Effect of the Modification of p24 Peptide Antigen on Dendritic Cell Uptake and T Cell Activation
Bibliographic record
Abstract
BACKGROUND: Vacc-4x is a candidate therapeutic vaccine consisting of 4 modified peptides based on conserved regions of HIV-1 p24Gag. Vacc4x has been shown to induce long term cellular immunity in immunized infected individuals resulting a reduction in viral load on treatment interruption. OBJECTIVE: Vacc-4x peptides are modified. In this study the effect of modification on uptake of the peptides into PBMC, their subsequent presentation and antigenicity was tested. The feasibility of using an in vitro culture system for testing immunogenicity of peptides using PBMC from uninfected donors was also assessed. METHODS: Labelled peptides were evaluated for uptake into PBMC using flow cytometry or confocal microscopy. Monocyte derived dendritic cells (DC) and autologous T cells were co-cultured with native and modified peptide antigens derived from p24. Activation was measured by flow cytometry and IFN-γ ELISPOT. RESULTS: Peptide modifications significantly increased peptide uptake by monocyte derived dendritic cells. Both the native (unmodified) and Vacc-4x (modified) peptide loaded DC could activate CD4+ and CD8+ T cell responses in vitro. Individual modified peptides induced greater responses than their native counterparts. The grouped Vacc-4x peptides elicited greater IFN γ responses than their native grouped counterparts at a lower concentration, however this effect was not detected at higher concentrations. CONCLUSION: These data indicate that the modifications increase uptake, alter the antigenicity of HIV- 1 p24 Vacc-4x peptides and increase the breadth of the response to the Vacc-4x peptides. The in vitro cell culture system is a suitable model for the antigenic assessment of peptide antigens.
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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 | 0.001 | 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) | 0.000 | 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".