دورية أكاديمية
A Plasmodium Parasite with Complete Late Liver Stage Arrest Protects against Preerythrocytic and Erythrocytic Stage Infection in Mice.
| العنوان: | A Plasmodium Parasite with Complete Late Liver Stage Arrest Protects against Preerythrocytic and Erythrocytic Stage Infection in Mice. |
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| المؤلفون: | Vaughan AM; Center for Infectious Disease Research, Seattle, Washington, USA ashley.vaughan@cidresearch.org stefan.kappe@cidresearch.org., Sack BK; Center for Infectious Disease Research, Seattle, Washington, USA., Dankwa D; Center for Infectious Disease Research, Seattle, Washington, USA., Minkah N; Center for Infectious Disease Research, Seattle, Washington, USA., Nguyen T; Center for Infectious Disease Research, Seattle, Washington, USA., Cardamone H; Center for Infectious Disease Research, Seattle, Washington, USA., Kappe SHI; Center for Infectious Disease Research, Seattle, Washington, USA ashley.vaughan@cidresearch.org stefan.kappe@cidresearch.org.; Department of Global Health, University of Washington, Seattle, Washington, USA. |
| المصدر: | Infection and immunity [Infect Immun] 2018 Apr 23; Vol. 86 (5). Date of Electronic Publication: 2018 Apr 23 (Print Publication: 2018). |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society For Microbiology Country of Publication: United States NLM ID: 0246127 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1098-5522 (Electronic) Linking ISSN: 00199567 NLM ISO Abbreviation: Infect Immun Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Washington, DC : American Society For Microbiology Original Publication: [Bethesda, Md.] American Society for Microbiology. |
| مواضيع طبية MeSH: | Erythrocytes/*immunology , Liver/*immunology , Malaria/*immunology , Malaria Vaccines/*immunology , Plasmodium yoelii/*immunology , Protozoan Proteins/*immunology , Sporozoites/*immunology, Animals ; Immunization/methods ; Malaria/prevention & control ; Mice ; Mice, Inbred BALB C ; Plasmodium yoelii/genetics ; Protozoan Proteins/genetics ; Sporozoites/genetics |
| مستخلص: | Genetically attenuated malaria parasites (GAP) that arrest during liver stage development are powerful immunogens and afford complete and durable protection against sporozoite infection. Late liver stage-arresting GAP provide superior protection against sporozoite challenge in mice compared to early live stage-arresting attenuated parasites. However, very few late liver stage-arresting GAP have been generated to date. Therefore, identification of additional loci that are critical for late liver stage development and can be used to generate novel late liver stage-arresting GAPs is of importance. We further explored genetic attenuation in Plasmodium yoelii by combining two gene deletions, PlasMei2 and liver-specific protein 2 ( LISP2 ), that each cause late liver stage arrest with various degrees of infrequent breakthrough to blood stage infection. The dual gene deletion resulted in a synthetic lethal phenotype that caused complete attenuation in a highly susceptible mouse strain. P. yoelii plasmei2 - lisp2 - arrested late in liver stage development and did not persist in livers beyond 3 days after infection. Immunization with this GAP elicited robust protective antibody responses in outbred and inbred mice against sporozoites, liver stages, and blood stages as well as eliciting protective liver-resident T cells. The immunization afforded protection against both sporozoite challenge and blood stage challenge. These findings provide evidence that completely attenuated late liver stage-arresting GAP are achievable via the synthetic lethal approach and might enable a path forward for the creation of a completely attenuated late liver stage-arresting P. falciparum GAP. (Copyright © 2018 American Society for Microbiology.) |
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| معلومات مُعتمدة: | R01 AI114699 United States AI NIAID NIH HHS; R01 AI125706 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: GAP; Plasmodium; attenuated; liver stage; malaria; preerythrocytic; protection; sporozoite; vaccine |
| المشرفين على المادة: | 0 (Malaria Vaccines) 0 (Protozoan Proteins) |
| تواريخ الأحداث: | Date Created: 20180215 Date Completed: 20181217 Latest Revision: 20200826 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC5913857 |
| DOI: | 10.1128/IAI.00088-18 |
| PMID: | 29440367 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1098-5522 |
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| DOI: | 10.1128/IAI.00088-18 |