• editor.aipublications@gmail.com
  • Track Your Paper
  • Contact Us
  • ISSN: 2456-8015

International Journal Of Medical, Pharmacy And Drug Research(IJMPD)

mRNA vaccines against emerging infectious diseases; A challenging approach of novel vaccine discovery

Utkalendu Suvendusekhar Samantaray , Rudra Prasad Khuntia

International Journal of Medical, Pharmacy and Drug Research(IJMPD), Vol-6,Issue-2, March - April 2022, Pages 52-57 , 10.22161/ijmpd.6.2.7

Download | Downloads : 7 | Total View : 826

Article Info: Received: 01 Apr 2022; Received in revised form: 22 Apr 2022; Accepted: 27 Apr 2022; Available online: 30 Apr 2022


Basic human biology is dealt with by mRNA, which creates instructions for making proteins that may aid in the fight against infectious illnesses using our bodies' own mechanisms. mRNA therapies are neither tiny compounds nor huge biological such as recombinant proteins or monoclonal antibodies. These are a series of instructions that assist our cells' machinery in producing proteins that protect us against a certain virus. Our bodies would be unable to perform their activities if mRNA was not introduced. mRNA, or messenger ribonucleic acid, is an important component of the living world, especially in the process of protein synthesis. mRNA is a single-stranded molecule that transmits genetic instructions from a cell's nucleus DNA to the ribosomes, which are the cell's protein-making machinery. The synthesis of an RNA copy from the coded sequence of DNA leads in the production of a particular protein. This copy of mRNA moves from the nucleus of the cell to the cytoplasm, where ribosomes reside. Ribosomes are a sort of sophisticated machinery organelle that aids and begins protein synthesis in cells. Ribosomes ‘read' the mRNA sequence and follow the instructions, progressively adding on various needed amino acids to make the intended protein during the translation process. The protein is subsequently expressed by the cell, and it goes on to execute its role in the cell or in the body. The use of mRNA as a medication offers up a whole new universe of possibilities in terms of illness treatment and prevention. This review contributes to the growing body of knowledge in the field of mRNA therapeutic delivery and the identification of appropriate antigens for mRNA target locations. Two major mRNA vaccines for protection against SARS-CoV-2 have recently been developed and approved for use in the general population by international health authorities. They've been demonstrated to defend against the SARS-CoV-2 virus, which is still active and evolving. This will draw attention to a variety of mRNA vaccines now being evaluated for infectious diseases in clinical studies. mRNA vaccines offer a number of advantages, including speedy design, fabrication, manufacturing, and administration, and they hold a lot of potential for future use against a wide range of diseases.

mRNA vaccines, SARS-CoV-2, DNA.

