OA021-01. Construction and characterization of replication competent attenuated NYVAC-based vectors as potential HIV vaccines
Bibliographic record
Abstract
Poxvirus viruses have been utilized for many years as vaccine vectors. Recent years have seen an increase in efforts to identify safer pox vectors to express heterologous antigens, in this case HIV antigens. Safer pox vectors have included MVA, ALVAC and NYVAC, which are all replication deficient in human cells. However, the loss of replication competence has also reduced antigen expression, and therefore, immunologic response to the vaccination. We have constructed vectors in a NYVAC background that are replication competent but attenuated for virulence. To restore replication competence in NYVAC that expresses clade C HIV gag, pol, nef and env (NYVAC-C), we inserted genes deleted in the parental vector: 1) NYVAC-C-KC includes the human host range genes K1L and C7L ; 2) NYVAC-C+12 includes the entire cassette of genes from K1L to C7L that is deleted from NYVAC. To decrease virulence, we deleted the E3L gene, which is required for interferon-resistance and virulence, and replaced it with a gene from Ambystoma tigrinum virus (ATV, the new virus is NYVAC-C+12-ATV), which restores a single round of replication. In vitro characterization of the constructs demonstrates restoration of replication in primary and human cell lines. NYVAC-C+12-ATV leads to induction of pro-inflammatory signal transduction pathways. Pathogenicity studies in newborn mice demonstrate attenuation of 3–5 logs when compared to wt vaccinia virus or to NYCBH. NYVAC constructs provide increased safety in the most sensitive of animal models. Because antigen expression is increased in these replication-competent constructs, they may be more immunogenic than replication-defective poxvirus vectors. Increased pro-inflammatory signal transduction in cells infected with NYVAC-C+12-ATV may also lead to an increase in immunogenicity of this highly attenuated vector. Thus, these replication competent, attenuated viral vectors may have improved immunogenicity over replication defective poxvirus vectors, while maintaining an improved safety profile.
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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) | 0.000 | 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".