly(A)-binding proteins (PABPs) while working synergistically with 5′ m7G cap sequences to regulate translational efficiency.146,147”

What the sources say

• Not checked yetcites [146] Goss, D. J. & Kleiman, F. E. Poly (A) binding proteins: are they all created equal? Wiley Interdiscip. Rev.: RNA 4, 167–179 (2013). source
• Not checked yetcites [147] Wang, Z. & Kiledjian, M. The poly (A)-binding protein and an mRNA stability protein jointly regulate an endoribonuclease activity. Mol. Cell. Biol. 20, 6334–6341 (2000). source

In the paper

“The current new generation of cap analogs is the CleanCap® cap analogs developed by TriLink BioTechnologies (San Diego, CA, USA),126 which can be co-transcribed with the target mRNA to obtain the cap1 structure, thus solving the issues of low efficiency and high enzyme costs of traditional capping methods.”

What the sources say

• Not checked yetcites [126] Henderson, J. M. et al. Cap 1 messenger RNA synthesis with co-transcriptional CleanCap® analog by in vitro transcription. Curr. Protoc. 1, e39 (2021). source

In the paper

“Lastly, saRNA vaccines are currently in preclinical and clinical trials.”

In the paper

“Studies have shown that adenylate-uridylate-rich elements are involved in mRNA degradation. Degradation rate and translation life cycle can be adjusted by replacing adenylate-uridylate-rich sequences found in the 3′ UTR.137–139”

What the sources say

• Not checked yetcites [137] Mayr, C. What are 3′ UTRs doing?. Cold Spring Harb. Perspect. Biol. 11, a034728 (2018). source
• Not checked yetcites [138] Fotin-Mleczek, M. et al. Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J. Immunother. 34, 1–15 (2011). source
• Not checked yetcites [139] Eberhardt, W., Doller, A., Akool, E.-S. & Pfeilschifter, J. Modulation of mRNA stability as a novel therapeutic approach. Pharmacol. Ther. 114, 56–73 (2007). source

In the paper

“Conversely, the function of the 3′ UTR is to maintain mRNA stability.135,136”

What the sources say

• Not checked yetcites [135] Mayr, C. Regulation by 3′-untranslated regions. Annu. Rev. Genet. 51, 171–194 (2017). source
• Not checked yetcites [136] Matoulkova, E., Michalova, E., Vojtesek, B. & Hrstka, R. The role of the 3’untranslated region in post-transcriptional regulation of protein expression in mammalian cells. RNA Biol. 9, 563–576 (2012). source

In the paper

“mRNA contains 5′ and 3′ UTRs, whose functions are related, respectively, to regulating translation and maintaining mRNA stability.131”

What the sources say

• Not checked yetcites [131] Zarghampoor, F., Azarpira, N., Khatami, S. R., Behzad-Behbahani, A. & Foroughmand, A. M. Improved translation efficiency of therapeutic mRNA. Gene 707, 231–238 (2019). source

In the paper

“The use of CleanCap® cap analogs reduces the probability of reverse capped, uncapped, and cap0 intermediates, and the co-transcribed mRNA only possesses a cap1 structure, therefore capping rate can be 90% or higher.52,126”

What the sources say

• Not checked yetcites [52] Linares-Fernández, S., Lacroix, C., Exposito, J. Y. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends Mol. Med. 26, 311–323 (2019). source
• Not checked yetcites [126] Henderson, J. M. et al. Cap 1 messenger RNA synthesis with co-transcriptional CleanCap® analog by in vitro transcription. Curr. Protoc. 1, e39 (2021). source

In the paper

“however, an mRNA of cap 0 is likely to be recognized as exogenous RNA by the host, which could stimulate the innate immune response of the host and ultimately trigger inflammatory responses.117”

What the sources say

• Not checked yetcites [117] To, K. K. & Cho, W. C. An overview of rational design of mRNA-based therapeutics and vaccines. Expert Opin. Drug Discov. 16, 1307–1317 (2021). source

In the paper

“A vaccine platform (RNActive®) was designed by CureVac186 combining the use of co-delivered RNA and protamine (a polycationic peptide) complex as adjuvant, which has been shown to effectively trigger innate immune responses and enhance vaccine immunogenicity.186–189”

What the sources say

• Not checked yetcites [186] Rauch, S., Lutz, J., Kowalczyk, A., Schlake, T. & Heidenreich, R. RNActive® technology: generation and testing of stable and immunogenic mRNA vaccines. Methods Mol. Biol. 1499, 89–107 (2017). source
• Not checked yetcites [187] Edwards, D. K. et al. Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response. J. Transl. Med 15, 1–18 (2017). source
• Not checked yetcites [188] Kallen, K.-J. et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive® vaccines. Hum. Vaccine Immunother. 9, 2263–2276 (2013). source
• Not checked yetcites [189] Kowalczyk, A. et al. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity. Vaccine 34, 3882–3893 (2016). source

In the paper

“In addition, considering that the length of nsP1–4 sequence is approximately 7 kb, the full length of a saRNA sequence is usually above 9 kb, which might hinder cloning construction.”