[1] Magini D, Giovani C, Mangiavacchi S, et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS One. 2016;11:e0161193. doi:10.1371/journal.pone.0161193
[2] Brazzoli M, Magini D, Bonci A, et al. Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin. J Virol. 2016;90:332–344. doi:10.1128/JVI.01786-15
[3] McCullough KC, Bassi I, Milona P, et al. Self-replicating replicon-RNA delivery to dendritic cells by Chitosan-nanoparticles for translation in vitro and in vivo. Mol Ther Nucleic Acids. 2014;3:e173. doi:10.1038/mtna.2014.24
[4] Hekele A, Bertholet S, Archer J, et al. Rapidly produced SAM ® vaccine against H7N9 influenza is immunogenic in mice. Emerg Microbes Infect. 2013;2:e52. doi:10.1038/emi.2013.54
[5] Schnee M, Vogel AB, Voss D, et al. An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl Trop Dis. 2016;10:e0004746. doi:10.1371/journal.pntd.0004746
[6] Alberer M, Gnad-Vogt U, Hong HS, et al. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet. 2017;390:1511–1520. doi:10.1016/S0140-6736(17)31665-3
[7] Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ. Developing mRNA-vaccine technologies. RNA Biol. 2012;9:1319–1330. doi:10.4161/rna.22269
[8] Andries O, Mc Cafferty S, De Smedt SC, et al. 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. 2015;217:337–344. doi:10.1016/j.jconrel.2015.08.051
[9] Kim J, Eygeris Y, Gupta M, Sahay G. Self-assembled mRNA vaccines. Adv Drug Deliv Rev. 2021;170:83–112. doi:10.1016/j.addr.2020.12.014
[10] Perri S, Greer CE, Thudium K, et al. An alphavirus replicon particle chimera derived from Venezuelan equine encephalitis and sindbis viruses is a potent gene-based vaccine delivery vector. J Virol. 2003;77:10394–10403. doi:10.1128/JVI.77.19.10394-10403.2003
[11] Fleeton MN, Chen M, Berglund P, et al. Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus. J Infect Dis. 2001;183:1395–1398. doi:10.1086/319857
[12] Geall AJ, Verma A, Otten GR, et al. Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci U S A. 2012;109:14604–14609. doi:10.1073/pnas.1209367109
[13] Bogers WM, Oostermeijer H, Mooij P, et al. Potent immune responses in rhesus macaques induced by nonviral delivery of a self-amplifying RNA vaccine expressing HIV type 1 envelope with a cationic nanoemulsion. J Infect Dis. 2015;211:947–955. doi:10.1093/infdis/jiu522
[14] Martinon F, Krishnan S, Lenzen G, et al. Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. Eur J Immunol. 1993;23:1719–1722. doi:10.1002/eji.1830230749
[15] Petsch B, Schnee M, Vogel AB, et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol. 2012;30:1210–1216. doi:10.1038/nbt.2436
[16] Zhao M, Li M, Zhang Z, Gong T, Sun X. Induction of HIV-1 gag specific immune responses by cationic micelles mediated delivery of gag mRNA. Drug Deliv. 2016;23:2596–2607. doi:10.3109/10717544.2015.1038856
[17] Li M, Zhao M, Fu Y, et al. Enhanced intranasal delivery of mRNA vaccine by overcoming the nasal epithelial barrier via intra- and paracellular pathways. J Control Release. 2016;228:9–19. doi:10.1016/j.jconrel.2016.02.043
[18] Kranz LM, Diken M, Haas H, et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 2016;534:396–401. doi:10.1038/nature18300
[19] Linares-Fernandez S, Lacroix C, Exposito JY, Verrier B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends Mol Med. 2020;26:311–323. doi:10.1016/j.molmed.2019.10.002
[20] Bahl K, Senn JJ, Yuzhakov O, et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol Ther. 2017;25:1316–1327. doi:10.1016/j.ymthe.2017.03.035
[21] Guevara ML, Persano F, Persano S. Advances in lipid nanoparticles for mRNA-based cancer immunotherapy. Front Chem. 2020;8:589959. doi:10.3389/fchem.2020.589959
[22] Eygeris Y, Patel S, Jozic A, Sahay G. Deconvoluting lipid nanoparticle structure for messenger RNA delivery. Nano Lett. 2020;20:4543–4549. doi:10.1021/acs.nanolett.0c01386
[23] Reichmuth AM, Oberli MA, Jaklenec A, Langer R, Blankschtein D. mRNA vaccine delivery using lipid nanoparticles. Ther Deliv. 2016;7:319–334. doi:10.4155/tde-2016-0006
[24] Edwards DK, Jasny E, Yoon H, et al. Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response. J Transl Med. 2017;15:1. doi:10.1186/s12967-016-1111-6
[25] Maruggi G, Zhang C, Li J, Ulmer JB, Yu D. mRNA as a transformative technology for vaccine development to control infectious diseases. Mol Ther. 2019;27:757–772. doi:10.1016/j.ymthe.2019.01.020
[26] Maruggi G, Chiarot E, Giovani C, et al. Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens. Vaccine. 2017;35:361–368. doi:10.1016/j.vaccine.2016.11.040
[27] Heine A, Juranek S, Brossart P. Clinical and immunological effects of mRNA vaccines in malignant diseases. Mol Cancer. 2021;20:52. doi:10.1186/s12943-021-01339-1
