Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status

Yu, Esther Dawen; Wang, Eric; Garrigan, Emily; Goodwin, Benjamin; Sutherland, Aaron; Tarke, Alison; Chang, James; Gálvez, Rosa Isela; Mateus, José; Ramirez, Sydney I.; Rawlings, Stephen A.; Smith, Davey M; Filaci, Gilberto; Frazier, April; Weiskopf, Daniela; Dan, Jennifer M.; Crotty, Shane; Grifoni, Alba; Sette, Alessandro; Antunes, Ricardo da Silva

doi:10.1016/j.chom.2022.02.003

Cited by 30 publications

(38 citation statements)

References 70 publications

(91 reference statements)

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“…The current results demonstrate an anamnestic humoral and cellular vaccine-elicited immunity in Omicron BTI including a CD8 T cell profile that resembled the more potent T cell activation found in infected, unvaccinated individuals 28 , 48 . This CD8 T cell profile contrasted with a terminal effector profile (phenotype and cytotoxic functions similar to vaccine boost responses 49 , 50 ) found in Delta breakthrough infection.…”

Section: Discussionmentioning

confidence: 56%

“…1f ). Emergence of specific responses to Spike and non-Spike was visualized in a biplot of Spike vs. non-Spike response as recently described 28 . Here responses can be divided into quadrants: infected and nonvaccinated (I + V − ), non-infected and vaccinated (I − V + ); or infected and vaccinated (I + V + ).…”

Section: Resultsmentioning

confidence: 99%

“…1f . e Biplot showing in vitro responses of CD4 + T cells to non-Spike peptide pools vs. Spike-peptides as described 28 : infected and nonvaccinated (I + V − ), non-infected and vaccinated (I − V + ); or infected and vaccinated (I + V + ). Mann–Whitney test P values are shown for ( b – d ).…”

Section: Resultsmentioning

confidence: 99%

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Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

et al. 2022

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The SARS-CoV-2 Omicron variant has more than 15 mutations in the receptor binding domain of the Spike protein enabling increased transmissibility and viral escape from antibodies in vaccinated individuals. It is unclear how vaccine immunity protects against Omicron infection. Here we show that vaccinated participants at a super-spreader event have robust recall response of humoral and pre-existing cellular immunity induced by the vaccines, and an emergent de novo T cell response to non-Spike antigens. Individuals with Omicron SARS-CoV-2 breakthrough infections have significantly increased activated SARS-CoV-2 wild type Spike-specific cytotoxic T cells, activated follicular helper (TFH) cells, functional T cell responses, boosted humoral responses, and rapid release of Spike and RBD-specific IgG+ B cell plasmablasts and memory B cells into circulation. Omicron breakthrough infection affords significantly increased de novo memory T cell responses to non-Spike viral antigens. Concerted T and B cell responses may provide durable and broad immunity.

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Section: Discussionmentioning

confidence: 56%

Section: Resultsmentioning

confidence: 99%

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Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

et al. 2022

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“…The number of PBMC available for analysis was limited, but 26 subjects had a sufficient number of cells available to perform additional analyses related to this issue. To examine T cell responses to the rest of the SARS-CoV-2 proteome, we utilized the approach recently described by Yu et al, based on CD4-RE, a pool of experimentally defined 15-mer epitopes derived from the whole SARS-CoV-2 proteome (excluding S) [21]. The CD4-RE epitope pool was tested in parallel with the S pool in the subset of 26 acute COVID-19 donors for which sufficient cells were available.…”

Section: Cd4 T Cell Reactivity To Spike and Non-spike Antigensmentioning

confidence: 99%

Early and Polyantigenic CD4 T Cell Responses Correlate with Mild Disease in Acute COVID-19 Donors

Tarke

Potesta

Varchetta

et al. 2022

IJMS

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We assessed SARS-CoV-2-specific CD4+ and CD8+ T cell responses in samples from 89 acute COVID-19 patients, utilizing blood samples collected during the first wave of COVID-19 in Italy. The goal of the study was to examine correlations between SARS-CoV-2-specific T cell responses in the early phase comparing mild, moderate, or severe COVID-19 disease outcomes. T cell responses to the spike (S) and non-S proteins were measured in a combined activation-induced marker (AIM) and intracellular cytokine staining (ICS) assay. Early CD4+ T cell responses to SARS-CoV-2 S correlated with milder disease by both AIM and IFNγ ICS readouts. The correlation of S-specific CD4+ T cell responses with milder disease severity was most striking within the first two weeks of symptom onset compared to later time points. Furthermore, donors with milder disease were associated with polyantigenic CD4+ T cell responses that recognized more prominently non-S proteins in addition to S, while severe acute COVID-19 was characterized by lower magnitudes of CD4+ T cell responses and a narrower repertoire. In conclusion, this study highlights that both the magnitude and breadth of early SARS-CoV-2-specific CD4+ T cell responses correlated with milder disease outcomes in acute COVID-19 patients.

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“…CD4+ T cell responses to the four prototypical CCC viruses (NL63, 229E, HKU1 and OC43) were measured, using the Activation Induced Marker (AIM) and the OX40/4-1BB markers combination 26 , which has been previously utilized to characterize viral responses and particularly SARS-CoV-2 CD4+ T cell responses [36][37][38][39][40] . Responses to other respiratory viruses (influenza, RSV, and rhinovirus), chronically infectious viruses (EBV, CMV, and VZV), and ubiquitous bacterial vaccine antigens (TT and PT) were measured using specific peptide sets (Table 2 and methods section).…”

Section: Frequency Of Ccc-specific Memory Cd4 + T Cells Are Comparabl...mentioning

confidence: 99%

Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

Dawen

Narowski

Wang

et al. 2022

Preprint

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Understanding immune memory to Common Cold Coronaviruses (CCCs) is relevant for assessing its potential impact on the outcomes of SARS-CoV-2 infection, and for the prospects of pan-corona vaccines development. We performed a longitudinal analysis, of pre-pandemic samples collected from 2016-2019. CD4+ T cells and antibody responses specific for CCC and to other respiratory viruses, and chronic or ubiquitous pathogens were assessed. CCC-specific memory CD4+ T cells were detected in most subjects, and their frequencies were comparable to those for other common antigens. Notably, responses to CCC and other antigens such as influenza and Tetanus Toxoid (TT) were sustained over time. CCC-specific CD4+ T cell responses were also associated with low numbers of HLA-DR+CD38+ cells and their magnitude did not correlate with yearly changes in the prevalence of CCC infections. Similarly, spike RBD-specific IgG responses for CCC were stable throughout the sampling period. Finally, high CD4+ T cell reactivity to CCC, but not antibody responses, was associated with high pre-existing SARS-CoV-2 immunity. Overall, these results suggest that the steady and sustained CCC responses observed in the study cohort are likely due to a relatively stable pool of CCC-specific memory CD4+ T cells instead of fast decaying responses and frequent reinfections.

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Development of a T cell-based immunodiagnostic system to effectively distinguish SARS-CoV-2 infection and COVID-19 vaccination status

Cited by 30 publications

References 70 publications

Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

Immune responses in Omicron SARS-CoV-2 breakthrough infection in vaccinated adults

Early and Polyantigenic CD4 T Cell Responses Correlate with Mild Disease in Acute COVID-19 Donors

Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

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