Information about the novel coronavirus (the virus that causes COVID-19) is constantly evolving. We will refresh our novel coronavirus content periodically based on newly published peer-reviewed findings to which we have access. For the most reliable and up-to-date information, please visit the CDC website or the WHO’s advice for the public.
COVID-19 vaccine development
With the emergence of the novel coronavirus (SARS-CoV-2), causing the global pandemic known as coronavirus disease 2019 (COVID-19), scientists worldwide have been working hard to develop a COVID-19 vaccine. According to the World Health Organization (WHO), there are 52 vaccine candidates currently in clinical trials (WHO, 2020).
- Thanks to Operation Warp Speed, the timeline for COVID-19 vaccine development has been compressed from years to months.
- Two vaccines (one made by Pfizer/BioNTech and one made by Moderna) have received Emergency Use Authorization from the FDA.
- Moderna reports their mRNA-1273 COVID-19 vaccine has a 94.5% efficacy rate in Phase 3 vaccine trials, with no serious safety concerns.
- Pfizer/BioNTech reports their COVID-19 vaccine candidate, BNT162b2, has a 95% efficacy rate in their Phase 3 trials, again with no significant safety concerns.
- AstraZeneca vaccine showed a 70% efficacy rate with no confirmed serious adverse events.
- One way these vaccines differ is in their storage requirements: Moderna’s vaccine can be stored in regular freezers, AstraZeneca’s in standard refrigerators and Pfizer’s vaccine needs to be kept at -70 degrees Celsius.
Creating a new vaccine (especially for a disease that is new to humans) usually takes years, on average, around ten years (Pronker, 2013). Why so long? The vaccine development process involves multiple phases: Phases 1, 2, and 3. Typically after many years in the laboratory, also called preclinical testing, the vaccine can advance to:
Phase 1, which evaluates the vaccine in a small group of people to determine the most appropriate dose and strength.
Phase 2 looks at a larger group, emphasizing how well the vaccine works (efficacy) and side effects (safety).
Before you can have large-scale manufacturing and distribution, the vaccine must go through phase 3 trials, which involve thousands of people for an extended period of time.
Once a vaccine or treatment is approved and marketed, it enters phase 4, which is a long-term evaluation of effectiveness and safety.
In light of this, the fact that we have several viable vaccine candidates for a disease that was unknown less than a year ago is extraordinary. Thanks to the collaboration between scientists and U.S. government agencies, this process is moving forward with unprecedented speed.
This collaborative program, fittingly called Operation Warp Speed (OWS), has pledged billions of dollars to develop, manufacture, and distribute 300 million doses of a safe and effective COVID-19 vaccine.
Researchers have compressed the timetable for the different phases, adopting the “pandemic paradigm,” allowing them to decrease the time from laboratory vaccine research to clinical trials from years down to weeks (Lurie, 2020).
How do the Moderna, Pfizer, and AstraZeneca vaccines work?
Of the 52 vaccine candidates, four are currently in phase 3 trials in the United States (NIH, 2020). Three of these potential vaccines for COVID-19 have recently published very encouraging data: BNT162b2 from Pfizer/BioNTech, mRNA-1273 from Moderna, and AZD1222 from AstraZeneca/Oxford University.
Before discussing how these vaccines work, let’s take a step back and look at the SARS-CoV-2 virus particles. Coronaviruses, like the SARS-CoV-2 virus, got their name because when you look at them under a microscope, they have an outer crown (or “corona”) of protein spikes.
These spikes are among the first things that the body encounters when the virus enters the body. When the body “sees” these spikes, it starts an immune response of developing antibodies against these foreign proteins.
However, this process takes time—which is why when you are first exposed to an infection, you may feel sick and experience symptoms.
Ideally, the second time your body encounters that same infection, you already have those antibodies in reserve, and they can recognize the invaders relatively quickly, allowing you to clear the infection without getting ill.
Vaccines work by exposing your immune system to a virus without causing a full infection. The goal is that if you were to come in contact with that pathogen in the future, your body would be ready to defend itself and fight off the invaders rapidly and with minimal or no symptoms.
