The Moderna vaccine
Clinical trials of the Moderna 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 94% effective at reducing the risk of developing COVID-19 after two injections were given.
How the vaccine works
The Moderna 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). 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 III clinical trials that Moderna used to collect data that was submitted for regulatory approval enrolled 14,206 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 28 days later
- an intramuscular injection of placebo on day one, followed by another injection 28 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:
- 53% men, 47% women
- age distribution: 18 to 64 years – 75%; 65 and older – 25%
- major ethno-racial groups: white – 80%; Hispanic – 20%; black – 10%; Asian – 5% (Note that due to the complexity of ethno-racial classification in the U.S., numbers do not total 100.)
- underlying conditions – 19% had an underlying condition that is associated with an increased risk for COVID-19, including chronic lung disease, cardiovascular disease, obesity, diabetes
Results
The distribution of people who developed confirmed COVID-19 two weeks after their second injection was as follows:
- vaccine – 11 cases
- placebo – 185 cases
Researchers calculated that this distribution meant that the vaccine reduced a person’s risk of developing COVID-19 by 94%. Among people aged 65 years and older, the efficacy of the vaccine was 86%.
Side effects
Commonly reported side effects were as follows:
- pain at the injection site – 90%
- fatigue – 70%
- headache – 65%
- muscle pain – 62%
- joint pain – 45%
- chills – 42%
In general, most of these side effects were of mild-to-moderate intensity and resolved within a few days.
According to the FDA, more people who received the vaccine (1.1%) vs. placebo (0.63%) developed swollen lymph nodes, usually under the arm. This type of reaction suggests that the immune system was responding the vaccine. It is not clear when this side effect resolved.
No one died from the vaccine (or placebo).
Hypersensitivity reactions
More people who received the vaccine (1.5%) developed hypersensitivity reactions compared to those on placebo (1.1%). According to Moderna, “this imbalance was mainly due to injection site rash and injection site swelling/redness[…].” Still, the findings raise the possibility that in rare cases the vaccine may cause hypersensitivity reactions. No one developed severe hypersensitivity reactions to the vaccine in clinical trials. However, three people who received the Moderna vaccine developed swelling of the lips/face about one and two days after vaccination. All three people had a history of having cosmetic fillers in their face. Unfortunately, the brands and formulations of these fillers are not known.
Note that people who had a history of allergic reactions to vaccines or PEG (polyethylene glycol; an ingredient in the vaccine) were excluded from the study.
Special populations
There were 196 study participants who had what researchers called “liver disease.” They did not specify the cause of liver disease, but it is likely that at least some people had chronic viral infections with hepatitis B or C viruses.
There were 176 participants with HIV infection.
In both cases of liver disease and HIV infection no issues of efficacy or safety were reported.
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 13 pregnancies distributed as follows:
- vaccine – 6 pregnancies
- placebo – 7 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
According to the FDA, Moderna plans to conduct studies to do the following:
- monitor the health of women who are vaccinated and who are or who become pregnant
- monitor participants to assess long-term safety of the vaccine
- further assess the efficacy of the vaccine
—Sean R. Hosein
REFERENCES:
- Vaccines and related biological products advisory committee meeting: Moderna COVID-19 vaccine. FDA Briefing Document. 17 December 2020.
- Moderna Therapeutics. Moderna COVID-19 vaccine. Product monograph. 23 December 2020.