Millions of people are now being immunized with mRNA vaccines from Pfizer-BioNTech and Moderna. Both vaccines have very high efficacy. In this article, we are going to analyze what we actually know about these vaccines and what we have yet to find out?
The first vaccine to be authorized was developed by Pfizer and BioNTech in December 2020, and the Moderna vaccine was authorized a week later. Both are messenger RNA or mRNA vaccines. They work by inducing an immune response to viral spike proteins.
These are the proteins that stud the surface of the SARS-CoV-2 virus and make it look like, which incidentally is where the coronavirus gets its name. You can think of a vaccine as target practice for your immune system: the target being the spike. But instead of the actual spike proteins, these vaccines contain the genetic information, in the form of mRNA, that codes for the spike. When the vaccine mRNA enters the cells in your body, it gets taken up by the machinery of the cells, which then make the spike proteins.
Carlos Del Rio of the Emory University School of Medicine explained that they are using the machinery of the cells to produce spike protein and put it on the surface of the cells so the immune system can then come and see the spike protein and then generate an immune response. This immune response to the spike would help you fight a future infection with the SARS-CoV-2 virus.
Importantly, the vaccine mRNA does not enter the cell nucleus, which contains the cell’s DNA. So, the vaccine has no effect on DNA or body genetics. The vaccine mRNA also does not replicate and it does not stick around permanently. As Dr. Rio says “The mRNA disappears, it goes away so it doesn’t even stay in the cytoplasm of the cells. This is what the cells normally do and mRNA in the cells disappears after it forms proteins”. Data suggests the higher levels of spike proteins are produced 48 hours after vaccination and are cleared by 72 hours. The mRNA is actually gone even sooner by 24 hours.
The overall efficacy for these vaccines was determined by comparing the number of participants who developed symptomatic COVID-19 in the vaccine and placebo groups in large phase III trials. In case of Pfizer, to calculate the efficacy, you divide the cumulative incidence of the disease in the vaccinated group by the cumulative incidence in the placebo group; this gets you the risk ratio. Then you subtract the risk ratio from 1, and the number you come up with is the efficacy.
The efficacy for Pfizer is 0.95 or 95%. Now in the case of Moderna, using the same calculation gets you the efficacy of 94%. These numbers are encouraging but it’s important to keep in mind that participants in both the Pfizer and Moderna trials were tested only if they developed symptoms of COVID-19. So, while these data tell us if the vaccine prevents clinically recognizable disease, they do not tell us if the vaccine also prevents infection and the transmission of the virus.
This means a few possible scenarios could be at work for those who are vaccinated: A typical scenario could be, (a) that someone is protected against infection, and certainly if against infection, against clinically recognizable disease. But there is another scenario (b) where someone was protected against clinically recognizable disease, but they still have a replication-competent virus in their nasopharynx. Hence, by definition, they are infected. If that second scenario is at play with these vaccines that is that people who are vaccinated don’t develop symptoms but still get infected.
A follow-up question is whether the vaccines might still prevent or at least decrease transmission. According to Dr. Fauci, it is conceivable that the immune response that protects someone from symptomatic disease would also lower the amount of virus in the nasopharynx. So, you could be infected, but not have enough virus in your nasopharynx to transmit it. Studies are already underway to figure out if these vaccines prevent infection and transmission as well as symptomatic disease.
Some very preliminary data indicate that they do, and more data is expected soon. But given the uncertainty, public health authorities are recommending continued preventive measures like mask-wearing and physical distancing, even for people who have been vaccinated. And there are other unknowns when it comes to efficacy that is still being researched, like the duration of immunity, whether evolving virus strains could make the vaccines less effective, or how efficacy varies for different demographic groups.
Now let’s take a look at the safety of the vaccines. The FDA would normally want to see at least two years of safety follow-up data for the vaccine. But given the urgency of making an effective vaccine available for pandemic control, when these vaccines were authorized for emergency use the available follow-up data was only about 6 months for the earliest participants and 2 months for the phase III trial participants. According to that data, the most common reactions were pain at the injection site, fatigue, and headache, most often after the second dose.
Most adverse events were mild to moderate and resolved within a few days. Such reactions are to be expected with all vaccines and are most often just a sign of the immune system working. Importantly, even though these vaccines have already been authorized, safety monitoring is ongoing.
Safety considerations go well beyond the clinical trial. There’s the observation of potential adverse events, well into the implementation of the vaccine distribution. So, if you look at the numbers of people in the clinical trial, there were 44 000 in the Pfizer trial” told Dr. Rio. Once you push the button and start distributing vaccines, you are going to be giving them to millions of people. And you’re only going to find out a rare serious adverse event post-approval.
But the good news is there are systems in places like the Vaccine Safety Datalink or VAERS or the CISA system to pick that up. These are government systems designed to detect post-approval safety signals. And the US has ramped up its safety surveillance capabilities for COVID-19 vaccines. An example of these systems at work is the recent publication by the CDC of data on severe allergic reactions, also called anaphylactic reactions. The US got a heads up about anaphylactic reactions after two cases were reported in the UK on December 9. A CDC analysis published in JAMA reports on more than 9 million administered doses of the Pfizer vaccine and more than 7 million doses of the Moderna vaccine.
The rate of anaphylactic reactions was 4.7 cases per million doses for the Pfizer vaccine and 2.5 cases per million doses for the Moderna vaccine. This is slightly higher than the rate of anaphylactic reactions following flu vaccination for example, but still extremely rare.
Two months into the vaccine rollout, both the Pfizer and Moderna vaccines still appear to be safe. Maurice Hilleman, who is considered to be the father of modern vaccines, said, “I never breathe a sigh of relief until the first 3 million doses are out there.” Well, the first 3 million doses are out there. The first 40 million doses are out there in the US, and hundreds of millions of doses are out there in the world.
FDA and CDC scientists and others are continuing to watch safety and efficacy signals vigilantly as more and more people get their doses. Continuing research should help us answer the key remaining questions. And some of the uncertainty is the byproduct of getting two remarkably effective vaccines to the public within just 11 months of the virus being sequenced, once 40 million people have been vaccinated, scientists and companies now have a large platform on which to stand. And undoubtedly scientists can say and claim that the effect is remarkable, and the safety, as far as scientists know, appears to be, reassuring.
Muneeb Ul Hassan
MS Industrial Biotechnology from NUST Islamabad. Writer and a Student of Comparative Religion, History, International Relations and Egyptology. Public Speaker and Debater for more than 12 years and have adjudicated many events including STAR ASIA (Daabistan e Adab), ILM KI DUNIYA national declamation and HEC Allama Iqbal Shield Zone C.