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Regulatory Considerations on the Development of mRNA Vaccines

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mRNA Vaccines

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 440))

Abstract

Developing traditional viral vaccines for infectious diseases usually takes years, as these are usually produced either by chemical inactivation of the virus or attenuation of the pathogen, processes that can take considerable time to validate and also require the live pathogen. With the advent of nucleic-acid vaccines (DNA and mRNA), the time to vaccine design and production is considerably shortened, since once the platform has been established, all that is required is the sequence of the antigen gene, its synthesis and insertion into an appropriate expression vector; importantly, no infectious virus is required. mRNA vaccines have some advantages over DNA vaccines, such as expression in non-dividing cells and the absence of the perceived risk of integration into host genome. Also, generally lower doses are required to induce the immune response. Based on experience in recent clinical trials, mRNA-based vaccines are a promising novel platform that might be useful for the development of vaccines against emerging pandemic infectious diseases. This chapter discusses some of the specific issues that mRNA vaccines raise with respect to production, quality, safety and efficacy, and how they have been addressed so as to allow their evaluation in clinical trials.

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References

  • Abdulhaqq SA, Weiner DB (2008) DNA vaccines: developing new strategies to enhance immune responses. Immunol Res 42:219–232

    Article  CAS  PubMed  Google Scholar 

  • Ahn J, Peng S, Hung CF, Roden RBS, Wu TC, Best SR (2017) Immunologic responses to a novel DNA vaccine targeting human papillomavirus-11 E6E7. Laryngoscope 127:2713–2720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Amri SS, Abbas AT, Siddiq LA, Alghamdi A, Sanki MA, Al-Muhanna MK, Alhabbab RY, Azhar EI, Li X, Hashem AM (2017) Immunogenicity of candidate MERS-CoV DNA vaccines based on the spike protein. Sci Rep 7:44875

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arnaud-Barbe N, Cheynet-Sauvion V, Oriol G, Mandrand B, Mallet F (1998) Transcription of RNA templates by T7 RNA polymerase. Nucleic Acids Res 26:3550–3554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barry M (2018) Single-cycle adenovirus vectors in the current vaccine landscape. Expert Rev Vaccines 17:163–173

    CAS  PubMed  PubMed Central  Google Scholar 

  • Borkotoky S, Murali A (2018) The highly efficient T7 RNA polymerase: a wonder macromolecule in biological realm. Int J Biol Macromol 118:49–56

    Article  CAS  PubMed  Google Scholar 

  • Brito LA, Kommareddy S, Maione D, Uematsu Y, Giovani C, Berlanda Scorza F, Otten GR, Yu D, Mandl CW, Mason PW, Dormitzer PR, Ulmer JB, Geall AJ (2015) Self-amplifying mRNA vaccines. Adv Genet 89:179–233

    Article  CAS  PubMed  Google Scholar 

  • Bryant PW, Lennon-Dumenil AM, Fiebiger E, Lagaudriere-Gesbert C, Ploegh HL (2002) Proteolysis and antigen presentation by MHC class II molecules. Adv Immunol 80:71–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerboni S, Gentili M, Manel N (2013) Diversity of pathogen sensors in dendritic cells. Adv Immunol 120:211–237

    Article  CAS  PubMed  Google Scholar 

  • Chen N, Xia P, Li S, Zhang T, Wang TT, Zhu J (2017) RNA sensors of the innate immune system and their detection of pathogens. IUBMB Life 69:297–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cheng MA, Farmer E, Huang C, Lin J, Hung CF, Wu TC (2018) Therapeutic DNA vaccines for human Papillomavirus and associated diseases. Hum Gene Ther 29:971–996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chi H, Zheng X, Wang X, Wang C, Wang H, Gai W, Perlman S, Yang S, Zhao J, Xia X (2017) DNA vaccine encoding middle east respiratory syndrome coronavirus S1 protein induces protective immune responses in mice. Vaccine 35:2069–2075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Conry RM, LoBuglio AF, Wright M, Sumerel L, Pike MJ, Johanning F, Benjamin R, Lu D, Curiel DT (1995) Characterization of a messenger RNA polynucleotide vaccine vector. Cancer Res 55:1397–1400

    CAS  PubMed  Google Scholar 

  • Crampton SP, Bolland S (2013) Spontaneous activation of RNA-sensing pathways in autoimmune disease. Curr Opin Immunol 25:712–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkic-Zrna S, Probst J, Kallen KJ (2011) Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother 34:1–15

