P18-13 LB. Immunogenicity of an autologous dendritic cell anti-HIV therapy in HIV-1 infected individuals
Bibliographic record
Abstract
The immunogenicity of an autologous dendritic cell (DC) anti-HIV therapy, AGS-004, was evaluated in a multicenter Phase 2 trial. The treatment regiment consisted of four intradermal doses, administered monthly in combination with anti-retroviral therapy (ART) followed by a well-controlled structured treatment interruption (STI). The immunotherapy consisted of monocyte-derived DC co-electroporated with CD40L in vitro transcribed (IVT) RNA along with amplified IVT RNA encoding for 4 HIV-1 antigens (GAG, NEF, REV and VPR). Cellular immunity was determined simultaneously by lymphocyte proliferation (CFSE) and cytokine production (ICS)) multi-parameter flow cytometry assays using peripheral blood mononuclear cells from vaccinated individuals stimulated in vitro with DC electroporated with either all 4 or the individual HIV RNA. The two assays were performed according to applicable GCLP guidelines. Among 28 subjects recruited until now, there were 8 subjects that had already undergone an initial cycle of this immunotherapy (CAN-HIV-1 pilot study). All other subjects that were naïve to this immunotherapy successfully completed the immune monitoring phase of the protocol and were on a treatment interruption of varying lengths. We performed an analysis of anti-HIV-specific response by evaluating the proliferation, IFNg production and the functionality in CD8+ and CD4+ T cells stimulated with autologous Gag, Nef, Rev and Vpr. Interestingly, the absolute number of proliferating CD8+ T-cells and those producing IFNg in response to GAG-peptides showed an impressive increase after the first vaccination and following ART interruption. Preliminary results of these roll-over subjects indicate an increase in HIV-specific CD8+ T-lymphocyte polyfunctional populations following immunotherapy which is accentuated after ART treatment interruption. These populations have mainly a CD27+CD8+CD45RA- phenotype. This immunotherapeutic approach may overcome the lack of polyvalent specificity of the immune response for autologous HIV-1 antigens that has been one of the reasons for the failure of prior immunotherapies that use consensus HIV-1 sequences.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".