COVID-19 VACCINE DEVELOPMENT
This review is designed to provide an overview of the science behind the development of the vaccines used to prevent or minimize illness associated with the SARS-Co-V-2 virus that causes COVID-19. Links to sources for this article, and information about current treatment methods including monoclonal antibodies, are provided at the end.
About the SARS-Co-V-2 Virus
This virus is a “novel” virus – that means it is new and different from other viruses. As a result, learning about the virus, and its behavior, is a work in progress. Recommendations are subject to change as new information is learned about the virus through scientific research and study. This is exactly how science works – the scientific method involves observing an event, analyzing it in a controlled setting such as a lab or research trial, testing theories in those controlled settings under safety protocols, discarding theories and solutions that do not “work” and continuing to test new theories as new ideas, truths and data emerge. As scientific study continues, experts’ understanding is modified to reflect new information. It can be frustrating to have guidelines change, especially when following the guidelines is critically important to solving a problem, but it is also critically important to adopt guidelines that are scientifically proven to be effective.
History of Coronavirus Vaccine Development
SARS-Co-V-2 is not the first coronavirus known to science. Different types of coronaviruses cause different types of illness, almost all of which affect the respiratory system. Other coronaviruses may result in the common cold or flu-like symptoms – these viruses were identified as early as 1960.
In 2002, SARS-CoV and in 2012, MERS-CoV appeared; both were “novel” at the time, and both caused severe respiratory disease and death. These coronaviruses are relatives of SARS-CoV-2 that causes COVID-19. A small group of physicians and scientists has studied these coronaviruses since 2002 and identified the “spike protein” in the viruses they had been studying. This early work on the spike protein was key in developing current COVID-19 vaccines. In particular, it gave vaccine developers insight into how the human immune system reacts to the coronavirus and its spike protein mechanism, to then produce the antibodies needed to limit infection, illness and death.
Since the discovery of DNA structure in 1953, scientists have learned to rapidly identify the genetic sequence of living organisms. In late 2019 and early 2020, as people developed a virus with respiratory symptoms that seemed similar to SARS and MERS, scientists started studying specimens from people with that illness to try to identify its cause. Researchers used DNA technology to determine that this was a new ‘novel’ virus and identify its unique genetic code so they could share that code with others doctors and scientists around the globe, who were trying to find a cure for deadly COVID-19.
Due to the pandemic nature of COVID-19, scientists, and governments, including the U.S., prioritized vaccine development while still searching for a cure to COVID-19. By making vaccine development a priority, funding from governments, philanthropic organizations, and drug companies allowed for simultaneous multiple trials of different types of vaccines, as well as support for more rapid manufacturing of the vaccine so that doses would be ready IF the vaccine was shown to be effective. Regulatory agencies, like the CDC and FDA, gave priority to evaluating the results of clinical trials of the COVID-19 vaccine.
The Clinical Trial Process Required for Vaccine Approval
Clinical trials for COVID-19 vaccines began in March of 2020, with the approval of Institutional Review Boards (IRB) which are responsible for making sure clinical trials are conducted ethically and safely and protect the rights and welfare of the study participants. In advance of the clinical trials, COVID-19 study participants received information about the trial and their rights as participants, including the right to withdraw from the study at any time. Participants in each trial were treated according to a specific protocol for that study. How and when the study product was administered on such studies is always strictly regulated, as are laboratory testing, physical exams, and patient interviews. This approach is designed to ensure that the reported results are accurate and true; and, importantly, to minimize risk to study participants. For example, testing for antibodies against COVID-19 was done at the same times and in the same manner for everyone in a particular study. Asking each participant at regular time intervals whether they have experienced any side effects or possible symptoms of COVID-19 is built into the study to support patient safety as well as an accurate study report. Any side effects and whether the participant became ill with COVID-19 are closely tracked on such trials and reported to the FDA. The research team usually continues to monitor study participants for longer periods of time even after making an application to the FDA to get authorization for use of the vaccine, typically for about two years.
COVID-19 vaccine clinical trials covered two different types of vaccines: “viral vector” (in the case of Johnson & Johnson and Astra-Zeneca) and nucleic-acid mRNA (in the case of Pfizer and Moderna). The trials followed a formal three-phase process for vaccine study, authorization, and approval. In Phase 1, vaccine experts determine what constitutes a safe dose for the vaccine. Phase 2 measures how well the vaccine produces an immune response, as measured by the presence of specific antibodies for the virus. Sometimes Phase 1 and Phase 2 can be combined. Once a vaccine has been shown to be safe and effective in producing an immune response, Phase 3 trials begin. Phase 3 trials typically enroll thousands of study participants. In the case of the original authorizations for use of COVID-19 vaccines in the U.S., over 30,000 participants were enrolled in each trial. At this point (Phase 3) of the clinical trials neither study participants nor the researcher knew if they received the active vaccine or a placebo. This type of “blind” study prevents bias in the reporting of results. If Phase 3 results show that a vaccine is safe and effective, the manufacturer applies to the FDA for approval.
Once a vaccine is approved, fully or with Emergency Use Authorization (EUA), Phase 4 study begins. In this phase the pharmaceutical manufacturer and the FDA continue to monitor for effectiveness and safety, watching closely for any new adverse side effects that may appear in more widespread use. Occasionally, an adverse side effect develops in the wider population and the use of the vaccine is paused to allow the medical community to investigate and determine if the adverse event is a direct or indirect result of the vaccine or is a rare event that occurs only in a small fraction of the population.
Researchers and the pharmaceutical manufacturers followed this rigorous multi-phase process to get to Emergency Use Authorization for the COVID-19 vaccines. Because research on CoV viruses and how spike proteins work in the immune system had been underway for decades, scientists were able to focus quickly on identifying the SARS-Co-V-2 virus genetic code and creating a vaccine that produced the right antibodies to fight that infection. This was not a rushed process. No corners were cut and no steps eliminated.
Further Research on COVID-19 Vaccine Effectiveness Against Variants
Research on the continued effectiveness of the available COVID-19 vaccines continues as variants emerge. Research published by the CDC (September 17, 2021) shows that after delta became the most common variant, those who were vaccinated were 5 times less likely to become infected, and more than 10 times less likely to be hospitalized or to die from COVID-19 (compared to unvaccinated).
For answers to Frequently Asked Questions about COVID-19 vaccines, go to https://www.cityofportsmouth.com/city-manager/vaccination-faqs
Treatments such as monoclonal antibodies, are not substitutes for vaccination. For information about treatments for COVID-19, visit: COVID-19 Treatment FAQs | City of Portsmouth.
Badgujar, Badgujar, and Badgudar. Vaccine development against coronavirus (2003 to present): An overview, recent advances, current scenario, opportunities, and challenges. Diabetes Metab Syndr, 2020 September-October; 14(5): 1361-1376.
Peter Hotez, MD, PhD, on his 10 years of work on coronavirus. AMA Public Health, February 15, 2021.
Ball, P. The lightning-fast quest for COVID vaccines – and what it means for other diseases. Nature, 2021, : 16-18
World Health Organization: How are vaccines developed? 8 December 2020
Scobie HM, Johnson AG, Suthar AB, et al. Monitoring Incidence of COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Status — 13 U.S. Jurisdictions, April 4–July 17, 2021. (ePub: 10 September 2021)