The Pfizer-BioNTech vaccine

Clinical trials of the Pfizer-BioNTech vaccine have found that it is generally safe. Local side effects (at the injection site) included pain, swelling and redness. Local and systemic side effects (including fever, fatigue, headache, joint pain and muscle pain) were usually mild to moderate and temporary. The vaccine was 95% effective at reducing the risk of developing COVID-19 after two injections were given.

How the vaccine works

The Pfizer-BioNTech vaccine contains a piece of microscopic messenger RNA enclosed with fatty molecules. Messenger RNA (mRNA) is a form of genetic information that contains instructions for making copies of a key protein used by SARS-CoV-2, the virus that causes COVID-19. As mRNA contains only instructions for making a piece of the virus, and not the whole virus, the vaccine cannot cause infection with SARS-CoV-2 or COVID-19. Furthermore, the mRNA in the vaccine is taken up by cells and is “read” by cellular machinery called ribosomes. The function of this cellular machinery is to make the proteins encoded by mRNA. The mRNA does not become part of a person’s genetic material (DNA) and is eventually broken down. Therefore, the vaccine does not alter a person’s genes.

As the ribosomes churn out copies of the viral proteins, these proteins move to the surface of a cell and are released into circulation. Once the viral proteins are in circulation, cells of the immune system capture them and take them back to lymph nodes and lymphoid tissues, where they educate the rest of the immune system about SARS-CoV-2. The immune system makes many copies of cells that learn to attack these proteins. These cells circulate and some remain in lymph nodes and lymphoid tissues. When the body encounters SARS-CoV-2, these cells make millions of copies of themselves and the immune response against the virus becomes amplified.

Study details

The phase II/III clinical trials that Pfizer-BioNTech used to collect data that was submitted for regulatory approval enrolled 43,651 people. Participants were randomly assigned to receive one of the following interventions:

• an intramuscular injection (into the upper arm) of the vaccine on day one, followed by another injection 21 days later
• an intramuscular injection of placebo on day one, followed by another injection 21 days later

People who initially received the vaccine were also given the vaccine on their second shot, and vice versa for placebo.

The average profile of participants upon study entry was as follows:

• 51% men, 49% women
• age distribution: 12 to 15 years – 0.2%; 16 to 55 years – 57%; 56 years and older – 43%; 65 years and older – 22%
• major ethno-racial groups: white – 83%; Hispanic – 27%; black – 9%; Asian – 4% (Note that due to the complexity of the ethno-racial classification system in the U.S., numbers may not total 100.)
• underlying conditions – 46% had at least one underlying condition that increased the risk for COVID-19, including chronic lung disease, diabetes, higher-than-normal blood pressure

Participants were monitored for about two months after vaccination for assessment of effectiveness.

Results

Cases of flu-like symptoms were assessed if they occurred seven days after the second injection. If these cases tested positive for SARS-CoV-2, they were considered to have COVID-19.

The distribution of cases of COVID-19 that occurred was as follows:

• people who were vaccinated – 8 cases
• people who received placebo – 162 cases

Researchers calculated that this distribution meant that the vaccine reduced a person’s chances of developing COVID-19 by 95%. The vaccine was highly effective in both young and older people.

A subset of participants (8,183 people) who were 18 years and older was closely monitored for safety. In this subset of people, common side effects from the vaccine were as follows:

• pain at the injection site – 84%
• fatigue – 63%
• headache – 55%
• muscle pain – 38%
• chills – 32%
• joint pain – 24%
• fever – 14%

These side effects were generally mild to moderate in intensity. They appeared within the first day of vaccination and tended to resolve within one to two days. The side effects suggest that the immune system is responding to the vaccine.

No deaths were caused by vaccination or placebo.

A relatively small number of people (64) who received the vaccine developed a swollen lymph node(s), usually under the arm. Again, this is likely suggestive that the immune system was responding to the vaccine. It is not clear how long it took for this symptom to resolve.

Hypersensitivity (allergic) reactions

According to the U.S. Food and Drug Administration (FDA), which analysed the data from the clinical trials, there was “a slight numerical imbalance of adverse events possibly representing hypersensitivity-related adverse reactions in [people who received the vaccine] compared to [people who received placebo].” This distribution was as follows:

• vaccine – 137 people (0.63%)
• placebo – 111 people (0.51%)

This suggests that the vaccine has the potential to trigger hypersensitivity reactions in some people. Note that clinical trials of the mRNA vaccines excluded people with a history of severe allergic reactions to vaccines or to an important ingredient in vaccines called PEG (polyethylene glycol). One person who received the Pfizer-BioNTech vaccine developed a serious allergic reaction (anaphylaxis) during the study.

Further information about allergic reactions appears later in this issue of TreatmentUpdate.

Changes to lab tests

The only laboratory test abnormalities noted were temporary decreases in a group of immune system cells called lymphocytes. This happened between one and three days after participants received their first dose of the vaccine. These decreases were judged to be mostly mild to moderate and resolved within a week. These changes were not associated with any symptoms. The decreased lymphocyte numbers did not occur after the second vaccination.

Pregnancy

Women of childbearing potential were screened for pregnancy prior to being scheduled for vaccination. Any women who tested positive for pregnancy were excluded from the study. Women who became pregnant after entering the study were excluded from getting a second dose of the vaccine. Subsequently (after the second dose), there were 23 pregnancies distributed as follows:

• vaccine – 12 pregnancies
• placebo – 11 pregnancies

The outcome of these pregnancies is not known at this time.

Given the public health emergency caused by SARS-CoV-2, some physicians and public health authorities may recommend that pregnant women get the vaccine.

Further study needed

As mentioned earlier, Pfizer-BioNTech will continue to monitor participants who were in clinical trials of the vaccine for several years. This is essential to capture data on any new side effects. Extended monitoring is also needed to find out how long protection provided by the vaccine lasts.

According to the FDA, Pfizer-BioNTech will conduct a study to assess the safety and effectiveness of the vaccine in pregnancy.

Vulnerable populations

There was a relatively small number of people with chronic viral infections—hepatitis B and C, HIV—in the study; data from the study suggests that the vaccine works and did not cause problems in these people. Note that doctors caring for people with chronic viral infections are likely to generally recommend the vaccine for these populations, particularly for people who are being treated with medicines for chronic viral infections and whose health is relatively stable and good. The doctors are likely to do this because the mRNA vaccines do not cause SARS-CoV-2 infection and many people with chronic viral infections have underlying conditions that increase their risk for COVID-19 should they become infected with SARS-CoV-2.

—Sean R. Hosein

REFERENCES:

1. Vaccines and related biological products advisory committee meeting: Pfizer-BioNTech COVID-19 vaccine. FDA Briefing Document. 10 December 2020.
2. Pfizer Canada. Pfizer-BioNTech COVID-19 vaccine. Product monograph. 9 December 2020.