In the paper

“Recently, two different saRNA vaccines developed independently by Arcturus Therapeutics and Imperial College London have shown favorable immune responses against SARS-CoV-2, and have entered clinical trials.211–213”

What the sources say

• Not checked yetcites [211] McKay, P. F. et al. Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat. Commun. 11, 1–7 (2020). source
• Not checked yetcites [212] Pollock, K. M. et al. Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against COVID-19: COVAC1, a Phase I, Dose-Ranging Trial. EClinicalMedicine, https://doi.org/10.1016/j.eclinm.2021.101262 (2022). source
• Not checked yetcites [213] de Alwis, R. et al. A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice. Mol. Ther. 29, 1970–1983 (2021). source

In the paper

“To avoid this, Karikó and colleagues found that adding modified nucleosides during IVT of mRNA can significantly reduce the host inflammatory response without affecting protein expression.81,159”

What the sources say

• Not checked yetcites [81] Karikó, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005). source
• Not checked yetcites [159] Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008). source

In the paper

“Current studies have shown that the segmented poly(A) tail extends mRNA half-life and improves translation efficiency compared to the long-chain poly(A) tail.154”

What the sources say

• Not checked yetcites [154] Trepotec, Z., Geiger, J., Plank, C., Aneja, M. K. & Rudolph, C. Segmented poly(A) tails significantly reduce recombination of plasmid DNA without affecting mRNA translation efficiency or half-life. RNA 25, 507–518 (2019). source

In the paper

“saRNA vaccines have nonetheless certain shortcomings, including the risk of excessive activation of the inflammatory response, and the production of viral nsP produced by the alphavirus replicon that may interfere with normal signal transduction in target host cells.214,215”

What the sources say

• Not checked yetcites [214] Maruggi, G., Zhang, C., Li, J., Ulmer, J. B. & Yu, D. mRNA as a transformative technology for vaccine development to control infectious diseases. Mol. Ther. 27, 757–772 (2019). source
• Not checked yetcites [215] Jensen, S. & Thomsen, A. R. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J. Virol. 86, 2900–2910 (2012). source

In the paper

“Studies have found that replacing original nucleosides with m6A and s2U inhibits activation of TLR3, whereas activation of TLR7 and TLR8 is blocked when using ψ, 5-methyluridine (m5U), m6A, and s2U, thereby inhibiting the innate immune responses and improving protein translation efficiency.81,159,171”

What the sources say

• Not checked yetcites [81] Karikó, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005). source
• Not checked yetcites [159] Karikó, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008). source
• Not checked yetcites [171] Yan, K. et al. Toll-like receptor 3 and RIG-I-like receptor activation induces innate antiviral responses in mouse ovarian granulosa cells. Mol. Cell. Endocrinol. 372, 73–85 (2013). source

In the paper

“Kormann and colleagues152 replaced 25% of mRNA cytosine with m5C and 25% of uridine with s2U, which improved mRNA stability and increased protein translation in mice.”

What the sources say

• Not checked yetcites [152] Kormann, M. S. et al. Expression of therapeutic proteins after deliveryof chemically modified mRNA in mice. Nat. Biotechnol. 29, 154–157 (2011). source

In the paper

“Both Moderna and BioNTech use pseudouridine modifications to ensure mRNA stability in their COVID-19 vaccine formulation.”

