The DOI matches its Crossref record; 91 of the 92 references it cites were found in a registry or an index.
Tailoring mRNA Vaccine to Balance Innate/Adaptive Immune Response
Open accessAbstract
mRNA vaccine platforms present numerous advantages, such as versatility, rapid production, and induction of cellular and humoral responses. Moreover, mRNAs have inherent adjuvant properties due to their complex interaction with pattern recognition receptors (PRRs). This recognition can be either beneficial in activating antigen-presenting cells (APCs) or detrimental by indirectly blocking mRNA translation. To decipher this Janus effect, we describe the different innate response mechanisms triggered by mRNA molecules and how each element from the 5' cap to the poly-A tail interferes with innate/adaptive immune responses. Then, we emphasize the importance of some critical steps such as production, purification, and formulation as key events to further improve the quality of immune responses and balance innate and adaptive immunity.
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In the citing paper
“It is known that UTRs are associated with processes of mRNA translation, and by interacting with RNA-binding proteins (RBPs) and microRNAs, UTRs can influence mRNA’s translation efficiency and resistance to degradation [3,4,5,6,7].”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [4]
In the citing 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”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [52]
In the citing 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”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [52]
In the citing 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”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [52]
In the citing 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”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [52]
In the citing paper
“Uridine depletion to reduce counterproductive immune reactions can be achieved by the replacement of uridine by codon optimization, but this must be balanced with regard to transfer RNA abundance.120, 121, 122”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [120]
In the citing paper
“The optimization of mRNA constructs, including the coding sequence, can regulate immunogenicity without incorporation of modified nucleosides.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [120]
In the citing paper
“Further, the 5′ cap protects the mRNA sterically from degradation by exonucleases, and it works synergistically with the poly(A) tail at the 3′ end, poly(A) binding proteins and translation initiation factor proteins to circularize mRNA and recruit ribosomes for initiating translation10,11.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [11]
In the citing paper
“A sufficiently long tail (100–150 bp) is necessary to interact with poly(A) binding proteins that form complexes necessary for initiating translation11,12 and protecting the cap from degradation by decapping enzymes13.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [11]
In the citing paper
“These engineered UTR sequences minimize mRNA degradation by excluding miRNA-binding sites11 and AU-rich regions in the 3′ UTR19.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [11]
Citations
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Delivering the Messenger: Advances in Technologies for Therapeutic mRNA Delivery
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mRNA capping: biological functions and applications
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Cited by
Sorted by citations
mRNA vaccines for infectious diseases: principles, delivery and clinical translation
Chaudhary, N., Weissman, D., & Whitehead, K. A. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00283-5 · Cited by 1,555
mRNA vaccine for cancer immunotherapy
Miao, L., Zhang, Y., & Huang, L. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01335-5 · Cited by 966
Cancer vaccines as promising immuno-therapeutics: platforms and current progress
Liu, J., Fu, M., Wang, M., Wan, D., Wei, Y., & Wei, X. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01247-x · Cited by 762
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601
mRNA vaccines manufacturing: challenges and bottlenecks
Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M., & Marques, M. P. C. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.03.038 · Cited by 545
Metadata
- Authors
- Linares-Fernández, S., Lacroix, C., Exposito, J.-Y., & Verrier, B.
- Affiliations
- Lyon 1 Université (FR)
- Corresponding author
- Verrier, Bernard
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 26
- Issue
- 3
- Pages
- 311-323
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W2986812831
- Cited by
- 376
- References
- 92
- Citations by year
- 2026: 43 · 2025: 67 · 2024: 65 · 2023: 69 · 2022: 76 · 2021: 47 · 2020: 9
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Trends in Molecular Medicine (acceptedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- EuroNanoMed III
- Agence Nationale de Recherches sur le Sida et les Hépatites Virales
- Fondation Mérieux
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- mRNA vaccines, innate immune response, adaptive immune response, pattern recognition receptors, antigen-presenting cells, 5' cap, poly(A) tail, mRNA translation inhibition, vaccine formulation
- MeSH terms
- mRNA Vaccines, Animals, Humans, Immunity, Innate, RNA, Messenger, Vaccines, Synthetic, Receptors, Pattern Recognition, Adaptive Immunity
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