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Hybrid Immunity to COVID-19: What It Is and How To Get It

Medically reviewed by Elizabeth Cueto, M.D.
Written by Emily Wagner, M.S.
Posted on October 13, 2023

Have you ever heard the phrase “Two is better than one?” In the case of immunity against COVID-19, doctors and researchers have found this age-old saying to be true.

Recent studies show that having immunity from both an updated vaccine and a natural infection offers better protection from COVID-19 infection. Known as hybrid immunity, it teaches your immune system to recognize new versions or variants of the SARS-CoV-2 virus, the virus that causes COVID-19.

In this article, we’ll cover how hybrid immunity works and why it helps protect you against COVID-19. If you’ve previously had a COVID-19 infection, staying up to date on your booster vaccination can offer even more protection this fall and winter.

The New Monovalent COVID-19 Vaccines

The U.S. Food and Drug Administration (FDA) has approved a new round of updated messenger RNA (mRNA) COVID-19 vaccines (2023-2024 formula) for everyone older than 6 months of age. These new versions of the Moderna and Pfizer vaccines are recommended by the Centers for Disease Control and Prevention (CDC).

The previous round of mRNA vaccines were bivalent, meaning they contained blueprints of spike proteins found in two different versions of the virus that causes COVID-19. These new vaccines are monovalent — they contain the blueprints of a single variant, called Omicron variant XBB.1.5 and nicknamed “Kraken.”

Health experts have identified XBB.1.5 as being highly transmissible and contagious. People who’ve received previous vaccinations or previously had COVID-19 have still been infected with this newer variant.

Who Should Get the New Vaccine?

Everyone aged 5 and up is eligible for one dose of the new vaccine as long as it’s been at least two months since their last vaccination. Infants aged 6 months to children up to 4 years old may receive more than one dose of the new vaccine, depending on their vaccination status. Additionally, those in this age group (6 months to 4 years) who haven’t been vaccinated can get three shots of the Pfizer COVID-19 vaccine or two shots of the Moderna COVID-19 vaccine.

People who are moderately or severely immunocompromised (have weakened immune systems) should also receive the new vaccine. The CDC cautions that these people are “at increased risk of severe COVID-19 illness and death.”

Are the New Vaccines Safe?

The FDA based its approval of the new mRNA vaccines on the safety and effectiveness of previous versions, which were manufactured in the same way as the new round. Per the CDC, millions of Americans have received COVID-19 vaccines “under the most intense safety monitoring program in U.S. history.”

The FDA noted that the benefits of receiving the vaccine outweigh any risks. Potential side effects — both common and rare but serious — are similar to those of previous versions of the vaccine. Common side effects are generally similar to flu symptoms, including temporary fever, chills, aches, and fatigue, along with irritation or soreness at the injection site.

How Your Immune System Protects You From Infection

To better understand how hybrid immunity works, it helps to learn how your immune system protects you against infections. When you become sick, your immune system recognizes the invading virus as foreign. It takes pieces of the virus — known as antigens — and shows them to specialized immune cells called T cells. The T cells then create inflammation and attack cells that have been infected with the virus.

Your T cells also activate specialized B cells. They’re responsible for creating immune system proteins, or antibodies, that tag the virus and infected cells. Another name for these proteins is “neutralizing antibodies” because they tag the virus and cells for destruction.

Once your body clears away the infection, some B cells continue to live in your body as memory B cells. If a virus tries to invade your body again, the memory B cells remember how to fight it.

What Is Hybrid Immunity?

Hybrid immunity refers to immunity from both vaccination and natural infection. Doctors and researchers have found that immunity from vaccination is different than the immunity your body makes after a COVID-19 infection.

When you receive the COVID-19 messenger RNA (mRNA) vaccine, the COVID-19 antigens are injected into your arm. Your immune system creates IgG antibodies or proteins that travel around your body. They look for COVID-19 virus particles and infected cells to destroy.

On the other hand, a natural COVID-19 infection enters your body through your mouth and nose. Your immune system creates a different type of antibody known as IgA. Your body still makes some IgG antibodies, but they don’t work as well in your mouth and nose to protect you.

When you have hybrid immunity, you have both types of antibodies (higher quality in your immune response). Studies show that this double layer of protection lowers your risk of severe disease, hospitalization, and chances of reinfection.

Why Is Hybrid Immunity Better Than Vaccination or Natural Infection Alone?

When someone gets the virus that causes COVID-19 and is vaccinated later, their immune system becomes super strong. This combo, which we can call hybrid immunity, makes the body very good at fighting off different versions of the virus. People with this hybrid immunity have a lot more memory cells (which remember how to fight the virus) than those who only got infected or only got vaccinated. This boost in protection happens whether or not the person shows symptoms from the virus. The more you come in contact with COVID-19 antigens, the stronger your immune system will be. The combination of vaccination and natural infection teaches your immune system to build a better antibody response.

