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mRNA Vaccine: An Advanced and Transformative Technology for Vaccine Development

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Delineating Health and Health System: Mechanistic Insights into Covid 19 Complications

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Abstract

Throughout the world, billions of people are infected with various diseases and continue to suffer from them despite various treatments. Vaccination is commonly regarded as one of the most advanced approaches to disease prevention. RNA-based innovations have sparked widespread interest in the production of prophylactic and therapeutic vaccines over the last two decades. Because of their high efficacy, safe administration, and low manufacturing cost, mRNA vaccines have emerged as a promising tool for disease prevention. In animal models and humans, mRNA vaccines can induce a healthy, long-lasting cellular and humoral immune response. Furthermore, mRNA is an intrinsically secure vector that is just a transient carrier of information that does not interfere with the genome and provides full production versatility. Following the outbreak of COVID-19 in December 2020, mRNA-based vaccines made headlines in 2020. This chapter covers mRNA vaccines (both traditional and alternative), their delivery, immune responses elicited by them, and mRNA vaccines for infectious disease prevention.

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References

  • Ablasser A, Poeck H, Anz D, Berger M, Schlee M, Kim S, Bourquin C, Goutagny N, Jiang Z, Fitzgerald KA, Rothenfusser S, Endres S, Hartmann G, Hornung V (2009) Selection of molecular structure and delivery of RNA oligonucleotides to activate TLR7 versus TLR8 and to induce high amounts of IL-12p70 in primary human monocytes. J Immunol 182:6824–6833

    PubMed  CAS  Google Scholar 

  • Agarwal P, Raghavan A, Nandiwada SL, Curtsinger JM, Bohjanen PR, Mueller DL, Mescher MF (2009) Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory. J Immunol 183:1695–1704

    PubMed  CAS  Google Scholar 

  • Alnylam Pharmaceuticals (2018). Alnylam announces first-ever FDA approval of an RNAi therapeutic, ONPATTROâ„¢ (patisiran) for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. http://investors.alnylam.com/news-releases/news-release-details/alnylam-announces-first-everfda-approval-rnai-therapeutic

  • Baeza Garcia A, Siu E, Sun T, Exler V, Brito L, Hekele A, Otten G, Augustijn K, Janse CJ, Ulmer JB (2018) Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. Nat Commun 9:2714

    PubMed  PubMed Central  Google Scholar 

  • Bahl K, Senn JJ, Yuzhakov O, Bulychev A, Brito LA, Hassett KJ, Laska ME, Smith M, Almarsson Ö, Thompson J (2017) Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol Ther 25:1316–1327

    PubMed  PubMed Central  CAS  Google Scholar 

  • Bogers WM, Oostermeijer H, Mooij P, Koopman G, Verschoor EJ, Davis D, Ulmer JB, Brito LA, Cu Y, Banerjee K (2015) 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 211:947–955

    PubMed  CAS  Google Scholar 

  • Chahal JS, Khan OF, Cooper CL, McPartlan JS, Tsosie JK, Tilley LD, Sidik SM, Lourido S, Langer R, Bavari S (2016) Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc Natl Acad Sci U S A 113:E4133–E4142

    PubMed  PubMed Central  CAS  Google Scholar 

  • Chahal JS, Fang T, Woodham AW, Khan OF, Ling J, Anderson DG, Ploegh HL (2017) An RNA nanoparticle vaccine against Zika virus elicits antibody and CD8+ T cell responses in a mouse model. Sci Rep 7:252

    PubMed  PubMed Central  Google Scholar 

  • Charles A, Janeway J, Travers P, Walport M, Shlomchik MJ (2001) B-cell activation by armed helper T cells. In: Janeway C, Travers P, Walport M, Shlomchik MJ (eds) Immunobiology: the immune system in health and disease, 5th edn. Garland Science, New York

    Google Scholar 

  • ClinicalTrials.gov (2020). A trial investigating the safety and effects of four BNT162 vaccines against COVID-2019 in healthy adults. NCT04380701. https://www.clinicaltrials.gov/ct2/show/ NCT04380701.

