By Rishitha Boddu

Ever since last year, the coronavirus has threatened the wellbeing of all of our lives, but despite the seemingly hopeless situation, medical experts and scientists fought back. Just recently, several COVID-19 vaccines have been approved for general public use, and many have been trying to find a nearby vaccination center to obtain this additional layer of protection against the virus. However, many questions remain — how did these companies initially create the vaccine? What was the development process? Is there more than one correct way to combat the virus? This article covers various common methods that pharmaceutical companies utilized to create an effective vaccine.

Process of Vaccine Development

The journey to create a vaccine may begin at a research lab in a university, medical center, or even a small biotech company. Many scientists collaborate on niche topics within the overarching realm of biology, but very few individuals  are able to obtain results that aid in the vaccine production process. For the ones that do, however, the process generally goes as follows. After the conclusion of a study, researchers write scientific articles/reviews, which then get published in scientific journals, or they can present their findings at various scientific conferences. If their research is determined to have potential, the researchers are given permission to conduct tests on small animals. If the tests generate promising results, the testing is allowed to be conducted on larger species. As countless researchers around the globe are conducting their own studies, scientists from pharmaceutical companies are sent out to gather information from these individual research groups to see if any are showing results that could be utilized to build the vaccine. If a scientist discovers any research and deems it promising, the pharmaceutical company that sent the scientist can reach out to the lab to use their research to create a product. 

After a partnership is established, three trial phases follow. In phase one, the product must be tested on several healthy adults. The experiment usually includes two randomly-created groups: the control group will receive a placebo, while the experimental group will receive the product. This is so that the effects of the products can accurately be assessed. Because the product is only in its early stages, these studies generally consist of less than 100 subjects. The objective of the study is to determine if the product is safe and  generates the expected result: immunity. Scientists also figure out a plan to produce the vaccine in large quantities for the preliminary trials. Afterwards, they collaborate to decide if any preservatives or stabilizers need to be added to ensure the vaccine does not break down. Finally, the company is also expected to register their ideas with the Food and Drug Administration so that their work can be approved.

  Phase two involves repeated testing between the control group and the experimental group. Observing results from the repeated testing trials, the pharmaceutical company must continuously alter their product to fulfill its maximized potential. They must also determine  the minimum dose required for the vaccine to provide viral immunity, as well as observe what safety precautions will be needed to mention when releasing the vaccine for public use. Furthermore, the company will need to figure out how to ensure that every batch of the vaccine produces consistent results. Finally, the logistics of the product distribution must be decided upon. This includes the  packaging and transportation of the vaccine so that it arrives at its various destinations properly. Finally,. 

Phase three trials will consist of thousands of participants who resemble the target population who will eventually receive the vaccine. The company will have to look over final details including how many doses to send to each location, how the vaccine will be stored when it arrives at the vaccination centers, and how long the vaccine can go before expiring to avoid any unwanted side effects. After perfecting all the details, the company can proceed to completing the product licensing forms. Before the vaccine is provided to the general public, the Food and Drug Administration (FDA) and the Center of Disease Control (CDC) must review the company’s data from the three trials phases and conduct thorough inspections to evaluate the status of development. Once everything seems to be in order, the vaccine will be approved by both the FDA and the CDC, and is finally ready to be given out to the public. While the vaccine is circulating within the population, the CDC will still have various post-licensure measures in place to monitor any rare negative reactions to a vaccine. If negative trends occur in the data collected by these health professionals, the CDC will immediately act on the issue. We recently saw this occur with the Johnson & Johnson coronavirus vaccine. Six individuals experienced blood clots following their vaccination, so the product was recalled until the pharmaceutical company and other scientists can pinpoint the issue.

Generally this entire development process takes up to 15 to 20 years, involves tests on thousands of trial participants, and requires hundreds of scientists to review the data and development. However, as we all know, the vaccines for the COVID-19 virus were created in less than two years, which is a very impressive feat. It really goes to show how humans can accomplish great things when we are pushed to the limit. 

