Doesn’t It All Come Down to Function? How To Correlate VAR2CSA Antibodies with Protection
Bibliographic record
Abstract
We wish to respond to the article “Going native, or the risk of overreliance on recombinant antigens” (1) by Dr. Lopez-Perez, which questions our findings that antibodies to VAR2CSA can arise outside pregnancy. She asserts that relying on antibody recognition of recombinant proteins can yield misleading data on VAR2CSA antibody responses. We agree; it is not surprising that VAR2CSA may be folded or modified differently when expressed in a variety of cell systems, and this is expected to alter the recognition of the recombinant protein by antibodies. We contend that the most important way to characterize VAR2CSA antibodies is not based exclusively on antigen recognition but on whether those antibodies block the adhesion of infected erythrocytes (IE) to the placental receptor chondroitin sulfate A (CSA). Antibodies with inhibitory activity strongly correlate with protection against pregnancy-associated malaria (PAM) (2–6). The importance of function was further emphasized by Khattab et al. in 2004 (5): “The identification of functional antibodies which appear to inhibit the binding of parasites to CSA in the placenta is crucial to developing a successful vaccination strategy against PAM.”
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.007 |
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; both teacher heads agree on what is shown here.
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".