[28] Mulligan MJ, Lyke KE, Kitchin N, et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature. 2020;586:589–593. doi:10.1038/s41586-020-2639-4
[29] Pu J, Yu Q, Yin Z, et al. The safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in Chinese adults aged 18–59 years: a phase I randomized, double-blinded, controlled trial. Vaccine. 2021;39:2746–2754. doi:10.1016/j.vaccine.2021.04.006
[30] Walsh EE, Frenck RW, Falsey AR, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383:2439–2450. doi:10.1056/NEJMoa2027906
[31] Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383:2603–2615. doi:10.1056/NEJMoa2034577
[32] Ji RR, Qu Y, Zhu H, et al. BNT162b2 vaccine encoding the SARS-CoV-2 P2 S protects transgenic hACE2 mice against COVID-19. Vaccines (Basel). 2021;9:324.
[33] Chen N, Xia P, Li S, et al. RNA sensors of the innate immune system and their detection of pathogens. IUBMB Life. 2017;69:297–304. doi:10.1002/iub.1625
[34] Kowalczyk A, Doener F, Zanzinger K, et al. Self-adjuvanted mRNA vaccines induce local innate immune responses that lead to a potent and boostable adaptive immunity. Vaccine. 2016;34:3882–3893. doi:10.1016/j.vaccine.2016.05.046
[35] Kell AM, Gale M. RIG-I in RNA virus recognition. Virology. 2015;479–480:110–121. doi:10.1016/j.virol.2015.02.017
[36] Saito T, Gale M. Differential recognition of double-stranded RNA by RIG-I-like receptors in antiviral immunity. J Exp Med. 2008;205:1523–1527. doi:10.1084/jem.20081210
[37] Loo YM, Gale M. Immune signaling by RIG-I-like receptors. Immunity. 2011;34:680–692. doi:10.1016/j.immuni.2011.05.003
[38] Yin X, Riva L, Pu Y, et al. MDA5 governs the innate immune response to SARS-CoV-2 in lung epithelial cells. Cell Rep. 2021;34:108628. doi:10.1016/j.celrep.2020.108628
[39] Pollard C, Rejman J, De Haes W, et al. Type I IFN counteracts the induction of antigen-specific immune responses by lipid-based delivery of mRNA vaccines. Mol Ther. 2013;21:251–259. doi:10.1038/mt.2012.202
[40] Lei X, Dong X, Ma R, et al. Activation and evasion of type I interferon responses by SARS-CoV-2. Nat Commun. 2020;11:3810. doi:10.1038/s41467-020-17665-9
[41] Park JW, Lagniton PNP, Liu Y, Xu RH. mRNA vaccines for COVID-19: what, why and how. Int J Biol Sci. 2021;17:1446–1460. doi:10.7150/ijbs.59233
[42] Chatzikleanthous D, O’Hagan DT, Adamo R. Lipid-based nanoparticles for delivery of vaccine adjuvants and antigens: toward multicomponent vaccines. Mol Pharm. 2021;18:2867–2888. doi:10.1021/acs.molpharmaceut.1c00447
[43] Cubas R, Zhang S, Kwon S, et al. Virus-like particle (VLP) lymphatic trafficking and immune response generation after immunization by different routes. J Immunother. 2009;32:118–128. doi:10.1097/CJI.0b013e31818f13c4
[44] Lindgren G, Ols S, Liang F, et al. Induction of robust B cell responses after influenza mRNA vaccination is accompanied by circulating hemagglutinin-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells. Front Immunol. 2017;8:1539. doi:10.3389/fimmu.2017.01539
[45] Cagigi A, Lore K. Immune responses induced by mRNA vaccination in mice, monkeys and humans. Vaccines (Basel). 2021;9. doi:10.3390/vaccines9010061
[46] De Silva NS, Klein U. Dynamics of B cells in germinal centres. Nat Rev Immunol. 2015;15:137–148. doi:10.1038/nri3804
[47] Hewitt EW. The MHC class I antigen presentation pathway: strategies for viral immune evasion. Immunology. 2003;110:163–169. doi:10.1046/j.1365-2567.2003.01738.x
[48] Blum JS, Wearsch PA, Cresswell P. Pathways of antigen processing. Annu Rev Immunol. 2013;31:443–473. doi:10.1146/annurev-immunol-032712-095910
[49] Buschmann MD, Carrasco MJ, Alishetty S, Paige M, Alameh MG, Weissman D. Nanomaterial delivery systems for mRNA vaccines. Vaccines (Basel). 2021;9:65.
[50] Rahman MM, Zhou N, Huang J. An overview on the development of mRNA-based vaccines and their formulation strategies for improved antigen expression in vivo. Vaccines (Basel). 2021;9:244.
[51] Jackson NAC, Kester KE, Casimiro D, Gurunathan S, DeRosa F. The promise of mRNA vaccines: a biotech and industrial perspective. NPJ Vaccines. 2020;5:11. doi:10.1038/s41541-020-0159-8
[52] Satarker S, Nampoothiri M. Structural proteins in severe acute respiratory syndrome Coronavirus-2. Arch Med Res. 2020;51:482–491. doi:10.1016/j.arcmed.2020.05.012
[53] Naqvi AAT, Fatima K, Mohammad T, et al. Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165878. doi:10.1016/j.bbadis.2020.165878
[54] Pal M, Berhanu G, Desalegn C, Kandi V. Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2): an update. Cureus. 2020;12:e7423. doi:10.7759/cureus.7423