  • Corbett KS, Flynn B, Foulds KE et al (2020) Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N Engl J Med. https://doi.org/10.1056/NEJMoa2024671

  • Cullis PR, Hope MJ (2017) Lipid nanoparticle systems for enabling gene therapies. Mol Ther 25:1467–1475

    PubMed  PubMed Central  CAS  Google Scholar 

  • CureVac (2018). CureVac announces first study participant enrolled in phase I clinical trial testing prophylactic mRNA. https://www.curevac.com/newsroom/news/curevac-announces-first-study-participant-enrolled-in-phase-i-clinical-trial-testingprophylactic-mr/.)

  • CureVac (2020). CureVac to trial Covid-19 vaccine in Germany and Belgium. https://www.clinicaltrialsarena.com/news/curevac-covid-19-vaccine-trial/).

  • De Beuckelaer A, Grooten J, De Koker S (2017) Type I interferons modulate CD8+ T cell immunity to mRNA vaccines. Trends Mol Med 23:216–226

    PubMed  Google Scholar 

  • Démoulins T, Milona P, Englezou PC, Ebensen T, Schulze K, Suter R, Pichon C, Midoux P, Guzmán CA, Ruggli N, McCullough KC (2016) Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines. Nanomedicine (Lond) 12:711–722

    Google Scholar 

  • Edwards DK, Jasny E, Yoon H, Horscroft N, Schanen B, Geter T, Fotin-Mleczek M, Petsch B, Wittman V (2017) Adjuvant effects of a sequence-engineered mRNA vaccine: translational profiling demonstrates similar human and murine innate response. J Transl Med 15:1

    PubMed  PubMed Central  Google Scholar 

  • Englezou PC, Sapet C, Démoulins T, Milona P, Ebensen T, Schulze K, Guzman CA, Poulhes F, Zelphati O, Ruggli N, McCullough KC (2018) Self-amplifying replicon RNA delivery to dendritic cells by cationic lipids. Mol Ther Nucleic Acids 12:118–134

    PubMed  PubMed Central  CAS  Google Scholar 

  • Erasmus JH, Khandhar AP, Guderian J, Granger B, Archer J, Archer M, Gage E, Fuerte-Stone J, Larson E, Lin S et al (2018) A nanostructured lipid carrier for delivery of a replicating viral RNA provides single, low-dose protection against Zika. Mol Ther 26:2507–2522

    PubMed  PubMed Central  CAS  Google Scholar 

  • Houseley J, Tollervey D (2009) The many pathways of RNA degradation. Cell 136:763–776

    PubMed  CAS  Google Scholar 

  • Iavarone C, O’Hagan TD, Yu D, Delahaye NF, Ulmer JB (2017) Mechanism of action of mRNA-based vaccines. Expert Rev Vaccines 16:871–881. https://doi.org/10.1080/14760584.2017.1355245

    Article  PubMed  CAS  Google Scholar 

  • Jackson LA, Anderson EJ, Rouphael NG et al (2020) An mRNA vaccine against SARS-CoV-2—preliminary report. N Engl J Med. NEJMoa2022483.

    Google Scholar 

  • Jansen RP (2001) mRNA localization: message on the move. Nat Rev Mol Cell Biol 2:247–256

    PubMed  CAS  Google Scholar 

  • Jirikowski GF, Sanna PP, Maciejewski-Lenoir D, Bloom FE (1992) Reversal of diabetes insipidus in Brattleboro rats: intrahypothalamic injection of vasopressin mRNA. Science 255:996–998

    PubMed  CAS  Google Scholar 

  • Johanning FW, Conry RM, LoBuglio AF, Wright M, Sumerel LA, Pike MJ, Curiel DT (1995) A Sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expression in vivo. Nucleic Acids Res 23:1495–1501

    PubMed  PubMed Central  CAS  Google Scholar 

  • Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, Weissman D (2008) Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther 16:1833–1840

    PubMed  Google Scholar 

  • Krammer F, Palese P (2015) Advances in the production of influenza virus vaccines. Nat Rev Drug Discov 14:167–182

    PubMed  CAS  Google Scholar 

  • Lee BL, Barton GM (2014) Tracking of endosomal Toll-like receptors. Trends Cell Biol 24:360–369

    PubMed  PubMed Central  CAS  Google Scholar 

  • Lindgren G, Ols S, Liang F, Thompson EA, Lin A, Hellgren F, Bahl K, John S, Yuzhakov O, Hassett KJ et al (2017) 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 8:1539

