ArticleThe American journal of pathology2007
Genetically attenuated Plasmodium berghei liver stages persist and elicit sterile protection primarily via CD8 T cells.
Article in The American journal of pathology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Pooled it
- A conserved Plasmodium nuclear protein is critical for late liver stage development.Communications biology · 2024Article
- A replication competent Plasmodium falciparum parasite completely attenuated by dual gene deletion.EMBO molecular medicine · 2024Article
- Malaria & mRNA Vaccines: A Possible Salvation from One of the Most Relevant Infectious Diseases of the Global South.Acta parasitologica · 2023Article
- [Malarial antigens in the era of mRNA vaccines].Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde · 2022Review
- The role of different components of the immune system against Plasmodium falciparum malaria: Possible contribution towards malaria vaccine development.Molecular and biochemical parasitology · 2021Review
- Chemoprophylaxis vaccination with a Plasmodium liver stage autophagy mutant affords enhanced and long-lasting protection.NPJ vaccines · 2021Article
- Immune responses to malaria pre-erythrocytic stages: Implications for vaccine development.Parasite immunology · 2021Review
- AttenuatedCancer biology & medicine · 2019Article
- Immunomic Identification of Malaria Antigens Associated With Protection in Mice.Molecular & cellular proteomics : MCP · 2019Article
- Protective immunity differs between routes of administration of attenuated malaria parasites independent of parasite liver load.Scientific reports · 2017Article
- Engineering of Genetically Arrested Parasites (GAPs) For a Precision Malaria Vaccine.Frontiers in cellular and infection microbiology · 2017Review
- Protective immunity to liver-stage malaria.Clinical & translational immunology · 2016Review
- Myeloid Cell Isolation from Mouse Skin and Draining Lymph Node Following Intradermal Immunization with Live Attenuated Plasmodium Sporozoites.Journal of visualized experiments : JoVE · 2016Article
- Review
- Plasmodium cellular effector mechanisms and the hepatic microenvironment.Frontiers in microbiology · 2015Review
- AAV8-mediated in vivo overexpression of miR-155 enhances the protective capacity of genetically attenuated malarial parasites.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Memory T cells maintain protracted protection against malaria.Immunology letters · 2014Review
- Correlates of protective immunity following whole sporozoite vaccination against malaria.Immunologic research · 2014Review
- An experimental model to study tuberculosis-malaria coinfection upon natural transmission of Mycobacterium tuberculosis and Plasmodium berghei.Journal of visualized experiments : JoVE · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Live-attenuated Plasmodium liver stages remain the only experimental model that confers complete sterile protection against malaria. Irradiation-attenuated Plasmodium parasites mediate protection primarily by CD8 T cells. In contrast, it is unknown how genetically attenuated liver stage parasites provide protection. Here, we show that immunization with uis3(-) sporozoites does not cause breakthrough infection in T and B-cell-deficient rag1(-/-) and IFN-gamma(-/-) mice. However, protection was abolished in these animals, suggesting a crucial role for adaptive immune responses and interferon-gamma. Although uis3(-) immunization induced Plasmodium-specific antibodies, B- cell-deficient mice immunized with uis3(-) sporozoites were completely protected against wild-type sporozoite challenge infection. T-cell depletion experiments before parasite challenge showed that protection is primarily mediated by CD8 T cells. In good agreement, adoptive transfer of total spleen cells and enriched CD8 T cells from immunized animals conferred sterile protection against malaria transmission to recipient mice, whereas adoptive transfer of CD4 T cells was less protective. Importantly, primaquine treatment completely abolished the uis3(-)-mediated protection, indicating that persistence of uis3(-)-attenuated liver stages is crucial for their protective action. These findings establish the basic immune mechanisms underlying protection induced by genetically attenuated Plasmodium parasites and substantiate their use as vaccines against malaria.
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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.