In the paper

“dsRNA can activate PRR such as TLR3,52,156 whereas ssRNA activates TLR7 and TLR8 to produce IFN-I, thus inducing inflammation in the host and interrupting mRNA translation.157,158”

What the sources say

• Not checked yetcites [52] Linares-Fernández, S., Lacroix, C., Exposito, J. Y. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends Mol. Med. 26, 311–323 (2019). source
• Not checked yetcites [156] 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, e142–e142 (2011). source
• Not checked yetcites [157] Vaidyanathan, S. et al. Uridine depletion and chemical modification increase Cas9 mRNA activity and reduce immunogenicity without HPLC purification. Mol. Ther. Nucleic Acids 12, 530–542 (2018). source
• Not checked yetcites [158] Isaacs, A., Cox, R. & Rotem, Z. Foreign nucleic acids as the stimulus to make interferon. Lancet, 282, 113–116 (1963). source

In the paper

“Li and colleagues developed an in vitro evolution strategy, and six mutations (namely A1979G, G3936C, A4311G, A4758G, G4796T, G4944A) were identified in the nsP2 and nsP3 of the VEEV replicon, which were shown to promote expression of subgenomic RNA in cells.210”

What the sources say

• Not checked yetcites [210] Li, Y. et al. In vitro evolution of enhanced RNA replicons for immunotherapy. Sci. Rep. 9, 1–10 (2019). source

In the paper

“Currently, nucleoside-modified mRNA vaccines employ 100% chemically modified nucleosides replacing natural nucleosides, and m1ψ is often used to replace uridine during IVT to improve the safety and stability of mRNA vaccines.52,134,172”

What the sources say

• Not checked yetcites [52] Linares-Fernández, S., Lacroix, C., Exposito, J. Y. & Verrier, B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends Mol. Med. 26, 311–323 (2019). source
• Not checked yetcites [134] Nance, K. D. & Meier, J. L. Modifications in an emergency: the role of N1-Methylpseudouridine in COVID-19 vaccines. ACS Cent. Sci. 7, 748–756 (2021). source
• Not checked yetcites [172] Mauger, D. M., Cabral, B. J., Presnyak, V., Su, S. V. & Mcfadyen, I. J. mRNA structure regulates protein expression through changes in functional half-life. Proc. Natl Acad. Sci. USA 116, 201908052 (2019). source

In the paper

“The idea of using in vitro synthesized saRNA as a preventive vaccine was first proposed by Zhou and colleagues in 1994, using a modified Semliki Forest virus (SFV) replicon to express the nucleoprotein (NP) of the influenza virus.197”

What the sources say

• Not checked yetcites [197] Zhou, X. et al. Self-replicating Semliki Forest virus RNA as recombinant vaccine. Vaccine 12, 1510–1514 (1994). source

In the paper

“Decades later, Geall and colleagues were the first to use LNP to encapsulate a saRNA chimera composed of the Venezuelan equine encephalitis virus (VEEV) and Sindbis virus (SINV) replicons into a vaccine which was used to immunize mice, and immunogenicity was significantly improved compared with unencapsulated group.199”

What the sources say

• Not checked yetcites [199] Geall, A. J. et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl Acad. Sci. USA 109, 14604–14609 (2012). source

In the paper

“With its highly stable properties without nucleotide modification, circRNA can potentially become a novel platform for vaccine and drug development.”

In the paper

“Studies have found that the S protein prefusion conformation induces better immunogenicity and can be therefore considered an ideal target antigen.237”

What the sources say

• Not checked yetcites [237] Yadav, T. et al. Recombinant vaccines for COVID-19. Hum. Vaccin Immunother. 16, 2905–2912 (2020). source

In the paper

“In summary, although considered a byproduct of the mRNA splicing process, circRNA has now emerged as an important new class of non-coding RNAs.”

In the paper

“The S1 subunit comprises the signal peptide (SP), RBD, N-terminal domain (NTD), C-terminal domain 1 (CTD1), and C-terminal domain 2 (CTD2), and primarily interacts with the cellular angiotensin-converting enzyme 2 (ACE2) receptor via RBD.”

In the paper

“the results revealed that circRNA prepared with sequences of Delta strains resulted in broad-spectrum protection and production of neutralizing antibodies against both Delta and Omicron.”

What the sources say

• Not checked yetcites [227] Qu, L. et al. Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants. BioRxiv, https://doi.org/10.1101/2021.03.16.435594 (2022). source

In the paper

“The S2 subunit comprises the fusion peptide (FP), double heptad repeat (HR), central helix region (CH), connector domain (CD), transmembrane domain (TMD), and cytoplasmic tail (CT), and the S2 subunit is responsible for mediating the fusion between the virus and the host cell membrane233–236”

What the sources say

• Not checked yetcites [233] Wang, Q. et al. Structural and functional basis of SARS-CoV-2 entry by using human ACE2. Cell 181, 894–904. e899 (2020). source
• Not checked yetcites [234] Shang, J. et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 581, 221–224 (2020). source
• Not checked yetcites [235] Singh, S. P., Pritam, M., Pandey, B. & Yadav, T. P. Microstructure, pathophysiology and potential therapeutics of COVID-19: A comprehensive review. J. Med. Virol. 93, 275–299 (2020). source
• Not checked yetcites [236] Cai, Y. et al. Distinct conformational states of SARS-CoV-2 spike protein. Science 369, 1586–1592 (2020). source

In the paper

“However, vaccines produced with circRNA prepared based on Omicron sequences provided a narrower protection, and produced neutralizing antibodies could protect only against Omicron but not against Delta.”

