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  1. AU="Ba, Aboubacar"
  2. AU="Prisca, Mirandolina"
  3. AU="Perez, Tate"
  4. AU="Bakkaloglu, Sevan"
  5. AU="Guernieri, Rebecca L"
  6. AU="Xing, Z Y"
  7. AU="Yu-Heng Cheng"
  8. AU=Freeman Richard B Jr
  9. AU="Wang, Qi-En"
  10. AU="Mallamaci, M"
  11. AU="Turk, Yael R"
  12. AU="Tinto, Monica"
  13. AU="Selvendiran, Karuppaiyah" AU="Selvendiran, Karuppaiyah"
  14. AU="Enns, Murray W"
  15. AU="Yaohua Yang" AU="Yaohua Yang"

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  1. Artikel: Leveraging genome editing to functionally evaluate Plasmodium diversity

    Thiam, Laty Gaye / Mangou, Khadidiatou / Ba, Aboubacar / Mbengue, Alassane / Bei, Amy K.

    Trends in parasitology. 2022,

    2022  

    Abstract: The ambitious goal of malaria elimination requires an in-depth understanding of the parasite’s biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the ... ...

    Abstract The ambitious goal of malaria elimination requires an in-depth understanding of the parasite’s biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the early stages of vaccine development will be critical for achieving the goal of malaria control, elimination, and, ultimately, eradication. Recent advances in targeted genome editing enabled the functional validation of resistance-associated markers in Plasmodium falciparum, the deadliest malaria causing pathogen and strain-specific immune neutralization. This review explores recent advances made in leveraging genome editing to aid the functional evaluation of Plasmodium diversity and highlights how these techniques can assist in prioritizing both therapeutic and vaccine candidates.
    Schlagwörter Plasmodium falciparum ; antigenic variation ; antimalarials ; genome ; immune evasion ; malaria ; neutralization ; parasites ; parasitology ; pathogens ; therapeutics ; vaccine development ; vaccines
    Sprache Englisch
    Erscheinungsort Elsevier Ltd
    Dokumenttyp Artikel
    Anmerkung Pre-press version
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2022.03.005
    Datenquelle NAL Katalog (AGRICOLA)

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  2. Artikel ; Online: Leveraging genome editing to functionally evaluate Plasmodium diversity.

    Thiam, Laty Gaye / Mangou, Khadidiatou / Ba, Aboubacar / Mbengue, Alassane / Bei, Amy K

    Trends in parasitology

    2022  Band 38, Heft 7, Seite(n) 558–571

    Abstract: The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the ... ...

    Abstract The ambitious goal of malaria elimination requires an in-depth understanding of the parasite's biology to counter the growing threat of antimalarial resistance and immune evasion. Timely assessment of the functional impact of antigenic diversity in the early stages of vaccine development will be critical for achieving the goal of malaria control, elimination, and ultimately eradication. Recent advances in targeted genome editing enabled the functional validation of resistance-associated markers in Plasmodium falciparum, the deadliest malaria-causing pathogen and strain-specific immune neutralization. This review explores recent advances made in leveraging genome editing to aid the functional evaluation of Plasmodium diversity and highlights how these techniques can assist in prioritizing both therapeutic and vaccine candidates.
    Mesh-Begriff(e) Gene Editing ; Humans ; Malaria/prevention & control ; Malaria, Falciparum/drug therapy ; Plasmodium/genetics ; Plasmodium falciparum/genetics
    Sprache Englisch
    Erscheinungsdatum 2022-04-22
    Erscheinungsland England
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2022.03.005
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

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    Verfügbar in ZB MED Köln/Königswinter

    Zs.B 2898: Hefte anzeigen Standort:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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    Zs.MG 16: Hefte anzeigen
    Zs.MO 251: Hefte anzeigen

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  3. Artikel: Two mosquito salivary antigens demonstrate promise as biomarkers of recent exposure to

    Lapidus, Sarah / Goheen, Morgan M / Sy, Mouhamad / Deme, Awa B / Ndiaye, Ibrahima Mbaye / Diedhiou, Younous / Mbaye, Amadou Moctar / Hagadorn, Kelly A / Sene, Seynabou Diouf / Pouye, Mariama Nicole / Thiam, Laty Gaye / Ba, Aboubacar / Guerra, Noemi / Mbengue, Alassane / Raduwan, Hamidah / Vigan-Womas, Inés / Parikh, Sunil / Ko, Albert I / Ndiaye, Daouda /
    Fikrig, Erol / Chuang, Yu-Min / Bei, Amy K

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to : Methods: We ... ...