There are different ways that vaccines can promote immunity; options include introducing live (but weakened) viruses, dead or inactive viruses, or even pieces of the virus into the body.
The Moderna (mRNA-1273) and Pfizer (BNT 162b2) coronavirus vaccine candidates are gene-based vaccines, specifically mRNA vaccines, a newer vaccine type. If you imagine your entire DNA genetic code as a comprehensive cookbook, then mRNA is a recipe for the particular dish you want to make copied out onto an index card.
Messenger RNA (or mRNA) is part of the genetic code that cells use to build proteins. The Moderna and Pfizer/BioNTech mRNA vaccines deliver the mRNA via nanoparticles that coat the mRNA, allowing it to get into your cells.
In the case of SARS-CoV2, specific pieces of mRNA code provide the blueprints for the spike proteins on the outer surface of the virus particles. The mRNA vaccines take this specific spike protein code and feed it to the protein factories in your cells the same way you would upload a plan to your 3D printer, creating the 3D structure you wanted.
The mRNA from the vaccine causes your cells to produce viral spike proteins within your cells. Since these are just the protein spikes and not the entire virus particle, you are not likely to feel sick or get an infection.
The AstraZeneca vaccine (AZD1222) is a viral vector vaccine rather than a gene-based vaccine like the two vaccines mentioned above. This vaccine uses a viral vector based on a weakened version of a common cold virus (adenovirus) that usually infects chimpanzees.
The virus has been modified so that it cannot grow and reproduce in humans. Scientists have put the genetic code for the coronavirus protein spikes into the vector. Once it gets into your body’s cells, it triggers the production of the SARS-CoV2 spike proteins (AstraZeneca, 2020).
Now that your immune system can see these foreign viral proteins (spike proteins), it can create antibodies against them. The next time you come in contact with the COVID-19 virus, your body is armed and ready to fight back!
Moderna vaccine (mRNA-1273)
The mRNA-1273 vaccine was created by the pharmaceutical company Moderna, in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Researchers recently announced the first interim analysis of the vaccine’s Phase 3 trial (also referred to as the COVE study) that began in July of 2020 (NIH, 2020). Moderna’s COVID-19 vaccine data shows a 94.5% efficacy rate (BW, 2020).
This efficacy rate reflects that the vaccine trial’s placebo arm had 90 cases of COVID-19, while the group treated with the mRNA-1273 vaccine only had 5 cases. The researchers identified 11 severe cases of COVID-19 (of the 95 total cases reported in the study), and all 11 severe cases occurred in the placebo group with none in the vaccine treatment group.
Efficacy in the vaccine trial was the same regardless of age, gender, race, or ethnicity demographics (BW, 2020).
The Data and Safety Monitoring Board (DSMB), a committee independent of the people running a clinical trial, analyzed the Phase 3 COVE study’s safety data. The committee found that the mRNA-1273 vaccine was well tolerated overall, and no serious safety concerns were noted.
Most of the side effects reported were mild, including pain or redness at the injection site, fatigue, muscle aches, joint pain, and headaches; all of these were generally short-lived (BW, 2020).
Researchers enrolled over 30,000 participants, 18 years or older; half received the mRNA-1273 vaccine, and the others got a saline injection. More than 7,000 were over the age of 65, and 5,000 were people younger than 65 but had chronic diseases that put them at a higher risk for severe COVID-19 (e.g., diabetes, obesity, heart disease, etc.).
In addition, approximately 37% of the people in the study represented people of color. Why does this matter? An accurate vaccine clinical trial needs to include a range of ages, races, risk groups, etc., to apply to the American population (BW, 2020).
Moderna’s COVID-19 vaccine series involves receiving two 100 microgram injections in a muscle (intramuscular, like the flu shot) approximately 28 days apart. Protection is achieved two weeks after the second dose (BW, 2020).
The mRNA-1273 vaccine can be stored in regular refrigerators for one month and ordinary freezers for six months (Callaway, 2020).
Pfizer vaccine (BNT162b2)
Pfizer and BioNTech created the BNT162b2 COVID-19 vaccine candidate; the companies have recently released their Phase 3 vaccine trial’s primary efficacy analysis. Researchers report that their vaccine has a 95% efficacy rate.
