By 2021, hundreds of millions of people will be vaccinated against SARS-CoV-2. The success of this Covid-19 vaccination campaign will depend on the trust of the people, the vaccines are not only effective, they are also safe. To build this trust, the medical and scientific communities have a responsibility to engage in difficult discussions about the important part of people who will suffer from the temporary side effects of these vaccines.
I am an immunologist who studies the basics of immune responses to the vaccine, so part of that responsibility falls on me.
Simply put, getting these vaccines will surely make a bunch of people feel it for a few days. It’s probably a good thing, and it’s much better than a long-term illness or death.
Immunology’s ‘dirty little secret’
In 1989, immunologist Charles Janeway published an article summarizing the state of immunology. Until then, immunologists had admitted that the immune response began when they encountered something foreign (bacteria, viruses, and parasites) that was “not one’s own”.
Janeway suspected that there was something more to the story, and he became famous for what he called the “dirty dirty secret of the immunologist”: Your immune system doesn’t just respond to foreign things. He responds to foreign things that he considers dangerous.
Now, 30 years later, immunologists know that your immune system uses a complex set of sensors to understand whether something is foreign or not, as well as what kind of threat a microbe can pose. It can detect differences between viruses (like SARS-CoV-2) and parasites (like tapeworms) and activate the specialized arms of your immune system to deal with these specific threats. Controlling tissue damage caused by an invader can also increase your immune response.
Perceiving the type of threat posed by a microbe and the level of intensity of that threat allows your immune system to select the right set of responses, use them accurately, and avoid the real risk of an overactive immune response.
The helper carries the risk we need
Vaccines work in a safe version of the pathogen in the patient’s immune system. Your immune system remembers past encounters and responds more effectively if it sees the same pathogen again. However, it creates memory if the vaccine contains enough risk signals to initiate a strong immune response.
As a result, it is very important to be aware of the risk before your immune system responds (think about whether it has started attacking thousands of species of friendly bacteria in your gut!) And very problematic.
Asking for risk means that your immune system is programmed not to respond unless a clear threat is identified. This means that if I am developing the vaccine I need to convince your immune system that it is a threat that the vaccine itself is worth taking seriously.
This can be achieved in several ways. One is to inject a weakened version of a pathogen (what immunologists call it) or even kill it. This approach has the advantage of being almost identical to the “real” pathogen, causing many of the same risk signs, and often causing strong long-term immunity, as seen in polio vaccines. It can also be dangerous: if you don’t weaken the pathogen enough and spread the vaccine too quickly, you may inadvertently infect many vaccine recipients. In addition to this unacceptable human cost, losing confidence in vaccines can lead to additional suffering because fewer people are taking other safer vaccines.
A safer approach is to use individual components of the pathogen that are inherently harmless but capable of training your immune system to know the real thing. However, these parts of the pathogen often do not have the risk signals needed to stimulate a strong memory response. As a result, they should be supplemented with synthetic risk signals, which immunologists call “assistants”.
The helpers are safe but designed to turn on
To make vaccines more effective, entire laboratories have been dedicated to testing and developing new collaborators. They are all designed with the same basic goal – to maximize the effectiveness and duration of the response to the immune system. By doing this, we maximize the number of people who will be vaccinated and the time it takes to protect those people.
To do this, we take advantage of the same sensors that your immune system uses to detect damage in an active infection. This means that while they will promote an effective immune response, they will produce temporary inflammatory effects.
At the cellular level, the vaccine causes inflammation at the injection site. The blood vessels in this area become “more elusive” to help immune cells recruit into muscle tissue so that the area is red and swollen. All of this triggers a complete immune response somewhere in a nearby lymph node that will play out for weeks.
Symptoms can include redness and swelling at the injection site, stiffness and pain in the muscle, tenderness and inflammation of the swollen lymph nodes, and, if the vaccine is strong enough, fever as well (and this is generally associated with poor feeling).
This is the balance of vaccine design: it maximizes protection and benefits by minimizing uncomfortable but necessary side effects. This does not mean that no serious side effects occur (it does), but they are very rare. Two of the most serious side effects discussed, anafhalaxia (severe allergic reaction) and Guillain-Barré syndrome (nerve damage due to inflammation), occur with a frequency of less than 1 in 1 dose.
Vaccine against SARS-CoV-2
Early data indicate that mRNA vaccines are highly effective in the development of SARS-CoV-2 – over 90%. This means that they are able to stimulate strong immune responses, with sufficient risk signaling, in more than nine out of 10 patients. This is a large number in any case, and suggests that these vaccines are powerful.
So let’s be clear here. You should get the vaccine and feel pain at the injection site the next day. You should expect some redness and swelling, and you can also expect to feel a day or two after the vaccine. All of these things are normal, even planned and thought out.
Although the data are not complete, more than 2% of Moderna vaccine recipients had what they classified as a serious temporary side effect, such as fatigue and headache. The percentage of people who experience side effects will be higher. Vaccines are signs of what is being designed. Train your immune system to respond against something you might otherwise ignore so you can have protection later. It doesn’t mean the vaccine gave you Covid-19.
Anyway, in the coming months they will give you some time to protect yourself, your loved ones and your community from a highly contagious and deadly disease, for a significant number of people who may otherwise have significant health consequences in the long run. It will cost you a few days to feel sick.
Please choose wisely.
Matthew Woodruff is a professor at the Lowance Center for Human Immunology at Emory University.
This article first appeared in The Conversation.