TWV Podcast Episode 440: COVID-19 Vaccines Part 1 - mRNA Vaccine Technology

Stacy and I have been inundated with thoughtful questions about the two approved covid-19 mRNA vaccines. This is a huge topic, so we’re going to cover all the relevant science in at least two episodes of The Whole View podcast, maybe three!

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Recommended Reading and Listening
Citations

In this first episode, we discuss: the history of vaccines, their safety and efficacy, the high morbidity and mortality of the infectious diseases we vaccinate against, how herd immunity protects communities, the actual statistics on vaccine-induced injury, the ingredients in traditional vaccines (antigen, adjuvant, and additives), why people with autoimmune disease can sometimes experience an increase in symptoms after a vaccine, the history of the discovery of mRNA and proof-of-concept of mRNA-based drugs, the amazing new science behind the mRNA vaccines, how mRNA vaccines differ from traditional vaccines, how basic scientific exploration and discovery over the last 5 years meant that the covid-19 mRNA vaccines could be produced so quickly, and how mRNA vaccines could change the landscape not just of vaccination but cancer therapy and so much more! Phew!

This is an info-packed show that lays the groundwork for next week’s discussion on the Moderna and Pfizer/BioNTech covid-19 vaccines specifically.

If you enjoy the show, please review it on iTunes!

Citations

Hsu JL. A brief history of vaccines: smallpox to the present. S D Med. 2013;Spec no:33-7. PMID: 23444589.

Boylston A. The origins of inoculation. J R Soc Med. 2012 Jul;105(7):309-13. doi: 10.1258/jrsm.2012.12k044. PMID: 22843649; PMCID: PMC3407399.

Adjuvants and Vaccines

Spencer JP, Trondsen Pawlowski RH, Thomas S. Vaccine Adverse Events: Separating Myth from Reality. Am Fam Physician. 2017 Jun 15;95(12):786-794. PMID: 28671426.

Karikó K, Buckstein M, Ni H, Weissman D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity. 2005 Aug;23(2):165-75. doi: 10.1016/j.immuni.2005.06.008. PMID: 16111635.

Guevara ML, Persano F, Persano S. Advances in Lipid Nanoparticles for mRNA-Based Cancer Immunotherapy. Front Chem. 2020 Oct 23;8:589959. doi: 10.3389/fchem.2020.589959. PMID: 33195094; PMCID: PMC7645050.

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Pardi N, Hogan MJ, Porter FW, Weissman D. mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov. 2018 Apr;17(4):261-279. doi: 10.1038/nrd.2017.243. Epub 2018 Jan 12. PMID: 29326426; PMCID: PMC5906799.

Karikó K, Muramatsu H, Welsh FA, Ludwig J, Kato H, Akira S, Weissman D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther. 2008 Nov;16(11):1833-40. doi: 10.1038/mt.2008.200. Epub 2008 Sep 16. PMID: 18797453; PMCID: PMC2775451.

Kauffman KJ, Webber MJ, Anderson DG. Materials for non-viral intracellular delivery of messenger RNA therapeutics. J Control Release. 2016 Oct 28;240:227-234. doi: 10.1016/j.jconrel.2015.12.032. Epub 2015 Dec 21. PMID: 26718856.

Guan S, Rosenecker J. Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 2017 Mar;24(3):133-143. doi: 10.1038/gt.2017.5. Epub 2017 Jan 17. PMID: 28094775.

Thess A, Grund S, Mui BL, Hope MJ, Baumhof P, Fotin-Mleczek M, Schlake T. Sequence-engineered mRNA Without Chemical Nucleoside Modifications Enables an Effective Protein Therapy in Large Animals. Mol Ther. 2015 Sep;23(9):1456-64. doi: 10.1038/mt.2015.103. Epub 2015 Jun 8. PMID: 26050989; PMCID: PMC4817881.

Karikó K, Muramatsu H, Ludwig J, Weissman D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 2011 Nov;39(21):e142. doi: 10.1093/nar/gkr695. Epub 2011 Sep 2. PMID: 21890902; PMCID: PMC3241667.

Espeseth AS, Cejas PJ, Citron MP, Wang D, DiStefano DJ, Callahan C, Donnell GO, Galli JD, Swoyer R, Touch S, Wen Z, Antonello J, Zhang L, Flynn JA, Cox KS, Freed DC, Vora KA, Bahl K, Latham AH, Smith JS, Gindy ME, Ciaramella G, Hazuda D, Shaw CA, Bett AJ. Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic and protective in rodent models of RSV infection. NPJ Vaccines. 2020 Feb 14;5(1):16. doi: 10.1038/s41541-020-0163-z. PMID: 32128257; PMCID: PMC7021756.