Skip to main content

Introduction to RNA Vaccines

  • Protocol
  • First Online:
RNA Vaccines

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1499))

Abstract

RNA vaccines are attractive, because they exhibit characteristics of subunit vaccines and live-attenuated vectors, including flexible production and induction of both humoral and cellular immunity. While human proof-of-concept for RNA vaccines is still pending, the nascent field of RNA therapeutics has already attracted substantial industry and government funding as well as record investments of private venture capital. Most recently, the WHO acknowledged messenger RNA (mRNA) as a new therapeutic class. In this chapter, we briefly review key developments in RNA vaccines and outline the contents of this volume of Methods in Molecular Biology.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Levine MM, Dougan G, Good MF, Liu MA, Nabel GJ, Nataro JP, Rappuoli R (eds) (2009) New generation vaccines, 4th edn. CRC Press, New York

    Google Scholar 

  2. Hilleman MR (1998) A simplified vaccinologists’ vaccinology and the pursuit of a vaccine against AIDS. Vaccine 16(8):778–793

    Article  CAS  PubMed  Google Scholar 

  3. Nakaya HI, Pulendran B (2015) Vaccinology in the era of high-throughput biology. Phil Trans R Soc Lond B Biol Sci 370. pii:20140146. doi:10.1098/rstb.2014.0146

  4. Sadanand S, Suscovich TJ, Alter G (2016) Broadly neutralizing antibodies against HIV: new insights to inform vaccine design. Annu Rev Med 67:185–200. doi:10.1146/annurev-med-091014-090749

    Article  CAS  PubMed  Google Scholar 

  5. Walker CM, Grakoui A (2015) Hepatitis C virus: why do we need a vaccine to prevent a curable persistent infection? Curr Opin Immunol 35:137–143. doi:10.1016/j.coi.2015.06.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. van der Burg SH, Arens R, Ossendorp F et al (2016) Vaccines for established cancer: overcoming the challenges posed by immune evasion. Nat Rev Cancer 16:219–233. doi:10.1038/nrc.2016.16

    Article  PubMed  Google Scholar 

  7. Nakaya HI, Hagan T, Duraisingham SS et al (2015) Systems analysis of immunity to influenza vaccination across multiple years and in diverse populations reveals shared molecular signatures. Immunity 43:1186–1198. doi:10.1016/j.immuni.2015.11.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Stern-Ginossar N (2015) Decoding viral infection by ribosome profiling. J Virol 89:6164–6166. doi:10.1128/JVI.02528-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immunotherapy. Science 348:69–74. doi:10.1126/science.aaa4971

    Article  CAS  PubMed  Google Scholar 

  10. Ulmer JB, Valley U, Rappuoli R (2006) Vaccine manufacturing: challenges and solutions. Nat Biotechnol 24(11):1377–1383

    Article  CAS  PubMed  Google Scholar 

  11. Hondowicz BD, Schwedhelm KV, Kas A et al (2012) Discovery of T cell antigens by high-throughput screening of synthetic minigene libraries. PLoS One 7(1):e29949

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  13. Pascolo S (2015) The messenger’s great message for vaccination. Expert Rev Vaccines 14:153–156. doi:10.1586/14760584.2015.1000871

    Article  CAS  PubMed  Google Scholar 

  14. Sahin U, Karikó K, Türeci Ö (2014) mRNA-based therapeutics--developing a new class of drugs. Nat Rev Drug Discov 13:759–780. doi:10.1038/nrd4278

    Article  CAS  PubMed  Google Scholar 

  15. Ulmer JB, Mansoura MK, Geall AJ (2015) Vaccines “on demand”: science fiction or a future reality. Expert Opin Drug Discov 10:101–106. doi:10.1517/17460441.2015.996128

    Article  CAS  PubMed  Google Scholar 

  16. Kramps T, Probst J (2013) Messenger RNA-based vaccines: progress, challenges, applications. Wiley Interdiscip Rev RNA 4:737–749. doi:10.1002/wrna.1189