Methods of Creating a Vaccine

One common approach scientists use to make a vaccine is to either weaken or inactivate the virus. Viruses replicate over thousands of times inside your body and spread their infectious genetic material to as many cells in your body as possible. However, weakening a virus will cause it to reproduce at a much slower rate, allowing your immune system to fight back. When we receive the vaccine, our immune system goes through a process to recognize the specific antigens, or markers,  on the virus and produces antibodies to attack the specific antigens. Specialized memory cells remember this information and “patrol” your body in preparation for another attack from the virus, so if you happen to catch the virus, these cells help ensure you experience minimal to no symptoms. The advantage of weakening viruses for the vaccine is that you can generally ensure lifelong immunity. However, one limitation of this approach is that these vaccines usually cannot be given to people with a weaker immune system. 

A method to work around this issue would be to create a vaccine from a completely deactivated virus sample, meaning that the virus has zero ability to replicate. This is suitable for all immune systems because there is no possibility of contracting the disease which the virus causes, but the immune system will still recognize it and produce the necessary antibodies to fend off the virus. The only flaw to this process is that multiple doses of the vaccine would be required to achieve a lifelong immunity. Another option for individuals with weakened immune systems would be a vaccine created from just a portion of the virus. One specific protein on the virus would be used, so the patients’ bodies can create the antibodies necessary for protection but the virus is unable to replicate quickly enough to affect them. 

Most of the vaccines currently available for COVID-19 use a completely different method from the three listed above. These vaccines give the recipient the genetic code for part of the virus, and this type of vaccine can be achieved in three ways – mRNA, DNA, or vector virus vaccines. The Pfizer and Moderna vaccines use the first approach, mRNA. The vaccine contains mRNA that is the blueprint for the spike protein on the SARS-CoV-2 virus. Dendritic cells can use the blueprint to create the spike protein which the immune system realizes is foreign. The immune system can appropriately respond and generate immunologic memory, similar to how it would if we had directly used weakened or inactive virus in the vaccine. DNA vaccines deliver the genetic code from which mRNA is made. Then the process listed previously is executed within the body using the body’s own mRNA. The Johnson & Johnson vaccine uses this final method, the vector virus vaccine. In this approach, the gene that codes for the spike protein is put into a virus which lacks the ability to reproduce. However, the virus can still enter cells in a vaccinated person’s body and deliver the gene.

Conclusion

As discussed in this article, the road to arriving at a successful vaccine is neither short nor easy. Although this article may make the process sound simple, the reality is much more complicated and research/development can be shut down at any phase of testing if it is deemed harmful. However, researchers and scientists always manage to persevere and for good reason. Without their constant efforts and hard work, we may not have been able to start recovering from this pandemic as soon as we did. Thanks to them and all the medical professionals risking their lives on their front line treating our loved ones, returning to our normal, pre-pandemic lifestyle seems closer than ever.

References and Sources

Alison Caldwell, P. D. (2020, December 14). How are vaccines made? UChicago Medicine. https://www.uchicagomedicine.org/forefront/coronavirus-disease-covid-19/how-are-vaccines-made. 

Centers for Disease Control and Prevention. (2012, March 14). Basics of Vaccines. Centers for Disease Control and Prevention. https://www.cdc.gov/vaccines/vpd/vpd-vac-basics.html. 

How Vaccines Are Made ” GraceMed Health Clinic. GraceMed Health Clinic. (2021, February 25). https://gracemed.org/how-vaccines-are-made. 

How Vaccines Are Made: History of Vaccines. How Vaccines Are Made | History of Vaccines. (n.d.). https://www.historyofvaccines.org/content/how-vaccines-are-made. 

The Children’s Hospital of Philadelphia. (2014, November 19). How Are Vaccines Made? Children’s Hospital of Philadelphia. https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/how-are-vaccines-made. 

The Children’s Hospital of Philadelphia. (2014, November 20). Process of Vaccine Development. Children’s Hospital of Philadelphia. https://www.chop.edu/centers-programs/vaccine-education-center/making-vaccines/process-vaccine-development.