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  1. Article ; Online: Monoclonal antibodies for malaria prevention.

    Aleshnick, Maya / Florez-Cuadros, Melina / Martinson, Thomas / Wilder, Brandon K

    Molecular therapy : the journal of the American Society of Gene Therapy

    2022  Volume 30, Issue 5, Page(s) 1810–1821

    Abstract: Monoclonal antibodies are highly specific proteins that are cloned from a single B cell and bind to a single epitope on a pathogen. These laboratory-made molecules can serve as prophylactics or therapeutics for infectious diseases and have an impressive ... ...

    Abstract Monoclonal antibodies are highly specific proteins that are cloned from a single B cell and bind to a single epitope on a pathogen. These laboratory-made molecules can serve as prophylactics or therapeutics for infectious diseases and have an impressive capacity to modulate the progression of disease, as demonstrated for the first time on a large scale during the COVID-19 pandemic. The high specificity and natural starting point of monoclonal antibodies afford an encouraging safety profile, yet the high cost of production remains a major limitation to their widespread use. While a monoclonal antibody approach to abrogating malaria infection is not yet available, the unique life cycle of the malaria parasite affords many opportunities for such proteins to act, and preliminary research into the efficacy of monoclonal antibodies in preventing malaria infection, disease, and transmission is encouraging. This review examines the current status and future outlook for monoclonal antibodies against malaria in the context of the complex life cycle and varied antigenic targets expressed in the human and mosquito hosts, and provides insight into the strengths and limitations of this approach to curtailing one of humanity's oldest and deadliest diseases.
    MeSH term(s) Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Protozoan ; Antineoplastic Agents, Immunological ; COVID-19/prevention & control ; Epitopes ; Humans ; Malaria/prevention & control ; Pandemics
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Protozoan ; Antineoplastic Agents, Immunological ; Epitopes
    Language English
    Publishing date 2022-04-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2022.04.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5640: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites.

    Minkah, Nana K / Wilder, Brandon K / Sheikh, Amina A / Martinson, Thomas / Wegmair, Lisa / Vaughan, Ashley M / Kappe, Stefan H I

    Nature communications

    2019  Volume 10, Issue 1, Page(s) 3950

    Abstract: Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN ...

    Abstract Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN (IFN-1) response, but whether this IFN-1 response has beneficial or adverse effects on vaccine-induced adaptive immunity is not known. Here, we show that IFN-1 signaling-deficient mice immunized with replication-competent sporozoites exhibit superior protection against infection. This correlates with superior CD8 T cell memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and increased numbers of memory CD8 T cells in the liver. Moreover, the adoptive transfer of memory CD8 T cells from the livers of previously immunized IFN-1 signaling-deficient mice confers greater protection against liver stage parasites. However, the detrimental role of IFN-1 signaling is not CD8 T cell intrinsic. Together, our data demonstrate that liver stage-engendered IFN-1 signaling impairs hepatic CD8 T cell memory via a CD8 T cell-extrinsic mechanism.
    MeSH term(s) Adaptive Immunity/immunology ; Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/parasitology ; Erythrocytes/immunology ; Erythrocytes/parasitology ; Female ; Immunity, Innate/immunology ; Immunization ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Liver/immunology ; Liver/metabolism ; Liver/parasitology ; Malaria/immunology ; Malaria/parasitology ; Malaria/prevention & control ; Malaria Vaccines/administration & dosage ; Malaria Vaccines/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Plasmodium yoelii/immunology ; Plasmodium yoelii/physiology ; Sporozoites/immunology ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology
    Chemical Substances Interferon Type I ; Malaria Vaccines ; Vaccines, Attenuated
    Language English
    Publishing date 2019-09-02
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-11819-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Plasmodium vivax

    Flannery, Erika L / Kangwanrangsan, Niwat / Chuenchob, Vorada / Roobsoong, Wanlapa / Fishbaugher, Matthew / Zhou, Kevin / Billman, Zachary P / Martinson, Thomas / Olsen, Tayla M / Schäfer, Carola / Campo, Brice / Murphy, Sean C / Mikolajczak, Sebastian A / Kappe, Stefan H I / Sattabongkot, Jetsumon

    Molecular therapy. Methods & clinical development

    2022  Volume 26, Page(s) 427–440

    Abstract: Plasmodium ... ...

    Abstract Plasmodium vivax
    Language English
    Publishing date 2022-08-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2872938-9
    ISSN 2329-0501 ; 2329-0501
    ISSN (online) 2329-0501
    ISSN 2329-0501
    DOI 10.1016/j.omtm.2022.07.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7107: Show issues Location:
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  4. Article ; Online: Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.

