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A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing

Author

Listed:
  • Wen-Wei Zhang

    (McGill University)

  • Subir Karmakar

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

  • Sreenivas Gannavaram

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

  • Ranadhir Dey

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

  • Patrick Lypaczewski

    (McGill University)

  • Nevien Ismail

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

  • Abid Siddiqui

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

  • Vahan Simonyan

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

  • Fabiano Oliveira

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Iliano V. Coutinho-Abreu

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Thiago DeSouza-Vieira

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Claudio Meneses

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • James Oristian

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Tiago D. Serafim

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Abu Musa

    (Nagasaki University, Nagasaki, Japan and Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program)

  • Risa Nakamura

    (Nagasaki University, Nagasaki, Japan and Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program)

  • Noushin Saljoughian

    (Ohio State University)

  • Greta Volpedo

    (Ohio State University)

  • Monika Satoskar

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA
    Northeast Ohio Medical University)

  • Sanika Satoskar

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA
    Northeast Ohio Medical University)

  • Pradeep K. Dagur

    (National Institute of Heart, Lung and Blood Institute, NIH)

  • J. Philip McCoy

    (National Institute of Heart, Lung and Blood Institute, NIH)

  • Shaden Kamhawi

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Jesus G. Valenzuela

    (Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Shinjiro Hamano

    (Nagasaki University, Nagasaki, Japan and Nagasaki University Graduate School of Biomedical Sciences Doctoral Leadership Program)

  • Abhay R. Satoskar

    (Ohio State University)

  • Greg Matlashewski

    (McGill University)

  • Hira L. Nakhasi

    (Division of Emerging and Transfusion Transmitted Diseases, CBER, FDA)

Abstract

Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa transmitted by infected sand flies. Vaccination through leishmanization with live Leishmania major has been used successfully but is no longer practiced because it resulted in occasional skin lesions. A second generation leishmanization is described here using a CRISPR genome edited L. major strain (LmCen−/−). Notably, LmCen−/− is a genetically engineered centrin gene knock-out mutant strain that is antibiotic resistant marker free and does not have detectable off-target mutations. Mice immunized with LmCen−/− have no visible lesions following challenge with L. major-infected sand flies, while non-immunized animals develop large and progressive lesions with a 2-log fold higher parasite burden. LmCen−/− immunization results in protection and an immune response comparable to leishmanization. LmCen−/− is safe since it is unable to cause disease in immunocompromised mice, induces robust host protection against vector sand fly challenge and because it is marker free, can be advanced to human vaccine trials.

Suggested Citation

  • Wen-Wei Zhang & Subir Karmakar & Sreenivas Gannavaram & Ranadhir Dey & Patrick Lypaczewski & Nevien Ismail & Abid Siddiqui & Vahan Simonyan & Fabiano Oliveira & Iliano V. Coutinho-Abreu & Thiago DeSou, 2020. "A second generation leishmanization vaccine with a markerless attenuated Leishmania major strain using CRISPR gene editing," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17154-z
    DOI: 10.1038/s41467-020-17154-z
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    Cited by:

    1. Ranadhir Dey & Jalal Alshaweesh & Kamaleshwar P. Singh & Patrick Lypaczewski & Subir Karmakar & Laura Klenow & Kayla Paulini & Swarnendu Kaviraj & Shaden Kamhawi & Jesus G. Valenzuela & Sanjay Singh &, 2023. "Production of leishmanin skin test antigen from Leishmania donovani for future reintroduction in the field," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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