Evidence for a model of conformational change by the <i>Plasmodium falciparum</i> circumsporozoite protein during sporozoite development in the mosquito host through the use of camelid single-domain antibodies
Bibliographic record
Abstract
ABSTRACT Plasmodium sporozoites (SPZs) are formed in the Anopheles mosquito midgut from where they travel to the salivary glands and subsequently to the mammalian liver after deposition into the skin. The SPZ’s main surface antigen, the circumsporozoite protein (CSP), plays a pivotal role in SPZ biology and constitutes the immunodominant target for host antibodies. In this study, we raised single-domain antibodies (sdAbs) against CSP from P. falciparum (PfCSP) by immunizing two alpacas with recombinant versions of the antigen. We found that all identified sdAbs specifically target PfCSP’s globular <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="u1" overflow="scroll"> <mml:mstyle displaystyle="true" scriptlevel="0"> <mml:mi>α</mml:mi> </mml:mstyle> </mml:math> TSR domain without cross-reacting with P. berghei CSP. Further characterization revealed that most sdAbs recognize native PfCSP on the SPZ surface, although they do not have any inhibitory effect on hepatocyte binding and invasion. Structural studies showed that all binders target the previously identified <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="u2" overflow="scroll"> <mml:mstyle displaystyle="true" scriptlevel="0"> <mml:mi>α</mml:mi> </mml:mstyle> </mml:math> -epitope, confirming the non-protective nature of this epitope. Comparison of sdAb binding to midgut and salivary gland SPZs revealed a shift in the exposure and accessibility of the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="u3" overflow="scroll"> <mml:mstyle displaystyle="true" scriptlevel="0"> <mml:mi>α</mml:mi> </mml:mstyle> </mml:math> -epitope. Hence, our findings provide further evidence that CSP undergoes structural changes during SPZ development in the mosquito host.
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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 | 0.001 | 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 | 0.001 | 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".