What the sources say

• Not checked yetcites [227] Qu, L. et al. Circular RNA Vaccines against SARS-CoV-2 and Emerging Variants. BioRxiv, https://doi.org/10.1101/2021.03.16.435594 (2022). source

In the paper

“Most neutralizing antibodies are molded based on epitopes of S protein in prefusion conformation, which is covered once the S protein acquires the postfusion conformation, thus reducing the production of neutralizing antibodies.238”

What the sources say

• Not checked yetcites [238] Walls, A. C. et al. Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181 (2020). source

In the paper

“CircRNA is a highly stable single-stranded RNA with a covalently closed loop structure (Fig. 3), including a large category of non-coding RNAs generated by backsplicing in eukaryotic cells.218–220”

What the sources say

• Not checked yetcites [218] Zhang, X.-O. et al. Complementary sequence-mediated exon circularization. Cell 159, 134–147 (2014). source
• Not checked yetcites [219] Kristensen, L. S. et al. The biogenesis, biology and characterization of circular RNAs. Nat. Rev. Genet. 20, 675–691 (2019). source
• Not checked yetcites [220] Chen, L.-L. The biogenesis and emerging roles of circular RNAs. Nat. Rev. Mol. Cell Biol. 17, 205–211 (2016). source

In the paper

“The S1/S2 cleavage site strategy employs direct deletion of the sequence Q677TNSPRRARYSV687 in wild-type SARS-CoV-2 protein S to Q677TILRYSV683238 or mutation of amino acids (RRAR to GGSG)141 that ultimately prevent the S protein from cleavage in the host cell, thus maintaining its structural stability and inducing stronger immune responses.”

What the sources say

• Not checked yetcites [238] Walls, A. C. et al. Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 181 (2020). source
• Not checked yetcites [141] Zhang, B. Vaccines and compositions based on S antigen protein of SARS-CoV-2. CN112480217A (2021).

In the paper

“After immunizing mice with the obtained vaccine, long-lasting neutralizing antibodies and Th1-biased cellular immune responses were produced.”

What the sources say

• Not checked yetcites [112] Qu, L. et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. BioRxiv, https://doi.org/10.1101/2021.03.16.435594 (2021). source

In the paper

“Although the optimized chemical structure of PEI has higher gene transfection efficiency, it still induces strong cytotoxicity due to the high cationic charge density.”

In the paper

“The mRNA vaccine BNT111 developed by BioNTech’s FixVac platform to treat advanced melanoma has entered phase II clinical trials and was assigned the FDA Fast Track designation on November 19, 2021.349”

What the sources say

• Not checked yetcites [349] BioNTech Receives FDA Fast Track Designation for its FixVac Candidate BNT111 in Advanced Melanoma, https://investors.biontech.de/news-releases/news-release-details/biontech-receives-fda-fast-track-designation-its-fixvac (2021).

In the paper

“Helper phospholipids are amphiphilic lipids that support the lipid bilayer structure, help promote fusion with endosomal membranes, and determine the specificity of target organs.293,294”

What the sources say

• Not checked yetcites [293] Cheng, X. & Lee, R. J. The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev. 99, 129–137 (2016). source
• Not checked yetcites [294] Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020). source

In the paper

“LNPs is a nano-scale vesicle which simulates the lipid structure of the cell membrane and can encapsulate mRNA in its cavity, being considered the most investigated mRNA vaccine delivery system.”

In the paper

“Moderna’s mRNA personalized cancer vaccine mRNA-4157 is comprised of 34 unique neoantigen genes (encoded by tumor-specific mutated genes) combined in a single mRNA vaccine; this vaccine was proven safe and tolerable in combination with pembrolizumab in phase I clinical trials.”

