Key takeaways:
COVID-19 vaccines train your immune system to recognize and fight the SARS-CoV-2 virus. They help prevent serious illness, hospitalization, and other complications from COVID.
Four COVID vaccines are available in the U.S. for the 2025-2026 respiratory illness season: Pfizer’s (Comirnaty), Moderna’s (Spikevax and mNEXSPIKE), and Novavax’s (Nuvaxovid).
The Pfizer and Moderna COVID vaccines use mRNA technology, while Novavax’s vaccine takes a protein subunit approach. Both types teach your immune system to recognize the coronavirus spike protein safely and effectively.
It’s been years since COVID-19 first appeared, but the virus that causes it remains part of everyday life. Staying protected matters as it continues to evolve. COVID can cause serious illness, especially in older adults and people with certain health conditions.
That’s where vaccines come in. COVID vaccines have helped us live more safely with the virus. They train your immune system to recognize and fight the virus before it can make you seriously ill. The newest COVID vaccines have been updated to target the latest variants and offer protection where it’s needed most.
Whether you’ve stayed up to date or it’s been a while since your last dose, understanding how COVID vaccines work and who they’re recommended for can help you make decisions that will protect your health — and the health of those around you.
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What different types of COVID vaccines are available?
Four COVID vaccines are available in the U.S. for the 2025-2026 respiratory illness season:
Comirnaty from Pfizer: This is an mRNA vaccine that’s FDA approved for people ages 5 years and older who are at higher risk for severe illness. It’s also approved for all adults ages 65 and older.
Spikevax and mNEXSPIKE from Moderna: These are both mRNA vaccines. Spikevax is approved for people ages 6 months and older who are at increased risk for severe illness, as well as all adults ages 65 and older. mNEXSPIKE is available for people 12 and older who are at increased risk of severe illness, and all adults ages 65 and older.
Nuvaxovid from Novavax: This is a protein subunit vaccine for people ages 12 and older who are at increased risk of severe illness. It’s also approved for all adults ages 65 and older.
At first glance, Moderna’s COVID vaccines seem quite similar to each other — which is true. But mNEXSPIKE is what’s sometimes called a next-generation vaccine, because it takes a more targeted approach. Instead of including the full spike protein, like Spikevax, it focuses only on the key parts that trigger a strong immune response. This refocused design means it can use a lower mRNA dose (10 mcg instead of 50 mcg) while still offering solid protection.
How do COVID vaccines work?
All COVID vaccines introduce your immune system to a part of the coronavirus — specifically, to its spike protein, which helps the virus enter your cells. That way, if you’re exposed to the virus later, your body already knows how to fight it off.
mRNA COVID vaccines
Pfizer and Modern’s vaccines use a tiny piece of genetic code called messenger RNA (mRNA). That’s why they’re called mRNA vaccines.
The mRNA in the vaccines gives your cells temporary instructions for making a harmless version of the coronavirus’ spike protein. The mRNA is packaged inside a protective bubble made of fat (called a lipid nanoparticle) so it can reach your cells in one piece.
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COVID vaccine updates: COVID variants and vaccines are constantly evolving and changing. We’ve got you covered on the most up-to-date vaccine news and approvals.
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Going beyond vaccines: Discover all you need to know about COVID treatments and preventative medications with our comprehensive guide.
Here’s what happens next:
Specific cells in your body use the mRNA’s instructions to create a harmless version of the spike protein for a short time.
Your immune system detects that spike protein, realizes it’s not supposed to be there, and starts building defenses.
Immune system components called B cells create antibodies against the spike protein, and T cells learn to find and destroy cells that display it.
After providing instructions to your cells, the mRNA breaks down and leaves your body. It never enters your DNA or changes your genetic code. What stays behind is your immune system’s memory of the spike protein, which helps protect you if you’re exposed to the real virus later on.
The mRNA vaccines can be updated quickly to match new variants. And advances in how they’re formulated have improved their stability and shelf life since the early days of the pandemic.
Protein subunit COVID vaccines
Protein subunit vaccines take a different approach to achieving the same goal. Novavax’s Nuvaxovid vaccine contains purified, lab-made pieces of the coronavirus spike protein — just enough to give your immune system an idea of what to look out for. It also includes an ingredient called an adjuvant, which boosts your body’s immune response so it remembers the spike protein more effectively.
Your immune system responds by creating antibodies and training specialized cells to recognize and attack the coronavirus if you’re exposed to it in the future.
Good to know: Protein subunit technology has been used safely for decades in other vaccines, like those for hepatitis B and whooping cough. These vaccines don’t contain live viruses or genetic material. This makes Nuvaxovid a solid choice for people who prefer a non-mRNA option or who may be sensitive to certain mRNA vaccine ingredients.
What are the known benefits of COVID vaccines?
COVID vaccines help prevent severe illness, hospitalization, and death from the virus. They also lower your risk of developing long COVID, which can cause symptoms like ongoing fatigue, shortness of breath, and brain fog for months after infection.
