SynthesisPloS one2010
Why functional pre-erythrocytic and bloodstage malaria vaccines fail: a meta-analysis of fully protective immunizations and novel immunological model.
Synthesis in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Identifying Fast and Slow-Acting Antimalarial Compounds of Pandemic Response Box Against Blood-Stage Culture of Plasmodium falciparum 3D7.Current microbiology · 2024Article
- Rethinking detection of pre-existing and interveningFrontiers in immunology · 2022Review
- Computational investigations of the immune response to repeated influenza infections and vaccinations.Royal Society open science · 2021Article
- Mapping immune variation andeLife · 2021Article
- A Peptide-Based PD1 Antagonist Enhances T-Cell Priming and Efficacy of a Prophylactic Malaria Vaccine and Promotes Survival in a Lethal Malaria Model.Frontiers in immunology · 2020Article
- To the Skin and Beyond: The Immune Response to African Trypanosomes as They Enter and Exit the Vertebrate Host.Frontiers in immunology · 2020Review
- Novel Strategies for Malaria Vaccine Design.Frontiers in immunology · 2018Review
- Protective immunity differs between routes of administration of attenuated malaria parasites independent of parasite liver load.Scientific reports · 2017Article
- Purification of Plasmodium Sporozoites Enhances Parasite-Specific CD8+ T Cell Responses.Infection and immunity · 2016Article
- Active migration and passive transport of malaria parasites.Trends in parasitology · 2015Review
- Phenotypic characterization of Plasmodium berghei responsive CD8+ T cells after immunization with live sporozoites under chloroquine cover.Malaria journal · 2014Article
- Malaria immunity in man and mosquito: insights into unsolved mysteries of a deadly infectious disease.Annual review of immunology · 2014Review
- Looking under the skin: the first steps in malarial infection and immunity.Nature reviews. Microbiology · 2013Review
- The pathogenesis of malaria: a new perspective.Pathogens and global health · 2013Article
- Chronic exposure to Plasmodium falciparum is associated with phenotypic evidence of B and T cell exhaustion.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- The generation and evaluation of two panels of epitope-matched mouse IgG1, IgG2a, IgG2b and IgG3 antibodies specific for Plasmodium falciparum and Plasmodium yoelii merozoite surface protein 1-19 (MSP1(19)).Experimental parasitology · 2012Article
- Our impasse in developing a malaria vaccine.Cellular and molecular life sciences : CMLS · 2011Article
- Intradermal infections of mice by low numbers of african trypanosomes are controlled by innate resistance but enhance susceptibility to reinfection.The Journal of infectious diseases · 2011Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundClinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. METHODOLOGY/PRINCIPAL
findingsWe identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. CONCLUSIONS/SIGNIFICANCE: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications for accelerated local eliminations of malaria, and significantly increases potential for eradication.
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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.