FDA Approved Vaccines for COVID-19

 
 FDA Approved Vaccines for COVID-19

This article provides detailed information about COVID-19 vaccines that are approved for use in the United States by the U.S. Food and Drug Administration (FDA) and will be updated as new approvals occur.

Vaccines are designed to protect us from being infected by pathogens, which are bacteria, viruses, toxins, fungi, parasites, or other microbes. The goal of vaccination is to present the immune system with some part of a pathogen, so that our immune cells will respond and eventually make memory cells. Those memory cells will provide protection if the person is exposed to the actual, active pathogen later in life (see Immunology Basics for more information). 

The trick for making vaccines is to be sure that the vaccine itself does not actually cause illness in the person who is vaccinated. Scientists design a vaccine that is just enough like the active pathogen to prompt the immune system to make protective memory cells without actually causing disease. Over the years, there have been many ideas of how to do this. These different ideas, or approaches, are called vaccine platforms. The different platforms are described in Vaccine Basics

Understanding SARS-CoV-2

To understand the specifics of approved COVID-19 vaccines, it is important to understand how active SARS-CoV-2, the virus that causes COVID-19, infects cells. Under a very powerful microscope, an active SARS-CoV-2 virus looks like a ball covered with spikes. These spikes are actually made of protein. The SARS-CoV-2 virus uses its spike protein to attach to the outside of a healthy human cell. Once attached, the virus is taken inside the cell. It forces the infected cell to make thousands of copies of SARS-CoV-2 viruses. These are then released from the cell to go infect other healthy cells. Therefore, the spike protein is a very important part of the way SARS-CoV-2 infects human cells. If the immune system makes antibodies that stick to the spike protein on active SARS-CoV-2, then the virus can no longer attach to cells and infect them. This is a key strategy for two FDA approved vaccines: one made by Pfizer-BioNTech and one made by Moderna. 

The Nuts and Bolts of Approved Messenger RNA Vaccines

On December 11, 2020, the FDA approved the use of the Pfizer-BioNTech COVID-19 Vaccine under an Emergency Use Authorization in individuals 16 years of age and older. One week later, on December 18, 2020, the FDA approved the use of the Moderna COVID-19 Vaccine under an Emergency Use Authorization in individuals 18 years of age and older. The platform that these vaccines use is a messenger RNA platform, which has been under study for at least 15 years. These vaccines do not contain any whole coronavirus or parts of coronavirus; therefore, it is impossible for these vaccines to cause a person to get COVID-19. 

If the vaccines do not contain any virus or parts of virus, how do they work to cause an immune reaction? Each vaccine contains snippets of genetic information. These bits of genetic information are called messenger RNA (mRNA). The mRNA holds a code which tells cells how to make just one thing – the spike protein from SARS-CoV-2 virus. Because it is fragile, the mRNA is carefully packed into tiny spheres made of lipid (fat) molecules so that the genetic material does not fall apart during transport and injection. The lipid coating is like the colorful shell on the outside of chocolate candies that protects the inside from melting or falling apart. An added benefit of the lipid coating is that it can prompt the innate immune system to react strongly (see Immunology Basics for more information). 

During vaccination, the lipid spheres with the mRNA inside are injected into a person’s arm. Inside the body, the lipid coating helps the spheres attach to healthy human cells. Once attached, the mRNA is taken inside the cells. The cells have a standard mechanism for reading genetic codes and making proteins from the code, because that is how our own genetic code system works. The human cells read the mRNA code for the SARS-CoV-2 spike proteins and then use the code to make spike proteins. The cells then display the spike proteins on their outer surfaces. These spike proteins are not infectious because they are only one part of the virus, not a whole virus. The spike proteins cannot cause COVID-19.

Other immune cells in the area recognize that the spike proteins are “not self” and sound the alarm that a pathogen must have invaded. It is a false alarm—no virus is present—but the immune system does not know that. Immune cells respond rapidly, just as if there were a real infection. The immune system will make many, many antibodies and will eventually make memory cells within weeks of receiving both doses of these vaccines. 

If a vaccinated person is exposed to active SARS-CoV-2 in the future, the immune system will recognize the spike proteins, and the memory cells will immediately ramp up to defend against infection. Both vaccines have an effectiveness rate of 94% to 95%. This means that, in the phase 3 studies, there was a 94% to 95% reduction in the number of cases of COVID-19 with symptoms in the vaccinated group compared to the number of cases in the placebo (salt water injection only) group. 

Both vaccines may cause some temporary side effects in some people, which in phase 3 trials included sore arm, headache, fever, chills, and body aches. These were usually mild or moderate, lasting one to two days (see more information below in Phase 3 Data). This does not mean the vaccine “caused COVID-19”. When the immune system ramps up and reacts to the spike proteins, the body briefly acts like it has an active infection even though no active infection is happening. That is the cause of the side effects. 

