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

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

Background

The high number of mutations found in the spike protein of the SARS-CoV-2 variant Omicron has raised concerns about its evasion of the immune system. Additionally, various studies have reported that the Omicron variant escapes neutralizing antibodies in people vaccinated or recovering from coronavirus disease 2019 (COVID-19).

About the study

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

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

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

Longitudinal analysis among persons infected with SARS-CoV-2 and doubly vaccinated was carried out at three distinct time points, for example 10 months after recovery from COVID-19 and before vaccination, and one and three months after the second vaccination. Additionally, the team assessed the polyfunctionality of memory T cells stimulated by the presence of WT or Omicron spike protein.

Results

Study results showed that the mean frequency of IFN-γ-producing CD4+ T cells detected against the SARS-CoV-2 Omicron S protein was 22% lower and 10% lower in PBMCs obtained from workers in health vaccinated with two and three dose vaccines, respectively. Additionally, BNT162b2-induced memory CD4+ T cell levels were significantly elevated against Omicron.

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

Longitudinal analysis showed that the frequency of IFN-γ-producing CD4+ T cells increased in individuals vaccinated with two doses against Omicron and WT S proteins. The team noted that the frequency of IFN-γ-producing CD4+ T cells IFN-γ-, TNF- and IL-2 against Omicron, compared to WT, had 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 vaccine-induced memory T cells responded significantly to the Omicron S protein.

The team also observed that the CD⁸⁺ T cell responses were relatively weak whereas no IL-2 producing cells were found in DC⁸⁺ T cells. Therefore, researchers assessed the production of IFN-γ and TNF from CD8+ T cells and found significant memory CD8+ T cell responses against Omicron. IFN-γ and TNF responses were not significantly diminished against Omicron compared to those against WT. Notably, higher responses were induced by vaccination against Omicron proteins as well as WT S in people with 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 protein and WT S OLPs. Additionally, individuals vaccinated with three Vaccine doses had higher mean fluorescence intensity (MFI) for each cytokine compared to those seen in individuals at one and two doses. The team also pointed out that compared to the WT S protein, the average percentage of polyfunctional cells against the Omicron S protein was reduced by 8% in the double-dose vaccinated cohorts and by 2% in the triple-dose vaccinated cohorts.

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

Conclusion

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