P173 Investigating varicella-zoster virus-specific T cells through the lenses of HIV
Bibliographic record
Abstract
<h3>Background</h3> Varicella-zoster virus (VZV), also known as chickenpox virus, constitutes a promising vector for a successful HIV vaccine. As an effort to scrutinize its potential, we are characterizing the susceptibility of VZV-specific CD4 T cells to HIV infection and the phenotypic profile of both CD4 and CD8 T cells. <h3>Methods</h3> Blood T cells isolated from a cohort of healthy Kenyan women with pre-immunity to VZV (NCT02514018) were stimulated <i>in vitro</i> using 15-mer peptides representing VZV glycoprotein E (gE) and VZV Open Reading Frame 4 (ORF4). CD4 and CD8 T cell memory phenotypes were characterized by flow cytometry based on the expression of CCR7/CD45RA. The activation status of VZV-specific CD4 T cells was measured by the expression of HLA-DR, CD69, and CD25 after 6-day stimulation with gE and ORF4 peptides. Susceptibility to HIV infection was assessed using <i>in vitro</i> infection with a CCR5-tropic virus. DMSO and CMV peptides were used as negative and positive controls, respectively. <h3>Results</h3> A similar frequency of central memory CD4 T cells (T<sub>CM</sub>) (median 24%, IQR 18%-32%) and effector memory CD4 T cells (T<sub>EM</sub>) (median 27%, IQR 20%-32%) was observed in our cohort. The predominant CD8 memory subtype was T<sub>EMRA</sub> (median 28%, IQR 21%-40%) followed by T<sub>EM</sub> cells (median 12%, IQR 8%-19%) (n=45). Preliminary results show our ability to expand VZV-specific cells in culture using gE and ORF4 as stimuli and that these cells highly express the marker HLA-DR. Their susceptibility to <i>in vitro HIV</i> infection is currently under investigation using CMV-specific cells as comparator. <h3>Conclusion</h3> A viral vector able to sustain CD8 T<sub>EM</sub> responses without fueling the immune system with HIV target cells constitutes an ideal candidate for an HIV vaccine. Hence, our study sheds light on key aspects of VZV-specific immunity that will help determining its future as a vector in an HIV vaccine. <h3>Disclosure</h3> No significant relationships.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".