Behind the SARS-CoV-2 RNA Vaccines: High-Quality DNA Purification at All Scales

The ability to vaccinate people against disease represented a massive sea change in how we conceptualize medicine. Instead of simply treating symptoms after a sickness has taken hold, we can prime the body’s immune system to suppress the invading pathogen before it’s too late. Heading off infections before they strike has been instrumental in the American response to the COVID-19 pandemic, and scientists have built off of centuries of work to deliver a safe and effective vaccine in record time.¹

The Earliest Days of Immunization

Humans have recognized the core principle of vaccination – that exposure to a pathogen results in some level of immunity – for well over 2,000 years, even if we didn’t quite understand how or why. By 430 B.C., people realized that those who had survived smallpox were immune to future infections and able to safely care for other smallpox patients.² The Chinese first documented success with vaccination in the 15th Century, with a method that involved blowing the pulverized dust of dried smallpox scabs up the noses of healthy people.³

A few centuries later and a couple of continents away, Lady Mary Wortley Montagu and Charles Maitland famously brought the practice of smallpox inoculation to England – though there’s evidence it had been utilized in Wales some decades earlier.⁴ Dr. Edward Jenner, an English country doctor, took the process one step further by vaccinating healthy people against smallpox with less-virulent cowpox.^2,5

Nearly one hundred years later, Louis Pasteur, used a dead culture of Pasteurella multocida (the pathogen responsible for chicken cholera) to innoculate healthy chickens, which developed mild symptoms, yet fully recovered. Amazingly, those chickens showed no signs of disease when injected with fresh P. multocida cultures.⁶ Pasteur went on to perform similar experiments (often publicly), with “attenuated” anthrax and rabies pathogens, which conferred protection to healthy subjects.⁷ 

A 20th Century Vaccine Boom

Vaccine research has made stunning progress through the 20th and 21st centuries. The first influenza vaccine was approved in 1945 and (with military leaders desperate to avoid the devastation of the 1918 wartime pandemic) produced for the US military.^8,9 In 1952, Jonas Salk developed an incredibly successful polio vaccine using attenuated poliovirus, followed by Albert Sabin’s live-attenuated poliovirus vaccine in the 1960s.¹⁰ By 1975, a new smallpox vaccine (using the vaccinia virus, not the nostril-born scab dust), helped eliminate the last naturally acquired smallpox case in Bangladesh.¹¹

21st Century Vaccine Research and Development in an Outbreak Paradigm

Since the days of Jenner and Pasteur – and certainly since the days of huffing pulverized scabs – our ability to rapidly develop and produce safe, effective vaccines has been expedited by several technological advances. Chief among these is our ability to extract, purify, and replicate high-quality nucleic acids.¹² This ability is critical because it speeds up the development process in multiple phases.

A traditional vaccine development cycle takes about ten years (at least), from target identification to pre-clinical and then phase I, II, and III clinical trials, followed by large-scale manufacturing^.13 In an outbreak paradigm, such as was utilized to develop the COVID-19 vaccines within a year of discovering the virus, this process was shortened.¹⁴ And not by cutting testing or regulatory corners, but by overlapping multiple phases simultaneously.

Typically, a company wouldn’t scale up manufacturing before establishing clinical proof-of- concept, but that’s exactly what companies like Pfizer and Moderna did. Such an immense financial risk would not even be possible to consider without the ability to extract, isolate, and replicate vast quantities of nucleic acids. The DNA needed to study the virus and potential vaccine targets, as well as the mRNA which ended up in the final vaccines all needed to be produced at high purity and an incredible scale.¹⁵

RNA and DNA Purification Kits for Vaccine Development and More

Thankfully, few labs face the pressures and demands of developing, testing, and manufacturing life-saving vaccines in the middle of a pandemic. But regardless of the timeline, high-quality nucleic acids are often necessary for some vaccine development and many therapeutics, whether it be for gene therapies, novel cardiovascular disease models, or the next global pandemic.^16,17 For all of these needs and more, Thermo Fisher Scientific has products to streamline the workflow from sample preparation through production.

For example, the MagMAX™ bead-based system allows for semi-automated extraction of nucleic acids for a variety of downstream applications, from PCR for wastewater surveillance to the isolation of mRNA vaccine candidates. With the KingFisher™ platform, these easy-to- execute extractions can be done in as little as 25 minutes without sacrificing quality.

