ArticleNature immunology2011
Therapeutic blockade of PD-L1 and LAG-3 rapidly clears established blood-stage Plasmodium infection.
Article in Nature immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04661579 (A Phase 2b Randomized, Open-label, Controlled, Single Center Study in Plasmodium Falciparum-infected and Uninfected Adults Age 18-55 Years Old in Kenya to Evaluate the Efficacy of the Delayed, Fractional Dose RTS,S/AS01E Malaria Vaccine in Subjects Treated With Artemisinin Combination Therapy Plus Primaquine), which is not on this map. Cited by 319 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2b Randomized, Open-label, Controlled, Single Center Study in Plasmodium Falciparum-infected and Uninfected Adults Age 18-55 Years Old in Kenya to Evaluate the Efficacy of the Delayed, Fractional Dose RTS,S/AS01E Malaria Vaccine in Subjects Treated With Artemisinin Combination Therapy Plus Primaquine
Who cites it
319 citing papers in PubMed, 472 citations in OpenAlex.
- Efficacy of RTS,S/AS01E Only Seen in Baseline Parasitemic and Not Baseline Aparasitemic Plasmodium falciparum-Exposed, Drug-Treated Kenyan Adults.The Journal of infectious diseases · 2025Trial
- Depletion of LAG-3Clinical pharmacology and therapeutics · 2021Trial
- Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria.Nature immunology · 2020Trial
- CD11a and CD49d enhance the detection of antigen-specific T cells following human vaccination.Vaccine · 2017Trial
- Exploring the functions of NKG7 in CD4+ and CD8+ T cells during malaria.PLoS pathogens · 2026Article
- Malaria exposure history shapes PD-1 expression across human B-cell subsets during acute Plasmodium falciparum infection.BMC microbiology · 2026Article
- Tobemstomig, a Novel Bispecific Antibody, Preferentially Blocks PD-1 and LAG-3 on CD8 TILs to Expand Stem-like T Cells for Sustained Tumor Control.Cancer research communications · 2026Article
- The LEF1-LAG3 axis regulates CD4Parasites & vectors · 2026Article
- Cellular Immune Response and T Cell Epitope Mapping ofVaccines · 2026Article
- mRNA vaccination overcomes haemozoin-mediated impairment of whole-parasite malaria vaccines in mice.Nature microbiology · 2026Article
- LAG-3Immunology · 2026Article
- The endemic dilemma: why whole sporozoite malaria vaccine efficacy falls in the field.Trends in parasitology · 2026Review
- Advanced immunotherapy across diseases and the role of artificial intelligence: A review.Biomolecules & biomedicine · 2026Review
- A Peptide Inhibitor of Lymphocyte Activation Gene-3 Interaction with Fibrinogen-like Protein 1 Synergizes with Programmed Death-Ligand 1 Blockade to Restore T Cell Activity and Inhibit Tumor Growth.Biomaterials research · 2026Article
- Combined anti-PD-1 and amphotericin B therapy reduces fungal burden and enhances control of murine paracoccidioidomycosis.Frontiers in cellular and infection microbiology · 2026Article
- Immune checkpoint inhibitors in infectious diseases: therapeutic reinvigoration, immunopathology, and precision targeting.Frontiers in immunology · 2026Review
- T follicular helper cell development during malaria.Current opinion in immunology · 2025Review
- mRNA vaccination overcomes hemozoin-mediated impairment of whole parasite vaccine efficacy for malaria.bioRxiv : the preprint server for biology · 2025Article
- Chimeric PRR T-cell-engager targeting cell surface β-1,3-glucan for invasive candidiasis.PLoS pathogens · 2025Article
- Regulatory T cell memory: implications for malaria.Journal of immunology (Baltimore, Md. : 1950) · 2025Review
259 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Infection of erythrocytes with Plasmodium species induces clinical malaria. Parasite-specific CD4(+) T cells correlate with lower parasite burdens and severity of human malaria and are needed to control blood-stage infection in mice. However, the characteristics of CD4(+) T cells that determine protection or parasite persistence remain unknown. Here we show that infection of humans with Plasmodium falciparum resulted in higher expression of the inhibitory receptor PD-1 associated with T cell dysfunction. In vivo blockade of the PD-1 ligand PD-L1 and the inhibitory receptor LAG-3 restored CD4(+) T cell function, amplified the number of follicular helper T cells and germinal-center B cells and plasmablasts, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, and proper function can be restored by inhibitory therapies to enhance parasite control.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.