    CAS  PubMed  Google Scholar 

  17. Youn H, Chung J-K (2015) Modified mRNA as an alternative to plasmid DNA (pDNA) for transcript replacement and vaccination therapy. Expert Opin Biol Ther 15:1337–1348. doi:10.1517/14712598.2015.1057563

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wolff JA, Malone RW, Williams P et al (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465–1468

    Article  CAS  PubMed  Google Scholar 

  19. Leitner WW, Ying H, Restifo NP (1999) DNA and RNA-based vaccines: principles, progress and prospects. Vaccine 18:765–777. doi:10.1016/S0264-410X(99)00271-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Weide B, Carralot J-P, Reese A et al (2008) Results of the first phase I/II clinical vaccination trial with direct injection of mRNA. J Immunother 31(2):180–188

    Article  CAS  PubMed  Google Scholar 

  21. Rittig SM, Haentschel M, Weimer KJ et al (2011) Intradermal vaccinations with RNA coding for TAA generate CD8+ and CD4+ immune responses and induce clinical benefit in vaccinated patients. Mol Ther 19(5):990–999

    Article  CAS  PubMed  Google Scholar 

  22. Vallazza B, Petri S, Poleganov MA et al (2015) Recombinant messenger RNA technology and its application in cancer immunotherapy, transcript replacement therapies, pluripotent stem cell induction, and beyond: Recombinant mRNA technology and its application. Wiley Interdiscip Rev RNA. doi:10.1002/wrna.1288

    PubMed  Google Scholar 

  23. Van Lint S, Heirman C, Thielemans K, Breckpot K (2013) mRNA: from a chemical blueprint for protein production to an off-the-shelf therapeutic. Hum Vaccin Immunother 9(2):265–274

    Article  PubMed  PubMed Central  Google Scholar 

  24. Granstein RD, Ding W, Ozawa H (2000) Induction of anti-tumor immunity with epidermal cells pulsed with tumor-derived RNA or intradermal administration of RNA. J Invest Dermatol 114(4):632–636

    Article  CAS  PubMed  Google Scholar 

  25. Boczkowski D, Nair SK, Snyder D, Gilboa E (1996) Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 184(2):465–472

    Article  CAS  PubMed  Google Scholar 

  26. Boczkowski D, Nair S (2010) RNA as performance-enhancers for dendritic cells. Expert Opin Biol Ther 10:563–574. doi:10.1517/14712591003614749

    Article  CAS  PubMed  Google Scholar 

  27. Petsch B, Schnee M, Vogel AB et al (2012) Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol 30(12):1210–1216

    Article  CAS  PubMed  Google Scholar 

  28. Geall AJ, Verma A, Otten GR et al (2012) Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci U S A 109(36):14604–14609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Brito LA, Chan M, Shaw CA et al (2014) A cationic nanoemulsion for the delivery of next-generation RNA vaccines. Mol Ther. doi:10.1038/mt.2014.133

    PubMed  PubMed Central  Google Scholar 

  30. Dolgin E (2015) Business: The billion-dollar biotech. Nature 522:26–28. doi:10.1038/522026a

    Article  CAS  PubMed  Google Scholar 

  31. Chambers M ChemIDplus - 1613055-09-6 - Nadorameran - Searchable synonyms, formulas, resource links, and other chemical information. http://chem.sis.nlm.nih.gov/chemidplus/rn/1613055-09-6. Accessed 29 Mar 2016

  32. WHO Drug Information Vol. 29, No. 2, 2015 - Proposed International Nonproprietary Names, List 113. http://apps.who.int/medicinedocs/en/m/abstract/Js22000en/. Accessed 29 Mar 2016

  33. Karikó K, Weissman D (2007) Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: implication for therapeutic RNA development. Curr Opin Drug Discov Devel 10(5):523–532

    PubMed  Google Scholar 

  34. Schlake T, Thess A, Fotin-Mleczek M, Kallen K-J (2012) Developing mRNA-vaccine technologies. RNA Biol 9:1319–1330. doi:10.4161/rna.22269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Brito LA, Kommareddy S, Maione D et al (2014) Self-amplifying mRNA vaccines. Adv Genet 89:179–233