    Franke-Fayard, Blandine / Marin-Mogollon, Catherin / Geurten, Fiona J A / Chevalley-Maurel, Séverine / Ramesar, Jai / Kroeze, Hans / Baalbergen, Els / Wessels, Els / Baron, Ludivine / Soulard, Valérie / Martinson, Thomas / Aleshnick, Maya / Huijs, Antonius T G / Subudhi, Amit K / Miyazaki, Yukiko / Othman, Ahmad Syibli / Kolli, Surendra Kumar / Lamers, Olivia A C / Roques, Magali /
    Stanway, Rebecca R / Murphy, Sean C / Foquet, Lander / Moita, Diana / Mendes, António M / Prudêncio, Miguel / Dechering, Koen J / Heussler, Volker T / Pain, Arnab / Wilder, Brandon K / Roestenberg, Meta / Janse, Chris J

    NPJ vaccines

    2022  Volume 7, Issue 1, Page(s) 139

    Abstract: Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ- ... ...

    Abstract Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models. Here we describe the generation of four putative P. falciparum LA-GAPs, generated by CRISPR/Cas9-mediated gene deletion. One out of four gene-deletion mutants produced sporozoites in sufficient numbers for further preclinical evaluation. This mutant, PfΔmei2, lacking the mei2-like RNA gene, showed late liver growth arrest in human liver-chimeric mice with human erythrocytes, absence of unwanted genetic alterations and sensitivity to antimalarial drugs. These features of PfΔmei2 make it a promising vaccine candidate, supporting further clinical evaluation. PfΔmei2 (GA2) has passed regulatory approval for safety and efficacy testing in humans based on the findings reported in this study.
    Language English
    Publishing date 2022-11-04
    Publishing country England
    Document type Journal Article
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-022-00558-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Plasmodium yoelii S4/CelTOS is important for sporozoite gliding motility and cell traversal.

    Steel, Ryan W J / Pei, Ying / Camargo, Nelly / Kaushansky, Alexis / Dankwa, Dorender A / Martinson, Thomas / Nguyen, Thao / Betz, Will / Cardamone, Hayley / Vigdorovich, Vladimir / Dambrauskas, Nicholas / Carbonetti, Sara / Vaughan, Ashley M / Sather, D Noah / Kappe, Stefan H I

    Cellular microbiology

    2018  Volume 20, Issue 4

    Abstract: Gliding motility and cell traversal by the Plasmodium ookinete and sporozoite invasive stages allow penetration of cellular barriers to establish infection of the mosquito vector and mammalian host, respectively. Motility and traversal are not observed ... ...

    Abstract Gliding motility and cell traversal by the Plasmodium ookinete and sporozoite invasive stages allow penetration of cellular barriers to establish infection of the mosquito vector and mammalian host, respectively. Motility and traversal are not observed in red cell infectious merozoites, and we have previously classified genes that are expressed in sporozoites but not merozoites (S genes) in order to identify proteins involved in these processes. The S4 gene has been described as criticaly involved in Cell Traversal for Ookinetes and Sporozoites (CelTOS), yet knockout parasites (s4/celtos¯) do not generate robust salivary gland sporozoite numbers, precluding a thorough analysis of S4/CelTOS function during host infection. We show here that a failure of oocysts to develop or survive in the midgut contributes to the poor mosquito infection by Plasmodium yoelii (Py) s4/celtos¯ rodent malaria parasites. We rescued this phenotype by expressing S4/CelTOS under the ookinete-specific circumsporozoite protein and thrombospondin-related anonymous protein-related protein (CTRP) promoter (S4/CelTOS
    MeSH term(s) Animals ; Cell Movement ; Host-Parasite Interactions ; Malaria/parasitology ; Mosquito Vectors ; Plasmodium yoelii/genetics ; Plasmodium yoelii/physiology ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Sporozoites/metabolism
    Chemical Substances Protozoan Proteins
    Language English
    Publishing date 2018-01-12
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1468320-9
    ISSN 1462-5822 ; 1462-5814
    ISSN (online) 1462-5822
    ISSN 1462-5814
    DOI 10.1111/cmi.12817
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5288: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: The Micronemal

    Arredondo, Silvia A / Swearingen, Kristian E / Martinson, Thomas / Steel, Ryan / Dankwa, Dorender A / Harupa, Anke / Camargo, Nelly / Betz, William / Vigdorovich, Vladimir / Oliver, Brian G / Kangwanrangsan, Niwat / Ishino, Tomoko / Sather, Noah / Mikolajczak, Sebastian / Vaughan, Ashley M / Torii, Motomi / Moritz, Robert L / Kappe, Stefan H I

    Frontiers in cellular and infection microbiology

    2018  Volume 8, Page(s) 413

    Abstract: Within the liver, ...