There were 170 cases of COVID-19 among the participants; 162 were in the placebo group, while only eight were reported in the vaccine group. Of the ten severe cases of COVID-19 among the participants, only one was found in the treatment group, with the other nine cases occurring in the placebo arm of the trial. Efficacy was the same regardless of age, gender, race, or ethnicity demographics (BW, 2020).
When this article was written, the DSMB had not looked at the safety data for the Phase 3 trial. However, preliminary data suggest that Pfizer’s vaccine is well tolerated, and any side effects experienced did not last long. The most “severe” adverse effects that occurred in more than 2% of people were headaches and fatigue. No serious safety concerns have been noted so far (BW, 2020).
The Phase 3 trial for BNT162b2 enrolled over 43,000 participants, with approximately half receiving the vaccine candidate and half the saline placebo injection. Around 30% of Americans participating in this trial have ethnically diverse backgrounds, and 45% are between 56–85 years of age.
The vaccine trial will continue to collect data for the next two years. Pfizer is also recruiting participants from other countries like Germany, Turkey, South Africa, Brazil, and Argentina (BW, 2020).
The Pfizer/BioNTech vaccine series involves receiving two 30-microgram injections in a muscle (intramuscular, like the flu shot) approximately 21 days apart. Protection is achieved one week after the second dose (BW, 2020).
The BNT162b2 vaccine candidate must be stored at the ultra-low temperature of -70 degrees Celsius. To this end, Pfizer has developed special shipping containers that use dry ice and can keep the vaccine at that temperature for up to 15 days (Pfizer, 2020).
AstraZeneca vaccine (AZD1222)
AstraZeneca, in collaboration with Oxford University, created the AZD1222 COVID-19 vaccine candidate. Preliminary results for Phase 3 trials in the United Kingdom and Brazil have been recently reported and are promising. Researchers report a 70% efficacy rate; however, the story is a bit more complicated. AstraZeneca looked at two different dosing regimens and noted differing efficacy rates for each.
One arm compared people who received a placebo saline injection with those who received a half dose of AZD1222 followed by the full dose four weeks later—this arm reported 90% vaccine efficacy. The other arm compared people who received two full doses of AZD1222 four weeks apart with the placebo group.
This dosing regimen reported a vaccine efficacy of 62%. Combining the analyses of the two arms gives an overall efficacy rate of 70% (AstraZeneca, 2020).
No serious adverse events have been confirmed at this time, and the AZD1222 candidate vaccine seems to be well tolerated in both dosing regimens.
The study participants’ specifics have not yet been released, but represent “diverse racial and geographic groups.” To date, over 12,000 participants from the U.K. and over 10,000 from Brazil have been enrolled. All are 18 years of age or older and are either healthy or have chronic medical conditions that put them at higher risk for developing severe COVID-19 infections.
AstraZeneca is also conducting clinical trials in the U.S., Japan, Russia, South Africa, Kenya, and Latin America, with plans to expand to other Asian and European nations (AstraZeneca, 2020).
The AZD1222 vaccine series involves receiving two injections. First, either a half-dose (~2.5 x1010 viral particles) or full-dose (~5×1010 viral particles) vaccine is given via intramuscular injection. This is then followed by a full-dose intramuscular injection one month later. The trials show protection from COVID-19 begins 14 days or more after receiving the second dose of the vaccine.
AZD1222 can be transported and stored in regular refrigerators (36-46 degrees Fahrenheit) for at least six months (AstraZeneca, 2020).
Here is a table summarizing the information (that we know so far) about the Moderna, Pfizer, and AstraZeneca vaccines.
|COVID-19 Vaccine Candidate (Company)||Type||Efficacy||Safety||Dosage||Protection||Storage|
|mRNA-1273 (Moderna)||mRNA-based||94.5%||Mild, short-lived effects including pain/redness at the injection site, fatigue, muscle aches, joint pain, and headaches||Two 100 mcg injections given 28 days apart||Protection achieved two weeks after the second shot||Stored in regular refrigerators for one month and ordinary freezers for six months|
|BNT162b2 (Pfizer/BioNTech)||mRNA-based||95%||Mild, short-lived effects including fatigue and headaches||Two 30 mcg injections given 21 days apart||Protection achieved one week after the second shot||Stored at ultra-low temperature of -70 degrees Celsius|
|AZD1222 (AstraZeneca)||virus-based||70%||No adverse events confirmed||Half-dose or full-dose injection followed by full-dose injection 28 days later||Protection achieved two weeks after the second shot||Stored and transported in regular refrigerators for up to six months
What are the next steps?