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. Uematsu Y, Vajdy M, Lian Y et al (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. doi:10.1128/CVI.00031-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Nielsen H (2011) RNA. Humana Press, Totowa, NJ

    Book  Google Scholar 

  39. Boisguérin V, Castle JC, Loewer M et al (2014) Translation of genomics-guided RNA-based personalised cancer vaccines: towards the bedside. Br J Cancer 111:1469–1475. doi:10.1038/bjc.2013.820

    Article  PubMed  PubMed Central  Google Scholar 

  40. Desmet CJ, Ishii KJ (2012) Nucleic acid sensing at the interface between innate and adaptive immunity in vaccination. Nat Rev Immunol 12(7):479–491

    Article  CAS  PubMed  Google Scholar 

  41. Scheel B, Teufel R, Probst J et al (2005) Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA. Eur J Immunol 35:1557–1566. doi:10.1002/eji.200425656

    Article  CAS  PubMed  Google Scholar 

  42. Rettig L, Haen SP, Bittermann AG et al (2010) Particle size and activation threshold: a new dimension of danger signaling. Blood 115(22):4533–4541

    Article  CAS  PubMed  Google Scholar 

  43. Fotin-Mleczek M, Duchardt KM, Lorenz C et al (2011) Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother 34(1):1–15

    Article  CAS  PubMed  Google Scholar 

  44. Barbalat R, Ewald SE, Mouchess ML, Barton GM (2011) Nucleic acid recognition by the innate immune system. Annu Rev Immunol 29:185–214

    Article  CAS  PubMed  Google Scholar 

  45. Wu J, Chen ZJ (2014) Innate immune sensing and signaling of cytosolic nucleic acids. Annu Rev Immunol 32:461–488. doi:10.1146/annurev-immunol-032713-120156

    Article  CAS  PubMed  Google Scholar 

  46. Kagan JC, Barton GM (2015) Emerging principles governing signal transduction by pattern-recognition receptors. Cold Spring Harb Perspect Biol 7:a016253. doi:10.1101/cshperspect.a016253

    Article  Google Scholar 

  47. Brencicova E, Diebold SS (2013) Nucleic acids and endosomal pattern recognition: how to tell friend from foe? Front Cell Infect Microbiol 3:37. doi:10.3389/fcimb.2013.00037

    Article  PubMed  PubMed Central  Google Scholar 

  48. Barchet W, Wimmenauer V, Schlee M, Hartmann G (2008) Accessing the therapeutic potential of immunostimulatory nucleic acids. Curr Opin Immunol 20(4):389–395

    Article  CAS  PubMed  Google Scholar 

  49. Van Lint S, Goyvaerts C, Maenhout S et al (2012) Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy. Cancer Res 72(7):1661–1671

    Article  PubMed  Google Scholar 

  50. Hammerich L, Binder A, Brody JD (2015) In situ vaccination: cancer immunotherapy both personalized and off-the-shelf. Mol Oncol 9:1966–1981. doi:10.1016/j.molonc.2015.10.016

    Article  CAS  PubMed  Google Scholar 

  51. Schlom J, Hodge JW, Palena C et al (2014) Chapter two - therapeutic cancer vaccines. In: Tew KD, Fisher PB (eds) Advances in cancer research. Academic, New York, pp 67–124

    Google Scholar 

  52. Mogler MA, Kamrud KI (2015) RNA-based viral vectors. Expert Rev Vaccines 14:283–312. doi:10.1586/14760584.2015.979798

    Article  CAS  PubMed  Google Scholar 

  53. Chiocca EA, Rabkin SD (2014) Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res 2:295–300. doi:10.1158/2326-6066.CIR-14-0015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10(11):787–796

    Article  CAS  PubMed  Google Scholar 

  55. Phua KKL, Nair SK, Leong KW (2014) Messenger RNA (mRNA) nanoparticle tumour vaccination. Nanoscale 6:7715–7729. doi:10.1039/c4nr01346h

