Understanding the COVID-19 Vaccines

How does the vaccine work?

The Pfizer-BioNTech and Moderna vaccines contain a molecule called RNA, which encodes the instructions for building a viral protein called "spike" — the protein that gives the novel coronavirus its spiky appearance and enables it to infiltrate and infect human cells. The RNA is injected into a muscle, entering the cells in the injection area, and causing them to produce numerous copies of the viral protein. A similar process of replication occurs when the virus infiltrates a cell, except that in the vaccine’s case, only one protein is manufactured by the cells, rather than the entire virus.

Within a short time, our immune system detects that something is "wrong." It picks up on the fact that its cells are expressing a foreign protein they normally shouldn't, and it takes a snapshot of that protein's structure. Later, if the vaccinated individual is exposed to a real virus, the immune system will recognize it immediately — and act against it. This allows vaccinated people to skip a long learning phase that would take about two weeks from the moment of infection with a real virus. Through vaccination, our body learns to recognize the virus without having to deal with a viral attack at the same time.

How does the mRNA vaccine work? Illustration: Noa Katz, based on a tweet by Zavén Sargsyan

What is the difference between the Pfizer and Moderna vaccines?

Both vaccines are based on a similar technology, have similar efficacy, and are administered in two doses. The interval between the doses is three weeks for the Pfizer vaccine and four weeks in Moderna’s case.

The main difference between the vaccines was in their storage requirements. Initially, the Pfizer vaccine had to be kept at -70 degrees Celsius. In February, the FDA approved storage at -20 degrees. The vaccine can be refrigerated at 2-8 degrees Celsius for five days, and can be left outside the refrigerator for up to two hours. The vaccine also needs to be diluted with a salt solution (saline) before use.

By contrast, the Moderna vaccine can be stored in standard freezers, at -20 degrees Celsius, for at least six months. It can also be refrigerated for 30 days and be kept at room temperature for up to 12 hours. It does not need to be diluted prior to its use.

Are the vaccines expected to end the pandemic?

It is very likely that the vaccines will spell the end of the pandemic, but their approval doesn't mean that we will be returning to normal any time soon. That will take at least a few more months. The first obstacle is making the vaccines widely available: It will take time until there are sufficient doses for the entire population of the country and the world. Initially, the vaccines will help protect the most vulnerable populations and critical healthcare workers. Until the majority of the public is vaccinated, we will have to continue employing the now-familiar protection means of physical distancing and masks as we return to conduct our everyday activities.

Another setback is that it takes time for each vaccinated person to develop immunity. The vaccine is administered in two doses, about one month apart. A person can be regarded as immunized only two weeks after the second dose.

It is not clear yet for how long the vaccine provides immunity  to COVID-19. Immunity may decline with time, so booster shots may be needed to maintain the immune memory and to ensure we are protected from the virus. It also remains to be seen whether the vaccine only  protects against severe illness or also prevents people from contracting COVID-19 and transmitting it to others, without getting sick themselves. As long as scientists are not certain the vaccine prevents infection, everyone will have to keep taking precautions, even after being vaccinated. Nevertheless, preliminary evidence suggests that the vaccine does prevent infection, or at least that it reduces the chances of infection, but as in many aspects of this crisis, we will have to be patient and wait for further evidence to be sure.

In any case, it is hard to believe that the vaccines will lead to the extinction of such a common virus, which has spread across the world. It seems that the novel coronavirus, SARS-CoV-2, is here to stay, and we will have to keep vaccinating people against it, as we do to protect against other viruses.

How do we know the vaccines work?

Here we will focus on the Pfizer vaccine, which is the main one used in Israel, although the principles are the same for all the vaccines approved for use in the US, Israel, EU member states and most other high-income countries. The Pfizer vaccine passed three phases of clinical trials, in which 44,000 participants were enrolled in total. It received an emergency use authorization from the FDA after meticulous inspection by a panel of experts. All of the methods and findings were made public on the FDA website and broadcast live on YouTube.

