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

International Journal of Medical, Pharmacy and Drug Research (IJMPD) [Vol-6, Issue-2, Mar-Apr, 2022] ISSN: 2456-8015 https://dx.doi.org/10.22161/ijmpd.6.2.7 Peer-Reviewed Journal

mRNA vaccines against emerging infectious diseases; A challenging approach of novel vaccine discovery Mr. Utkalendu Suvendusekhar Samantaray1, Rudra Prasad Khuntia2 1BSc

MSc, Utkal University, Bhuaneswar, Odisha, India utkalgenome@gmail.com 2BSc MSc, Sikhsha 'O' Anusandhan University, Bhubaneswar, Odisha, India

Received: 01 Apr 2022; Received in revised form: 22 Apr 2022; Accepted: 27 Apr 2022; Available online: 30 Apr 2022 ©2022 The Author(s). Published by AI Publications. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/)

Abstract— 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.

Keywords— mRNA vaccines, SARS-CoV-2, DNA. I.

INTRODUCTION TO MRNA

A single-stranded RNA molecule that matches the genetic sequence of a gene and is read by a ribosome during the protein synthesis process is known as messenger ribonucleic acid (mRNA). mRNA medications can directly trigger protein creation within the cytosol, unlike other pharmacological techniques that cannot get inside cells to direct protein production. They have the potential to cure or

prevent illnesses that are now incurable, ultimately enhancing human health and having a global effect. mRNA vaccines are a viable alternative to conventional vaccination techniques because of their great potential for rapid development, low-cost manufacture, and safe delivery. the recent technological developments, of multiple mRNA vaccination systems against infectious diseases and a variety of cancers, have demonstrated promising results in both animal models and humans. This Review, like that of

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recombinant DNA medicines, looks at the opportunities and challenges of bringing this potential vaccine platform into widespread therapeutic use. They combine the ability of mRNA to encode practically any protein with a high level of safety and a flexible manufacturing method.

Over the past decade, mRNA vaccines have grown in popularity as a flexible tool for developing novel creative therapies, not only in infectious illness settings but also in cancer. An mRNA vaccine is traditionally made up of a messenger RNA synthesized in vitro using a bacteriophage RNA polymerase and a template DNA encoding the antigen(s) of interest. After being given and internalized by host cells, mRNA transcripts are immediately found in the cytoplasm of the cell. Antigens produced by the cell are subsequently delivered to immune system cells, triggering an immunological response. Dendritic cells may be employed as a carrier by loading their cytoplasm with tumor-associated antigen mRNAs or total tumor RNA, then delivering the mRNA-loaded dendritic cells to the host to trigger a particular immune response. Two mRNA vaccines for COVID-19 infection prevention were recently licensed for human use, creating enthusiasm about the future prospects of this method for cancer immunotherapy and other infectious disease prevention. The increased demand for mRNA vaccines needs the creation of a technological platform as well as a cost-effective production method with well-defined product features. In the large-scale manufacture of mRNA vaccines, a single or two-step in vitro reaction is followed by a purification platform with numerous phases that might involve DNase digestion, precipitation, chromatography, or tangential flow filtering.

To create mRNA vaccines, the encoded antigen is placed into a DNA template, from which the mRNA is generated in vitro. In contrast to DNA, mRNA simply needs to enter the cytoplasm in order to be transcribed into antigen by the cell machinery in vivo. This method allows any desired sequence to be created, synthesized in vitro, and given to any cell type. Endosomal or cytosolic receptors in the cells recognize RNA, which activates the type I interferon (IFNI) pathway and promotes the production of chemokines and proinflammatory cytokines. These signal molecules stimulate antigen-presenting cells (APCs), resulting in a powerful adaptive response. The creation of mRNA, which is done in a cell-free environment, does not involve any animal-derived raw materials. As a consequence, there are no contaminants or contaminations originating from cells, making the manufacturing of these compounds safer.

