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ALY, AHMED SAYED IBRAHıM

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AHMED SAYED IBRAHıM
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2020 - 20226
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Author: ALY, AHMED SAYED IBRAHıM × End date: 2022 × Start date: 2020 ×

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Now showing 1 - 6 of 6
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    PublicationOpen Access
    Synthetic DNA Vaccines Adjuvanted with pIL-33 Drive Liver-Localized T Cells and Provide Protection from <i>Plasmodium</i> Challenge in a Mouse Model.
    (2020-01-10T00:00:00Z) Reeder, SM; Reuschel, EL; Bah, MA; Yun, K; Tursi, NJ; Kim, KY; Chu, J; Zaidi, FI; Yilmaz, I; Hart, RJ; Perrin, B; Xu, Z; Humeau, L; Weiner, DB; Aly, Ahmed Sayed Ibrahım; ALY, AHMED SAYED IBRAHıM
    The need for a malaria vaccine is indisputable. A single vaccine for Plasmodium pre-erythrocytic stages targeting the major sporozoite antigen circumsporozoite protein (CSP) has had partial success. Additionally, CD8+ T cells targeting liver-stage (LS) antigens induced by live attenuated sporozoite vaccines were associated with protection in human challenge experiments. To further evaluate protection mediated by LS antigens, we focused on exported pre-erythrocytic proteins (exported protein 1 (EXP1), profilin (PFN), exported protein 2 (EXP2), inhibitor of cysteine proteases (ICP), transmembrane protein 21 (TMP21), and upregulated in infective sporozoites-3 (UIS3)) expressed in all Plasmodium species and designed optimized, synthetic DNA (synDNA) immunogens. SynDNA antigen cocktails were tested with and without the molecular adjuvant plasmid IL-33. Immunized animals developed robust T cell responses including induction of antigen-specific liver-localized CD8+ T cells, which were enhanced by the co-delivery of plasmid IL-33. In total, 100% of mice in adjuvanted groups and 71%–88% in non-adjuvanted groups were protected from blood-stage disease following Plasmodium yoelii sporozoite challenge. This study supports the potential of synDNA LS antigens as vaccine components for malaria parasite infection.
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    PublicationOpen Access
    An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge
    (2022-02-01T00:00:00Z) Rider, Paul J. F.; KAMIL, MOHD; Yilmaz, Ilknur; Atmaca, Habibe N.; Kalkan-Yazici, Merve; Ziya Doymaz, Mehmet; Kousoulas, Konstantin G.; ALY, Ahmed Sayed Ibrahım; KAMIL, MOHD; YAZICI, MERVE; ALY, AHMED SAYED IBRAHıM
    Here, we present the construction of an attenuated herpes simplex virus type-1 (HSV-1)-vectored vaccine, expressing three liver-stage (LS) malaria parasite exported proteins (EXP1, UIS3 and TMP21) as fusion proteins with the VP26 viral capsid protein. Intramuscular and subcutaneous immunizations of mice with a pooled vaccine, composed of the three attenuated virus strains expressing each LS antigen, induced sterile protection against the intravenous challenge of Plasmodium yoelii 17X-NL salivary gland sporozoites. Our data suggest that this malaria vaccine may be effective in preventing malaria parasite infection using practical routes of immunization in humans.
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    Single Dose Mixed Species Malaria Vaccination of Genetically Attenuated Blood Stage Malaria Parasites Induce Sterile Immunity Against Lethal Challenge by Both Species
    (2021-09-13T00:00:00Z) Deveci, Gözde; Temel, Binnur; Aly, Ahmed Sayed Ibrahım; DEVECİ, GÖZDE; TEMEL, BİNNUR; ALY, AHMED SAYED IBRAHıM
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    PublicationOpen Access
    Automated wide-field malaria parasite infection detection using Fourier ptychography on stain-free thin-smears
    (2022-07-01T00:00:00Z) AKÇAKIR, OSMAN; Celebi, Lutfi Kadir; KAMIL, MOHD; ALY, Ahmed Sayed Ibrahım; AKÇAKIR, OSMAN; KAMIL, MOHD; ALY, AHMED SAYED IBRAHıM
    Diagnosis of malaria in endemic areas is hampered by the lack of a rapid, stain-free and sensitive method to directly identify parasites in peripheral blood. Herein, we report the use of Fourier ptychography to generate wide-field high-resolution quantitative phase images of erythrocytes infected with malaria parasites, from a whole blood sample. We are able to image thousands of erythrocytes (red blood cells) in a single field of view and make a determination of infection status of the quantitative phase image of each segmented cell based on machine learning (random forest) and deep learning (VGG16) models. Our random forest model makes use of morphology and texture based features of the quantitative phase images. In order to label the quantitative images of the cells as either infected or uninfected before training the models, we make use of a Plasmodium berghei strain expressing GFP (green fluorescent protein) in all life cycle stages. By overlaying the fluorescence image with the quantitative phase image we could identify the infected subpopulation of erythrocytes for labelling purposes. Our machine learning model (random forest) achieved 91% specificity and 72% sensitivity while our deep learning model (VGG16) achieved 98% specificity and 57% sensitivity. These results highlight the potential for quantitative phase imaging coupled with artificial intelligence to develop an easy to use platform for the rapid and sensitive diagnosis of malaria.
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    Mitochondrial Spermidine Synthase is Essential for Blood-stage growth of the Malaria Parasite
    (2022-12-01T00:00:00Z) KAMIL, MOHD; KINA, ÜMİT YAŞAR; DEVECİ, GÖZDE; Akyuz, Sevim N.; Yilmaz, Ilknur; ALY, Ahmed Sayed Ibrahım; KAMIL, MOHD; KINA, ÜMİT YAŞAR; DEVECİ, GÖZDE; ALY, AHMED SAYED IBRAHıM
    © 2022Positively-charged polyamines are essential molecules for the replication of eukaryotic cells and are particularly important for the rapid proliferation of parasitic protozoa and cancer cells. Unlike in Trypanosoma brucei, the inhibition of the synthesis of intermediate polyamine Putrescine caused only partial defect in malaria parasite blood-stage growth. In contrast, reducing the intracellular concentrations of Spermidine and Spermine by polyamine analogs caused significant defects in blood-stage growth in Plasmodium yoelii and P. falciparum. However, little is known about the synthesizing enzyme of Spermidine and Spermine in the malaria parasite. Herein, malaria parasite conserved Spermidine Synthase (SpdS) gene was targeted for deletion/complementation analyses by knockout/knock-in constructs in P. yoelii. SpdS was found to be essential for blood-stage growth. Live fluorescence imaging in blood-stages and sporozoites confirmed a specific mitochondrial localization, which is not known for any polyamine-synthesizing enzyme so far. This study identifies SpdS as an excellent drug targeting candidate against the malaria parasite, which is localized to the parasite mitochondrion.
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    Gene Targeting Studies of the Malaria Parasite DNA Photolyase gene using CRISPR-Cas9 Genome Editing Technology
    (2021-01-08T00:00:00Z) Yılmaz, İlknur; Palabıyık, Bedia; Temel, Binnur; Aly, Ahmed Sayed Ibrahım; TEMEL, BİNNUR; ALY, AHMED SAYED IBRAHıM