P04-03. Cross-clade neutralization analysis of plasmas from clade B, C and CRF01_AE HIV-infected donors
Bibliographic record
Abstract
The genetic diversity of HIV-1, particularly in Env, is considered a major challenge for vaccine researchers, especially those attempting to elicit broadly neutralizing antibodies. Categorizing HIV strains into neutralization serotypes may help determine the requirements for maximal vaccine immune coverage. HIV is divided into clades, based on genetic relatedness, principally in Env. Investigations as to whether these clades might help to define neutralizing serotypes have so far mostly been confined to small studies, and have been hampered by the challenges of traditional PBMC-blast neutralization assays. The observation that some HIV+ plasmas neutralize viruses from several major clades hints of an undercurrent of conserved neutralization, but its potency relative to any clade-restricted activity is unknown. High throughput pseudovirus neutralization assays provide a way to investigate. Here, we measured neutralization of 45 primary viruses from clades B, C and CRF_01 AE by 12 broad plasmas from the same 3 clades. Significant cross-neutralization was observed, and well-defined neutralizing serotypes was absent. However, each plasma exhibited a unique pattern against the spectrum of viruses. Increased intraclade neutralization titers was observed in many cases. These were most pronounced for clade B-E viruses that were neutralized 2–10 fold more potently by clade-matched plasmas in several cases. We also investigated binding serotypes by gp120 ELISA, where we observed greater intraclade binding titers for B-E plasmas, mirroring the intraclade neutralization. Mapping analyses suggested that in some cases, the cross-neutralizing activity is mostly directed to gp120 and overlaps the CD4 binding site. The generally broad neutralization observed suggests that an immunogen based on one or a few Envs could, in principle, provide worldwide HIV-1 protection. Clade C Envs may be worth special attention, considering the particularly broad plasma neutralizing activities. The challenge remains to better define the cross-neutralizing specificities and moreover, to find immunogens able to induce them.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.001 | 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".