The vaccine candidate Liver Stage Antigen 3 is exported during Plasmodium falciparum infection and required for liver-stage development
Bibliographic record
Abstract
Abstract Plasmodium falciparum, which causes the most severe malaria, remodels infected erythrocytes by exporting several hundred effector proteins. Parasites express the aspartyl protease plasmepsin V that processes proteins containing a PEXEL motif and the PTEX translocon to successfully export proteins. During liver-stage infection, PTEX is required for P. falciparum development, but which proteins are exported remain unknown; these proteins may serve important biological functions and be presented by MHC-I molecules, thereby representing potential vaccine candidates. Here, we investigated liver stage antigen 3 (LSA3), an immunogenic protein of the Laverania subgenus of Plasmodium. We show that LSA3 possesses a PEXEL motif processed by plasmepsin V and is targeted to one or more membranes surrounding the blood-stage parasite, suggestive of the parasitophorous vacuole membrane (PVM). A subset of LSA3 also localizes in the erythrocyte, where it forms punctate structures that are not Maurers clefts but are soluble in biochemical fractionation assays reminiscent of J-dot proteins. During infection of human hepatocytes, antibodies to LSA3 co-localize with EXP1 and EXP2 at the PVM, yet these antibodies were rarely detected beyond this membrane. Finally, genetic disruption of LSA3 in P. falciparum NF54 attenuated fitness at the liver stage, manifest as a 40% reduction in parasite liver load by day 5 postinfection of humanized mice. The identification of LSA3 as a previously unrecognized member of the P. falciparum exportome, essential for normal liver-stage development and capable of eliciting protective pre-erythrocytic immunity, confirms the hypothesized potential of exported proteins as promising malaria vaccine candidates, underscoring the need for continued investigation into their discovery and biological characterization.
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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 | 0.000 | 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) | 0.001 | 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 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".