What the sources say

• Not checked yetcites [355] Moderna Announces Clinical Updates on Personalized Cancer Vaccine Program, https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-clinical-updates-personalized-cancer-vaccine (2020).
• Not checked yetcites [356] Burris, H. A. et al. A phase I multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in patients with resected solid tumors and in combination with pembrolizumab in patients with unresectable solid tumors. J. Clin. Oncol. 37, 2523 (2019). source
• Not checked yetcites [357] Bauman, J. et al. 798 Safety, tolerability, and immunogenicity of mRNA-4157 in combination with pembrolizumab in subjects with unresectable solid tumors (KEYNOTE-603): an update. J. Immunother. Cancer 8, A846–A846 (2020).
• Not checked yetcites [358] Burris, H. A. III et al. A phase 1, open-label, multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with pembrolizumab in subjects with unresectable solid tumors (Keynote-603). J. Clin. Oncol. 37, 2523–2523 (2019). source

In the paper

“Yang and colleagues330 applied similar LPP technology to encapsulate mRNA in two steps using ionizable lipid, DOPE and PEG-lipid to generate COVID-19 mRNA vaccine with a core-shell structure, which showed significant protection in mice and non-human primates.”

What the sources say

• Not checked yetcites [330] Yang, R. et al. A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity. Signal Transduct. Target. Ther. 6, 1–10 (2021). source

In the paper

“However, it was later found that the di-linoleic alkyl tail in DLin-MC3-DMA is prone to degradation, and repeated booster doses can potentially lead to cumulative toxicity.289”

What the sources say

• Not checked yetcites [289] Buschmann, M. D. et al. Nanomaterial delivery systems for mRNA vaccines. Vaccines 9, 65 (2021). source

In the paper

“Based on these observations, Moderna has developed an ionizable lipid (namely Lipid H, SM-102), whose tail adopts larger branches which in turn increases potency, and whose introduced ester bonds increase biodegradability (Fig. 7).290,291”

What the sources say

• Not checked yetcites [290] Sabnis, S. et al. A novel amino lipid series for mRNA delivery: improved endosomal escape and sustained pharmacology and safety in non-human primates. Mol. Ther. 26, 1509–1519 (2018). source
• Not checked yetcites [291] Hassett, K. J. et al. Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol. Ther. Nucleic Acids 15, 1–11 (2019). source

In the paper

“Ionizable lipids are neutral at physiological pH, thus making them safer and more stable for use as delivery systems in vaccines.285”

What the sources say

• Not checked yetcites [285] Cullis, P. R. & Hope, M. J. Lipid nanoparticle systems for enabling gene therapies. Mol. Ther. 25, 1467–1475 (2017). source

In the paper

“Previous studies have demonstrated that the use of BNT111 alone or in combination with PD-1 antibody can activate tumor antigen-specific CD4+ and CD8+ T cells and elicit durable immune responses.345,350–352”

What the sources say

• Not checked yetcites [345] Sahin, U. et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature 585, 107–112 (2020). source
• Not checked yetcites [350] Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Rev. Mater. 66, 1078–1094 (2021). source
• Not checked yetcites [351] Tay, B. Q. et al. Evolution of cancer vaccines—challenges, achievements, and future directions. Vaccines 9, 535 (2021). source
• Not checked yetcites [352] Jin, M.-Z. & Wang, X.-P. Immunogenic cell death-based cancer vaccines. Front. Immunol. 12, 697964 (2021). source

In the paper

“Finally, the overall response rate (ORR) for the treatment of 10 cases of HPV-negative head and neck squamous cell carcinoma (HPV-HNSCC) with the mRNA-4157 vaccine was 50%, of which 2 cases achieved complete remission (CR).355–358”

What the sources say

• Not checked yetcites [355] Moderna Announces Clinical Updates on Personalized Cancer Vaccine Program, https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-clinical-updates-personalized-cancer-vaccine (2020).
• Not checked yetcites [356] Burris, H. A. et al. A phase I multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in patients with resected solid tumors and in combination with pembrolizumab in patients with unresectable solid tumors. J. Clin. Oncol. 37, 2523 (2019). source
• Not checked yetcites [357] Bauman, J. et al. 798 Safety, tolerability, and immunogenicity of mRNA-4157 in combination with pembrolizumab in subjects with unresectable solid tumors (KEYNOTE-603): an update. J. Immunother. Cancer 8, A846–A846 (2020).
• Not checked yetcites [358] Burris, H. A. III et al. A phase 1, open-label, multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with pembrolizumab in subjects with unresectable solid tumors (Keynote-603). J. Clin. Oncol. 37, 2523–2523 (2019). source

