tetano
Editor, Senior Moderator
Front Immunol
. 2024 Aug 29:15:1423766.
doi: 10.3389/fimmu.2024.1423766. eCollection 2024. Antigen-specific T helper cells and cytokine profiles predict intensity and longevity of cellular and humoral responses to SARS-CoV-2 booster vaccination
Lukas Page[SUP] 1 [/SUP], Kevin Dennehy[SUP] 1 [/SUP], Katharina Mueller[SUP] 2 [/SUP], Philipp Girl[SUP] 2 3 4 [/SUP], Eva Loell[SUP] 1 [/SUP], Hellen Buijze[SUP] 1 [/SUP], Johanna-Maria Classen[SUP] 5 [/SUP], Helmut Messmann[SUP] 5 [/SUP], Christoph Roemmele[SUP] 5 [/SUP], Reinhard Hoffmann[SUP] 1 [/SUP], Sebastian Wurster[SUP] #[/SUP][SUP] 6 [/SUP], Andre Fuchs[SUP] #[/SUP][SUP] 5 [/SUP]
Affiliations
Introduction: Pre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period.
Methods: Blood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics.
Results: Spike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL‑2 (r=0.58), and spike-induced IFN‑γ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL‑2 release, and spike-induced IFN‑γ release after 6 months were significantly associated with increased IL‑2 & IL‑4, IP‑10 & MCP1, and IFN‑γ & IP‑10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00.
Discussion: In summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.
Keywords: COVID-19; antibodies; cytokines; immune monitoring; immunity; memory cells; transcriptomics.
. 2024 Aug 29:15:1423766.
doi: 10.3389/fimmu.2024.1423766. eCollection 2024. Antigen-specific T helper cells and cytokine profiles predict intensity and longevity of cellular and humoral responses to SARS-CoV-2 booster vaccination
Lukas Page[SUP] 1 [/SUP], Kevin Dennehy[SUP] 1 [/SUP], Katharina Mueller[SUP] 2 [/SUP], Philipp Girl[SUP] 2 3 4 [/SUP], Eva Loell[SUP] 1 [/SUP], Hellen Buijze[SUP] 1 [/SUP], Johanna-Maria Classen[SUP] 5 [/SUP], Helmut Messmann[SUP] 5 [/SUP], Christoph Roemmele[SUP] 5 [/SUP], Reinhard Hoffmann[SUP] 1 [/SUP], Sebastian Wurster[SUP] #[/SUP][SUP] 6 [/SUP], Andre Fuchs[SUP] #[/SUP][SUP] 5 [/SUP]
Affiliations
- PMID: 39267758
- PMCID: PMC11390417
- DOI: 10.3389/fimmu.2024.1423766
Introduction: Pre-existent pools of coronavirus-specific or cross-reactive T cells were shown to shape the development of cellular and humoral immune responses after primary mRNA vaccination against SARS-CoV-2. However, the cellular determinants of responses to booster vaccination remain incompletely understood. Therefore, we phenotypically and functionally characterized spike antigen-specific T helper (Th) cells in healthy, immunocompetent individuals and correlated the results with cellular and humoral immune responses to BNT162b2 booster vaccination over a six-month period.
Methods: Blood of 30 healthy healthcare workers was collected before, 1, 3, and 6 months after their 3rd BNT162b2 vaccination. Whole blood was stimulated with spike peptides and analyzed using flow cytometry, a 13-plex cytokine assay, and nCounter-based transcriptomics.
Results: Spike-specific IgG levels at 1 month after booster vaccination correlated with pre-existing CD154+CD69+IFN-γ+CD4+ effector memory cells as well as spike-induced IL-2 and IL-17A secretion. Early post-booster (1-month) spike IgG levels (r=0.49), spike-induced IL‑2 (r=0.58), and spike-induced IFN‑γ release (r=0.43) correlated moderately with their respective long-term (6-month) responses. Sustained robust IgG responses were significantly associated with S-specific (CD69+±CD154+±IFN-γ+) Th-cell frequencies before booster vaccination (p=0.038), especially double/triple-positive type-1 Th cells. Furthermore, spike IgG levels, spike-induced IL‑2 release, and spike-induced IFN‑γ release after 6 months were significantly associated with increased IL‑2 & IL‑4, IP‑10 & MCP1, and IFN‑γ & IP‑10 levels at 1 month post-booster, respectively. On the transcriptional level, induction of pathways associated with both T-cell proliferation and antigen presentation was indicative of sustained spike-induced cytokine release and spike-specific IgG production 6 months post-booster. Using support vector machine models, pre-booster spike-specific T-cell frequencies and early post-booster cytokine responses predicted sustained (6-month) responses with F1 scores of 0.80-1.00.
Discussion: In summary, spike-specific Th cells and T-cellular cytokine signatures present before BNT162b2 booster vaccination shape sustained adaptive cellular and humoral responses post-booster. Functional T-cell assays might facilitate early identification of potential non-responders.
Keywords: COVID-19; antibodies; cytokines; immune monitoring; immunity; memory cells; transcriptomics.