Selection of human anti-HIV broadly neutralizing antibodies occurs within the context of frozen 1F7-idiotypic repertoire
Bibliographic record
Abstract
OBJECTIVE: Most HIV-infected individuals develop HIV-specific antibodies (Abs) exhibiting a common idiotype designated as 1F7. Expression of this idiotype establishes idiotypic-driven repertoire freeze, maintaining antibody responses ineffective at controlling autologous contemporaneous viruses. As such, this study investigated the temporal dynamics of 1F7-idiotype expression, as well as the role of this idiotype in the selection of HIV-specific broadly neutralizing antibodies (BnAbs). DESIGN: This study investigated the timing of appearance and persistence of 1F7-idiotypic HIV-specific Abs by screening plasma samples from individuals followed longitudinally starting in primary HIV infection. The expression of 1F7 on HIV-specific BnAbs was also investigated to determine whether their development occurs within the context of 1F7-idiotypic repertoire freeze. METHODS: The 1F7 idiotype was detected on gp120, gp41 and membrane proximal external region (MPER) peptide-specific Abs using an enzyme-linked immunosorbent assay (ELISA). HIV-specific Abs in longitudinal plasma samples from six patients and six BnAbs were tested for the presence of the 1F7 idiotype. RESULTS: The idiotype was expressed on HIV-specific Abs within 3 months of infection, with the magnitude of 1F7 detection increasing with time from infection. The 1F7 idiotype was also expressed on all BnAbs tested. CONCLUSION: These results demonstrate that HIV-specific antibody responses are restricted within the 1F7 idiotype from early infection onwards, and that six well characterized BnAbs developed within the context of 1F7-idiotypic repertoire freeze. Future research should evaluate the necessity of the 1F7 idiotype for broad neutralization, and determine if vaccines should target Abs within or outside this idiotypic space.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".