In the paper

“LPPs have higher stability, low cytotoxicity, cell delivery and endosomal escape efficiency.327–329”

What the sources say

• Not checked yetcites [327] Rezaee, M., Oskuee, R. K., Nassirli, H. & Malaekeh-Nikouei, B. Progress in the development of lipopolyplexes as efficient non-viral gene delivery systems. J. Control. Rel. 236, 1–14 (2016). source
• Not checked yetcites [328] Guevara, M. L., Jilesen, Z., Stojdl, D. & Persano, S. Codelivery of mRNA with α-Galactosylceramide using a new lipopolyplex formulation induces a strong antitumor response upon intravenous administration. ACS Omega 4, 13015–13026 (2019). source
• Not checked yetcites [329] Kaczmarek, J. C. et al. Polymer–lipid nanoparticles for systemic delivery of mRNA to the lungs. Angew. Chem. Int Ed. Engl. 128, 14012–14016 (2016). source

In the paper

“mRNA vaccines have shown good efficacy in the treatment of acute myelocytic leukemia (AML),339–341 non-small cell lung cancer (NSCLC),342,343 and melanoma344–348 (Table 3).”

What the sources say

• Not checked yetcites [339] Van Tendeloo, V. F. et al. Induction of complete and molecular remissions in acute myeloid leukemia by Wilms’ tumor 1 antigen-targeted dendritic cell vaccination. Proc. Natl Acad. Sci. USA 107, 13824–13829 (2010). source
• Not checked yetcites [340] Anguille, S. et al. Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood 130, 1713–1721 (2017). source
• Not checked yetcites [341] Khoury, H. J. et al. Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia. Cancer 123, 3061–3072 (2017). source
• Not checked yetcites [342] Sebastian, M. et al. Messenger RNA vaccination and B-cell responses in NSCLC patients. J. Clin. Oncol. 30, 2573–2573 (2012). source
• Not checked yetcites [343] Sebastian, M. et al. A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. Cancer Immunol. Immunother. 68, 799–812 (2019). source

In the paper

“LNPs are composed of four components: ionizable lipids, helper phospholipids, cholesterol, and PEGylated lipids, among which, ionizable lipids are considered the key components.”

In the paper

“Specific immune responses against at least one antigen were detected in 63% of patients after treatment, and the frequency of activated IgD+ CD38hi B cells increased by more than two-fold in 60% of evaluated patients.343,353,354”

What the sources say

• Not checked yetcites [343] Sebastian, M. et al. A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer. Cancer Immunol. Immunother. 68, 799–812 (2019). source
• Not checked yetcites [353] Tang, X. et al. Therapeutic prospects of mRNA-based gene therapy for glioblastoma. Front. Oncol. 9, 1208 (2019). source
• Not checked yetcites [354] Jarzebska, N. T., Mellett, M., Frei, J., Kuendig, T. M. & Pascolo, S. Protamine for RNA transfection: from heparin antagonist to RNA delivery. Pharmaceutics 13, 877 (2021). source

In the paper

“In LNPs formulations, cholesterol increases stability by filling gaps among LNPs molecules and aiding fusion with endosomal membranes, thereby promoting uptake of the vaccine complex.302”

What the sources say

• Not checked yetcites [302] Yang, S.-T., Kreutzberger, A. J., Lee, J., Kiessling, V. & Tamm, L. K. The role of cholesterol in membrane fusion. Chem. Phys. Lipids 199, 136–143 (2016). source

In the paper

“Moreover, this LPP-based mRNA vaccine exhibited intrinsic adjuvant activity, which stimulates dendritic cells (DCs) to secrete cytokines and inhibit tumor growth by activating the TLR7/8 signaling pathway, resulting in a significant antitumor activity.”

What the sources say

• Not checked yetcites [326] Persano, S. et al. Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination. Biomaterials 125, 81–89 (2017). source

In the paper

“The efficacy of the vaccine at preventing COVID-19 infection in individuals aged 16 was 95%, and over the six subsequent months, vaccine efficacy was 91.3%.385–387”

What the sources say

• Not checked yetcites [385] Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020). source
• Not checked yetcites [386] Thomas, S. J. et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months. N. Engl. J. Med., NEJMoa2110345, https://doi.org/10.1056/NEJMoa2110345 (2021). source
• Not checked yetcites [387] Tober-Lau, P. et al. Long-term immunogenicity of BNT162b2 vaccination in the elderly and in younger health care workers. medRxiv, https://doi.org/10.1101/2021.08.26.21262468 (2021). source

