Immune Responses Support COVID-19 Vaccination, Regardless of When Infection Occurred


Individuals with immunity obtained through having the disease still experienced expanded T-cell memory and immune activation after being immunized, study results show.

Immunity by infection is not better than vaccination, because both have similar T-cell responses, according to the results of a study by investigators from St. Jude Children’s Research Hospital.

Individuals who had a COVID-19 infection still experienced expanded T-cell memory and immune activation after vaccination, the results of the study published in Nature Immunology showed.

“If you've been infected, the vaccines still activate and expand your immune response in ways that can be protective,” Paul Thomas, PhD, from the St. Jude Department of Immunology, said in a statement.

“If you’ve been vaccinated and then get infected, the vaccine still helps protect you. Very importantly, it doesn't limit your ability to develop new immune responses to the strains that you're infected with,” Thomas said.

The type of immunity on the T-cell side that the vaccine gives you look very similar to, and in some ways superior to, the response that you get from infection,” he said.

Investigators used data from the St. Jude Tracking Study of Immune Responses Associated with COVID-19, which started in 2020, and enrolled St. Jude employees and monitored their vaccinations and immune responses to the virus.

Additionally, they used specialized techniques to determine which small pieces of virus that T-cells identify in different individuals. They found that single-cell sequencing of the RNA and T-cell receptors provided a glimpse into T-cell activity and helped identify which T-cell receptors were most important.

Investigators also created tools, including monoclonal T-cell receptor cell lines, to help examine immune responses. The cell lines were used by investigators to help identify different parts of the virus.

“We have a number of tools and techniques that allow us to analyze T-cell receptors effectively, to identify receptors that may be different but basically have the same function,” Thomas said. “We’ve gained an understanding of how this virus is evolving and mutating and how our immune responses adapt to these changes.”

Additionally, the results showed that the order of exposure, whether the vaccination occurred first or the infection, determined whether the immune response was geared toward the spike protein.

The results showed that the mRNA vaccines that fight SARS-CoV-2 targeted the spike proteins in the virus. Furthermore, vaccination after infection led to further expansion of spike-specific T-cells, whereas a breakthrough infection caused robust non-spike-specific responses that diversify T-cell memory.

“This creative and comprehensive T-cell work emphasizes the importance of the prospective study design that allowed us to collect samples from participants before they had COVID-19,” Joshua Wolf, PhD, MBBS, from St. Jude Department of Infectious Diseases, said in the statement. “Properly understanding the T-cell response to COVID-19 infection and vaccination is really challenging, but it's essential to developing a long-term control strategy for this virus.”

The study was supported by the Center for Influenza Vaccine Research for High-Risk Populations, the St. Jude Center of Excellence for Influenza Research and Surveillance, and American Lebanese Syrian Associated Charities, the fundraising and awareness organization of St. Jude.


Immune responses support COVID-19 vaccination regardless of when people were infected. EurekAlert. News release. April 5, 2022. Accessed April 8, 2022.

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