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kreiter S, Selmi A, Diken M et al (2010) Intranodal vaccination with naked antigen-encoding RNA elicits potent prophylactic and therapeutic antitumoral immunity. Cancer Res 70(22):9031–9040

    Article  CAS  PubMed  Google Scholar 

  57. Ravi AD, Sadhna D, Nagpaal D, Chawla L (2015) Needle free injection technology: a complete insight. Int J Pharm Investig 5:192–199. doi:10.4103/2230-973X.167662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Foged C (2016) Thermostable subunit vaccines for pulmonary delivery: how close are we? Curr Pharm Des 22(17):2561–2576

    Article  CAS  PubMed  Google Scholar 

  59. Etschel JK, Hückelhoven AG, Hofmann C et al (2012) HIV-1 mRNA electroporation of PBMC: a simple and efficient method to monitor T-cell responses against autologous HIV-1 in HIV-1-infected patients. J Immunol Methods 380:40–55. doi:10.1016/j.jim.2012.03.005

    Article  CAS  PubMed  Google Scholar 

  60. Van Camp K, Cools N, Stein B et al (2010) Efficient mRNA electroporation of peripheral blood mononuclear cells to detect memory T cell responses for immunomonitoring purposes. J Immunol Methods 354:1–10. doi:10.1016/j.jim.2010.01.009

    Article  PubMed  Google Scholar 

  61. Cools N, Van Camp K, Van Tendeloo V, Berneman Z (2013) mRNA electroporation as a tool for immunomonitoring. Methods Mol Biol 969:293–303

    Article  CAS  PubMed  Google Scholar 

  62. Scully IL, Swanson K, Green L et al (2015) Anti-infective vaccination in the 21st century — new horizons for personal and public health. Curr Opin Microbiol 27:96–102. doi:10.1016/j.mib.2015.07.006

    Article  PubMed  Google Scholar 

  63. Lopalco PL, DeStefano F (2015) The complementary roles of Phase 3 trials and post-licensure surveillance in the evaluation of new vaccines. Vaccine 33:1541–1548. doi:10.1016/j.vaccine.2014.10.047

    Article  PubMed  Google Scholar 

  64. Goetz KB, Pfleiderer M, Schneider CK (2010) First-in-human clinical trials with vaccines—what regulators want. Nat Biotechnol 28:910–916. doi:10.1038/nbt0910-910

    Article  CAS  PubMed  Google Scholar 

  65. Rabinovich PM (2013) Synthetic messenger RNA and cell metabolism modulation: methods and protocols, 2013th edn. Humana Press, New York

    Google Scholar 

  66. Johansson DX, Ljungberg K, Kakoulidou M, Liljeström P (2012) Intradermal electroporation of naked replicon RNA elicits strong immune responses. PLoS One 7:e29732. doi:10.1371/journal.pone.0029732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Cu Y, Broderick KE, Banerjee K et al (2013) Enhanced delivery and potency of self-amplifying mRNA vaccines by electroporation in situ. Vaccines 1:367–383. doi:10.3390/vaccines1030367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Broderick KE, Humeau LM (2015) Electroporation-enhanced delivery of nucleic acid vaccines. Expert Rev Vaccines 14(2):195–204. doi:10.1586/14760584.2015.990890

    Article  CAS  PubMed  Google Scholar 

  69. Britten CM, Singh-Jasuja H, Flamion B et al (2013) The regulatory landscape for actively personalized cancer immunotherapies. Nat Biotechnol 31:880–882. doi:10.1038/nbt.2708

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank colleagues in the field for continuing discussions. We also thank Dr. Michel Pairet and Dr. Holger Gellermann of Boehringer Ingelheim for support.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Thomas Kramps or Knut Elbers .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media New York

About this protocol

Cite this protocol

Kramps, T., Elbers, K. (2017). Introduction to RNA Vaccines. In: Kramps, T., Elbers, K. (eds) RNA Vaccines. Methods in Molecular Biology, vol 1499. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6481-9_1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6481-9_1

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6479-6

  • Online ISBN: 978-1-4939-6481-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics