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

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

Background

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 waning of vaccine-induced neutralizing antibodies has led to the development of the COVID-19 booster vaccination strategy.

Several studies have reported the immediate benefits of COVID-19 booster immunizations, with respect to neutralization capacity against SARS-CoV-2 variants. However, there is a lack of data regarding the effect of the mRNA booster vaccine on the spike-specific CD8⁺ T cell response.

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

New study

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

Scientists recruited thirty-eight individuals, from the Freiburg University Medical Center, 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, BNT162b/Comirnaty or mRNA-1273/Spikevax vaccine. 

Scientists reported that the study cohort included five participants who received four doses of the vaccine and were without a 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 booster vaccination exhibited mild symptoms without respiratory insufficiency.

In this study, the authors analyzed spike-specific CD8⁺ T cell responses, on 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-two months post the fourth vaccination regime. The authors also evaluated spike-specific CD8⁺ T cell responses in breakthrough infections with the Omicron and Delta variants, post booster vaccination.

Findings

Researchers reported a fast and vigorous increase of spike-specific CD8⁺ T cell responses after third and fourth doses of the vaccine, with respect to breakthrough infection with the Delta and Omicron variants. Scientists reported that the magnitude and kinetics of immune response of this study cohort were similar 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⁺ T cell booster responses after third and fourth doses of COVID-19 booster vaccination declined after around one to two months and, subsequently, reached a concentration similar to prior booster vaccination. This observation is extremely important and should be considered while formulating the booster vaccination strategy. Interestingly, in contrast to the steep waning off of the spike-specific CD8⁺ T cell boost response, a prolonged contraction after natural infection, irrespective of the infecting variant, has been observed.

A previous study reported the prolonged contraction of non-spike epitope-specific CD8⁺ T cells after COVID-19 infection. These differences in antigen half-life, antigen presentation, cytokines, innate immunity, and CD4⁺ T cell responses might 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 post-vaccination.

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

Conclusion

The authors revealed that mRNA booster vaccination is a powerful tool that can induce rapid and functional CD8⁺ T cell responses, which can be extremely beneficial to immediate alleviation of high viral burden. This strategy could effectively protect the vulnerable population and reduce the overwhelming burden of the healthcare system. However, the rapid decline in the spike-specific CD8⁺ T cell response has to be considered while 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 regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.