    PubMed  PubMed Central  Google Scholar 

  • Ljungberg K, Liljeström P (2015) Self-replicating alphavirus RNA vaccines. Expert Rev Vaccines 14:177–194

    PubMed  CAS  Google Scholar 

  • Luo F, Zheng L, Hu Y, Liu S, Wang Y, Xiong Z, Hu X, Tan F (2017) Induction of protective immunity against Toxoplasma gondii in mice by nucleoside triphosphate hydrolase-II (NTPase-II) self-amplifying RNA vaccine encapsulated in lipid nanoparticle (LNP). Front Microbiol 8:605

    PubMed  PubMed Central  Google Scholar 

  • Lutz J, Lazzaro S, Habbeddine M, Schmidt KE, Baumhof P, Mui BL, Tam YK, Madden TD, Hope MJ, Heidenreich R, Fotin-Mleczek M (2017) Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. NPJ Vaccines 2:29

    PubMed  PubMed Central  Google Scholar 

  • Magini D, Giovani C, Mangiavacchi S, Maccari S, Cecchi R, Ulmer JB, De Gregorio E, Geall AJ, Brazzoli M, Bertholet S (2016) Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS One 11:e0161193

    PubMed  PubMed Central  Google Scholar 

  • Maruggi G, Chiarot E, Giovani C, Buccato S, Bonacci S, Frigimelica E, Margarit I, Geall A, Bensi G, Maione D (2017) Immunogenicity and protective efficacy induced by self-amplifying mRNA vaccines encoding bacterial antigens. Vaccine 35:361–368

    PubMed  CAS  Google Scholar 

  • Maruggi G, Zhang C, Li J, Ulmer JB, Yu D (2019) mRNA as a transformative technology for vaccine development to control infectious diseases. Mol Ther 27(4):757–772

    PubMed  PubMed Central  CAS  Google Scholar 

  • Mauro VP, Chappell SA (2014) A critical analysis of codon optimization in human therapeutics. Trends Mol Med 20:604–613

    PubMed  PubMed Central  CAS  Google Scholar 

  • Pardi N, Tuyishime S, Muramatsu H, Kariko K, Mui BL, Tam YK, Madden TD, Hope MJ, Weissman D (2015) Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J Control Release 217:345–351

    PubMed  PubMed Central  CAS  Google Scholar 

  • Pardi N, Hogan MJ, Pelc RS, Muramatsu H, Andersen H, DeMaso CR, Dowd KA, Sutherland LL, Scearce RM, Parks R et al (2017) Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543:248–251

    PubMed  PubMed Central  CAS  Google Scholar 

  • Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, Moody MA, Verkerke HP, Myles A, Willis E et al (2018) Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med 215:1571–1588

    PubMed  PubMed Central  CAS  Google Scholar 

  • Pepini T, Pulichino AM, Carsillo T, Carlson AL, Sari-Sarraf F, Ramsauer K, Debasitis JC, Maruggi G, Otten GR, Geall AJ et al (2017) Induction of an IFN-mediated antiviral response by a self-amplifying RNA vaccine: implications for vaccine design. J Immunol 198:4012–4024

    PubMed  PubMed Central  CAS  Google Scholar 

  • Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, Schlake T, Thess A, Kallen KJ, Stitz L, Kramps T (2012) Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol 30:1210–1216

    PubMed  CAS  Google Scholar 

  • Pilkinton MA, Nicholas KJ, Warren CM, Smith RM, Yoder SM, Talbot HK, Kalams SA (2017) Greater activation of peripheral T follicular helper cells following high dose influenza vaccine in older adults forecasts seroconversion. Vaccine 35:329–336

    PubMed  CAS  Google Scholar 

  • Rauch S, Lutz J, Kowalczyk A, Schlake T, Heidenreich R (2017) RNActive technology: generation and testing of stable and immunogenic RNA vaccines. Methods Mol Biol 1499:89–107

    PubMed  CAS  Google Scholar 

  • Richner JM, Jagger BW, Shan C, Fontes CR, Dowd KA, Cao B, Himansu S, Caine EA, Nunes BTD, Medeiros DBA et al (2017) Vaccine mediated protection against Zika virus-induced congenital disease. Cell 170:273–283.e12