In the paper

“On September 22, 2021, the FDA approved the BNT162b2 vaccine for administration in high-risk populations as a booster,395 then expanded eligibility on November 19, 2021 as a single booster of both BNT162b2 and mRNA-1273 to individuals aged 18 and older after completion of the primary vaccination scheme with any FDA-authorized or previously approved COVID-19 vaccine.396”

What the sources say

• Not checked yetcites [395] FDA. FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations, https://www.fda.gov/news-events/press-announcements/fda-authorizes-booster-dose-pfizer-biontech-covid-19-vaccine-certain-populations (2021).
• Not checked yetcites [396] FDA. Coronavirus (COVID-19) Update: FDA Expands Eligibility for COVID-19 Vaccine Boosters, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-expands-eligibility-covid-19-vaccine-boosters (2021).

In the paper

“The BNT162b2 mRNA vaccine was then added to the WHO Emergency Use Listing (EUL) on December 31, 2020,383 and approved on May 10 and May 28, 2021 by the US government and the European Union, respectively, for administration in adolescents aged 12 to 15.384”

What the sources say

• Not checked yetcites [383] World Health Organisation. WHO issues its first emergency use validation for a COVID-19 vaccine and emphasizes need for equitable global access, https://www.who.int/news/item/31-12-2020-who-issues-its-first-emergency-use-validation-for-a-covid-19-vaccine-and-emphasizes-need-for-equitable-global-access (2020).
• Not checked yetcites [384] Coronavirus (COVID-19) Update: FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Adolescents in Another Important Action in Fight Against Pandemic, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use (2021).

In the paper

“Real-world data from Qatar indicated that the BNT162b2 vaccine had only 51.9% effectiveness against the Delta variant, which was significantly lower compared to 75.0% and 89.5% effectiveness conferred by the vaccine against Beta and Alpha variants, respectively.102”

What the sources say

• Not checked yetcites [102] Tang, P. et al. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar. Nat. Med. 27, 2136–2143 (2021). source

In the paper

“Studies have shown that the protective effect of BNT162b2 against SARS-CoV-2 infection peaks after the second dose and then quickly declines, with the humoral immune response sharply decreasing.388–391”

What the sources say

• Not checked yetcites [388] Chemaitelly, H. et al. Waning of BNT162b2 vaccine protection against SARS-CoV-2 infection in Qatar. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2114114 (2021). source
• Not checked yetcites [389] Levin, E. G. et al. Waning Immune humoral response to BNT162b2 Covid-19 vaccine over 6 months. N. Engl. J. Med. 385, e84 (2021). source
• Not checked yetcites [390] Moustsen-Helms, I. R. et al. Vaccine effectiveness after 1st and 2nd dose of the BNT162b2 mRNA Covid-19 Vaccine in long-term care facility residents and healthcare workers–a Danish cohort study. MedRxiv, https://doi.org/10.1101/2021.03.08.21252200 (2021). source
• Not checked yetcites [391] Levine-Tiefenbrun, M. et al. Viral loads of Delta-variant SARS-CoV2 breakthrough infections following vaccination and booster with the BNT162b2 vaccine. medRxiv, https://doi.org/10.1101/2021.08.29.21262798 (2021). source

In the paper

“The FDA granted BNT162b2 emergency approval for use in children and adolescents aged 5 to 11 on October 29, 2021.103,106”

What the sources say

• Not checked yetcites [103] Walter, E. B. et al. Evaluation of the BNT162b2 Covid-19 vaccine in children 5 to 11 years of age. N. Engl. J. Med 386, 35–46 (2021). source
• Not checked yetcites [106] FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Children 5 through 11 Years of Age, https://www.fda.gov/news-events/press-announcements/fda-authorizes-pfizer-biontech-covid-19-vaccine-emergency-use-children-5-through-11-years-age (2021). source

In the paper

“The US FDA officially authorized BNT162b2 for vaccination of individuals aged 16 and older on August 23, 2021.105”

What the sources say

• Not checked yetcites [105] FDA Approves First COVID-19 Vaccine | FDA, https://www.fda.gov/news-events/press-announcements/fda-approves-first-covid-19-vaccine (2021).

In the paper

“Current clinical trials showed that the mRNA-1440 vaccine against H10N8 and the mRNA-1851 vaccine against H7N9 influenza viruses were well tolerated and elicited robust humoral immune responses when tested separately (Table 4).360”

What the sources say

• Not checked yetcites [360] Feldman, R. A. et al. mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials. Vaccine 37, 3326–3334 (2019). source

In the paper

“The neutralization effect of the booster in each immunization group against SARS-CoV-2 variants Beta, Gamma and Delta reached a level comparable to that observed against the wild-type D614G strain.”

