Trial reportPloS one2014
Sterile immunity to malaria after DNA prime/adenovirus boost immunization is associated with effector memory CD8+T cells targeting AMA1 class I epitopes.
Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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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.
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Who cites it
45 citing papers in PubMed, 64 citations in OpenAlex.
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- Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.The Journal of infectious diseases · 2016Trial
- Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.The Journal of infectious diseases · 2015Trial
- Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming.Human vaccines & immunotherapeutics · 2015Trial
- Natural selection on apical membrane antigen 1 (AMA1) of an emerging zoonotic malaria parasite Plasmodium inui.Scientific reports · 2024Article
- Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines.Viruses · 2023Review
- Structure-based design of a strain transcending AMA1-RON2L malaria vaccine.Nature communications · 2023Article
- Memory CD8+ T cell-mediated protection against liver-stage malaria.Immunological reviews · 2023Review
- Systematic Determination of TCR-Antigen and Peptide-MHC Binding Kinetics among Field Variants of aJournal of immunology (Baltimore, Md. : 1950) · 2022Article
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- Article
- Comparison of the impact of allelic polymorphisms in PfAMA1 on the induction of T Cell responses in high and low malaria endemic communities in Ghana.Malaria journal · 2021Article
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- Adenoviral Vector-Based Vaccine Platforms for Developing the Next Generation of Influenza Vaccines.Vaccines · 2020Review
- Identification of Plasmodium falciparum circumsporozoite protein-specific CD8+ T cell epitopes in a malaria exposed population.PloS one · 2020Article
- Comprehensive Review of HumanFrontiers in immunology · 2019Review
- Detection of EXP1-Specific CD4+ T Cell Responses Directed Against a Broad Range of Epitopes Including Two Promiscuous MHC Class II Binders During AcuteFrontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFifteen volunteers were immunized with three doses of plasmid DNA encoding P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1) and boosted with human adenovirus-5 (Ad) expressing the same antigens (DNA/Ad). Four volunteers (27%) demonstrated sterile immunity to controlled human malaria infection and, overall, protection was statistically significantly associated with ELISpot and CD8+ T cell IFN-γ activities to AMA1 but not CSP. DNA priming was required for protection, as 18 additional subjects immunized with Ad alone (AdCA) did not develop sterile protection. METHODOLOGY/PRINCIPAL
findingsWe sought to identify correlates of protection, recognizing that DNA-priming may induce different responses than AdCA alone. Among protected volunteers, two and three had higher ELISpot and CD8+ T cell IFN-γ responses to CSP and AMA1, respectively, than non-protected volunteers. Unexpectedly, non-protected volunteers in the AdCA trial showed ELISpot and CD8+ T cell IFN-γ responses to AMA1 equal to or higher than the protected volunteers. T cell functionality assessed by intracellular cytokine staining for IFN-γ, TNF-α and IL-2 likewise did not distinguish protected from non-protected volunteers across both trials. However, three of the four protected volunteers showed higher effector to central memory CD8+ T cell ratios to AMA1, and one of these to CSP, than non-protected volunteers for both antigens. These responses were focused on discrete regions of CSP and AMA1. Class I epitopes restricted by A*03 or B*58 supertypes within these regions of AMA1 strongly recalled responses in three of four protected volunteers. We hypothesize that vaccine-induced effector memory CD8+ T cells recognizing a single class I epitope can confer sterile immunity to P. falciparum in humans. CONCLUSIONS/SIGNIFICANCE: We suggest that better understanding of which epitopes within malaria antigens can confer sterile immunity and design of vaccine approaches that elicit responses to these epitopes will increase the potency of next generation gene-based vaccines.
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