VACCINE RESOURCE COMMITTEE
of the Edmonton Zone Medical Staff Association
View Full List of Vaccine Questions Here
COVID-19 Vaccine Question #6:
How was the COVID mRNA vaccine researched and approved?
As with any vaccine approval, Health Canada experts reviewed data from the required clinical trials and approved vaccines meeting safety standards, effectively reducing risk of disease, and meeting manufacturing standards. Vaccination guidelines assess the benefit of vaccination in the context of risks of disease and adverse events. There continues to be ongoing safety monitoring after release.
The COVID-19 mRNA vaccines were developed with National Institute of Health support and research, to create a protective antibody response to a protein found on the SARS-CoV-2 virus. Clinical trials for the COVID-19 vaccines in people were established and completed in what seemed like record time compared to other vaccines, but in reality, the science was well underway before the pandemic - more than 50 years of public and private laboratory research laid the groundwork for the development of these life-saving vaccines. In addition, many vaccine trials need a long time to recruit and follow participants because the disease being prevented is so uncommon, it may take years to count enough cases to show if the vaccine makes a difference (for example the zoster vaccine trial). However, the COVID-19 pandemic was so aggressive that it did not take long for there to be a statistically appropriate number of cases in trial participants.
The science of pandemic vaccines - timeline
1961-1990
Scientists discover that mRNA is produced in cells and that it carries “instructions” to make proteins in cells. They start to study its use in medicine.
1987-2000s
Development of rapid response capability and work on designed vaccines: The NIH launched the HIV/AIDS Clinical Trials Networks whose flexibility and rapid-response design of these networks acted as a framework for rapid future responses. In this time work was done at NIH on NIH scientists lay the foundation for structure-based vaccine design .by finding that the structure of a protein on the surface of the human immunodeficiency virus allows it to enter human cells.
2005
A laboratory breakthrough shows that modified mRNA can safely deliver instructions to cells without over-activating the body’s immune system.
2005 to 2016
Lipid nanoparticles are used to deliver mRNA vaccines against influenza, and certain types of cancer. Using lipid envelopes to ds as envelopes to deliver information to the cells of the body has been researched since 1978, and liposomes and lipids have been used to deliver licensed medications since 1995.
2013
NIH scientists discover the structure of virus proteins that let viruses invade cells. This finding leads scientists to create the first stabilized proteins for use in vaccines that provoke a strong immune response to viruses such as RSV, a major cause of severe disease in infants and older adults.
2014 to 2018
Streamlined International vaccination response developed: NIH’s response to the Ebola epidemic in the Democratic Republic of Congo helps establish pathways to streamline and speed up regulatory review and emergency use of investigational treatments during critical disease outbreaks.
2016
Scientists are able to research coronavirus immunity by using a stabilized coronavirus “spike protein” from the coronavirus HKU1, a form of the common cold.
Scientists from NIH and the pharmaceutical company Moderna collaborate on a general vaccine design that uses viral mRNA. This design is chosen to allow rapid development of vaccines against emerging viruses such as Nipah virus and the Middle East respiratory syndrome (MERS) coronavirus (a relative of SARS-CoV-2).
2017
NIH scientists stabilize the spike protein that MERS uses to invade cells to study MERS immunity. A study of a Zika virus DNA-based vaccine shows that nucleic acid (gene-based) vaccines - which use DNA or mRNA, are safe and effective, paving the way for development of mRNA vaccines.
2018
Pfizer and BioNTech begin a research collaboration to develop an mRNA based influenza vaccine.
2019
NIH and Moderna scientists map out Phase 1 clinical trials to test the safety of mRNA vaccines for Nipah virus.; the trials began in 2022.
In late 2019, an aggressive respiratory illness outbreak is noted in Wuhan, China.
2020
January 10, 2020: full virus genome sequences from SARS-CoV-2 were released by the Chinese[1] [2] CDC, and work began on switching mRNA vaccines in development to target COVID-19, by teams at both Pfizer and Moderna.
February 7, 2020 the first batch of the Moderna vaccine prepared and ready for initial testing.
March 11, 2020
The World Health Organization (WHO) declares COVID-19 a pandemic.
March 16, 2020
NIH clinical trials for the Moderna mRNA vaccine begin.
April 17, 2020
NIH launches Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), a first-of-its-kind public-private partnership for developing COVID-19 treatments and vaccines.
