Predictive markers of SARS-CoV-2 spike-specific cytotoxic T cell activity following Omicron breakthrough infection
Bibliographic record
Abstract
At a population level, evaluation of vaccine efficacy and of immunity in general focuses on measuring humoral immunity, especially antibody-mediated neutralization. However, antibody-dependent cell-mediated cytotoxicity (ADCC) and cellular immunity are key processes for pathogen clearance and often provide broader protection against emerging variants. More information on vaccine and infection-related determinants or markers of cell-mediated cytotoxicity is needed to inform design of standardized, high throughput tests assessing these processes. We previously showed that persons infected with SARS-CoV-2 prior to vaccination (hybrid immunity) had polyfunctional CD8+ T cells and robust ADCC against SARS-CoV-2 spike (S), while persons infected with Omicron after vaccination (breakthrough infection) had weak ADCC. In the current study, we investigated the impact of Omicron breakthrough infection on S-specific cellular immunity, including polyfunctional CD8+ T cell and cytotoxic T lymphocyte (CTL) levels of 28 previously uninfected individuals vaccinated either two or three times against SARS-CoV-2. In the group with three vaccinations, Omicron breakthrough infection significantly increased the frequency of circulating SARS-CoV-2 S-specific T cells, polyfunctional interferon-gamma and interleukin-2-producing SARS-CoV-2 S-specific CD8+ T cells and CTL after in vitro stimulation. Matrix testing with overlapping S peptides indicated recognition of one to two CTL epitopes per individual and revealed two previously unreported epitopes. Circulating S-specific cellular immune response magnitude neither correlated with, nor predicted CTL activity against SARS-CoV-2 S, but polyfunctional S-specific CD8+ T cell frequency seven days after stimulation and antibody reactivity against determinants indicating robust ADCC were both associated with day 10 CTL activity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".