ArticlePLoS pathogens2009
An inhibitory antibody blocks interactions between components of the malarial invasion machinery.
Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed.
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- Computational Development of Transmission-Blocking Vaccine Candidates Based on Fused Antigens of Pre- and Post-fertilization Gametocytes AgainstBioinformatics and biology insights · 2025Article
- A broadly cross-reactive i-body to AMA1 potently inhibits blood and liver stages of Plasmodium parasites.Nature communications · 2024Article
- Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates in Plasmodium falciparum.EBioMedicine · 2024Article
- Diversity and selection analyses identify transmission-blocking antigens as the optimal vaccine candidates inmedRxiv : the preprint server for health sciences · 2024Article
- Defining species-specific and conserved interactions of apical membrane protein 1 during erythrocyte invasion in malaria to inform multi-species vaccines.Cellular and molecular life sciences : CMLS · 2023Article
- The WD40-ProteinFrontiers in cellular and infection microbiology · 2022Article
- Retrospective study of toxoplasmosis prevalence in pregnant women in Benin and its relation with malaria.PloS one · 2022Article
- The Cellular and Molecular Interaction Between Erythrocytes andFrontiers in cellular and infection microbiology · 2022Review
- Molecular Assessment of Domain I of Apical Membrane Antigen I Gene inThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2022Article
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- Autocatalytic activation of a malarial egress protease is druggable and requires a protein cofactor.The EMBO journal · 2021Article
- An Alveolata secretory machinery adapted to parasite host cell invasion.Nature microbiology · 2021Article
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- Specific EtMIC3-binding peptides inhibit Eimeria tenella sporozoites entry into host cells.Veterinary research · 2021Article
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- Isolation and light chain shuffling of a Plasmodium falciparum AMA1-specific human monoclonal antibody with growth inhibitory activity.Malaria journal · 2021Article
- The malaria parasite sheddase SUB2 governs host red blood cell membrane sealing at invasion.eLife · 2020Article
39 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
Host cell invasion by apicomplexan pathogens such as the malaria parasite Plasmodium spp. and Toxoplasma gondii involves discharge of proteins from secretory organelles called micronemes and rhoptries. In Toxoplasma a protein complex comprising the microneme apical membrane antigen 1 (AMA1), two rhoptry neck proteins, and a protein called Ts4705, localises to the moving junction, a region of close apposition between parasite and host cell during invasion. Antibodies against AMA1 prevent invasion and are protective in vivo, and so AMA1 is of widespread interest as a malaria vaccine candidate. Here we report that the AMA1 complex identified in Toxoplasma is conserved in Plasmodium falciparum. We demonstrate that the invasion-inhibitory monoclonal antibody (mAb) 4G2, which recognises P. falciparum AMA1 (PfAMA1), cannot bind when PfAMA1 is in a complex with its partner proteins. We further show that a single completely conserved PfAMA1 residue, Tyr251, lying within a conserved hydrophobic groove adjacent to the mAb 4G2 epitope, is required for complex formation. We propose that mAb 4G2 inhibits invasion by preventing PfAMA1 from interacting with other components of the invasion complex. Our findings should aid the rational design of subunit malaria vaccines based on PfAMA1.
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