    Article  CAS  PubMed  Google Scholar 

  • Fotin-Mleczek M, Zanzinger K, Heidenreich R, Lorenz C, Thess A, Duchardt KM, Kallen KJ (2012) Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. J Gene Med 14:428–439

    Article  CAS  PubMed  Google Scholar 

  • Freund I, Eigenbrod T, Helm M, Dalpke AH. 2019. RNA Modifications Modulate Activation of Innate Toll-Like Receptors. Genes (Basel) 10

    Google Scholar 

  • Fukui R, Miyake K (2012) Controlling systems of nucleic acid sensing-TLRs restrict homeostatic inflammation. Exp Cell Res 318:1461–1466

    Article  CAS  PubMed  Google Scholar 

  • Gorden KK, Qiu X, Battiste JJ, Wightman PP, Vasilakos JP, Alkan SS (2006a) Oligodeoxynucleotides differentially modulate activation of TLR7 and TLR8 by imidazoquinolines. J Immunol 177:8164–8170

    Article  CAS  PubMed  Google Scholar 

  • Gorden KK, Qiu XX, Binsfeld CC, Vasilakos JP, Alkan SS (2006b) Cutting edge: activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides. J Immunol 177:6584–6587

    Article  CAS  PubMed  Google Scholar 

  • Gurunathan S, Klinman DM, Seder RA (2000) DNA vaccines: immunology, application, and optimization*. Annu Rev Immunol 18:927–974

    Article  CAS  PubMed  Google Scholar 

  • Hassett KJ, Benenato KE, Jacquinet E, Lee A, Woods A, Yuzhakov O, Himansu S, Deterling J, Geilich BM, Ketova T, Mihai C, Lynn A, McFadyen I, Moore MJ, Senn JJ, Stanton MG, Almarsson O, Ciaramella G, Brito LA (2019) Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol Ther Nucleic Acids 15:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3:196–200

    Article  CAS  PubMed  Google Scholar 

  • Hinz T, Kallen K, Britten CM, Flamion B, Granzer U, Hoos A, Huber C, Khleif S, Kreiter S, Rammensee HG, Sahin U, Singh-Jasuja H, Tureci O, Kalinke U (2017) The European regulatory environment of RNA-based vaccines. Methods Mol Biol 1499:203–222

    Article  CAS  PubMed  Google Scholar 

  • Hobernik D, Bros M (2018) DNA vaccines-how far from clinical use? Int J Mol Sci 19

    Google Scholar 

  • Hoerr I, Obst R, Rammensee HG, Jung G (2000) In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol 30:1–7

    Article  CAS  PubMed  Google Scholar 

  • Huang J, Ma R, Wu CY (2006) Immunization with SARS-CoV S DNA vaccine generates memory CD4+ and CD8+ T cell immune responses. Vaccine 24:4905–4913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jalkanen AL, Coleman SJ, Wilusz J (2014) Determinants and implications of mRNA poly(A) tail size–does this protein make my tail look big? Semin Cell Dev Biol 34:24–32

    Article  CAS  PubMed  Google Scholar 

  • Jemielity J, Fowler T, Zuberek J, Stepinski J, Lewdorowicz M, Niedzwiecka A, Stolarski R, Darzynkiewicz E, Rhoads RE (2003) Novel “anti-reverse” cap analogs with superior translational properties. RNA 9:1108–1122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia J, Yao P, Arif A, Fox PL (2013) Regulation and dysregulation of 3’UTR-mediated translational control. Curr Opin Genet Dev 23:29–34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G, Bauer S (2002) Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Nat Immunol 3:499

    Article  CAS  PubMed  Google Scholar 

  • Kaczmarek JC, Kowalski PS, Anderson DG (2017) Advances in the delivery of RNA therapeutics: from concept to clinical reality. Genome Med 9:60

    Article  PubMed  PubMed Central  Google Scholar 

  • Kallen KJ, Thess A (2014) A development that may evolve into a revolution in medicine: mRNA as the basis for novel, nucleotide-based vaccines and drugs. Ther Adv Vaccines 2:10–31