We also know that the vaccines are safe and effective because since the vaccine was approved, several large-scale follow-up studies were conducted in Israel and elsewhere, with findings that corroborate those of the clinical trials. Additionally, there is preliminary evidence that vaccines reduce the viral load in vaccinated persons. Of course, some open questions remain, such as how long immunological memory lasts, how effective the vaccine is against variants and how long it confers protection against infection. The answers to these questions will be discovered over time. For further information about the vaccine’s efficacy

How long is the vaccine good for?

As the trials with the COVID-19 vaccine started only about a year ago, it's impossible to determine exactly how long vaccine-induced immunity lasts. However, the experiments in humans and animals show that antibody levels remain high for at least four months after receiving the vaccine, indicating a strong immune response. We may have to get another booster dose after one year, as we do with other vaccines, but it’s too soon to determine that.

How do we know the vaccine is safe?

The Pfizer vaccine was administered to hundreds of millions of people over the past few months and no severe side effects were found. Authorization was granted two months after half of the clinical study participants received their second vaccine dose — providing sufficient time to identify any unusual side effects. The participants are still being monitored to ensure that no unexpected side effects emerge in the future. Additionally, national health authorities, including the Israel Ministry of Health, are monitoring the side effects in the vaccinated populations in their respective jurisdictions. For further information about vaccine safety.

Who is the vaccine not recommended for?

The Pfizer vaccine is approved for use in individuals 16 years of age or older. It is not intended for use in younger children and youth at the current time, because the trials did not include this age group. Additionally, you should not get the vaccine if you have a history of severe allergic reactions (anaphylaxis) to any of the components of the vaccine or to a previous dose of the vaccine.

It is permitted to give the vaccine to pregnant and breastfeeding women. Although the vaccine trials were not intended for these populations, the American College of Obstetricians and Gynecologists and its Israeli counterpart, as well as the CDC and the Israel Ministry of Health, based on preliminary evidence, including findings of pre-clinical trials and evidence regarding the vaccine’s mechanism. The approval was given bearing in mind that pregnant women are at increased risk for COVID-19 complications.

What are the known side effects?

Based on the clinical trials, which conducted intensive follow-ups with the participants, the most common side effect is pain in the injection area (84 percent). Other common side effects are dizziness (62 percent), headaches (55 percent), chills (38 percent), joint pain (23 percent), and fever (14 percent). The risk of more severe side effects is less than half a percent, and no life-endangering side effects were found in the large-scale trial. 

Very rarely, there is a allergic reaction to the vaccine, especially among people with a history of severe allergic reactions, who usually have to carry an epinephrine autoinjector (EpiPen). This occurs shortly after receiving the vaccine, which is why vaccinated people are asked to wait for 15 minutes in a designated area before leaving the premises. “Real-world” data report a lower rate of mild adverse reactions, probably because of under-reporting. According to Israel Ministry of Health data, the rate of significant adverse effects is about 0.03% and in most cases, they are about as common in vaccinated people as in unvaccinated people. For further information about vaccine safety.

What about rare or long-term side effects?

As far as we know, these side effects should not exist. It's very rare for a vaccine to have side effects that appear long after it was given. However, science is about assuming less and testing more; therefore, the clinical trials are still ongoing and the volunteers who received the vaccines are being monitored for any side effects or complications.

So why aren't we waiting a year or two, until we can be sure? The reason is simple - the cost would be much too high. Although this may be the first approved vaccine based on  this technology, other trials of RNA technologies have been conducted in recent years and did not lead to any long-term side effects that should be a cause for concern. Furthermore, the virus causes many short-term complications, and, as time goes by, we are also seeing long-term complications, so it seems that any potential vaccination risks are significantly outweighed by the dangers of COVID-19.

I heard a scary rumor about the vaccine. How can I tell if I should believe it?