Vaccination is particularly beneficial for:
Adults ages 65 and older
People with chronic health conditions, such as diabetes, heart disease, or lung disease
Pregnant women
Anyone living or working in a group setting, such as a nursing home or shelter
Even if you’ve already had COVID, vaccination can strengthen and extend your protection over time. Getting vaccinated also helps protect others around you. When more people in a household, school, workplace, or community are vaccinated, it reduces the overall spread of the virus and helps protect those who might not respond as strongly to a vaccine.
How quickly do COVID vaccines work?
Most people develop immune system protection about 2 weeks after vaccination. Getting an updated COVID shot each fall can help your body prepare for possible exposure to the virus, especially before case numbers rise in the colder months.
Getting vaccinated a few weeks before respiratory illness season peaks gives your immune system time to strengthen its defenses.
Which kind of COVID vaccine should you get?
For the 2025-2026 season, the CDC recommends that everyone ages 6 months and older consider vaccination through a shared decision-making approach. That means the choice to get vaccinated should be based on your personal health situation, risk level, and preferences — ideally after discussing it with a pharmacist, physician, or another trusted healthcare professional.
Here are some key factors to think about:
Higher-risk groups: People who are 65 or older, have a chronic or immune condition, live or work in a group setting, or are pregnant are encouraged to get vaccinated.
Children and teens: Families can discuss the risks and benefits of vaccinating younger members with a healthcare professional. If a child — or someone in their household — has a health condition that raises their risk for severe illness, this is particularly important.
Personal preference: Even if you’re not in a high-risk group, you may still choose vaccination for extra peace of mind and community protection.
All available COVID vaccines are considered safe and effective. For most people in an age group with multiple vaccine options, there isn’t a preferred brand. Your prescriber, pharmacist, or another healthcare professional can help you decide which vaccine best fits your health history and goals.
Frequently asked questions
There’s no limit to how many times you can get COVID. Reinfections can happen — even within the same year — because immunity fades over time and new variants can form.
Yes, a breakthrough infection is when someone tests positive for COVID despite being vaccinated. This occurs because no vaccine offers complete protection. But vaccination still makes severe illness, hospitalization, and death much less likely. Many vaccinated people have only mild symptoms and recover relatively quickly from COVID.
Many people experience only mild COVID vaccine side effects, such as arm soreness, tiredness, or a low-grade fever for a day or two after vaccination. Serious reactions are very rare, but get medical attention right away if you notice signs of an allergic reaction or other severe symptoms.
There’s no limit to how many times you can get COVID. Reinfections can happen — even within the same year — because immunity fades over time and new variants can form.
Yes, a breakthrough infection is when someone tests positive for COVID despite being vaccinated. This occurs because no vaccine offers complete protection. But vaccination still makes severe illness, hospitalization, and death much less likely. Many vaccinated people have only mild symptoms and recover relatively quickly from COVID.
Many people experience only mild COVID vaccine side effects, such as arm soreness, tiredness, or a low-grade fever for a day or two after vaccination. Serious reactions are very rare, but get medical attention right away if you notice signs of an allergic reaction or other severe symptoms.
The bottom line
COVID-19 vaccines remain one of the best ways to prevent serious illness, hospitalization, and other complications from the virus.
The mRNA COVID vaccines — Comirnaty, Spikevax, and mNEXSPIKE — use temporary genetic instructions that teach your cells to make a harmless version of the coronavirus spike protein. This helps your immune system build antibodies and train T cells to recognize and destroy the virus quickly if you’re exposed. Nuvaxovid works a little differently. It uses purified pieces of the spike protein, along with an ingredient that boosts and extends your immune response.
If you’re unsure about COVID vaccination, a prescriber, pharmacist, or another healthcare professional can help you decide what’s best for you. They can also talk to you more about how COVID vaccines work.
Why trust our experts?
References
Centers for Disease Control and Prevention. (2024). About reinfection.
Centers for Disease Control and Prevention. (2025). Variants and genomic surveillance.
Durier, C., et al. (2024). Incidence of COVID-19 mRNA vaccine symptomatic breakthrough infections during Omicron circulation in adults with or without infection prior to vaccination. Infectious Diseases Now.
Granet, R. (2020). The enemy within: How SARS-CoV-2 uses our own proteins to infect our cells. American Chemical Society.
National Human Genome Research Institute. (2025). Lymphocyte. National Institutes of Health.
Rizkalla, B. (2025). Overview of Moderna’s investigational next generation COVID-19 vaccine, mRNA-1283, in individuals ≥12 years of age. Moderna.
Schoenmaker, L., et al. (2021). mRNA-lipid nanoparticle COVID-19 vaccines: Structure and stability. International Journal of Pharmaceutics.
U.S. Department of Health and Human Services. (2025). CDC immunization schedule adopts individual-based decision-making for COVID-19 and standalone vaccination for chickenpox in toddlers.
VaccinesWork. (2020). What are protein subunit vaccines and how could they be used against COVID-19? Gavi.
World Health Organization. (2025). How do vaccines work?
