دورية أكاديمية
أعرض في EDS

A recombinant antibody against Plasmodium vivax UIS4 for distinguishing replicating from dormant liver stages.

التفاصيل البيبلوغرافية
العنوان: A recombinant antibody against Plasmodium vivax UIS4 for distinguishing replicating from dormant liver stages.
المؤلفون: Schafer C; Center for Infectious Disease Research, Seattle, WA, USA.; Seattle Children's Research Institute, Seattle, WA, USA., Dambrauskas N; Center for Infectious Disease Research, Seattle, WA, USA.; Seattle Children's Research Institute, Seattle, WA, USA., Steel RW; Center for Infectious Disease Research, Seattle, WA, USA.; The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia., Carbonetti S; Center for Infectious Disease Research, Seattle, WA, USA., Chuenchob V; Center for Infectious Disease Research, Seattle, WA, USA., Flannery EL; Center for Infectious Disease Research, Seattle, WA, USA.; Novartis Institute for Tropical Diseases, Emeryville, CA, USA., Vigdorovich V; Center for Infectious Disease Research, Seattle, WA, USA.; Seattle Children's Research Institute, Seattle, WA, USA., Oliver BG; Center for Infectious Disease Research, Seattle, WA, USA.; Seattle Children's Research Institute, Seattle, WA, USA., Roobsoong W; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Maher SP; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA., Kyle D; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA, USA., Sattabongkot J; Mahidol Vivax Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand., Kappe SHI; Center for Infectious Disease Research, Seattle, WA, USA.; Seattle Children's Research Institute, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, USA., Mikolajczak SA; Center for Infectious Disease Research, Seattle, WA, USA. Sebastian.mikolajczak@cidresearch.org.; Novartis Institute for Tropical Diseases, Emeryville, CA, USA. Sebastian.mikolajczak@cidresearch.org., Sather DN; Center for Infectious Disease Research, Seattle, WA, USA. noah.sather@seattlechildrens.org.; Seattle Children's Research Institute, Seattle, WA, USA. noah.sather@seattlechildrens.org.; Department of Global Health, University of Washington, Seattle, USA. noah.sather@seattlechildrens.org.
المصدر: Malaria journal [Malar J] 2018 Oct 17; Vol. 17 (1), pp. 370. Date of Electronic Publication: 2018 Oct 17.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BioMed Central Country of Publication: England NLM ID: 101139802 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2875 (Electronic) Linking ISSN: 14752875 NLM ISO Abbreviation: Malar J Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : BioMed Central, [2002-
مواضيع طبية MeSH: Antibodies, Protozoan/*physiology , Liver/*parasitology , Plasmodium vivax/*isolation & purification , Sporozoites/*immunology, Biomarkers/analysis
مستخلص: Background: Plasmodium vivax is the most geographically widespread of the human malaria parasites, causing 50,000 to 100,000 deaths annually. Plasmodium vivax parasites have the unique feature of forming dormant liver stages (hypnozoites) that can reactivate weeks or months after a parasite-infected mosquito bite, leading to new symptomatic blood stage infections. Efforts to eliminate P. vivax malaria likely will need to target the persistent hypnozoites in the liver. Therefore, research on P. vivax liver stages necessitates a marker for clearly distinguishing between actively replicating parasites and dormant hypnozoites. Hypnozoites possess a densely fluorescent prominence in the parasitophorous vacuole membrane (PVM) when stained with antibodies against the PVM-resident protein Upregulated in Infectious Sporozoites 4 (PvUIS4), resulting in a key feature recognizable for quantification of hypnozoites. Thus, PvUIS4 staining, in combination with the characteristic small size of the parasite, is currently the only hypnozoite-specific morphological marker available.
Results: Here, the generation and validation of a recombinant monoclonal antibody against PvUIS4 (α-rUIS4 mAb) is described. The variable heavy and light chain domains of an α-PvUIS4 hybridoma were cloned into murine IgG1 and IgK expression vectors. These expression plasmids were co-transfected into HEK293 cells and mature IgG was purified from culture supernatants. It is shown that the α-rUIS4 mAb binds to its target with high affinity. It reliably stains the schizont PVM and the hypnozoite-specific PVM prominence, enabling the visual differentiation of hypnozoites from replicating liver stages by immunofluorescence assays in different in vitro settings, as well as in liver sections from P. vivax infected liver-chimeric mice. The antibody functions reliably against all four parasite isolates tested and will be an important tool in the identification of the elusive hypnozoite.
Conclusions: The α-rUIS4 mAb is a versatile tool for distinguishing replicating P. vivax liver stages from dormant hypnozoites, making it a valuable resource that can be deployed throughout laboratories worldwide.
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معلومات مُعتمدة: R01 AI117234 United States AI NIAID NIH HHS; SCHA 2047/1-1 Deutsche Forschungsgemeinschaft; AI117234 National Institute of Allergy and Infectious Diseases
فهرسة مساهمة: Keywords: Hypnozoite; Plasmodium vivax; Recombinant antibody; UIS4
المشرفين على المادة: 0 (Antibodies, Protozoan)
0 (Biomarkers)
تواريخ الأحداث: Date Created: 20181019 Date Completed: 20181211 Latest Revision: 20181211
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6192329
DOI: 10.1186/s12936-018-2519-7
PMID: 30333026
قاعدة البيانات: MEDLINE
الوصف
تدمد:1475-2875
DOI:10.1186/s12936-018-2519-7