COVID Vaccines and Infection Offer Similar Protection, Study Finds

Some researchers have questioned whether natural immunity against COVID-19 would provide better protection or a stronger immune response against infection and severe disease compared to vaccination. However, new evidence is putting that idea to rest.

In a recent study, published in Nature Immunology, scientists at St. Jude Children’s Research Hospital in Tennessee, evaluated how vaccination and infection with COVID-19 affect the immune system. While they found some differences in the immune response when a person got COVID-19 before vaccination versus after, it did not necessarily mean people with natural immunity had a better response.

In fact, researchers confirmed that immunity by infection is not better than getting vaccinated against COVID-19 since both produced similar T-cell responses. T-cells help protect the body from infection and can fight off viruses.

Paul Thomas, PhD, faculty in the department of immunology at St. Jude’s Children's Research Hospital and co-corresponding author, told Verywell in an email they found that if you’ve been infected prior to vaccination, the vaccine still activates your immune response. If you’ve been vaccinated and then get infected (also known as a breakthrough case), the vaccine still provides protection.

In other words, regardless of when you may have been infected with COVID-19, getting vaccinated before or after a primary infection still produces a strong immune response.

“The goal of the study was to examine how the diverse exposures people are receiving to SARS-CoV-2 antigens (which are molecules that the immune system uses to recognize an infection and help produce antibodies), including by vaccination and infection, affect their CD8 T-cell responses,” Thomas said. “CD8 T-cells are the ‘killers’ of the immune system by removing infected cells and in many viral infections they are essential to viral control and the healthy resolution of infection.” 

Thomas and his colleagues analyzed 55 individuals and 85 distinct samples from those individuals using “major histocompatibility complex multimers,” which allowed them to look precisely at the antigens that each individual person’s T-cells look at. The data used also came from the St. Jude Tracking Study of Immune Responses Associated with COVID-19 (SJTRC), a research study of faculty and staff across St. Jude that started in 2020.

“This high resolution, in-depth analysis allowed us to be confident in the robustness of our results for the broader population,” Thomas said. “Our cohort represented otherwise reasonably healthy adults—we would like to understand if the same dynamics and findings hold in the elderly, in children and infants, and in populations with specific immune deficiencies.”

While the study can’t give us a final answer about exactly how much protection someone has if they get both a vaccine and an infection, the findings can still help us understand the basic science of the human immune system and how T-cell signatures change after vaccination and infection, Anna Bershteyn, PhD, assistant professor in the department of population health at NYU Langone Health who was not a part of the study, told Verywell via email.

“Although a group of just 55 people can’t include every population we might be interested in, the authors did look at one of the main forms of diversity when it comes to the immune system: the HLA genes. These genes determine which types of viruses your T-cells can ‘see,’” Bershteyn explained. “So, even though the study was relatively small, it is great that this important form of genetic diversity was taken into account.”

Vaccination Expands Immunity

According to Bershteyn, when the immune system gets triggered, either by a vaccine or an actual infection, it remembers what triggered it so that it can respond faster and better next time.

She added that this process also applies to antibodies, which are proteins that provide protection against future exposures to a foreign substance or virus. Antibodies also stick to T-cells, which find viruses that are already inside your cells and prevent the body from turning into a “virus factory.” 

“This study showed that the more times your immune system is triggered, either by repeated vaccination or infections, the better it will be at responding next time,” Bershteyn said. “Amazingly, not only does the immune system get faster and stronger, but it also gets broader, meaning it can protect against a wider range of variants.”

However, she emphasized this isn’t always true. For some other diseases, repeated exposures either from vaccine or infection can make the immune system more narrow in its focus, or even get “exhausted” and stop responding.

“So it is good news that the authors saw the broadening and strengthening after repeated exposures to [COVID-19] vaccines and viruses,” she added.

Overall, getting vaccinated and boosted should help expand your immune response.

“In some vaccinations, if you had robust memory (as you have from infection) you might expect that response to eliminate the vaccine before it had a chance to activate further immune responses,” Thomas explained. “Here we see that even in someone with an established memory response, the vaccine is able to cause the immune system to expand further. We see some real-world evidence of this today with the boosters.”

Importance of Vaccination 

The study reinforced that it’s better to get vaccinated before infection, Bershteyn said. While immune responses were very strong and broad no matter what order it happened, “people who got vaccinated before infection ended up with a stronger response to other partners of the virus besides spike.”

When you compare variants like Delta versus Omicron, most of the mutations happen in the spike protein, Bershteyn explained. But having strong immune responses outside of the spike protein could give better protection against different variants.

“With that said, if you’re not vaccinated and you have been infected, definitely still go and get vaccinated,” she said. “It is much better than going without.”

While vaccines are not perfect at preventing infection since breakthrough infections can still occur, vaccinations are much less likely to cause hospitalization and death. The study found that breakthrough infections in vaccinated people still strengthen and broaden T-cell responses, which is thought to give longer and broader protection against future variants, Bershteyn added.

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