ArticleProceedings of the National Academy of Sciences of the United States of America2014
Immunization with a functional protein complex required for erythrocyte invasion protects against lethal malaria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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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.
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Who cites it
51 citing papers in PubMed, 93 citations in OpenAlex.
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- A strain-transcending anti-AMA1 human monoclonal antibody neutralizes malaria parasites independent of direct RON2L receptor blockade.Cell reports. Medicine · 2025Article
- PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults.EBioMedicine · 2024Article
- A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.Nature communications · 2024Article
- The Need for Novel Asexual Blood-Stage Malaria Vaccine Candidates forBiomolecules · 2024Review
- Hiding in plain sight: an epitope-based strategy for a subunit malaria vaccine.Trends in parasitology · 2023Review
- Structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies.Nature communications · 2023Article
- Structure-based design of a strain transcending AMA1-RON2L malaria vaccine.Nature communications · 2023Article
- Structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies.Research square · 2023Article
- Invasion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Preliminary evaluation of the protective effects of recombinant AMA1 and IMP1 against Eimeria stiedae infection in rabbits.Parasites & vectors · 2022Article
- The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts.PLoS pathogens · 2022Article
- Characterization of AMA1-RON2L complex with native gel electrophoresis and capillary isoelectric focusing.Electrophoresis · 2022Article
- Vesicular stomatitis virus-based vaccine targeting plasmodium blood-stage antigens elicits immune response and protects against malaria with protein booster strategy.Frontiers in microbiology · 2022Article
- Bliss' and Loewe's additive and synergistic effects in Plasmodium falciparum growth inhibition by AMA1-RON2L, RH5, RIPR and CyRPA antibody combinations.Scientific reports · 2020Article
- The RH5-CyRPA-Ripr Complex as a Malaria Vaccine Target.Trends in parasitology · 2020Review
- A Hetero-Multimeric Chitinase-ContainingFrontiers in cellular and infection microbiology · 2020Article
- Identification of a Novel RAMA/RON3 Rhoptry Protein Complex inFrontiers in cellular and infection microbiology · 2020Article
- RON2, a novel gene inParasitology · 2019Article
- Immunomic Identification of Malaria Antigens Associated With Protection in Mice.Molecular & cellular proteomics : MCP · 2019Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
An essential step in the invasion of red blood cells (RBCs) by Plasmodium falciparum (Pf) merozoites is the binding of rhoptry neck protein 2 (RON2) to the hydrophobic groove of apical membrane antigen 1 (AMA1), triggering junction formation between the apical end of the merozoite and the RBC surface to initiate invasion. Vaccination with AMA1 provided protection against homologous parasites in one of two phase 2 clinical trials; however, despite its ability to induce high-titer invasion-blocking antibodies in a controlled human challenge trial, the vaccine conferred little protection even against the homologous parasite. Here we provide evidence that immunization with an AMA1-RON2 peptide complex, but not with AMA1 alone, provided complete protection against a lethal Plasmodium yoelii challenge in mice. Significantly, IgG from mice immunized with the complex transferred protection. Furthermore, IgG from PfAMA1-RON2-immunized animals showed enhanced invasion inhibition compared with IgG elicited by AMA1 alone. Interestingly, this qualitative increase in inhibitory activity appears to be related, at least in part, to a switch in the proportion of IgG specific for certain loop regions in AMA1 surrounding the binding site of RON2. Antibodies induced by the complex were not sufficient to block the FVO strain heterologous parasite, however, reinforcing the need to include multiallele AMA1 to cover polymorphisms. Our results suggest that AMA1 subunit vaccines may be highly effective when presented to the immune system as an invasion complex with RON2.
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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.