May 15, 2020
Operation Warp Speed launches to coordinate federal government efforts that speed up processes forthe approval and production of reliable COVID-19 diagnostics, vaccines, and treatments without administrative lags. This included starting Phase 2 trials when enough promising results were received from phase 1, and starting Phase 3 trials with the initial results of phase 2 - however, each phase finished it’s full length, and adjustments to trials were built in to account for changes such as identifying the need for a higher or lower dose. It also allowed for manufacturing processes to begin in case the phase three trials were successful so vaccines could be ready[3] as soon as possible if shown to be effective. This was an investment by governments for an opportunity to save more lives.
May 2020
Pfizer Phase I-II trial launched (at this point, there were 5 million cases and 150,000 deaths globally.
July 8, 2020
NIH launches the COVID-19 Prevention Network (CoVPN), which uses the existing structure of NIH clinical trial networks to support trials of COVID-19 vaccines and other prevention tools.
July-August 2020
Both Moderna and Pfizer vaccines, with excellent phase 1 and 2 trial data, start phase 3 trials of efficacy and safety. Pfizer Phase III study enrolls 43,448 volunteers, Moderna phase III study enrolls 30,240 volunteers
November 2020
Pfizer phase III trial concluded - showed 95% efficacy against infection.
Phase 3 clinical trial of the Moderna mRNA vaccine announces preliminary efficacy of 94%
December 11, 2020
The FDA grants an emergency use authorization (EUA) to the Pfizer-BioNTech mRNA vaccine for people age 16 and older.
December 18, 2020
The FDA grants an EUA to the Moderna mRNA vaccine for people age 18 and older.
August 23, 2021
The FDA grants full approval to the Pfizer-BioNTech mRNA vaccine for people age 16 and older.
October 29, 2021
The FDA grants an EUA to the Pfizer-BioNTech mRNA vaccine for children age 5 to 11.
January 31, 2022
The FDA grants full approval to the Moderna mRNA vaccine for people age 18 and older.
March 14, 2022
NIH launches Phase 1 clinical trials for three mRNA HIV vaccines. These vaccines apply lessons learned from the development of mRNA vaccines for COVID-19.
March 2022
Data show that the U.S. COVID-19 vaccination program is estimated to have prevented 2 million deaths, 17 million hospitalizations, and 66 million infections through March 2022. Vaccination is also estimated to have saved nearly $900 billion in health-care costs.
June 17, 2022
The FDA grants an EUA to the Pfizer-BioNTech and Moderna mRNA vaccines for children age 6 months or older.
July 11, 2022
NIH launches a Phase 1 clinical trial for an mRNA Nipah virus vaccine.
August 31, 2022
The FDA grants an EUA of the Moderna and Pfizer-BioNTech COVID-19 vaccines to authorize bivalent formulations for use as a booster dose. These updated boosters contain mRNA components for both the original strain of SARS-CoV-2 and its Omicron variant.
December 8, 2022
The FDA grants an EUA to the Pfizer-BioNTech and Moderna bivalent COVID-19 vaccines for children age 6 months or older.
The key points in this triumph of research and science include:
There was extensive previous work on lipid-based drug and vaccine delivery and on stabilizing mRNA for use as vaccines, and with specific work on mRNA vaccine against other coronaviruses
The researchers and pharmaceutical companies started developing processes to make the vaccine in large amounts at the SAME time as researching the specific vaccine formulations, so there was enough vaccine to do large trials quickly.
This included developing ways to make the key lipids in large amounts, methods to scale up lipid nanoparticle mRNA vaccine production with collaborating manufacterurers, through to developing supply chains and shipping boxes that track temperature to assure vaccines are not damaged in transit. All of this was done IN CASE they had a good vaccine candidate after phase 1 and 2 trials.
The lab-based vaccine formulation development, animal testing and early human testing to determine the best dose, early safety, and antibody responses was streamlined so there were no gaps in assessing data, and the next phases were planned while the current phase was still going.
Vaccine trials are predesigned - the number of participants to be randomized and number of disease cases to be counted are set in advance to be able to assess whether the vaccine works (by comparing the number of cases in vaccinated and unvaccinated cases after the number of cases is reached). The aggressiveness of COVID-19 spread meant that this number of documented cases in the trial was met very quickly (other modern vaccines have taken years of follow-up to see enough cases of the disease in the trial to determine efficacy).
Sources:
National Institute of Allergy and Infectious Diseases-Decades in the Making: mRNA COVID-19 Vaccines
The Lancet: Microbe: First shared SARS-CoV-2 genome: GISAID vs virological.org
Human Vaccines & Immunotherapeutics: A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson &Johnson
CBC Lite: How scientists aim to make a safe COVID-19 vaccine in record time