I recently spoke about COVID-19 and vaccines during a webinar for the American Society for Pharmacology and Experimental Therapeutics. There are a few vaccines being administered and many more in development. Whatever COVID-19 vaccine you’ve received or will receive, how does it work? Here are five things you need to know:

I like to put SARS-CoV-2 and coronaviruses in the context of flu viruses in part because I study flu viruses, but I also think it makes coronaviruses more accessible because that’s what we’re familiar with. Coronavirus genomes are almost twice as big as flu viruses, which means they make more proteins. They are, in a way, more sophisticated in how they interact with the immune response of an infected person. This is why figuring out where someone will fall on the spectrum of disease, from asymptomatic to critical, has been difficult—there’s still a lot we don’t understand.

1. How does the vaccine work with your immune system to fight the virus?

Our adaptive immune system works to clear all types of pathogens and other bad actors from our bodies. This part of the immune system also remembers the proteins (antigens) and is better prepared to rapidly destroy the invader if it returns. For viruses like flu and coronavirus, there are two main methods of viral clearance.

Antibodies

Antibodies are made in the lymph nodes by white blood cells called B cells. B cells are designed to recognize and react to the proteins (antigens) on the surface of invaders such as viruses.

Once a pathogen is identified, B cells work with a subset of white blood cells called T cells to launch antibody production. The resulting antibodies are like tiny missiles the B cell release, and they circulate throughout the body, ready to recognize, destroy and rally the immune response against the invader.

Cytolytic event

If our cells are infected, the immune system takes a different approach and summons specialized white blood cells called killer T cells. Killer T cells recognize and kill virus-infected cells using a variety of mechanisms. T cells also serve as guardians to recognize and destroy returning viruses or other pathogens.

2. The spike protein: What is its role in viral infection?

Flu and coronavirus infect cells by attaching to the cell membrane, getting into the cell, dumping their contents and starting to replicate. Coronaviruses have a large protein on their surface — the spike protein — that binds to a specific protein, ACE2, on the surface of human cells. From there, the virus accesses the cell and takes over the cellular machinery to produce more virus.

If we are lucky, we have circulating antibodies that recognize the virus and block its ability to bind to the ACE2 protein. This process is called neutralizing protection.

3. Vaccines: Why is non-specific inflammation important?

In addition to adaptive immunity, our innate immunity also responds to viral infections. The symptoms include swelling, sweating, fever and more.

Nonspecific inflammation triggers adaptive immune cells to go to lymph nodes and start making antibodies and other immune responses. It’s a sense the cells have that something is wrong by recognizing patterns in viruses that wouldn’t normally be in a healthy body. In contrast, since vaccines don’t have a virus in them, they need something to kickstart that response. Called an adjuvant, it’s telling the immune system that this is something to respond to.

There are three types of COVID-19 vaccines in use or in clinical trials.

Recombinant proteins vaccines: This classic vaccine formulation creates a synthetic version of a viral protein. The coronavirus vaccine includes the spike protein, but not genetic material from the virus.

Viral vector vaccines: This newer class of vaccines uses a different virus and replaces part of its genome with part of the coronavirus. In this case, the vaccine uses a common cold virus, removes most of its genome, and replaces it with the part of the genome containing the spike protein. The resulting vaccine is not an active virus because it doesn’t have a complete genome. But the immune system recognizes and mounts a protective reaction to the spike protein.

RNA vaccines: This is also a newer class of vaccines where an RNA molecule is packaged inside lipid droplets. The droplets mimic cellular or viral membranes and fuse with the cells near the vaccination site. The RNA and the lipid membrane serve as an adjuvant. The RNA enters the cells and begins making spike protein. The immune system then recognizes and mounts a protective response to the spike protein.

4. Reactogenicity: How do you know the vaccine is working?

The vaccine side effects are a sign the vaccine is working. Injection at site pain, headache, fatigue, and mild infection symptoms are part of the immune system building that response. We’ve become accustomed to the relatively mild side effects of flu vaccines, which are relatively weak vaccines. All of the COVID vaccines are very effective, particularly against severe and life-threatening infections.

5. Variants: What are they and does the vaccine protect you from them?

Coronaviruses are relatively stable and less likely than flu viruses to generate new versions of themselves. But they do still change over time. Currently, there are at least three COVID-19 variants of concern: B.1.1.7, B.1.351 and P.1. The variations involve the binding protein site — the spike — as well as other parts of the virus. We are most worried about changes in the spike, though, because they might allow the virus to avoid being recognized by antibodies we’ve made after infection or vaccination.

• B.1.1.7, the variant first found in Britain, is a slightly more infectious variant, but there is no strong evidence that it causes more severe disease.

• B.1.351, the variant first detected in South Africa, is more infectious but there isn’t strong evidence that it causes more severe disease.

• P.1, the variant first discovered in Brazil, is similar to the South African variant in terms of infectivity and disease severity.

While some vaccine effectiveness is reduced against these variants, the vaccines appear to be highly effective at preventing severe disease. In other words, you may get sick, but you won’t get as sick. As more people receive vaccinations, COVID-19 will have fewer opportunities to mutate.