Phase 3 Trial Data for the Pfizer-BioNTech COVID-19 Vaccine

In the phase 3 trial, the researchers investigated the safety and efficacy of two 30-μg doses of the COVID-19 vaccine given 21 days apart, as compared with placebo injections (salt water). Participants in the trial were recruited from 152 sites worldwide: the United States (130 sites); Argentina (1 site); Brazil (2 sites); South Africa (4 sites); Germany (6 sites); and Turkey (9 sites). Adults 16 years of age or older could enroll in the study. People who already had COVID-19 disease were not included in the trial. In addition, people who were undergoing immunosuppressive therapy or who had an immunocompromising condition were not included in the trial.

A total of 21,720 participants received the vaccine and 21,728 received placebo. The median age was 52 years. The youngest participants were 16 years old and the oldest was 91 years old. The gender breakdown was 50.6% male and 49.4% female. The racial/ethnic breakdown was: 82.9% white; 28.0% Hispanic/Latino/Latina; 9.3% Black/African-American; 4.3% Asian; 0.5% Native American or Alaskan Native; 0.2% Native Hawaiian or Pacific Islander; 2.3% multiracial; and 0.6% did not report. About 35% of the participants were obese (had a body mass index of at least 30). About 21% of the participants had at least one chronic condition. The most common chronic medical conditions in the study population were chronic pulmonary disease (7.8%), uncomplicated diabetes (7.8%), any type of cancer/malignancy (3.7%), cerebrovascular disease (1.0%) and history of heart attack (1.0%). Other chronic conditions were present in less than 1% each, including HIV positive status, heart failure, liver disease, rheumatic disease, peptic ulcer, and kidney disease. 

The definition for a “confirmed COVID-19 case” that the investigators used in this study was the presence of at least one COVID-19 symptom combined with a positive SARS-COV-2 test by polymerase chain reaction (PCR, also called a “molecular test”). 

The vaccine was very effective in this study. In the vaccine group, there were 9 cases of confirmed COVID-19 disease that happened 7 days or later after the second dose of vaccine. In the placebo group, there were 169 cases of confirmed COVID-19 disease that happened 7 days or later after the second “dose” of placebo. This corresponds to 94.6% vaccine efficacy. The authors looked at the vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition as well. The efficacy rate was between 89.3% and 100% for these various subgroups. 

Between the first dose and the second dose, 39 cases of confirmed COVID-19 disease were seen in the vaccine group and 82 cases in the placebo group, for a vaccine efficacy of 52% during the time between the two doses. 

The researchers also looked at severe COVID-19 disease. Four participants had severe COVID-19 disease at least 7 days after the second injection. One was in the vaccine group and three were in the placebo group. The person in the vaccine group with severe disease did not need to be hospitalized but had an oxygen saturation of 93% on room air. The three placebo recipients who had severe COVID-19 disease met the severe case definition for the following reasons: one had an oxygen saturation of 92% on room air, one was hospitalized with bilateral pneumonia, and one had an oxygen saturation of 92% and was admitted to the ICU admission for heart block. 

There were some side effects in the study, as is commonly seen with vaccines. The side effects were more common after the first injection rather than the second injection. They were also more common in younger participants (16 years to 55 years) than in older participants (over 55 years). 

The information below about pain, redness, and swelling is about the first injection in younger participants (16 years to 55 years) because that is when the highest number of side effects happened. The most common side effect was pain at the injection site in the arm, which 83% of the vaccine group and 14% of the placebo group reported. The pain was generally mild to moderate and lasted 1-2 days. Only 1% of the vaccine group reported the pain as severe. Redness at the injection site was reported by 4.7% of the vaccine group and 1.1% of the placebo group. Swelling at the injection site was reported by 5.8% of the vaccine group and 0.5% of the placebo group. 

Other side effects were fever, chills, headache, fatigue and body aches. These were more common after the second injection, rather than the first, and were more common in younger participants than in older participants. These effects usually lasted 1 to 2 days and were managed with over-the-counter pain relievers/fever reducers. The information below is about these side effects after the second injection in younger participants: fever (15.8% of the vaccine group and 0.5% of the placebo group); fatigue (59.4% and 22.8%); headache (51.7% and 24.1%); chills (35.1% and 3.8%); muscle pain (37.3% and 8.2%); diarrhea (10.4% and 8.4%) and vomiting (1.9% and 1.2%). 

There were two serious adverse events in the vaccine group that the FDA considered may have been related to the vaccine: a shoulder injury possibly related to vaccine administration or to the vaccine itself and a case of severely swollen glands in the armpit. There were four cases of Bell’s palsy (facial paralysis) in the vaccine group and none in the placebo group. These symptoms have all resolved. It is unclear if these cases are related to the vaccine, because Bell’s palsy occurs in the general population at about the same rate. The FDA will be monitoring this reaction carefully. 

Studies are ongoing to determine if people who have been vaccinated can still carry SARS-CoV-2 and give it to others, even if they do not develop any symptoms. The answer to this question is not yet known. It is also not known how long protection from COVID-19 disease will last after vaccination. 

