Discriminating Protective from Nonprotective <i>Plasmodium</i>-Specific CD8+ T Cell Responses
Bibliographic record
Abstract
Despite decades of research, malaria remains a global health crisis. Current subunit vaccine approaches do not provide efficient long-term, sterilizing immunity against Plasmodium infections in humans. Conversely, whole parasite vaccinations with their larger array of target Ags have conferred long-lasting sterilizing protection to humans. Similar studies in rodent models of malaria reveal that CD8(+) T cells play a critical role in liver-stage immunity after whole parasite vaccination. However, it is unknown whether all CD8(+) T cell specificities elicited by whole parasite vaccination contribute to protection, an issue of great relevance for enhanced subunit vaccination. In this article, we show that robust CD8(+) T cell responses of similar phenotype are mounted after prime-boost immunization against Plasmodium berghei glideosome-associated protein 5041-48-, sporozoite-specific protein 20318-325-, thrombospondin-related adhesion protein (TRAP) 130-138-, or circumsporozoite protein (CSP) 252-260-derived epitopes in mice, but only CSP252-260- and TRAP130-138-specific CD8(+) T cells provide sterilizing immunity and reduce liver parasite burden after sporozoite challenge. Further, CD8(+) T cells specific to sporozoite surface-expressed CSP and TRAP proteins, but not intracellular glideosome-associated protein 50 and sporozoite-specific protein 20, efficiently recognize sporozoite-infected hepatocytes in vitro. These results suggest that: 1) protection-relevant antigenic targets, regardless of their immunogenic potential, must be efficiently presented by infected hepatocytes for CD8(+) T cells to eliminate liver-stage Plasmodium infection; and 2) proteins expressed on the surface of sporozoites may be good target Ags for protective CD8(+) T cells.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".