    Abstract Background: Measuring malaria transmission intensity using the traditional entomological inoculation rate is difficult. Antibody responses to mosquito salivary proteins such as SG6 have previously been used as biomarkers of exposure to
    Methods: We tested population-level human immune responses in longitudinal and cross-sectional plasma samples from individuals with known
    Results: AgSAP and AgTRIO were the best indicators of recent exposure to infected mosquitoes. Antibody responses to AgSAP, in a moderate endemic area, and to AgTRIO in both low and moderate endemic areas, were significantly higher than responses in a healthy non-endemic control cohort (p-values = 0.0245, 0.0064, and <0.0001 respectively). No antibody responses significantly differed between the low and moderate transmission area, or between equivalent groups during and outside the malaria transmission seasons. For AgSAP and AgTRIO, reactivity peaked 2-4 weeks after clinical
    Discussion: Reactivity to both AgSAP and AgTRIO peaked after infection and did not differ seasonally nor between areas of low and moderate transmission, suggesting reactivity is likely reflective of exposure to infectious mosquitos or recent biting rather than general mosquito exposure. Kinetics suggest reactivity is relatively short-lived. AgSAP and AgTRIO are promising candidates to incorporate into multiplexed assays for serosurveillance of population-level changes in
    Sprache Englisch
    Erscheinungsdatum 2024-04-22
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2024.04.20.24305430
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Structure-guided insights into potential function of novel genetic variants in the malaria vaccine candidate PfRh5.

    Mangou, Khadidiatou / Moore, Adam J / Thiam, Laty Gaye / Ba, Aboubacar / Orfanó, Alessandra / Desamours, Ife / Ndegwa, Duncan Ndungu / Goodwin, Justin / Guo, Yicheng / Sheng, Zizhang / Patel, Saurabh D / Diallo, Fatoumata / Sene, Seynabou D / Pouye, Mariama N / Faye, Awa Thioub / Thiam, Alassane / Nunez, Vanessa / Diagne, Cheikh Tidiane / Sadio, Bacary Djilocalisse /
    Shapiro, Lawrence / Faye, Ousmane / Mbengue, Alassane / Bei, Amy K

    Scientific reports

    2022  Band 12, Heft 1, Seite(n) 19403

    Abstract: The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While ... ...

    Abstract The recent stall in the global reduction of malaria deaths has made the development of a highly effective vaccine essential. A major challenge to developing an efficacious vaccine is the extensive diversity of Plasmodium falciparum antigens. While genetic diversity plays a major role in immune evasion and is a barrier to the development of both natural and vaccine-induced protective immunity, it has been under-prioritized in the evaluation of malaria vaccine candidates. This study uses genomic approaches to evaluate genetic diversity in next generation malaria vaccine candidate PfRh5. We used targeted deep amplicon sequencing to identify non-synonymous Single Nucleotide Polymorphisms (SNPs) in PfRh5 (Reticulocyte-Binding Protein Homologue 5) in 189 P. falciparum positive samples from Southern Senegal and identified 74 novel SNPs. We evaluated the population prevalence of these SNPs as well as the frequency in individual samples and found that only a single SNP, C203Y, was present at every site. Many SNPs were unique to the individual sampled, with over 90% of SNPs being found in just one infected individual. In addition to population prevalence, we assessed individual level SNP frequencies which revealed that some SNPs were dominant (frequency of greater than 25% in a polygenomic sample) whereas most were rare, present at 2% or less of total reads mapped to the reference at the given position. Structural modeling uncovered 3 novel SNPs occurring under epitopes bound by inhibitory monoclonal antibodies, potentially impacting immune evasion, while other SNPs were predicted to impact PfRh5 structure or interactions with the receptor or binding partners. Our data demonstrate that PfRh5 exhibits greater genetic diversity than previously described, with the caveat that most of the uncovered SNPs are at a low overall frequency in the individual and prevalence in the population. The structural studies reveal that novel SNPs could have functional implications on PfRh5 receptor binding, complex formation, or immune evasion, supporting continued efforts to validate PfRh5 as an effective malaria vaccine target and development of a PfRh5 vaccine.
    Mesh-Begriff(e) Humans ; Malaria Vaccines/genetics ; Malaria, Falciparum/prevention & control ; Plasmodium falciparum/metabolism ; Antibodies, Protozoan ; Antigens, Protozoan/genetics ; Carrier Proteins/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism
    Chemische Substanzen Malaria Vaccines ; Antibodies, Protozoan ; Antigens, Protozoan ; Carrier Proteins ; Protozoan Proteins
    Sprache Englisch
    Erscheinungsdatum 2022-11-12
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-23929-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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