Phase 3 Trial Data for the Moderna COVID-19 Vaccine

In this phase 3 trial, the safety and efficacy of the Moderna COVID-19 vaccine administered in two 100 µg doses 28 days apart was compared with placebo injection (salt water) in adults 18 years of age and older. The study took place in 99 sites in the United States. 

A total of 15,181 participants received the vaccine, and 15,170 received the placebo. The gender breakdown was 47.4% female and 52.6% male. The median age was 53 years, with the youngest participant being 18 years old and the oldest being 95 years old. The racial/ethnic breakdown was 79.4% white; 20.0% Hispanic/Latino/Latina; 9.7% Black/African-American; 4.7% Asian; 0.8% Native American or Alaskan Native; 0.2% Native Hawaiian or Pacific Islander; and 2.1% were multiracial or did not report. A majority of the participants (82%) were considered at occupational risk for SARS-CoV-2 exposure, and 25.4% of participants were healthcare workers. A high-risk chronic condition for severe COVID-19 was present in 22.3% of participants, and 4% of participants had two or more high-risk conditions. The high-risk conditions included diabetes (9.4% of the study population), obesity with a body mass index of 40 or higher (6.5%), significant cardiac disease (4.9%), chronic lung disease (4.8%), HIV positive status (0.6%), and liver disease (0.6%). 

The definition for a “confirmed COVID-19 case” that the investigators used in this study was the presence of at least one respiratory COVID-19 symptom OR two system-wide symptoms (fever, chills, body aches, etc.) combined with a positive SARS-COV-2 test by PCR (“molecular test”). 

The vaccine was very effective for the prevention of symptomatic COVID-19 disease in this study. In the vaccine group, there were 11 cases of confirmed COVID-19 disease that happened 14 days or later after the second dose of vaccine. In the placebo group, there were 185 cases of confirmed COVID-19 disease that happened 14 days or later after the second “dose” of placebo. This corresponds to 94.1% vaccine efficacy. The authors looked at the vaccine efficacy among subgroups defined by age, sex, race and ethnicity, and presence of one or more risk factors for severe COVID-19. The efficacy rate was between 86.4% and 100% for these various subgroups.

The researchers also looked at severe COVID-19 disease. Thirty participants had severe COVID-19 disease at least 14 days after the second injection. All of these were in the placebo group. Nine of the severe cases required the participant to be hospitalized. One participant with severe COVID-19 died of the disease (a 54-year-old with diabetes). 

As with the Pfizer-BioNTech vaccine study, there were side effects in this study as well. The side effects were more common after the second injection. They were also more common in younger participants (18 years to 64 years) than in older participants (64 years and over). 

The information below about pain, redness, and swelling is about the second injection in younger participants, because that is when the highest number of side effects happened. The most common side effect reported was pain at the injection site in the arm, by 90.1% of the vaccine group and 18.8% of the placebo group. The pain was generally mild to moderate and lasted 1-2 days, although 4.6% of the vaccine group and 0.2% of the placebo group reported the pain as severe. Redness at the injection site was reported by 9.0% of the vaccine group and 0.4% of the placebo group. Swelling at the injection site was reported by 12.6% of the vaccine group and 0.3% of the placebo group. Swollen glands in the armpit of the injection arm were reported by 16.0% of the vaccine group and 4.3% of the placebo group. 

Other side effects were fever, chills, headache, fatigue and body aches. These were more common after the second injection, rather than the first, and were more common in younger participants than in older participants. These effects usually lasted 1 to 2 days and were managed with over-the-counter pain relievers/fever reducers. The information below is about these side effects after the second injection in younger participants: fever (17.4% of the vaccine group and 0.4% of the placebo group); fatigue (67.6% and 24.5%); headache (62.8% and 25.4%); chills (48.3% and 5.9%); joint pain (45.2% and 10.5%); nausea/vomiting (21.3% and 7.3%). 

There were three serious adverse events that the FDA considers may be related to the vaccine: 1 case of severe vomiting and 2 cases of severe facial swelling. These all resolved with supportive treatment. There were 3 cases of Bell’s palsy (facial paralysis) in the vaccine group and 1 in the placebo group. It is unclear if these were related to the vaccine or not, because all four patients had predisposing factors, and Bell’s palsy occurs in the general population at a similar rate. Three of the 4 cases resolved, and 1 is improving. The FDA recommends continued surveillance for this side effect.

As with the Pfizer-BioNTech vaccine, studies are ongoing to determine if people who have been vaccinated with the Moderna vaccine can still carry SARS-CoV-2 and give it to others, even if they do not develop any symptoms. The answer to this question is not yet known. It is also not known how long protection from COVID-19 disease will last after vaccination.

— Jillian Lokere and Aliaa Barakat 

References

  1. FDA Briefing Document. Pfizer-BioNTech COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting, December 10, 2020.
  2. FDA Briefing Document. Moderna COVID-19 Vaccine. Vaccines and Related Biological Products Advisory Committee Meeting, December 17,2020.
  3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 VaccineN Engl J Med. 2020 Dec 10.