    Article  PubMed  PubMed Central  Google Scholar 

  • Kallen KJ, Heidenreich R, Schnee M, Petsch B, Schlake T, Thess A, Baumhof P, Scheel B, Koch SD, Fotin-Mleczek M (2013) A novel, disruptive vaccination technology: self-adjuvanted RNActive((R)) vaccines. Hum Vaccin Immunother 9:2263–2276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kariko K, Buckstein M, Ni H, Weissman D (2005) Suppression of RNA recognition by toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23:165–175

    Article  CAS  PubMed  Google Scholar 

  • Kariko 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

    Article  CAS  PubMed  Google Scholar 

  • Kariko K, Muramatsu H, Ludwig J, Weissman D (2011) 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kindler E, Thiel V (2014) To sense or not to sense viral RNA—essentials of coronavirus innate immune evasion. Curr Opin Microbiol 20:69–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klinman DM, Takeno M, Ichino M, Gu M, Yamshchikov G, Mor G, Conover J (1997) DNA vaccines: safety and efficacy issues. Springer Semin Immunopathol 19:245–256

    Article  CAS  PubMed  Google Scholar 

  • Klinman DM, Takeshita F, Kamstrup S, Takeshita S, Ishii K, Ichino M, Yamada H (2000) DNA vaccines: capacity to induce auto-immunity and tolerance. Dev Biol (Basel) 104:45–51

    CAS  PubMed  Google Scholar 

  • Kowalski PS, Rudra A, Miao L, Anderson DG (2019) Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Mol Ther 27:710–728

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krieg PA, Melton DA (1984) Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic Acids Res 12:7057–7070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krieg PA, Melton DA (1987) In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol 155:397–415

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni JA, Cullis PR, van der Meel R (2018) Lipid Nanoparticles enabling gene therapies: from concepts to clinical utility. Nucleic Acid Ther 28:146–157

    Article  CAS  PubMed  Google Scholar 

  • Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9:776–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langer B, Renner M, Scherer J, Schule S, Cichutek K (2013) Safety assessment of biolistic DNA vaccination. Methods Mol Biol 940:371–388

    Article  CAS  PubMed  Google Scholar 

  • Ledwith BJ, Manam S, Troilo PJ, Barnum AB, Pauley CJ, Griffiths TG, Harper LB, Beare CM, Bagdon WJ, Nichols WW (2000) Plasmid DNA vaccines: Investigation of integration into host cellular DNA following intramuscular injection in mice. Intervirology 43:258–272

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Chuang TH, Redecke V, She L, Pitha PM, Carson DA, Raz E, Cottam HB (2003) Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of toll-like receptor 7. Proc Natl Acad Sci U S A 100:6646–6651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee J, Arun Kumar S, Jhan YY, Bishop CJ (2018) Engineering DNA vaccines against infectious diseases. Acta Biomater 80:31–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Saade F, Petrovsky N (2012) The future of human DNA vaccines. J Biotechnol 162:171–182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lv H, Zhang S, Wang B, Cui S, Yan J (2006) Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release 114:100–109

    Article  CAS  PubMed  Google Scholar 

  • Maier MA, Jayaraman M, Matsuda S, Liu J, Barros S, Querbes W, Tam YK, Ansell SM, Kumar V, Qin J, Zhang X, Wang Q, Panesar S, Hutabarat R, Carioto M, Hettinger J, Kandasamy P, Butler D, Rajeev KG, Pang B, Charisse K, Fitzgerald K, Mui BL, Du X, Cullis P, Madden TD, Hope MJ, Manoharan M, Akinc A (2013) Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol Ther 21:1570–1578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Manam S, Ledwith BJ, Barnum AB, Troilo PJ, Pauley CJ, Harper LB, Griffiths TG 2nd, Niu Z, Denisova L, Follmer TT, Pacchione SJ, Wang Z, Beare CM, Bagdon WJ, Nichols WW (2000) Plasmid DNA vaccines: tissue distribution and effects of DNA sequence, adjuvants and delivery method on integration into host DNA. Intervirology 43:273–281

    Article  CAS  PubMed  Google Scholar 

  • Manickan E, Karem KL, Rouse BT (2017) DNA vaccines—a modern gimmick or a boon to vaccinology? Crit Rev Immunol 37:483–498

    Article  PubMed  Google Scholar 

  • Martinon F, Krishnan S, Lenzen G, Magne R, Gomard E, Guillet JG, Levy JP, Meulien P (1993) Induction of virus-specific cytotoxic T lymphocytes in vivo by liposome-entrapped mRNA. Eur J Immunol 23:1719–1722