What the sources say

• Not checked yetcites [415] Choi, A. et al. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat. Med., https://doi.org/10.1038/s41591-021-01527-y (2021). source
• Not checked yetcites [416] Wu, K. et al. Preliminary analysis of safety and immunogenicity of a SARS-CoV-2 variant vaccine booster. Medrxiv, https://doi.org/10.1101/2021.05.05.21256716 (2021). source

In the paper

“ARCoV is reportedly safe and well-tolerated at an amount of 15 μg, which induced high titers of neutralizing antibodies titers (approximately two-fold higher that those of patients which had recovered from COVID-19 infection).439”

What the sources say

• Not checked yetcites [438] A Phase III Clinical Study of a SARS-CoV-2 Messenger Ribonucleic Acid (mRNA) vaccine candidate against COVID-19 in population aged 18 years and above, https://clinicaltrials.gov/ct2/show/NCT04847102 (2021).
• Not checked yetcites [439] Chen, G.-L. et al. Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Microbe., https://doi.org/10.1016/s2666-5247(21)00280-9 (2022). source

In the paper

“Results of preclinical trials showed that MRT5500 induced a Th1-biased immune response in mice and non-human primates and prevented Th2-bias response which can induce vaccine-related enhanced respiratory disease (VAERD).433–435”

What the sources say

• Not checked yetcites [433] Graham, B. S. Rapid COVID-19 vaccine development. Science 368, 945–946 (2020). source
• Not checked yetcites [434] Kalnin, K. V. et al. Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models. npj Vaccines 6, 61 (2021). source
• Not checked yetcites [435] Kalnin, K. V. et al. Immunogenicity of novel mRNA COVID-19 vaccine MRT5500 in mice and non-human primates. BioRxiv, https://doi.org/10.1101/2020.10.14.337535 (2020). source

In the paper

“Real-world data showed that effectiveness of mRNA-1273 against Alpha and Beta variants was 100% and 96.4%, respectively,417,418 whereas effectiveness against Delta was slightly lower (73.1%).102”

What the sources say

• Not checked yetcites [417] Chemaitelly, H. et al. mRNA-1273 COVID-19 vaccine effectiveness against the B.1.1.7 and B.1.351 variants and severe COVID-19 disease in Qatar. Nat. Med. 27, 1614–1621 (2021). source
• Not checked yetcites [418] Günl, F. et al. Shooting at a moving target—effectiveness and emerging challenges for SARS-CoV-2 vaccine development. Vaccines 9, 1052 (2021). source
• Not checked yetcites [102] Tang, P. et al. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar. Nat. Med. 27, 2136–2143 (2021). source

In the paper

“No serious safety concerns have been identified so far, and most adverse events were mild or moderate”

What the sources say

• Not checked yetcites [410] Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021). source
• Not checked yetcites [411] Moderna announces TeenCOVE study of its COVID-19 vaccine in adolescents meets primary endpoint and plans to submit data to regulators in early June, https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-teencove-study-its-covid-19-vaccine (2021).

In the paper

“administration of three doses of mRNA-1273 provided a high and durable protection against Delta infection (95.2%) but lower protection against Omicron (62.5%).”

What the sources say

• Not checked yetcites [421] Tseng, H. F. et al. Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants. medRxiv, 2022.2001.2007.22268919, https://doi.org/10.1101/2022.01.07.22268919 (2022). source

In the paper

“In previously preclinical trials, CVnCoV was shown to induce high levels of neutralizing antibodies in rodents and non-human primates, outbalancing immune responses mediated by CD4+ and CD8+ T cells as well as showing better efficacy against SARS-CoV-2 D614G variant.426”

What the sources say

• Not checked yetcites [426] Rauch, S. et al. mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. npj Vaccines 6, 57 (2021). source

In the paper

“In phase II clinical trials, 228 COVID-19 cases were reported, from which 204 have been sampled for whole-genome sequencing, which showed that only 3% of the patients had been infected by wild-type SARS-CoV-2, whereas 14 variants have been identified in the remaining patients.425”

What the sources say

• Not checked yetcites [425] Kremsner, P. G. et al. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial. Lancet Infect. Dis., https://doi.org/10.1016/s1473-3099(21)00677-0 (2021). source