Comparison of the Development of SARS-Coronavirus-2-Specific Cellular Immunity, and Central Memory CD4+ T-Cell Responses Following Infection versus Vaccination

Abstract

Memory T-cell responses following infection with coronaviruses are reportedly long-lived and provide long-term protection against severe disease. Whether vaccination induces similar long-lived responses is not yet clear since, to date, there are limited data comparing memory CD4+ T-cell responses induced after SARS-CoV-2 infection versus following vaccination with BioNTech/Pfizer BNT162b2. We compared T-cell immune responses over time after infection or vaccination using ELISpot, and memory CD4+ T-cell responses three months after infection/vaccination using activation-induced marker flow cytometric assays. Levels of cytokine-producing T-cells were remarkably stable between three and twelve months after infection, and were comparable to IFNγ+ and IFNγ+IL-2+ T-cell responses but lower than IL-2+ T-cell responses at three months after vaccination. Consistent with this finding, vaccination and infection elicited comparable levels of SARS-CoV-2 specific CD4+ T-cells after three months in addition to comparable proportions of specific central memory CD4+ T-cells. By contrast, the proportions of specific effector memory CD4+ T-cells were significantly lower, whereas specific effector CD4+ T-cells were higher after infection than after vaccination. Our results suggest that T-cell responses—as measured by cytokine expression—and the frequencies of SARS-CoV-2-specific central memory CD4+T-cells—indicative of the formation of the long-lived memory T-cell compartment—are comparably induced after infection and vaccination.

Post-COVID-19 Fatigue and SARS-CoV-2 Specific Humoral and T-Cell Responses in Male and Female Outpatients

“…Positive responses were defined by stimulation index (stimulated spot-forming units/2 × 105 cells divided by unstimulated spot-forming units/2 × 105 cells) as clearly positive with a stimulation index of ≥7 and clearly negative with a stimulation index of ≤3. Samples with values that fell in between were defined as negative unless the unstimulated control value was >2 staining units/2 × 105 cells and the stimulation index was >3, as described by the manufacturer ( 12 ). In the present manuscript, measurements are shown as stimulation index (SI) values and not as spot-forming units due to the different background levels in the IFN-γ and IL-2 assays.…”

Peculiarities of the T Cell Immune Response in COVID-19

“…showed that vaccination and infection induced comparable levels of specific SARS-CoV-2 CD4+ T cells after three months in addition to comparable proportions of specific central CD4+ memory T cells. In contrast, the proportion of specific effector CD4+ memory T cells was significantly lower and specific effector CD4+ memory T cells were higher after infection than after vaccination [106].…”

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“…The assessment criteria for the ELISpots were a minimum of 50 SFU in the positive control and a maximum of 10 SFU in the negative control according to the manufacturer’s definitions (19, 20). When those criteria were fulfilled, the stimulation index (SI) was calculated by dividing the mean SFU numbers in the antigen-specific wells with the mean SFU numbers of the negative control.…”