    Article  CAS  PubMed  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 27:757–772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumoto M, Oshiumi H, Seya T (2011) Antiviral responses induced by the TLR3 pathway. Rev Med Virol 21:67–77

    Article  CAS  PubMed  Google Scholar 

  • Mauro VP (2018) Codon Optimization in the Production of Recombinant Biotherapeutics: Potential Risks and Considerations. BioDrugs 32:69–81

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mauro VP, Chappell SA (2018) Considerations in the use of codon optimization for recombinant protein expression. Methods Mol Biol 1850:275–288

    Article  CAS  PubMed  Google Scholar 

  • Medjitna TD, Stadler C, Bruckner L, Griot C, Ottiger HP (2006) DNA vaccines: safety aspect assessment and regulation. Dev Biol (Basel) 126:261–270; discussion 327

    Google Scholar 

  • Mestas J, Hughes CC (2004) Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738

    Article  CAS  PubMed  Google Scholar 

  • Midoux P, Pichon C (2015) Lipid-based mRNA vaccine delivery systems. Expert Rev Vaccines 14:221–234

    Article  CAS  PubMed  Google Scholar 

  • Modjarrad K, Roberts CC, Mills KT, Castellano AR, Paolino K, Muthumani K, Reuschel EL, Robb ML, Racine T, Oh MD, Lamarre C, Zaidi FI, Boyer J, Kudchodkar SB, Jeong M, Darden JM, Park YK, Scott PT, Remigio C, Parikh AP, Wise MC, Patel A, Duperret EK, Kim KY, Choi H, White S, Bagarazzi M, May JM, Kane D, Lee H, Kobinger G, Michael NL, Weiner DB, Thomas SJ, Maslow JN (2019) Safety and immunogenicity of an anti-middle east respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis 19:1013–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morrow MP, Kraynyak KA, Sylvester AJ, Dallas M, Knoblock D, Boyer JD, Yan J, Vang R, Khan AS, Humeau L, Sardesai NY, Kim JJ, Plotkin S, Weiner DB, Trimble CL, Bagarazzi ML (2018) Clinical and immunologic biomarkers for histologic regression of high-grade cervical dysplasia and clearance of HPV16 and HPV18 after immunotherapy. Clin Cancer Res 24:276–294

    Article  CAS  PubMed  Google Scholar 

  • Muthumani K, Falzarano D, Reuschel EL, Tingey C, Flingai S, Villarreal DO, Wise M, Patel A, Izmirly A, Aljuaid A, Seliga AM, Soule G, Morrow M, Kraynyak KA, Khan AS, Scott DP, Feldmann F, LaCasse R, Meade-White K, Okumura A, Ugen KE, Sardesai NY, Kim JJ, Kobinger G, Feldmann H, Weiner DB (2015) A synthetic consensus anti-spike protein DNA vaccine induces protective immunity against Middle East respiratory syndrome coronavirus in nonhuman primates. Sci Transl Med 7:301ra132

    Google Scholar 

  • Muthumani K, Block P, Flingai S, Muruganantham N, Chaaithanya IK, Tingey C, Wise M, Reuschel EL, Chung C, Muthumani A, Sarangan G, Srikanth P, Khan AS, Vijayachari P, Sardesai NY, Kim JJ, Ugen KE, Weiner DB (2016) Rapid and long-term immunity elicited by DNA-encoded antibody prophylaxis and DNA vaccination against Chikungunya Virus. J Infect Dis 214:369–3678

    Article  CAS  PubMed  Google Scholar 

  • Myhr AI (2017) DNA vaccines: regulatory considerations and safety aspects. Curr Issues Mol Biol 22:79–88

    Article  PubMed  Google Scholar 

  • Nielsen H (2011) Working with RNA. Methods Mol Biol 703:15–28

    Article  CAS  PubMed  Google Scholar 

  • Pardi N, Weissman D (2017) Nucleoside modified mRNA vaccines for infectious diseases. Methods Mol Biol 1499:109–121

    Article  CAS  PubMed  Google Scholar 

  • Pardi N, Muramatsu H, Weissman D, Kariko K (2013) In vitro transcription of long RNA containing modified nucleosides. Methods Mol Biol 969:29–42

    Article  CAS  PubMed  Google Scholar 

  • Pardi N, Hogan MJ, Porter FW, Weissman D (2018) mRNA vaccines—a new era in vaccinology. Nat Rev Drug Discov 17:261–279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pascolo S (2004) Messenger RNA-based vaccines. Expert Opin Biol Ther 4:1285–1294