We are exposed to many rumors about the vaccine making the rounds over social media, messaging apps, and other media outlets. First, it's important not to get stressed out. Chances are that the more outlandish the rumor, the more baseless it is. Check reliable sources, consult with authorized health professionals, and do not make decisions based on unverified information under any circumstances. Remember, if a warning is of consequence, you will run into it in several places, such as news programs, science websites, Ministry of Health announcements, and others - not just in random WhatsApp messages.

Is the vaccine really better than catching the disease?

Absolutely! The vaccine is effective, has few side effects, and even if it turns out to induce just a short immune memory, we can get a booster shot next year. By contrast, the disease can cause pneumonia, an extended stay at the ICU and even death - and not just for the elderly. Many recovering patients feel weak and have a hard time getting back to normal. If that's not enough, there is evidence that being sick once does not prevent another infection. The virus has been around for only a year, so we don't know what are the long-term effects of the disease. Experiments conducted in tens of thousands of people show that by any metric, getting the vaccine is better than catching the virus.

Weren’t shortcuts taken in the development of the vaccine?

Vaccine development usually takes several years. A large part of that time is wasted on bureaucracy, fundraising, recruiting volunteer study participants, and waiting for regulatory bodies like the Food and Drug Administration (FDA) to check every step of the trials.

From the outset of the pandemic, it was clear that any exit strategy would require a vaccine. This is why any step of the process that didn't affect the safety and efficacy was shortened. Many governments, and chiefly the United States, invested billions of dollars in companies that showed potential to develop a vaccine within a reasonable timeframe. Additionally, some of the trial phases slightly overlapped their previous phases, and participant recruitment was simple, because people were lining up to join the clinical trials.

Finally, one factor causing much of the delay in the development of new vaccines is waiting for enough participants to catch the disease, so that the researchers can check to see which group they belonged to: The intervention group or the control group. Since we are in the midst of a pandemic caused by a highly infectious virus, this milestone was reached very quickly.

The only part in which a certain risk was taken was the timing of the emergency approval. A clinical trial should last about two years to identify long-term side effects. Since waiting that long would cost many human lives and cause significant suffering, the developers waited only two months after the second dose was given before submitting the vaccine for emergency approval. The trial isn't over, and the participants are still being monitored, but the vaccine was already approved to save lives. The risk is not high, and is definitely lower than the risks of catching the disease.

I heard that the vaccine damages fertility in women. Is this true?

Absolutely not. There is no biological reason for that to happen. The vaccine causes the body to produce antibodies against a small part of the novel coronavirus and they can only target that part. Furthermore, the viral infection  causes both the COVID-19 disease and the production of antibodies against the virus. If this rumor was based, we would expect women who recovered from COVID-19 to have reduced fertility - but this is not the case at all. Additionally, unlike what a common rumor claims, there is no indication that the vaccine harms male fertility, and there is no plausible biological mechanism that would make that happen. For further information.

What about the Russian vaccine?

The Sputnik 5 vaccine, developed in Russia, has passed two phases of clinical trials and was approved for use without passing the third phase. This phase is being conducted in several countries worldwide, but the findings have not yet been published and checked by independent sources, so it is difficult to ascertain whether it is safe and effective.

The vaccine itself is based on a viral vector; this means that its developers took a virus that is not dangerous for humans and cloned instructions to build one of the proteins of the novel coronavirus into it. The engineered virus should infect cells in the bodies of the vaccine recipients and induce them to produce the protein. This is a well-known method that has been approved for use in humans and is considered safe. However, before the vaccine passes all three clinical trials phases and the results are inspected by an objective health authority, there is no way of knowing if it is safe and effective.

What about the Israel Institute for Biological Research (IIBR) vaccine?

The IIBR vaccine recently started the first phase of clinical trials , meant to test its safety. The IIBR states that the second phase, testing its efficacy, will be starting soon. This vaccine is also based on a virus that is not dangerous for humans, which was modified to contain the instructions for a viral protein. We will have to wait patiently to see whether this vaccine passes the clinical trials.