[55] Dhama K, Patel SK, Sharun K, et al. SARS-CoV-2 jumping the species barrier: zoonotic lessons from SARS, MERS and recent advances to combat this pandemic virus. Travel Med Infect Dis. 2020;37:101830. doi:10.1016/j.tmaid.2020.101830
[56] Haque SM, Ashwaq O, Sarief A, Azad John Mohamed AK. A comprehensive review about SARS-CoV-2. Future Virol. 2020;15:625–648. doi:10.2217/fvl-2020-0124
[57] Wei J, Hui A-M. Journey of the COVID-19 vaccine from 10 years to 1 year - reassured with real world evidence. Am J Transl Med. 2021;5:1–12.
[58] Lamb YN. BNT162b2 mRNA COVID-19 vaccine: first approval. Drugs. 2021;81:495–501. doi:10.1007/s40265-021-01480-7
[59] Anand P, Stahel VP. Review the safety of Covid-19 mRNA vaccines: a review. Patient Saf Surg. 2021;15:20. doi:10.1186/s13037-021-00291-9
[60] Anderson EJ, Rouphael NG, Widge AT, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020;383:2427–2438. doi:10.1056/NEJMoa2028436
[61] Kyriakidis NC, Lopez-Cortes A, Gonzalez EV, Grimaldos AB, Prado EO. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines. 2021;6:28. doi:10.1038/s41541-021-00292-w
[62] Roth N, Schön J, Hoffmann D, et al. CV 2 CoV, an enhanced mRNA based SARS-CoV-2 vaccine candidate, supports higher protein expression and improved immunogenicity in rats. 2021. Available from https://www.biorxiv.org/content/10.1101/2021.05.13.443734v1. Accessed December 02, 2021.
[63] Rauch S, Roth N, Schwendt K, et al. mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. NPJ Vaccines. 2021;6:57. doi:10.1038/s41541-021-00311-w
[64] Kremsner PG, Guerrero RA, Arana E, et al.Efficacy and Safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate: results from Herald, a phase 2b/3, randomised, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. Lancet. 2021
[65] Zhang NN, Li X-F, Deng Y-Q, et al. A thermostable mRNA vaccine against COVID-19. Cell. 2020;182:1271–1283 e1216. doi:10.1016/j.cell.2020.07.024
[66] Granados-Riveron JT, Aquino-Jarquin G. Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2. Biomed Pharmacother. 2021;142:111953. doi:10.1016/j.biopha.2021.111953
[67] Laczko D, Hogan MJ, Toulmin SA, et al. A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice. Immunity. 2020;53:724–732 e727. doi:10.1016/j.immuni.2020.07.019
[68] Samantaray, M. U. S., & Santra, M. P. (2021). Human Adenovirus Serotypes Efficiently Transducing HEK293 Cells: An In Vitro Propagation of HAdv. International Journal for Research in Applied Sciences and Biotechnology, 8(5), 17-21. https://doi.org/10.31033/ijrasb.8.5.3
[69] Mr. Utkalendu Suvendusekhar Samantaray, & Ms. Swapnarani Sethi. (2021). Isolation and Biochemical Characterization of Indole-3-Acetic Acid (IAA) Produced in Pseudomonas Sp. Isolated from Rhizospheric Soil. International Journal for Research in Applied Sciences and Biotechnology, 8(4), 1-14. https://doi.org/10.31033/ijrasb.8.4.1
[70] Mr. Utkalendu Suvendusekhar Samantaray, & Ms. Tanima Singh. (2021). Optimization of Modified Murashige and Skoog (MS) Medium Promoting Efficient Callus Induction in Zinnia elegans. International Journal for Research in Applied Sciences and Biotechnology, 8(3), 202-211. https://doi.org/10.31033/ijrasb.8.3.25
[71] Samantaray, M. U. suvendusekhar, & Tripathy, M. S. (2021). Quantitative Analysis of Nutrients and Biochemical Evaluation in Pomfret Fish (Pampus argenteus) During Frozen Storage. International Journal for Research in Applied Sciences and Biotechnology, 8(3), 180-195. https://doi.org/10.31033/ijrasb.8.3.23
[72] Samantaray, M. U. suvendusekhar, & Patro, M. A. (2021). Comparative Study of Antioxidant Activity and ROS Production Profile among Clarias batrachus, Cirrhinus reba, Channa punctatus (Freshwater Species). International Journal for Research in Applied Sciences and Biotechnology, 8(3), 160-179. https://doi.org/10.31033/ijrasb.8.3.22
[73] Samantaray, M. U. S., & Sahu, S. (2021). Characterization and Cellulase Production Activity of different Aspergillus Sp. Isolated from “Puri, Odisha” Marine Fungal Strains. International Journal for Research in Applied Sciences and Biotechnology, 8(3), 71-87. https://doi.org/10.31033/ijrasb.8.3.11
[74] Mr. Utkalendu Suvendusekhar Samantaray, Ms. Ankita Mishra, & Yengkhom D. Singh. (2020). Biosynthesis and Antimicrobial activities of Silver Nanoparticles (AgNPs) by using Leaf Extracts of Tagetes erecta (Marigold) and Tridax procumbens (Tridax). International Journal for Research in Applied Sciences and Biotechnology, 7(6), 209-226. https://doi.org/10.31033/ijrasb.7.6.31
[75] Samantaray US, Sahu S, Patro A, Tripathy S, Sethi S, Phytochemicals: A novelantiviraltherapeutic approach for Prevention of lung injury and respiratory infection during COVID 19,SPR, Volume 2, issue 1, Page No.: 528-540. DOI: https://doi.org/10.52152/spr/2021.177