For the highest-purity plasmid DNA purifications – in-vivo gene therapies and vaccines, primary and stem cell transfection, and more – the PureLinkTM Expi Entodoxin-free Plasmid DNA kit provides the highest yields in half the time of competitors, with equivalent endotoxin levels. By using a vacuum manifold instead of gravity columns to isolate plasmid DNA, PureLink Expi can meet the highest demands of modern vaccine and biotechnology development.

Vaccine science has brought us far from dried scabs. Modern scientists use the most advanced tools available to efficiently extract, isolate, and replicate high-purity nucleic acids for large-scale testing, therapeutics, and vaccine development. The monumental achievement of SARS-CoV-2 vaccine development highlights the incredible power and potential within every DNA Purification and Thermo Fisher Scientific has the tools and expertise to help labs of all sizes unleash that potential to solve the next great challenge in modern medicine.

To learn more about how we can help every stage of SARS-CoV-2 vaccine research and development, browse our solutions.

 

 

 

This article is for Research Use Only. Not for use in diagnostic procedures.

 

 

 

 

 

 

References

1. Science Brief: COVID-19 Vaccines and Vaccination. Available at: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/fully-vaccinated- people.html. Published July 27, 2021. Accessed July 27, 2021.
2. Riedel S. Edward Jenner and the history of smallpox and vaccination. Proc (Bayl Univ Med Cent). 2005;18(1):21-25.

 

3. The History of Vaccines, From Smallpox to COVID-19 | Time. Available at: https://time.com/5835668/vaccine-history/. Published May 15, 2020. Accessed July 27, 2021.
4. Huth E. Quantitative evidence for judgments on the efficacy of inoculation for the prevention of smallpox: England and New England in the 1700s. J R Soc Med. 2006;99(5):262-266.
5. Boylston A. The origins of vaccination: myths and reality. J R Soc Med. 2013;106(9):351- 354.
6. The first live attenuated vaccines. Nature website: https://www.nature.com/articles/d42859-020-00008-5. Published September 28, 2020. Accessed July 27, 2021.
7. Louis Pasteur and the Development of the Attenuated Vaccine. VBI Vaccines website: https://www.vbivaccines.com/evlp-platform/louis-pasteur-attenuated-vaccine/. Published November 23, 2016. Accessed: 27th July 2021
8. Influenza Historic Timeline. CDC website: https://www.cdc.gov/flu/pandemic- resources/pandemic-timeline-1930-and-beyond.htm. Published January 30, 2019. Accessed July 27, 2021.
9. 1918 Pandemic Influenza Historic Timeline. CDC website: https://www.cdc.gov/flu/pandemic-resources/1918-commemoration/pandemic-timeline- 1918.htm. Published March 20, 2018. Accessed July 27, 2021.
10. Jonas Salk. Britannica website: https://www.britannica.com/biography/Jonas- Salk#ref201334. Published June 19, 2021. Accessed July 27, 2021.
11. History of Smallpox. CDC website: https://www.cdc.gov/smallpox/history/history.html. Published February 20, 2021. Accessed July 27, 2021.
12. What are nucleic acid vaccines and how could they be used against COVID-19? Gavi website: https://www.gavi.org/vaccineswork/what-are-nucleic-acid-vaccines-and-how- could-they-be-used-against-covid-19. Published December 23, 2020. Accessed July 27, 2021.
13. How have Covid-19 vaccines been made quickly and safely? Wellcome website: https://wellcome.org/news/quick-safe-covid-vaccine-development. Published January 20, 2021. Accessed July 27, 2021.
14. Lurie N, Saville M, Hatchett R, Halton J. Developing Covid-19 Vaccines at Pandemic Speed. N Engl J Med. 2020;382(21):1969-1973.
15. Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol. 2021;21(2):73-82.
16. Wu X, Wu T, Liu J, Ding B. Gene Therapy Based on Nucleic Acid Nanostructure. Adv Healthc Mater. 2020;9(19):e2001046.
17. Rychak JJ, Klibanov AL. Nucleic acid delivery with microbubbles and ultrasound. Adv Drug Deliv Rev. 2014;72:82-93.
18. Vlassov S, Chapman L, Pedersen KW, and McKenna M. Innovations in Vaccine Research and Development [webinar]. June 8, 2021. https://www.youtube.com/watch? v=XRBPseQVC4o. Accessed July 27, 2021.