The Safety Behind Synthetic Biology Vaccines

Jennifer Zhong, Grade 11

As COVID-19 deaths and cases rise, rapid vaccine safety, development, and distribution become extremely important to potentially solve this world crisis. A myriad of people, over 105 million, have been infected with COVID-19 and well over 2 million have passed away as of February 2021 [7]. The numbers continue to climb. During a global pandemic such as the current COVID-19 pandemic, vaccines need to be manufactured in large quantities and at a low cost in order to fulfill the availability of vaccines needed for herd immunity [10]. Synthetic biology is a field that has been utilized to speed the development of COVID-19 vaccines using synthetically engineered organic molecules [2]. DNA and RNA vaccines contain synthetic nucleotide transcripts delivered into the patient to produce translated proteins in the cells. There is an immune response triggered by these proteins that can protect the body from the virus [2,5]. Synthetic biology has the potential to make a safe, quicker option for vaccine development compared to traditional vaccines and advance medical research worldwide.
There are various benefits to using DNA and RNA vaccines compared to traditional vaccines. Non-viral vaccines provide a less costly, faster option for vaccine development. Previous development has taken an exceptionally long time to develop and manufacture, anywhere between 10 to 15 years, while it has taken less than one year for the COVID-19 vaccines [3]. After viral genome sequencing, Moderna started human tests for the development of their current mRNA vaccine after only 66 days [10]. Although live vaccines produce a very strong immune response, the dead or weakened pathogen may revert [6]. There is a chance a live vaccine can become pathogenic if it recombines with a wild strain in nature, which coronaviruses such as SARS-CoV2 have done in the past [6]. On the other hand, RNA vaccines are considered to be safe because the spike protein is unable to reactivate and become dangerous. Despite many concerns, there is also no risk of integration of RNA into the patient’s genome [10]. However, there are a few drawbacks to non-viral vaccines. They require multiple vaccinations to achieve immunity. Pfizer BioNTech and Moderna have each produced mRNA vaccines that are currently approved by the Food & Drug Association for emergency use [1]. Both Moderna and Pfizer, frontrunners for COVID-19 vaccines, require two doses to be fully vaccinated due to the first dose only resulting in a weak immune response [6]. Pfizer also requires storage at -70 degrees Celsius which can pose a major issue during the transportation and storage of these vaccines at such low temperatures due to necessary special equipment [3]. We do not have the industrial capacity needed to produce amounts of doses in the hundreds of millions for future vaccine development yet [12].
Safety is considerably important while developing vaccines for rapid mass immunization such as the case of the COVID-19 pandemic, and potential safety risks must be weighed against benefits. Safety is a necessity for public use and lack of trust can create hesitancy and can fuel the anti-vaccination movement, making it extremely difficult to reach herd immunity during times when it is needed [6]. Researchers have used the published SARS-CoV2 sequence in order to synthesize the virus using synthetic biology which can benefit the development of a vaccine as well as drug research. Unfortunately, this may cause increased leakage of the virus and other safety hazards [11]. There is also a large safety risk concerning DNA and RNA vaccines in that they have a higher chance of causing an adverse event after vaccination compared to a live attenuated vaccine [7]. There have been major adverse events shown in patients during the development of the COVID-19 vaccine, including those that suspended the vaccine trials for review of such events [11]. During the Pfizer Phase II trials, it was shown that 27% of people who had the vaccine reported an adverse event compared to 12% in the placebo group [9]. Both mRNA vaccines can cause an allergic reaction such as anaphylaxis, preventing patients with allergies to the ingredients from having the vaccine administered [1]. The development of RNA vaccines has had many obstacles and limitations in the past due to the result of inflammatory responses and also to the instability of RNA, which we need to be cautious of during synthetic vaccine development as well [8].
Due to the scarcity of vaccines and other resources during the pandemic, the distribution of COVID-19 vaccines has differences for different populations and socioeconomic levels. More people lower in social class have been severely affected by COVID-19. Even if vaccines were funded publicly, those with a lower income have previously had lower vaccination rates [4]. The distribution of vaccines can deepen disparities between socioeconomic status by further separating those who have the availability to be vaccinated and those who don’t. However, with the quick development of synthetic vaccines, doses may become widely available for the public despite socioeconomic level.
As well as in vaccine development, synthetic biology can be incredibly useful in many other cases in medical advancement and research. Cells engineered by synthetic biology can be used for medical diagnosis and treatments. Viruses have been synthetically engineered to kill bacteria that are now resistant to most antibiotics and to attack and prevent the growth of tumor cells for cancer treatment [11]. Unfortunately with the advantages of synthetic biology techniques, come detriments. Because of the rapid growth of synthetic biology research, there have been patient deaths and serious side effects due to research rushed without biosafety considerations.
Synthetic biology can be used in developing immunogenic vaccines and furthering medical research beyond vaccinology. DNA and RNA synthetic vaccines can be extremely beneficial, especially during a pandemic. They ensure a quicker development and distribution of vaccines for the public to create immunity [10]. Synthetic biology can help the world become more prepared for future health crises, but we still need to be wary of the potential biosafety risks and be considerate of other factors, including socioeconomic disparities.

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[2] Bruynseels, Koen “Responsible Innovation in Synthetic Biology in Response to COVID-19:
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[3] Burgos, Rodrigo M., et al. “The Race to a COVID-19 Vaccine: Opportunities and
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[4] Ismail, Shainoor J., et al. “Navigating Inequities: A Roadmap Out of the Pandemic” BMJ
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[7] Kashte, Shivaji, et al. “COVID-19 Vaccines: Rapid Development, Implications, Challenges
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[8] Pardi, Norbert, et al. “Recent Advances in mRNA Vaccine Technology” Current Opinion in
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[10] Sandbrink, Jonas B. et al. “RNA Vaccines: A Suitable Platform for Tackling Emerging
Pandemics?” Frontiers in Immunology 11 (2020): 1-9.
[11] Li, Jing et al. “Advances in Synthetic Biology and Biosafety Governance” Frontiers in
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[12] Rappuoli, Rina, et al. “Vaccinology in the Post COVID-19 Era” PNAS 118 (2021): 1-7.

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