Because it does not need the utilization of cell cultures, mRNA synthesis is more cost-effective than other biological processes. Because of the short response time, the danger of contamination is smaller than with other sophisticated vaccine production techniques.

II.

DELIVERY OF MRNA VACCINES

Since mRNA antibodies are intrinsically delicate, their organization is basic. Intravenous infusion of unmodified mRNA expands the inborn safe reaction by making it be processed by ribonucleases. mRNA circulation ought to enact safe framework cells, for example, antigenintroducing cells (APCs), B cells, and T cells. Since mRNA particles are multiple times greater than different atoms, conveying them is troublesome. Besides, since mRNA is adversely charged, it is repulsed by the cell film. This obstruction could be overwhelmed by utilizing adjusted RNA and further developed conveyance frameworks. mRNA stages have been made utilizing lipid nanoparticles and protamine, dendrimers, polyethyleneimine. Lipid nanoparticles (LNP) are lipid nanoparticles that include nucleoside changed nucleoside Phospholipids, cholesterol, ionizable lipids, and lipid-moored polyethylene glycol (PEG). Cytoplasmic conveyance, cell take-up, and endosomal take-up are completely improved by LNPs. By impeding mRNA from being distinguished by endosomes and cost-like receptors, LNPs likewise keep the natural invulnerable framework from becoming overactive (TLRs).

A few mRNA immunizations have adjuvant properties, which could be useful. mRNAs can be changed to advance safe enactment without compelling mRNA articulation.

One example is the modification of a nucleoside with the TLR-4 agonist monophosphorylate lipid A (MPLA), which aids T cell activation. A short stretch of the double-stranded region in the poly-A tail or 3UTR of mRNA is also used as a method. The insertion of a short poly U or poly-A tail increases dendritic cell activation and migration by inducing IFN-B and IL-6. TLR3 and RIG-I both identify the ds poly U or poly-A tail. Two SARS-CoV-2 RNA lipid nanoparticle vaccines were recently developed using nucleoside modified mRNA (modRNA). BNT162b1 is a modRNA with a reduced ability to activate immunological sensors and increased RBD expression. 41 BNT162b2 is a P2 mutant, perfusion spike glycoprotein-expressing modRNA vaccine (P2S).

III.

IMMUNE RESPONSE TO MRNA VACCINES

The immune response to the mRNA vaccine is being studied right now. RIG-I-like receptors and TLRs are two kinds of RNA sensors distinguished in people. TLR7, TLR3, TLR9, and TLR8 are four TLRs found in macrophages, monocytes, and dendritic cells, separately. TLR3 can differentiate between twofold abandoned RNA (dsRNA) and singleabandoned RNA (sRNA) (ssRNA). TLR7 perceives both ssRNA and dsRNA, while TLR8 perceives just ssRNA. RIG-I, MDA-5, and LGP2 are all RIG-I relatives. By

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recognizing ssRNA and dsRNA, RIG-I helps interferon creation. MDA5 is a cytosolic RNA sensor that recognizes long twofold abandoned RNA that is made during viral RNA replication. IRF-3 and NF-KB are enacted because of the recognizable proof of ds RNA, and IFN-I creation is improved. Interferon (IFN) acceptance utilizing mRNA immunizations is subject to the in vitro interpreted mRNA, infusion course, and conveyance vehicle. Design acknowledgment receptors (PRRs) are actuated after mRNA vaccination, and type I IFN creation is expanded.

IFN creation might be positive or negative contingent upon whether the resistant reaction is initiated or mRNA interpretation is obstructed.

IV.

VACCINE-INDUCED IMMUNITY

Rather than a humoral safe reaction that kills the infection, a cell insusceptible reaction like cytotoxic T lymphocytes (CTLs) straightforwardly targets virally tainted cells. How much counter acting agent not entirely set in stone by the size of LNPs that are conveyed to depleting lymph hubs and enact B cells. B cells might consume mRNA-containing LNPs, permitting the mRNA to be converted into protein.