Could the different variants such as the British and South-African hinder the vaccine’s effectiveness?

Recently, several new variants of the coronavirus have been discovered, such as the British, Brazilian, and South African variants. These variants are of the same virus with some minor changes. Some of the changes are in the protein targeted by the vaccine, and so theoretically could lessen its effect. A rise in the reinfection rate was observed in some variants, which could indicate a partial decline in its protective abilities. Studies show that the vaccine is still likely to be effective against the variants. Its effectivity may be lower against some of the variants; however, it is still effective, especially in preventing severe illness. If at any point in time there would be a need to update the vaccine, it can be done relatively easily and quickly in RNA vaccines, without the long process of development and complex approval processes like the ones seen in recent months. 

I heard the vaccine can alter my DNA, is that possible?

No. The vaccine contains a molecule called RNA, this molecule exists in our cells naturally and allows the transfer of information from our genetic material (DNA) to the manufacturing of proteins that build the cell and activate it. Within the cell’s conditions, the RNA molecule cannot reach the nucleus, where the DNA is.  Even if it could reach the nucleus, there is no mechanism that would allow it to turn into the genetic material, DNA, and integrate itself within it. If that were possible, we would have been in a lot of trouble, not because of the vaccine but because of integration of our natural RNA molecules into our DNA.

I heard the vaccine is already effective after the first dose, so why should we not give up on the second dose and allow more people to get vaccinated?

The vaccine is somewhat effective after the first dose, roughly two weeks after its administration. However, one dose does not confer the maximum effectivity, as evident by the level of antibodies among people who received the second dose. It does provide some protection, but the risk of infection still exists. In addition, it is not clear for how long this protection lasts, as the trials were done on the administration of two doses. The second dose, given 21 days following the first (for the Pfizer vaccine), allows preservation of the immunological memory and provides better protection. Do not miss the second dose and do not postpone it.

What about the AstraZeneca and Johnson & Johnson vaccines?

These vaccines work in a similar technology to the Sputnik V described above and have yet to be approved for use in Israel. Their clinical trials indicate that they are less effective than the RNA vaccines currently administered in Israel, however they have other advantages such as significantly easier transportation and storage conditions, and in the case of Johnson & Johnson, the requirement of only one dose.

Can people who recovered from COVID-19 get vaccinated?

Until February, people who recovered from COVID-19 were not allowed to vaccinate due to the concern that there would not be enough vaccinations, as the recovery itself grants some immunity following the exposure to the virus. Research published in recent months has shown that the immunological response to the vaccine is better than the one provided by “natural exposure” and so nowadays recovered people can receive one dose of the vaccine in order to “upgrade” their defense levels and raise it to a similar level to those who were fully vaccinated.

Is it true that the vaccine can cause ADE?

In certain diseases, re-exposure could lead to a more severe illness, due to a mechanism termed “Antibody Dependent Enhancement” (ADE). This phenomenon is found in viruses that attack certain cells of the immune system. Antibodies against such viruses can assist them to penetrate and invade cells of the immune system. This phenomenon does not occur after the coronavirus vaccines: it was not detected in the pre-clinical trials on animals or in the human trials. Moreover, it was not seen among COVID-19 patients that were re-exposed to the virus. In addition, the SARS-CoV-2 virus does not replicate within the relevant cells of the immune system so there is no reason to be concerned about ADE.

I heard some people got paralyzed in half of their face after vaccination, is that true?

Bell’s Palsy is a transient neurological phenomenon where half of the face becomes paralyzed. The reasons why this happens are not totally clear, but it is not very rare. Its prevalence is about 13-20 cases for every one hundred thousand people. Among the first 4.7 million vaccinated people, 73 cases were documented, meaning 0.002 percent of the vaccinated people. This prevalence is lower than the prevalence in the general population, so it is likely that the phenomenon is not related to the vaccine.

Last update: March 18th, 2021