Study: Short-lived booster effect and stable CD8+ T cell memory after 3rd COVID-19 vaccine dose. Image Credit: KT Stock photos/Shutterstock

Study on the short-term efficacy of the COVID-19 booster vaccine and stable CD8+ T-cell memory after three doses

Since the first global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the 2019 coronavirus disease (COVID-19) pandemic, continuous evolution of the virus has been observed. The emergence of new SARS-CoV-2 variants, classified as variants of concern (VOC) and variants of interest (VOI), has decreased the efficacy of the COVID-19 vaccines and has therefore fueled the pandemic situation.

Study: Short-term booster effect and stable CD8+ T-cell memory after 3rd COVID-19 vaccine dose† 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 from SARS-CoV-2 infection. However, the incidence of breakthrough infections related to the Omicron variant and the decline 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 immunizations, in terms of neutralization capacity against SARS-CoV-2 variants. However, there is a lack of data on the effect of the mRNA booster vaccine on the spike-specific CD8 T cell response.

In addition, not much evidence has been documented regarding the effectiveness of the three-dose vaccine regimens, their response to the breakthrough infection, and the duration of immune protection.

A new study

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

Scientists recruited thirty-eight individuals from Freiburg University Medical Center, Germany, who had been immunized with the COVID-19 mRNA booster vaccine. They took blood samples from 31 individuals who had received three doses of one of two mRNA vaccines, namely BNT162b/Comirnaty or mRNA-1273/Spikevax vaccine.

Scientists reported that the study cohort included five participants who 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 booster vaccination. All participants with breakthrough infection after booster vaccination showed mild symptoms without respiratory failure.

In this study, the authors analyzed spike-specific CD8 T-cell responses, at a single epitope level, in participants who received 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 evaluated spike-specific CD8 T-cell responses in breakthrough infections with the Omicron and Delta variants, after booster vaccination.


Researchers reported a rapid and powerful increase in spike-specific CD8 T cell responses after the third and fourth doses of the vaccine, with regard to breakthrough infection with the Delta and Omicron variants. Scientists reported that the magnitude and kinetics of the immune response of this study cohort were comparable to the spike-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 reported that the spike-specific CD8 The response to T-cell booster after the third and fourth doses of COVID-19 booster vaccination decreased after approximately one to two months and then reached a concentration comparable to previous booster vaccination. This observation is extremely important and should be taken into consideration when formulating the booster vaccination strategy. Interestingly, in contrast to the precipitous decline in the spike-specific CD8 T cell boost response, a prolonged contraction after natural infection, regardless of the infecting variant, has been observed.

A previous study reported the prolonged contraction of non-spike epitope-specific CD8 T cells after being infected with COVID-19. These differ in antigen half-life, antigen presentation, cytokines, innate immunity and CD4 T cell responses may be due to differences in responses after mRNA vaccination and COVID-19 infection. Therefore, there is a need for a better understanding of the interactions of immune components during natural infection and their responses after vaccination.

In this study, researchers reported that the promising spike-specific CD8 The response to T cell memory is not significantly affected by the third vaccination dose. The current study revealed that the third dose did not increase long-term CD8 T cell immunity and did not affect CD8 . aging T-cell memory pool. This finding is consistent with a previous study reporting that antigen exposure does not cause T cell depletion of spike-specific CD8. T cells. Researchers believe that the spike-specific CD8 T cell booster response is an effector response based on a stable memory pool.


The authors revealed that mRNA booster vaccination is a powerful tool that kills rapid and functional CD8. can induce T-cell responses, which can be highly beneficial for immediate relief of high viral loads. This strategy could effectively protect the vulnerable population and reduce the overwhelming burden on the health care system. The rapid decline of the spike-specific CD8 The response of T cells should be taken into account when formulating the booster vaccination strategy against COVID-19.

*Important announcement

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

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