Innovations to Address Complex Challenges: 22<sup>nd</sup> Annual Canadian Conference on HIV/AIDS Research
Bibliographic record
Abstract
An estimated 2.7 million people are newly infected by HIV-1 every year.For every 2 persons starting treatment, 5 become newly infected.A safe and effective preventative HIV-1 vaccine is the only way to stop the new infections and control the pandemic.The protease of HIV-1 is a small 99-amino acid aspartic enzyme that mediates the cleavage of Gag, Gag-Pol and Nef precursor polyproteins.The process is highly specific, temporally regulated and essential for the production of infectious viral particles.A total of twelve proteolytic reactions are required to generate a viable virion.Therefore, a vaccine targeting the 12 protease cleavage sites of HIV-1 could be effective.Since the protease cleavage sites of HIV-1 are highly conserved among major subtypes of HIV-1, direct immune responses against these cleavage sites would yield two major advantages.First, the host immune response could destroy the virus before its permanent establishment in the host.Second, the vaccine could force the virus to accumulate mutations eliminating the normal function of the HIV protease thus eliminating viable virions.We have conducted a proof of concept study to investigate the feasibility and effectiveness of this approach.The recombinant VSV-peptides were used to immunize cynomolgus macaques and nanopackaged peptides were used to boost the immune response to the peptides overlapping the 12 protease cleavage sites of SIVmac239.The immunized macaques and controls were cumulatively challenged intrarectally with increased dosage of SIVmac239.Results showed that antibody and T cell responses to the 12 protease cleavage site can protect macaques against higher dosage of SIVmac239 challenge (p=0.005,R=0.42) and the vaccine group maintains significantly higher CD4 + counts (p=0.0002)than the controls weeks after being infected.Viral sequence analysis detected extensive mutations in the PCS and the flanking region.The break-through viruses of the vaccine group have higher mutation rate in PCS regions than that of the control group.The extensive mutations at/around PCS sequences correlated with lower viral load (P<0.0001).
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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 | 0.021 | 0.018 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.003 | 0.003 |
| Science and technology studies | 0.010 | 0.011 |
| Scholarly communication | 0.018 | 0.005 |
| Open science | 0.005 | 0.009 |
| Research integrity | 0.010 | 0.016 |
| Insufficient payload (model declined to judge) | 0.031 | 0.009 |
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".