Study explores polyfunctionality of BNT162b2 COVID-19 vaccine-induced memory T-cells

In a recent study published in the journal Nature Medicine, researchers assessed the impact of the BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced memory T cells on the SARS-CoV-2 Omicron variant.

Study: BNT162b2-induced memory T cells respond to the Omicron variant with preserved polyfunctionality. Image Credit: siam.pukkato/Shutterstock


The high number of mutations found in the spike protein of the SARS-CoV-2 Omicron variant has raised concerns regarding its evasion of the immune system. Moreover, various studies have reported that the Omicron variant escaped antibody neutralization in vaccinated or coronavirus disease 2019 (COVID-19) convalescent individuals.   

About the study

In the present study, researchers explored whether the memory T cells induced by COVID-19 vaccines responded to the SARS-CoV-2 Omicron spike protein.

The team enrolled healthcare workers who reported no history of SARS-CoV-2 infection and were vaccinated with two or three doses of the BNT162b2 messenger ribonucleic acid (mRNA) vaccine. A longitudinal investigation was also conducted on participants who were previously infected with COVID-19 and were vaccinated with two doses of the BNT162b2 vaccine.

Intracellular cytokine staining (ICS) assays were performed for interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor (TNF) present in peripheral blood mononuclear cells (PBMCs). The release of these factors was induced using overlapping peptide (OLP) pools comprising the spike (S) protein of the SARS-CoV-2 wild-type (WT) strain and the Omicron variant. The team also compared the number of times the IFN-γ-producing CD4+ T cells were detected against the WT S and the Omicron S proteins.

The longitudinal analysis among SARS-CoV-2-infected and double vaccinated individuals was performed at three distinct time points, such as 10 months after recovery from COVID-19 and before vaccination, and one and three months post-second vaccination. Furthermore, the team assessed the polyfunctionality of the memory T cells that were stimulated by the presence of WT or Omicron spike protein.  


The study results showed that the average frequency of IFN-γ-producing CD4+ T cells detected against the SARS-CoV-2 Omicron S protein was 22% and 10% lower in the PBMCs obtained from healthcare workers who were vaccinated with two and three vaccine doses, respectively. Moreover, the levels of memory CD4+ T cells induced by BNT162b2 were significantly high against Omicron.

As compared to the SARS-CoV-2 WT S protein, the frequency of TNF-producing CD4+ T cells produced against the Omicron S protein was reduced by 14% in the double and 6% in the triple-dosed cohorts. Moreover, in comparison to the WT S protein, the frequency of IL-2-producing CD4+ T cells against the Omicron S protein was reduced by 21% and 3% in the two- and three-dose vaccination cohorts.   

The longitudinal analysis showed that the frequency of IFN-γ-producing CD4+ T cells increased in the individuals vaccinated with two doses against both the Omicron and the WT S proteins. The team noted that the frequency of the IFN-γ-, TNF-, and the IL-2-producing CD4+ T cells against Omicron, as compared to WT, was decreased by 26%, 19%, and 3% before vaccination, 5%, 7%, and 8% one month after, and 9%, 19%, and 11% three months after the second vaccination. This indicated that the memory T-cells induced by the vaccine reacted significantly to the Omicron S protein.

The team also observed that the CD8+ T cell responses were comparatively weak while no IL-2-producing cells were found in the CD8+ T cells. Therefore, the researchers assessed the production of IFN-γ and TNF from CD8+ T cells and found significant responses from the memory CD8+ T cells against Omicron. The responses of both IFN-γ and TNF were not substantially decreased against Omicron in comparison to that against WT. Notably, higher responses were induced by vaccination against the Omicron as well as WT S proteins among persons having a history of SARS-CoV-2 infection.      

The team noted that a proportion of CD4+ T cells released IFN-γ, TNF, and IL-2 against Omicron and WT S protein OLPs. Moreover, the individuals vaccinated with three vaccine doses had higher mean fluorescence intensity (MFI) for each cytokine as compared to those observed in the one and two-doses individuals. The team also highlighted that as compared to the WT S protein, the mean percentage of polyfunctional cells against the Omicron S protein was reduced by 8% in the double-dose and 2% in the triple-dose vaccinated cohorts.

Moreover, among individuals having a history of previous COVID-19 infection, two doses of BNT162b2 increased the proportion of polyfunctional cells generated against both Omicron and WT S proteins. At the three time points including before vaccination and one and three months before the second vaccination, the number of polyfunctional cells did not differ significantly between the CD4+ cells when compared to the WT and the Omicron S proteins. The team also found no significant difference in the percentage of polyfunctional cells among the CD8+ T cells released against the WT or Omicron S proteins.


Overall, the study findings showed that memory T cells induced by the BNT162b2 COVID-19 vaccine reserved their polyfunctionality against the SARS-CoV-2 Omicron variant.  

Journal reference:
  • Jung, M.K., Jeong, S.D., Noh, J.Y. et al. (2022). BNT162b2-induced memory T cells respond to the Omicron variant with preserved polyfunctionality. Nature Microbiologydoi:

Posted in: Medical Science News | Medical Research News | Disease/Infection News

Tags: Antibody, Blood, CD4, Cell, Coronavirus, Coronavirus Disease COVID-19, covid-19, Cytokine, Fluorescence, Frequency, Healthcare, Immune System, Interferon, Interleukin, Interleukin-2, Intracellular, Medicine, Necrosis, Omicron, Protein, Respiratory, Ribonucleic Acid, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Tumor, Tumor Necrosis Factor, Vaccine

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Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.

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