Besides, B cells have B cell receptors that express unfamiliar antigens. B cells in depleting lymph hubs (which contain LNP-mRNA) produce explicit low-liking antibodies, and a portion of these antibodies might arrive at a germinal community (GC). In B cells that enter GC, substantial hypermutation (SHM) and proclivity development result. Partiality created B cells produce highliking antibodies subsequent to becoming plasmablasts.

They may be that as it may, reappear GCs after SHM and structure memory B cells. For successful CTL induction, the antigen must enter the antigen processing pathway. After then, the pathogenic antigens are carried to the cytosol and digested by proteasomes. The peptides produced by the proteasomal pathway are subsequently delivered to the endoplasmic reticulum (ER) by the antigen processing transporter (TAP). These peptides bind to the major histocompatibility complex (MHC) class I in the ER (MHC). CD8 T lymphocytes then recognize the MHC Iantigen peptide complex on the cell surface. mRNA-based vaccines are particularly well suited to inducing robust CTL responses because they can express the antigen in the cytoplasm of antigen-presenting cells.

V.

ANTIGEN SELECTION

Several issues, such as the antigen selection for vaccination, vaccine routes, vaccination area, and regimen, must be considered while creating mRNA-based vaccines. Antigen selection is an important stage in vaccine development. The structural proteins in SARS-CoV-2 include S protein, N

protein, matrix protein (M), and envelope protein (E). The covering of the vast positive-strand RNA genome contained in a lipid envelope produced from the host cell membrane is the responsibility of N protein. The proteins S, E, and M are introduced into this membrane. Only antibodies against the S protein have been identified to neutralize the virus and prevent infection in SARS-CoV-2. As a result, the majority of SARS-CoV-2 vaccines target the S1 domain of the receptor-binding domain.

VI.

ADVANTAGES AND CHALLENGES ASSOCIATED WITH MRNA VACCINES

mRNA does not integrate into the genome; mRNA vaccines are favorable. Incorporating changed nucleosides into the mRNA sequence also decreases its inflammatory potential.

As a result, mRNA-based vaccinations are less dangerous than virus-based immunizations. mRNA-based vaccines provide various advantages over traditional vaccinations, including precision, the ability to express just a certain antigen, and the ability to produce a targeted immune response. These vaccines stimulate the innate immune system and enhance both humoral and cellular immunological responses. Because mRNA expression in the body does not need nuclear entrance, genomic integration is less likely. Following the activation of an immunological response, mRNA is rapidly destroyed by cellular mechanisms. Because a change in the antigen has no effect on the physical-chemical features of the mRNA backbone, mRNA vaccine production may be readily standardized. Furthermore, since the synthesis is based on an in vitro cell-free transcription process, the risk of viral contamination is decreased. mRNA vaccines have various advantages, but they also have certain drawbacks. There is currently no well-established manufacturing platform for the synthesis of mRNA, necessitating a number of different manufacturing stages. can be divided into two categories.

Furthermore, the need for cold chain storage of mRNA vaccines presents logical challenges. There is a result, the development of thermostable mRNA vaccines for warm countries or those without a compatible cold storage system is required.

VII.

CONCLUSION REMARKS

In spite of the way that mRNA vaccines have been around for very nearly thirty years, the FDA endorsed them for use in serious patients during the SARS-CoV-2 pandemic. The molecular mechanism of activity of mRNA antibodies should be perceived. Nonstop improvement of UTRs and coding mRNA will expand the immunization's security and strength as far as antigen creation in the body. Besides, base or sugar alterations can be utilized to work on the