    Article  CAS  PubMed  Google Scholar 

  • Pascolo S (2008) Vaccination with messenger RNA (mRNA). Handb Exp Pharmacol. https://doi.org/10.1007/978-3-540-72167-3_11:221-235

    Article  PubMed  Google Scholar 

  • Plotkin SA, Orenstein WA, Offit PA, Edwards KM (2017) Plotkin’s vaccines, 7th ed. Elsevier Saunders

    Google Scholar 

  • Porter KR, Raviprakash K (2017) DNA vaccine delivery and improved immunogenicity. Curr Issues Mol Biol 22:129–138

    Article  PubMed  Google Scholar 

  • Reynolds TD, Buonocore L, Rose NF, Rose JK, Robek MD (2015) Virus-like vesicle-based therapeutic vaccine vectors for chronic Hepatitis B virus infection. J Virol. https://doi.org/10.1128/jvi.01184-15:10407-10415

    Article  PubMed  PubMed Central  Google Scholar 

  • Rock KL, York IA, Saric T, Goldberg AL (2002) Protein degradation and the generation of MHC class I-presented peptides. Adv Immunol 80:1–70

    Article  CAS  PubMed  Google Scholar 

  • Rock KL, Reits E, Neefjes J (2016) Present yourself! By MHC class I and MHC class II molecules. Trends Immunol 37:724–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rose NF, Publicover J, Chattopadhyay A, Rose JK (2008) Hybrid alphavirus-rhabdovirus propagating replicon particles are versatile and potent vaccine vectors. Proc Natl Acad Sci U S A 105:5839–5843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saade F, Petrovsky N (2012) Technologies for enhanced efficacy of DNA vaccines. Expert Rev Vaccines 11:189–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlake T, Thess A, Fotin-Mleczek M, Kallen KJ (2012) Developing mRNA-vaccine technologies. RNA Biol 9:1319–1330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schlake T, Thess A, Thran M, Jordan I (2019) mRNA as novel technology for passive immunotherapy. Cell Mol Life Sci 76:301–328

    Article  CAS  PubMed  Google Scholar 

  • Sedic M, Senn JJ, Lynn A, Laska M, Smith M, Platz SJ, Bolen J, Hoge S, Bulychev A, Jacquinet E, Bartlett V, Smith PF (2018) Safety evaluation of lipid nanoparticle-formulated modified mRNA in the Sprague-Dawley rat and cynomolgus monkey. Vet Pathol 55:341–354

    Article  CAS  PubMed  Google Scholar 

  • Sergeeva OV, Koteliansky VE, Zatsepin TS (2016) mRNA-based therapeutics—advances and perspectives. Biochemistry (Mosc) 81:709–722

    Article  CAS  PubMed  Google Scholar 

  • Sheets RL, Stein J, Manetz TS, Andrews C, Bailer R, Rathmann J, Gomez PL (2006a) Toxicological safety evaluation of DNA plasmid vaccines against HIV-1, Ebola, severe acute respiratory syndrome, or West Nile virus is similar despite differing plasmid backbones or gene-inserts. Toxicol Sci 91:620–630

    Article  CAS  PubMed  Google Scholar 

  • Sheets RL, Stein J, Manetz TS, Duffy C, Nason M, Andrews C, Kong WP, Nabel GJ, Gomez PL (2006b) Biodistribution of DNA plasmid vaccines against HIV-1, Ebola, severe acute respiratory syndrome, or West Nile virus is similar, without integration, despite differing plasmid backbones or gene inserts. Toxicol Sci 91:610–619

    Article  CAS  PubMed  Google Scholar 

  • Sioud M (2006) Innate sensing of self and non-self RNAs by toll-like receptors. Trends Mol Med 12:167–176

    Article  CAS  PubMed  Google Scholar 

  • Svitkin YV, Cheng YM, Chakraborty T, Presnyak V, John M, Sonenberg N (2017) N1-methyl-pseudouridine in mRNA enhances translation through eIF2alpha-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res 45:6023–6036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tews BA, Meyers G (2017) Self-replicating RNA. Methods Mol Biol 1499:15–35