Both Pfizer/BioNTech and Moderna have received Emergency Use Authorization (EUA) for their vaccines from the U.S. Food and Drug Administration (FDA) (FDA, 2020).
AstraZeneca is planning on asking the WHO for an emergency use listing to pursue an accelerated pathway to make the vaccine available in low-income countries; it is still waiting on the data from U.S. trials before it can apply for EUA from the FDA (AstraZeneca, 2020). ]
Emergency Use Authorization is not the same as FDA approval. It is a way that the FDA can allow unapproved medical products or unapproved uses of medical products, in emergency situations, like the current COVID-19 pandemic.
The FDA looks at the risks and benefits of the data available and decides whether or not to give EUA—in emergencies, there is often not enough time to collect all of the necessary information needed for full FDA approval (FDA, 2020).
EUA allows manufacturers and healthcare providers to start providing the treatment to specific groups of people. Dr. Stephen M. Hahn, Commissioner of Food and Drugs at the FDA, spoke to the US Senate Health Committee on September 30th, 2020. “We are committed to expediting the development of COVID-19 vaccines, but not at the expense of sound science and decision making. We will not jeopardize the public’s trust in our science-based, independent review of these or any vaccines. There’s too much at stake.” (FDA, 2020)
More research on these vaccines is needed, and all of these companies will continue to collect data from these and future trials. This data also needs to be published and peer-review for a complete analysis.
Many questions remain—for instance, scientists don’t know how long any of these vaccines protect you against COVID-19. People will still need to wear face masks and practice social distancing until told otherwise despite getting vaccinated.
When can you get a COVID-19 vaccine?
In the United States, the first doses of Pfizer’s vaccine were administered on Monday, Dec. 14th, 2020 to healthcare workers in New York and since then, other states have also begun distributing the vaccine.
However, this does not mean that you will be able to get a COVID-19 vaccine anytime soon, as there won’t likely be enough doses to vaccinate everyone, especially at first. The Operation Warp Speed team is working with scientists and healthcare professionals to prioritize who should get the vaccines first until enough can be made to give it to everyone (CDC, 2020).
Based on current company projections, Moderna plans to have approximately 20 million doses of mRNA-1273 ready to ship in the U.S. and is on track to manufacture 500 million to 1 billion doses in 2021 (BW, 2020). Likewise, Pfizer announced their goal of producing up to 1.3 billion doses in 2021 (BW, 2020). AstraZeneca is working towards manufacturing 3 billion doses of the vaccine in 2021, pending regulatory approval (AstraZeneca, 2020).
The Phase 3 trials of these vaccine candidates are very encouraging. In August of 2020, Dr. Anthony Fauci, chief of the National Institute of Health and Infectious Diseases, said that he would like a COVID-19 vaccine to have an effectiveness of “75% or more” (NPR, 2020). In light of two vaccine candidates having over 94% efficacy rates, Dr. Fauci has said that these developments are crucial for “trying to stop this outbreak” (NPR, 2020).
These three coronavirus vaccines are not the only options out there, and the vaccine race is by no means over. Other companies like Johnson & Johnson also have Phase 3 vaccine trials underway, and other trials are ongoing globally (NIH, 2020). Also, other vaccines have already been approved and distributed outside the US. The critical thing to remember is that this information is new and continually changing.
These vaccine trials have not yet been published in the medical literature and have not had their data subjected to peer review. As more people get vaccines and more time elapses, scientists will gather more data and hopefully be able to answer more questions.
While COVID-19 fatigue is a real thing, everyone must remain vigilant. Wear your face masks and practice social distancing. Vaccines are a light at the end of the tunnel, but we may still have a ways to go.