Exploring short-term effectiveness of COVID-19 booster vaccine and stable CD8+ T cell memory after three doses

Since the world’s first outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, a continuous evolution of the virus has been observed. The emergence of new variants of SARS-CoV-2, which have been categorized into variants of concern (VOC) and variants of interest (VOI), has reduced the effectiveness of COVID-19 vaccines and thus fueled the pandemic situation.

Study: Short-term recall effect and stable memory of CD8+ T cells after the 3rd dose of COVID-19 vaccine. Image credit: KT Stock photos/Shutterstock


Previous studies have reported that mRNA-based COVID-19 vaccines effectively elicit robust antibody and T-cell responses, and protect individuals against SARS-CoV-2 infection. However, the incidence of breakthrough infections related to the Omicron variant and the decrease in vaccine-induced neutralizing antibodies led to the development of the COVID-19 booster vaccination strategy.

Several studies have reported the immediate benefits of COVID-19 booster vaccinations, in terms of neutralizing capacity against SARS-CoV-2 variants. However, there is a lack of data regarding the effect of mRNA booster vaccine on peak-specific CD8+ T cell response.

Additionally, little evidence has been documented regarding the efficacy of three-dose vaccine regimens, their response to breakthrough infection, and the duration of immune protection.

A new study

A new preprint study, published on Research Square*, addressed the aforementioned gap in research and plotted and longitudinally profiled CD8+ T cell responses after COVID-19 mRNA booster vaccination.

The scientists recruited thirty-eight people, from the University Medical Center in Freiburg, Germany, who were immunized with the COVID-19 mRNA booster vaccine. They obtained blood samples from thirty-one individuals who received three doses of one of two mRNA vaccines, namely the BNT162b/Comirnaty or mRNA-1273/Spikevax vaccine.

The scientists reported that the study cohort included five participants who had received four doses of the vaccine and had no history of COVID-19 infection. Thirteen participants had a history of breakthrough infection after the third dose of a booster vaccination. All participants with breakthrough infection after the booster vaccination had mild symptoms without respiratory failure.

In this study, the authors analyzed peak-specific CD8+ T-cell responses, at the single-epitope level, in participants who received a COVID-19 mRNA-based booster vaccination (third and fourth) after four months of the third dose and one to two months after the fourth vaccination regimen. The authors also assessed peak-specific CD8+ T-cell responses in breakthrough infections with Omicron and Delta variants, after booster vaccination.


Researchers reported a rapid and vigorous increase in peak-specific CD8+ T-cell responses after the third and fourth doses of the vaccine, compared to breakthrough infection with the Delta and Omicron variants. Scientists reported that the magnitude and kinetics of immune response in this study cohort were similar to those of peak-specific CD8+ T cell response after the second dose of the COVID-19 vaccine. This was observed by detecting a high level of expression and proliferation of CD38 and Ki-67. This finding strongly supports the rapid induction of functional CD8+ T cell responses after COVID-19 mRNA vaccination.

Scientists have reported that peak-specific CD8+ T-cell booster responses after the third and fourth doses of COVID-19 booster vaccination waned after approximately one to two months and subsequently reached a concentration similar to the previous booster vaccination. This observation is extremely important and must be taken into account when formulating the booster vaccination strategy. Interestingly, in contrast to the sharp decrease in peak-specific CD8+ A T-cell stimulation response, prolonged contraction after natural infection, regardless of the infecting variant, was observed.

A previous study reported sustained CD8 contraction not specific to a spike epitope+ T cells after COVID-19 infection. These differences in antigenic half-life, antigenic presentation, cytokines, innate immunity, and CD4+ T cell responses could be due to differences in responses after mRNA vaccination and COVID-19 infection. Therefore, there is a need to better understand the interactions of immune components during natural infection and their responses after vaccination.

In this study, the researchers reported that promising spike-specific CD8+ The T cell memory response is not significantly affected by the third dose of vaccination. The current study found that the third dose did not increase long-term CD8 counts+ T cell immunity and had no influence on CD8 senescence+ T cell memory pool. This finding is consistent with a previous study which reported that antigen exposure does not cause peak-specific CD8 T cell depletion.+ T cells. Researchers believe that spike-specific CD8+ The T cell recall response is an effector response based on a stable memory pool.


The authors revealed that mRNA booster vaccination is a powerful tool that can induce fast and functional CD8.+ T-cell responses, which can be extremely beneficial for immediate relief from a high viral load. This strategy could effectively protect the vulnerable population and reduce the overwhelming burden on the healthcare system. However, the rapid decline of peak-specific CD8+ The T cell response should be considered when formulating the COVID-19 booster vaccination strategy.

*Important Notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

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