    Article  CAS  PubMed  Google Scholar 

  • Thran M, Mukherjee J, Ponisch M, Fiedler K, Thess A, Mui BL, Hope MJ, Tam YK, Horscroft N, Heidenreich R, Fotin-Mleczek M, Shoemaker CB, Schlake T (2017) mRNA mediates passive vaccination against infectious agents, toxins, and tumors. EMBO Mol Med 9:1434–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tregoning JS, Kinnear E (2014) Using plasmids as DNA vaccines for infectious diseases. Microbiol Spectr 2

    Google Scholar 

  • Uematsu Y, Vajdy M, Lian Y, Perri S, Greer CE, Legg HS, Galli G, Saletti G, Otten GR, Rappuoli R, Barnett SW, Polo JM (2012) Lack of interference with immunogenicity of a chimeric alphavirus replicon particle-based influenza vaccine by preexisting antivector immunity. Clin Vaccine Immunol 19:991–998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ulmer JB, Mason PW, Geall A, Mandl CW (2012) RNA-based vaccines. Vaccine 30:4414–4418

    Article  CAS  PubMed  Google Scholar 

  • Weide B, Pascolo S, Scheel B, Derhovanessian E, Pflugfelder A, Eigentler TK, Pawelec G, Hoerr I, Rammensee HG, Garbe C (2009) Direct injection of protamine-protected mRNA: results of a phase 1/2 vaccination trial in metastatic melanoma patients. J Immunother 32:498–507

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Weissman D, Kariko K (2015) mRNA: fulfilling the promise of gene therapy. Mol Ther 23:1416–1417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weissman D, Pardi N, Muramatsu H, Kariko K (2013) HPLC purification of in vitro transcribed long RNA. Methods Mol Biol 969:43–54

    Article  CAS  PubMed  Google Scholar 

  • Whitehead KA, Langer R, Anderson DG (2009) Knocking down barriers: advances in siRNA delivery. Nat Rev Drug Discov 8:129–138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilkie GS, Dickson KS, Gray NK (2003) Regulation of mRNA translation by 5’- and 3’-UTR-binding factors. Trends Biochem Sci 28:182–188

    Article  CAS  PubMed  Google Scholar 

  • Williams JA (2014) Improving DNA vaccine performance through vector design. Curr Gene Ther 14:170–189

    Article  CAS  PubMed  Google Scholar 

  • Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  CAS  PubMed  Google Scholar 

  • Wu J, Chen ZJ (2014) Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol 32:461–488

    Article  CAS  PubMed  Google Scholar 

  • Zakhartchouk AN, Viswanathan S, Moshynskyy I, Petric M, Babiuk LA (2007) Optimization of a DNA vaccine against SARS. DNA Cell Biol 26:721–726

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou WZ, Hoon DS, Huang SK, Fujii S, Hashimoto K, Morishita R, Kaneda Y (1999) RNA melanoma vaccine: induction of antitumor immunity by human glycoprotein 100 mRNA immunization. Hum Gene Ther 10:2719–2724

    Article  CAS  PubMed  Google Scholar 

  • Zhou J, Shum KT, Burnett JC, Rossi JJ (2013) Nanoparticle-based delivery of RNAi therapeutics: progress and challenges. Pharmaceuticals (Basel) 6:85–107

    Article  CAS  PubMed  Google Scholar 

  • Zhu B, Tabor S, Richardson CC (2014) Syn5 RNA polymerase synthesizes precise run-off RNA products. Nucleic Acids Res 42:e33

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Robin Levis, Haruhiko Murata, Elizabeth Sutkowski, Marion Gruber, and Theresa Finn for discussions and/or review of the manuscript.

Author information

Authors and Affiliations

  1. Division of Vaccines and Related Products Applications, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Building 71, Room 3045, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Ramachandra Naik

  2. Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Building 52/72, Room 1220, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA

    Keith Peden

Authors
  1. Ramachandra Naik
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  2. Keith Peden
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Correspondence to Keith Peden .

Editor information

Editors and Affiliations

  1. Senior Vice President of Research, Dynavax Technologies, Emeryville, CA, USA

    Dong Yu

  2. CureVac AG, Tübingen, Germany

    Benjamin Petsch

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© 2020 This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

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Naik, R., Peden, K. (2020). Regulatory Considerations on the Development of mRNA Vaccines. In: Yu, D., Petsch, B. (eds) mRNA Vaccines. Current Topics in Microbiology and Immunology, vol 440. Springer, Cham. https://doi.org/10.1007/82_2020_220

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