    Abstract Within the liver,
    MeSH term(s) Animals ; CD36 Antigens/metabolism ; Culicidae ; Cytoplasm/metabolism ; Female ; Gene Deletion ; Gene Knockout Techniques ; Glycosylphosphatidylinositols ; Hepatocytes/parasitology ; Hepatocytes/pathology ; Malaria/metabolism ; Mice ; Mice, Inbred BALB C ; Plasmodium yoelii/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Receptor, EphA2/metabolism ; Salivary Glands/parasitology ; Salivary Glands/pathology ; Sporozoites/metabolism
    Chemical Substances CD36 Antigens ; Glycosylphosphatidylinositols ; Protozoan Proteins ; Receptor, EphA2 (EC 2.7.10.1)
    Language English
    Publishing date 2018-11-27
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2018.00413
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: ELQ-331 as a prototype for extremely durable chemoprotection against malaria.

    Smilkstein, Martin J / Pou, Sovitj / Krollenbrock, Alina / Bleyle, Lisa A / Dodean, Rozalia A / Frueh, Lisa / Hinrichs, David J / Li, Yuexin / Martinson, Thomas / Munar, Myrna Y / Winter, Rolf W / Bruzual, Igor / Whiteside, Samantha / Nilsen, Aaron / Koop, Dennis R / Kelly, Jane X / Kappe, Stefan H I / Wilder, Brandon K / Riscoe, Michael K

    Malaria journal

    2019  Volume 18, Issue 1, Page(s) 291

    Abstract: Background: The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and ... ...

    Abstract Background: The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice.
    Methods: Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.2% benzyl alcohol; the ELQ-300 content of the doses ranged from 2.5 to 30 mg/kg. Initial blood stage challenges with Plasmodium yoelii were used to establish the model, but the definitive study measure of efficacy was outcome after sporozoite challenge with a luciferase-expressing P. yoelii, assessed by whole-body live animal imaging. Snapshot determinations of plasma ELQ-300 concentration ([ELQ-300]) were made after all prodrug injections; after the highest dose of ELQ-331 (equivalent to 30 mg/kg ELQ-300), both [ELQ-331] and [ELQ-300] were measured at a series of timepoints from 6 h to 5½ months after injection.
    Results: A single intramuscular injection of ELQ-331 outperformed four other ELQ-300 prodrugs and, at a dose equivalent to 30 mg/kg ELQ-300, protected mice against challenge with P. yoelii sporozoites for at least 4½ months. Pharmacokinetic evaluation revealed rapid and essentially complete conversion of ELQ-331 to ELQ-300, a rapidly achieved (< 6 h) and sustained (4-5 months) effective plasma ELQ-300 concentration, maximum ELQ-300 concentrations far below the estimated threshold for toxicity, and a distinctive ELQ-300 concentration versus time profile. Pharmacokinetic modeling indicates a high-capacity, slow-exchange tissue compartment which serves to accumulate and then slowly redistribute ELQ-300 into blood, and this property facilitates an extremely long period during which ELQ-300 concentration is sustained above a minimum fully-protective threshold (60-80 nM).
    Conclusions: Extrapolation of these results to humans predicts that ELQ-331 should be capable of meeting and far-exceeding currently published duration-of-effect goals for anti-malarial LAI-C. Furthermore, the distinctive pharmacokinetic profile of ELQ-300 after treatment with ELQ-331 may facilitate durable protection and enable protection for far longer than 3 months. These findings suggest that ELQ-331 warrants consideration as a leading prototype for LAI-C.
    MeSH term(s) Animals ; Antimalarials/adverse effects ; Antimalarials/pharmacokinetics ; Female ; Mice ; Plasmodium yoelii/drug effects ; Prodrugs/adverse effects ; Prodrugs/pharmacokinetics ; Quinolones/adverse effects ; Quinolones/pharmacokinetics
    Chemical Substances 6-Chloro-7-methoxy-2-methyl-3-(4-(4-(trifluoromethoxy)phenoxy)phenyl)quinolin-4(1H)-one ; Antimalarials ; Prodrugs ; Quinolones
    Language English
    Publishing date 2019-08-27
    Publishing country England
    Document type Comparative Study ; Journal Article
    ISSN 1475-2875
    ISSN (online) 1475-2875
    DOI 10.1186/s12936-019-2921-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Book ; Thesis: 'N bedryfsekonomiese ondersoek na boerderydoeltreffendheid in die Suidelike Swartland

    Martinson, Thomas Johannes

    1975  

    Title translation A business economic analysis of farming efficiency in the Southern Swartland.
    Author's details deur Thomas Johannes Martinson. --
    Keywords Farm management
    Language Afrikaans
    Size 173 leaves ;, 30 cm.
    Publisher s.n.
    Publishing place Pretoria
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Thesis (M.S.)--Universiteit van Pretoria, 1975
    Note Summary in English.
    Database NAL-Catalogue (AGRICOLA)

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