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dependability of mRNA immunizations, bringing about better translational properties. The advancement of ionizable lipids and details, as well as worked on cell takeup, endosomal delivery, and strength, are on the whole helpful upgrades to transporter frameworks. For arrangement streamlining of coding mRNA successions, bioinformatics instruments can be utilized. These devices can likewise assist with foreseeing the connection among preclinical and clinical mRNA immunization studies. The objective of the present mRNA antibodies is to augment immunogenicity and adequacy while additionally checking immunization security in people. Resistant reaction actuation can be advantageous, yet it can likewise prompt entanglements. Subsequently, there is a need to advance antibody portion titers, which requires the plan of clinical preliminaries in a manner that actually catches the insusceptible reaction. To distinguish these invulnerable reactions, an assortment of advances, for example, transcriptomics and proteomics-based approaches can be utilized. The humoral reaction evoked by mRNA immunizations has up until this point been substandard than that inspired by live lessened inoculations. Thus, a careful examination is important to foster details that would permit the proper immunological reactions to be accomplished.

Regulatory measures for the clinical improvement of mRNA antibodies are presently being concluded. Rules for the examination of new transporters of mRNA antibodies, as well as their security and adequacy, should be created.

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14] REFERENCES [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 broadbased 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 Chitosannanoparticles 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:

[15]

[16]

[17]

[18]

[19]

[20]

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 Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ. Developing mRNA-vaccine technologies. RNA Biol.

2012;9:1319–1330. doi:10.4161/rna.22269 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 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 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 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 Geall AJ, Verma A, Otten GR, et al. Nonviral delivery of selfamplifying RNA vaccines. Proc Natl Acad Sci U S A. 2012;109:14604–14609. doi:10.1073/pnas.1209367109 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 Martinon F, Krishnan S, Lenzen G, et al. Induction of virusspecific cytotoxic T lymphocytes in vivo by liposomeentrapped mRNA. Eur J Immunol. 1993;23:1719–1722. doi:10.1002/eji.1830230749 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 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 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 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 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 Bahl K, Senn JJ, Yuzhakov O, et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines

Int. J. Med. Phar. Drug Re. 2022 Vol-6, Issue-2; Online Available at: https://www.aipublications.com/ijmpd/

55

Samantaray et al./ mRNA vaccines against emerging infectious diseases; A challenging approach of novel vaccine discovery

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35] [36]

against H10N8 and H7N9 influenza viruses. Mol Ther.

2017;25:1316–1327. doi:10.1016/j.ymthe.2017.03.035 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 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 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/tde2016-0006 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 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 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 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 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 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 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 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 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.

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 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 Kell AM, Gale M. RIG-I in RNA virus recognition. Virology.

2015;479–480:110–121. doi:10.1016/j.virol.2015.02.017 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

Int. J. Med. Phar. Drug Re. 2022 Vol-6, Issue-2; Online Available at: https://www.aipublications.com/ijmpd/

56

Samantaray et al./ mRNA vaccines against emerging infectious diseases; A challenging approach of novel vaccine discovery

[54]

[55]

[56]

[57]

[58]

[59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

therapies: structural genomics approach. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165878. doi:10.1016/j.bbadis.2020.165878 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 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 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 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.

Lamb YN. BNT162b2 mRNA COVID-19 vaccine: first approval. Drugs. 2021;81:495–501. doi:10.1007/s40265021-01480-7 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 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 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 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/10.1101/2021.05.13.44373 4v1. Accessed December 02, 2021.

Rauch S, Roth N, Schwendt K, et al. mRNA-based SARSCoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. NPJ Vaccines. 2021;6:57. doi:10.1038/s41541-02100311-w 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 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 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 Laczko D, Hogan MJ, Toulmin SA, et al. A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against

[68]

[69]

[70]

[71]

[72]

[73]

[74]

[75]

SARS-CoV-2 in mice. Immunity. 2020;53:724–732 e727. doi:10.1016/j.immuni.2020.07.019 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 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 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 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 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 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 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 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

Int. J. Med. Phar. Drug Re. 2022 Vol-6, Issue-2; Online Available at: https://www.aipublications.com/ijmpd/

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