    PubMed  PubMed Central  CAS  Google Scholar 

  • Ross J (1995) mRNA stability in mammalian cells. Microbiol Rev 59:423–450

    PubMed  PubMed Central  CAS  Google Scholar 

  • Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S (2009) Activation of innate immune antiviral responses by Nod2. Nat Immunol 10:1073–1080

    PubMed  PubMed Central  CAS  Google Scholar 

  • Sanofi and Translate Bio. (2021) Sanofi and translate bio initiate phase 1/2 clinical trial of mRNA COVID-19 vaccine candidate. https://investors.translate.bio/news-releases/news-release-details/sanofi-and-translate-bio-initiate-phase-12-clinical-trial-mrna.

  • Schnee M, Vogel AB, Voss D, Petsch B, Baumhof P, Kramps T, Stitz L (2016) 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 10:e0004746

    PubMed  PubMed Central  Google Scholar 

  • Stanton MG (2018) Current status of messenger RNA delivery systems. Nucleic Acid Ther 28:158–165

    PubMed  CAS  Google Scholar 

  • Suan D, Sundling C, Brink R (2017) Plasma cell and memory B cell differentiation from the germinal center. Curr Opin Immunol 45:97–102

    PubMed  CAS  Google Scholar 

  • Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140:805–820

    PubMed  CAS  Google Scholar 

  • Tanabe Y, Nishibori T, Su L, Arduini RM, Baker DP, David M (2005) Cutting edge: role of STAT1, STAT3, and STAT5 in IFN—responses in T lymphocytes. J Immunol 174:609–613

    PubMed  CAS  Google Scholar 

  • Thess A et al (2015) Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol Ther 23:1456–1464

    PubMed  PubMed Central  CAS  Google Scholar 

  • Vogel AB, Lambert L, Kinnear E, Busse D, Erbar S, Reuter KC, Wicke L, Perkovic M, Beissert T, Haas H et al (2018) Self-amplifying RNA vaccines give equivalent protection against influenza to mRNA vaccines but at much lower doses. Mol Ther 26:446–455

    PubMed  CAS  Google Scholar 

  • Weissman D (2015) mRNA transcript therapy. Expert Rev Vaccines 14:265–281

    PubMed  CAS  Google Scholar 

  • Wen Y, Monroe J, Linton C, Archer J, Beard CW, Barnett SW, Palladino G, Mason PW, Carfi A, Lilja AE (2014) Human cytomegalovirus gH/gL/UL128/UL130/UL131A complex elicits potently neutralizing antibodies in mice. Vaccine 32:3796–3804

    PubMed  CAS  Google Scholar 

  • Wolff JA et al (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    PubMed  CAS  Google Scholar 

  • Zhang C, Maruggi G, Shan H, Li J (2019) Advances in mRNA vaccines for infectious diseases. Front Immunol 10:594

    PubMed  PubMed Central  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Biotechnology, Panjab University, Sector-25, South Campus, Chandigarh, Punjab, India

    Vikas Kushwaha & R. C. Sobti

  2. Department of Botany, Goswami Ganesh Dutta Sanathan Dharm College, Sector-32, Chandigarh, Punjab, India

    Anuprabha

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  1. Vikas Kushwaha
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  2. Anuprabha
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  3. R. C. Sobti
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Editors and Affiliations

  1. Department of Biotechnology, Panjab University, Chandigarh, Punjab, India

    R. C. Sobti

  2. Institute of Cardiovascular Sciences, University of Manitoba, Winnipeg, MB, Canada

    Naranjan S. Dhalla

  3. School of Medicine, Mie University, Kurimamachiya-cho, Mie, Japan

    Masatoshi Watanabe

  4. Department of Immunotechnology, Lund University, Lund, Sweden

    Aastha Sobti

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Kushwaha, V., Anuprabha, Sobti, R.C. (2021). mRNA Vaccine: An Advanced and Transformative Technology for Vaccine Development. In: Sobti, R.C., Dhalla, N.S., Watanabe, M., Sobti, A. (eds) Delineating Health and Health System: Mechanistic Insights into Covid 19 Complications. Springer, Singapore. https://doi.org/10.1007/978-981-16-5105-2_15

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