Hybrid Immunity Exposes You to More Antigens

Vaccines typically contain only a few specific antigens from certain versions or variants of the virus that causes COVID-19. You’ve likely heard of Omicron and Delta, referring to different variants. Researchers have developed booster vaccinations specifically targeting antigens from these variants to teach your immune system how to fight them.

However, COVID-19 continues to change over time, finding new ways to trick our immune systems and avoid immunity. This means new variants will keep developing. A natural infection may expose you to more variants than a booster vaccine will.

As a result, the combination of both vaccines targeting common variants and natural infection exposes you to many different antigens. This means your immune system is more likely to recognize a COVID-19 infection down the road and know how to fight it.

Hybrid Immunity Is Stronger and May Last Longer

While both vaccines and natural infection offer some immunity, the amount can vary from person to person. Studies from the journal Biomedicine show that natural immunity offers 93 percent to 100 percent protection from severe COVID-19 for up to eight months. However, there’s still a chance you can become infected with COVID-19 again within this period.

A recent review of 40 studies also looked at how long immunity lasts from the COVID-19 mRNA vaccines. The authors found that the primary vaccine offered in 2021 and 2022 wasn’t as effective against the newer Omicron variant. Over the course of five months, the vaccine’s efficacy dropped from 52.8 percent to 14.3 percent against Omicron, as cited in an article in the Journal of the American Medical Association.

On the other hand, hybrid immunity is broader and stronger. Another study reported that memory B cell levels are five to 10 times higher with hybrid immunity compared to vaccination or natural immunity alone. This means you have more memory cells waiting to jump into action as soon as you’re infected with COVID-19. Researchers have also found that hybrid immunity protects you against a symptomatic infection (an infection when you experience symptoms) for six to eight months.

Talk to Your Doctor About an Updated COVID-19 Vaccine

One of the best ways to protect yourself against COVID-19 is by staying up to date on your vaccinations. Talk to your doctor or health care provider about the latest vaccine recommendations from the CDC.

By timing your vaccinations correctly, you can stay immune and prevent breakthrough infections (infections that occur after vaccination). Even if you do get a COVID-19 infection after your booster dose, the hybrid immunity can help protect you against future infections. One study found that people with hybrid immunity were least likely to be reinfected with COVID-19 compared to those who had two vaccine doses or natural immunity.

Be sure to get all vaccine doses as recommended. Your doctor or health care provider will have specific recommendations if you’re unvaccinated or have recently been infected with COVID-19.

Find Your Team

On myCOVIDteam, the social network for people with COVID-19 and their loved ones, more than 8,500 members come together to ask questions, give advice, and share their stories with others who understand life with COVID-19 and long COVID.

Do you have more questions about hybrid immunity? Share them in the comments below, or start a conversation by posting on your Activities page.

References
  1. Why Hybrid Immunity Is so Triggering — The Lancet Infectious Diseases
  2. Covid Continues To Rise, but Experts Remain Optimistic — The New York Times
  3. FDA Takes Action on Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants — U.S. Food and Drug Administration
  4. CDC Recommends Updated COVID-19 Vaccine for Fall/Winter Virus Season — Centers for Disease Control and Prevention
  5. Omicron XBB.1.5 ‘Kraken’ Subvariant Is on the Rise: What To Know — Yale Medicine
  6. COVID-19 Vaccines for People Who Are Moderately or Severely Immunocompromised — Centers for Disease Control and Prevention
  7. Selected Adverse Events Reported After COVID-19 Vaccination — Centers for Disease Control and Prevention
  8. Antigen — Cleveland Clinic
  9. T-Cells — Cleveland Clinic
  10. T Cells, B Cells and the Immune System — The University of Texas MD Anderson Cancer Center
  11. B-Cells — Cleveland Clinic
  12. Hybrid Immunity More Protective Than Prior SARS-CoV-2 Infection Alone — JAMA
  13. Hybrid Immunity — Science
  14. Hybrid Immunity to SARS-CoV-2 From Infection and Vaccination — Evidence Synthesis and Implications for New COVID-19 Vaccines — Biomedicines
  15. Evaluation of Waning of SARS-CoV-2 Vaccine-Induced Immunity: A Systematic Review and Meta-Analysis — JAMA Network Open
  16. Stay Up to Date With COVID-19 Vaccines — Centers for Disease Control and Prevention
  17. What Is a Breakthrough Infection? — Infectious Diseases Society of America
  18. SARS-CoV-2 Hybrid Immunity: Silver Bullet or Silver Lining? — Nature Reviews Immunology
  19. FDA OKs New Monovalent COVID-19 Vaccines — American Academy of Pediatrics
  20. Protective Effectiveness of Previous SARS-CoV-2 Infection and Hybrid Immunity Against the Omicron Variant and Severe Disease: A Systematic Review and Meta-Regression — The Lancet Infectious Diseases

Posted on October 13, 2023
All updates must be accompanied by text or a picture.

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Elizabeth Cueto, M.D. graduated from the National Polytechnic Institute in Mexico City. Learn more about her here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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