{"doi":"10.1128/iai.00225-07","title":"<i>Plasmodium yoelii</i>\n            Sporozoites with Simultaneous Deletion of P52 and P36 Are Completely Attenuated and Confer Sterile Immunity against Infection","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. Sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. The formation of a parasitophorous vacuole (PV) establishes their intracellular niche. Recently, two members of the 6-Cys domain protein family, P52 and P36, were each shown to play an important albeit nonessential role in\n            <jats:italic>Plasmodium berghei</jats:italic>\n            sporozoite infectivity for the rodent host. Here, we generated\n            <jats:italic>p52/p36</jats:italic>\n            -deficient\n            <jats:italic>Plasmodium yoelii</jats:italic>\n            parasites by the simultaneous deletion of both genes using a single genetic manipulation.\n            <jats:italic>p52/p36</jats:italic>\n            -deficient parasites exhibited normal progression through the life cycle during blood-stage infection, transmission to mosquitoes, mosquito-stage development, and sporozoite infection of the salivary glands.\n            <jats:italic>p52/p36</jats:italic>\n            -deficient sporozoites also showed normal motility and cell traversal activity. However, immunofluorescence analysis and electron microscopic observations revealed that\n            <jats:italic>p52/p36</jats:italic>\n            -deficient parasites did not form a PV within hepatocytes in vitro and in vivo. The\n            <jats:italic>p52/p36</jats:italic>\n            -deficient parasites localized as free entities in the host cell cytoplasm or the host cell nucleoplasm and did not develop as liver stages. Consequently, they did not cause blood-stage infections even at high sporozoite inoculation doses. Mice immunized with\n            <jats:italic>p52/p36</jats:italic>\n            -deficient sporozoites were completely protected against infectious sporozoite challenge. Our results demonstrate for the first time the generation of two-locus gene deletion-attenuated parasites that infect the liver but do not progress to blood-stage infection. The study will critically guide the design of\n            <jats:italic>Plasmodium falciparum</jats:italic>\n            live attenuated malaria vaccines.\n          </jats:p>","journal":"Infection and Immunity","year":2007,"id":662648,"datarank":0.7565137675378871,"base_score":5.043425116919247,"endowment":5.043425116919247,"self_citation_contribution":0.7565137675378871,"citation_network_contribution":0.0,"self_endowment_contribution":0.7565137675378871,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":154,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1430041,"name":"Anke Harupa","orcid":null,"position":1,"is_corresponding":false},{"id":1729953,"name":"Ronald F. Dumpit","orcid":null,"position":2,"is_corresponding":false},{"id":353145,"name":"Isabelle Coppens","orcid":"0000-0001-5549-2362","position":3,"is_corresponding":false},{"id":699583,"name":"Sebastian A. Mikolajczak","orcid":"0000-0003-1996-9703","position":4,"is_corresponding":false},{"id":491808,"name":"Stefan H. I. Kappe","orcid":"0000-0003-1540-1731","position":5,"is_corresponding":false},{"id":1729952,"name":"Mehdi Labaied","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"<i>Plasmodium yoelii</i>\n            Sporozoites with Simultaneous Deletion of P52 and P36 Are Completely Attenuated and Confer Sterile Immunity against Infection","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. Sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. The formation of a parasitophorous vacuole (PV) establishes their intracellular niche. Recently, two members of the 6-Cys domain protein family, P52 and P36, were each shown to play an important albeit nonessential role in\n            <jats:italic>Plasmodium berghei</jats:italic>\n            sporozoite infectivity for the rodent host. Here, we generated\n            <jats:italic>p52/p36</jats:italic>\n            -deficient\n            <jats:italic>Plasmodium yoelii</jats:italic>\n            parasites by the simultaneous deletion of both genes using a single genetic manipulation.\n            <jats:italic>p52/p36</jats:italic>\n            -deficient parasites exhibited normal progression through the life cycle during blood-stage infection, transmission to mosquitoes, mosquito-stage development, and sporozoite infection of the salivary glands.\n            <jats:italic>p52/p36</jats:italic>\n            -deficient sporozoites also showed normal motility and cell traversal activity. However, immunofluorescence analysis and electron microscopic observations revealed that\n            <jats:italic>p52/p36</jats:italic>\n            -deficient parasites did not form a PV within hepatocytes in vitro and in vivo. The\n            <jats:italic>p52/p36</jats:italic>\n            -deficient parasites localized as free entities in the host cell cytoplasm or the host cell nucleoplasm and did not develop as liver stages. Consequently, they did not cause blood-stage infections even at high sporozoite inoculation doses. Mice immunized with\n            <jats:italic>p52/p36</jats:italic>\n            -deficient sporozoites were completely protected against infectious sporozoite challenge. Our results demonstrate for the first time the generation of two-locus gene deletion-attenuated parasites that infect the liver but do not progress to blood-stage infection. The study will critically guide the design of\n            <jats:italic>Plasmodium falciparum</jats:italic>\n            live attenuated malaria vaccines.\n          </jats:p>","is_dataset_classified":null,"base_score":5.043425116919247,"endowment":5.043425116919247,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17517871","pmcid":"PMC1951999","openalex_id":"https://openalex.org/W2113206880","authors":[],"funders":[],"total_grants":0,"fwci":14.4138,"citation_percentile":0.99213314,"influential_citations":0,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":17},{"year":2014,"count":12},{"year":2015,"count":8},{"year":2016,"count":7},{"year":2017,"count":12},{"year":2018,"count":8},{"year":2019,"count":2},{"year":2020,"count":4},{"year":2021,"count":3},{"year":2022,"count":5},{"year":2023,"count":3},{"year":2024,"count":3},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://iai.asm.org/content/iai/75/8/3758.full.pdf","host_type":"journal"},{"url":"https://iai.asm.org/content/iai/75/8/3758.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/IAI.00225-07","host_type":"publisher"},{"url":"https://doi.org/10.1128/iai.00225-07","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17517871","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1951999","host_type":"repository"}],"fields_of_study":["Malaria Research and Control","Mosquito-borne diseases and control","Invertebrate Immune Response Mechanisms","Animals","Culicidae","Cytoplasm","Disease Models, Animal","Female","Gene Deletion","Gene Targeting","Hepatocytes","Malaria","Mice","Microscopy, Electron, Transmission","Microscopy, Fluorescence","Plasmodium yoelii","Protozoan Proteins","Rats","Rats, Wistar","Sporozoites","Vacuoles"],"mesh_terms":["Animals","Cytoplasm","Disease Models, Animal","Female","Malaria","Microscopy, Fluorescence","Culicidae","Plasmodium yoelii","Vacuoles","Protozoan Proteins","Rats, Wistar","Gene Deletion","Gene Targeting","Hepatocytes","Sporozoites","Microscopy, Electron, Transmission","Mice","Rats"],"keywords":["Biology","Plasmodium yoelii","Virology","Infectivity","Plasmodium berghei","Plasmodium falciparum","Plasmodium (life cycle)","Malaria","Microbiology","Immunology","Parasite hosting","Parasitemia","Virus"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Responsible consumption and production"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T16:42:54.326001Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}